Layering method and layering device

Abstract

Provided are a layering method and a layering device, the layering method comprising: an obtaining step of obtaining, for each of a plurality of classification subjects having mild cognitive impairment, a score of a result of a clinical psychological test performed on the classification subject, and a hippocampus volume of the classification subject; a classification step of classifying each of the plurality of classification objects according to the score of the classification object and the hippocampus volume of the classification object, classifying the object to be classified into one of a plurality of groups including at least a first group in which the risk of developing into Alzheimer's disease in the future is relatively high and a second group in which the risk of developing into Alzheimer's disease in the future is relatively low; and an output step of outputting a classification result obtained through the classification step.

Description

[0001] This application is a divisional of an invention patent application with an application date of December 16, 2022, application number 202280061563.4, and invention name “Layering method and layering device”. Technical Field

[0002] The present invention relates to a stratification method for disease risk, which accurately stratifies the risk of each of a plurality of classified subjects suffering from mild cognitive impairment (MCI) according to the possibility of developing Alzheimer's disease. Background Art

[0003] Among the mild cognitive impairment group, there are people who will develop Alzheimer's disease in the future and those who will not.

[0004] If clinical trials can be conducted with people with mild cognitive impairment who are at a relatively high risk of developing Alzheimer's disease in the future as research subjects, such clinical trials can be conducted effectively and effective prevention methods can be established.

[0005] In the prior art, a plurality of subjects suffering from mild cognitive impairment are classified into one of a plurality of groups corresponding to the risk of developing Alzheimer's disease in the future. For example, there is a known technique described in Non-Patent Document 1.

[0006] (Prior art literature)

[0007] (Non-patent literature)

[0008] Non-patent literature 1 Bin Zhou et.al, Protective Factors Modulate the Risk of Beta Amyloid in Alzheimer's Disease, Behavioral Neurology, Volume 2020, ArticleID 7029642 Summary of the invention

[0009] Problem that the invention aims to solve

[0010] In the conventional technology described in Non-Patent Document 1, the above-mentioned classification is performed using the results of brain β-amyloid protein PET examination.

[0011] Brain β-amyloid PET examination is relatively expensive. Therefore, the above classification performed by the conventional technology described in Non-Patent Document 1 is difficult to be widely popularized. In addition, in the brain β-amyloid PET examination, only about 41% of people who were found to have abnormalities developed Alzheimer's disease in an average follow-up survey of 26 months.

[0012] Therefore, in view of the above problems, the purpose of the present invention is to provide a stratification method, etc., which adopts a method different from the previous technology using brain β-amyloid protein PET examination results to classify each individual with mild cognitive impairment into a corresponding group according to the risk of developing Alzheimer's disease in the future.

[0013] Means used to solve problems

[0014] The stratification method involved in one embodiment of the present invention includes the following steps: an acquisition step, for each of a plurality of classification objects with mild cognitive impairment, obtaining the score of the classification object in a clinical psychological test and the hippocampal volume of the classification object; a classification step, for each of the plurality of classification objects, according to the score of the Alzheimer's Disease Assessment Scale-Cognitive Component Scale and the hippocampal volume of the classification object, classifying the classification object into one of a plurality of groups including at least a first group with a relatively high risk of developing Alzheimer's disease in the future and a second group with a relatively low risk of developing Alzheimer's disease in the future; and an output step, outputting the stratification result of the stratification step.

[0015] The stratification device involved in one embodiment of the present invention includes: a data acquisition part, which obtains individual clinical psychological test results and hippocampal volume for each of a plurality of classification objects suffering from mild cognitive impairment; a data classification part, which classifies each of the plurality of classification objects into at least a high-risk group with a relatively high risk of developing Alzheimer's disease in the future and a low-risk group with a relatively low risk of developing Alzheimer's disease in the future according to the score and hippocampal volume of the classification object; and a data output part, which outputs the classification results obtained by the steps.

[0016] Effects of the Invention

[0017] According to the stratification method and the like according to one embodiment of the present invention, each of a plurality of classification subjects having mild cognitive impairment can be classified into one of a plurality of groups corresponding to the risk of developing Alzheimer's disease in the future in a method different from the conventional technology. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is a schematic diagram showing an example of the content of risk evaluation performed by the present inventors with various factors as the subject.

[0019] Figure 2 This is a block diagram showing an example of the structure of the hierarchical method involved in Implementation Example 1.

[0020] Figure 3 The figure is a Kaplan-Meier curve (Kaplan-Meier survival curve) showing the results of the follow-up investigation conducted by the present inventors.

[0021] Figure 4 : is a Kaplan-Meier curve (Kaplan-Meier survival curve) showing the results of the follow-up investigation of each group conducted by the present inventors.

[0022] Figure 5 This is a flowchart of the first classification process involved in Implementation Example 1.

[0023] Figure 6 This is a block diagram showing an example of the structure of the hierarchical method involved in Implementation Example 2.

[0024] Fig. 7A : is a Kaplan-Meier curve (Kaplan-Meier survival curve) showing the results of the follow-up investigation of each group conducted by the present inventors.

[0025] Figure 7B : is a Kaplan-Meier curve (Kaplan-Meier survival curve) showing the results of the follow-up investigation of each group conducted by the present inventors.

[0026] Fig. 8A This is a flowchart of the second classification process involved in Implementation Method 2.

[0027] Figure 8B This is a flowchart of the second classification process involved in Implementation Method 2.

[0028] Fig. 9 This is a block diagram showing an example of the structure of the hierarchical method involved in Implementation Example 3.

[0029] Fig. 10A : is a Kaplan-Meier curve (Kaplan-Meier survival curve) showing the results of the follow-up investigation of each group conducted by the present inventors.

[0030] Fig. 10B : is a Kaplan-Meier curve (Kaplan-Meier survival curve) showing the results of the follow-up investigation of each group conducted by the present inventors.

[0031] Fig.11 This is a flowchart of the third classification process involved in Implementation Method 3.

[0032] Fig.12This is a block diagram showing an example of the structure of the hierarchical method involved in Implementation Example 4.

[0033] Fig.13A This is a flowchart of the fourth classification process involved in Implementation Method 4.

[0034] Fig. 13B This is a flowchart of the fourth classification process involved in Implementation Method 4.

[0035] Fig.14 This is a block diagram showing an example of the structure of the hierarchical method involved in Implementation Example 5.

[0036] Fig.15A : is a Kaplan-Meier curve (Kaplan-Meier survival curve) showing the results of the follow-up investigation of each group conducted by the present inventors.

[0037] Fig. 15B : is a Kaplan-Meier curve (Kaplan-Meier survival curve) showing the results of the follow-up investigation of each group conducted by the present inventors.

[0038] Fig.16 This is a flowchart of the fifth classification process involved in implementation mode 5.

[0039] Fig.17 This is a schematic diagram showing an example of the content of risk assessment based on various factors further performed by the present inventors on subjects who tested positive for brain β-amyloid protein PET.

[0040] Fig.18 This is a block diagram showing an example of the structure of the hierarchical method involved in Implementation Example 6.

[0041] Fig.19 This is an example of survival prediction using the product limit method showing the results of follow-up studies for each group conducted by the inventors of the present invention.

[0042] Fig. 20 This is a flowchart of the sixth classification process involved in implementation mode 6.

[0043] Fig.21 This is a block diagram showing an example of the structure of the hierarchical method involved in the first modification.

[0044] Fig. 22 This is an example of survival prediction using the product limit method showing the results of follow-up studies for each group conducted by the inventors of the present invention.

[0045] Fig.23 This is a flowchart of the seventh classification process involved in Modification Example 1.

[0046] Fig.24 This is a block diagram showing an example of the structure of the hierarchical method involved in the second modification.

[0047] Fig.25 This is an example of survival prediction using the product limit method showing the results of follow-up studies for each group conducted by the inventors of the present invention.

[0048] Fig.26 This is a flowchart of the eighth classification process involved in Modification Example 2.

[0049] Fig. 27 This is a block diagram showing an example of the structure of the hierarchical method involved in Modification Example 3.

[0050] Fig.28 This is an example of survival prediction using the product limit method showing the results of follow-up studies for each group conducted by the inventors of the present invention.

[0051] Fig.29 This is a flowchart of the ninth classification process involved in Modification Example 3.

[0052] Fig.30 This is a block diagram showing an example of the structure of the hierarchical method involved in Implementation Example 7.

[0053] Fig.31 This is a correspondence table showing the relationship between the volume fraction value (Cog_Vol) and the number of subjects classified as having progressed from mild cognitive impairment to Alzheimer's disease.

[0054] Fig.32 This is a correlation diagram showing the relationship between the volume fraction value (Cog_Vol) and the period from mild cognitive impairment to progression to Alzheimer's disease.

[0055] Fig.33 This is a correspondence table showing the relationship between the volume fraction value (Cog_Vol), a plurality of threshold values, and the number of classification subjects that progress from mild cognitive impairment to Alzheimer's disease.

[0056] Fig.34 This is a correlation diagram showing the relationship between the volume fraction value (Cog_Vol), the period from mild cognitive impairment to progression to Alzheimer's disease, or the period that does not progress to Alzheimer's disease.

[0057] Fig.35 This is a correspondence table showing the relationship between the volume fraction value (Cog_Vol), a plurality of threshold values, and the transition of the rate of classification targets progressing from mild cognitive impairment to Alzheimer's disease.

[0058] Fig.36This is a correspondence table showing the relationship between the volume fraction value (Cog_Vol), a plurality of threshold values, and the number of classification subjects that progress from mild cognitive impairment to Alzheimer's disease.

[0059] Fig.37 This is a correlation diagram showing the relationship between the volume fraction value (Cog_Vol), the period from mild cognitive impairment to progression to Alzheimer's disease, or the period that does not progress to Alzheimer's disease.

[0060] Fig.38 This is a correspondence table showing the relationship between the volume fraction value (Cog_Vol), a plurality of threshold values, and the transition of the rate of classification targets progressing from mild cognitive impairment to Alzheimer's disease.

[0061] Fig.39 This is a correspondence table showing the relationship between the volume fraction value (Cog_Vol_ab), a plurality of threshold values, and the transition of the rate of progression of classification targets from mild cognitive impairment to Alzheimer's disease.

[0062] Fig.40 This is a flowchart of the tenth classification process involved in Implementation Example 7. DETAILED DESCRIPTION

[0063] (Process of obtaining one embodiment of the present invention)

[0064] In order to obtain a stratification method that can more accurately classify each of multiple classification subjects with mild cognitive impairment into one of multiple groups corresponding to the risk of developing Alzheimer's disease in the future, the inventors evaluated the risk of developing from mild cognitive impairment to Alzheimer's disease based on various factors.

[0065] Figure 1 This is a schematic diagram showing an example of the content of risk evaluation performed by the present inventors with various factors as the subject.

[0066] In the process of risk assessment of various factors, the inventors of the present invention have discovered that by combining the scores obtained from clinical psychological tests on classified subjects with the hippocampal volume of the classified subjects, the risk of progression from mild cognitive impairment to Alzheimer's disease can be assessed relatively accurately.

[0067] Therefore, the inventors of the present invention further studied and explored based on the above findings, and thus formed the following stratification method and the like.

[0068] The stratification method involved in one embodiment of the present invention includes the following steps: an acquisition step, for each of a plurality of classification objects with mild cognitive impairment, obtaining a score of a result of a clinical psychological test conducted on the classification object and a hippocampal volume of the classification object; a classification step, for each of the plurality of classification objects, according to the score of the classification object and the hippocampal volume of the classification object, classifying the classification object into one of a plurality of groups including at least a first group with a relatively high risk of developing Alzheimer's disease in the future and a second group with a relatively low risk of developing Alzheimer's disease in the future; and an output step, outputting the classification result obtained by the classification step.

[0069] The above-mentioned stratification method can classify each of a plurality of classification subjects with mild cognitive impairment into one of a plurality of groups corresponding to the risk of developing Alzheimer's disease in the future, in a method different from the conventional technique using brain β-amyloid PET examination results.

[0070] Furthermore, the hippocampal volume of each of the plurality of classification targets may be the right hippocampal volume of each of the plurality of classification targets.

[0071] Furthermore, the clinical psychological test may be the Alzheimer's Disease Rating Scale-Cognitive Subscale.

[0072] It may also be that in the classification step, for each of the multiple classification objects, when the score of the classification object is greater than the first threshold and the right hippocampal volume of the classification object is smaller than the second threshold, the classification object is classified into the first group, and when the score of the classification object is smaller than the first threshold and the right hippocampal volume of the classification object is greater than the second threshold, the classification object is classified into the second group.

[0073] Furthermore, the first threshold value may be 20.0, and the second threshold value may be 3.651 [cm 3 ].

[0074] Furthermore, the clinical psychological test may be a preclinical Alzheimer's cognitive function test comprehensive score.

[0075] It may also be that in the classification step, for each of the multiple classification objects, when the score of the classification object is smaller than the third threshold and the right hippocampal volume of the classification object is smaller than the fourth threshold, the classification object is classified into the first group, and when the score of the classification object is larger than the third threshold and the right hippocampal volume of the classification object is larger than the fourth threshold, the classification object is classified into the second group.

[0076] Furthermore, the third threshold value may be 0.111, and the fourth threshold value may be 3.651 [cm 3 ].

[0077] It may also be that, in the obtaining step, for each of the multiple classification objects, information indicating whether the classification object has the apolipoprotein Eε4 gene is further obtained, and in the classification step, for each of the multiple classification objects, the classification object is also classified into one of the multiple groups based on the information.

[0078] Alternatively, the clinical psychological test includes: the Alzheimer's Disease Rating Scale-Cognitive Component Scale, and a preclinical Alzheimer's cognitive function test comprehensive score. In the obtaining step, for each of the multiple classification objects, information indicating whether the classification object has the apolipoprotein Eε4 gene is further obtained. In the classification step, for each of the multiple classification objects, (1) the first score of the classification object is smaller than the fifth threshold value, and the right hippocampal volume of the classification object is larger than the sixth threshold value, and the information of the classification object shows that it has the apolipoprotein Eε4 gene, and the second score of the classification object is greater than the sixth threshold value. The first score is smaller than the seventh threshold, the first score is the score obtained as a result of the Alzheimer's Disease Rating Scale-Cognitive Component Scale conducted on the classification object, and the second score is the score obtained by the comprehensive results of the preclinical Alzheimer's cognitive function test conducted on the classification object; (2) the first score of the classification object is larger than the fifth threshold, and the right hippocampal volume of the classification object is larger than the sixth threshold, and the information of the classification object shows that the apolipoprotein Eε4 gene is present, and the second score of the classification object is smaller than the seventh threshold; (3) the first score of the classification object is larger than the fifth threshold, and the right hippocampal volume of the classification object is larger than the sixth threshold, and the information of the classification object shows that the apolipoprotein Eε4 gene is present, and the second score of the classification object is smaller than the seventh threshold; (4) the first score of the classification object is larger than the fifth threshold, and the right hippocampal volume of the classification object is larger than the sixth threshold, and the information of the classification object shows that the apolipoprotein Eε4 gene is present, and the second score of the classification object is smaller than the seventh threshold; (5) the first score of the classification object is larger than the fifth threshold, and the right hippocampal volume of the classification object is larger than the sixth threshold, and the information of the classification object is larger than the seventh threshold; (1) the case where the score of the classified object is greater than the fifth threshold value, and the right hippocampal volume of the classified object is smaller than the sixth threshold value; (4) the first score of the classified object is smaller than the fifth threshold value, and the right hippocampal volume of the classified object is smaller than the sixth threshold value, and the information of the classified object shows that it has the apolipoprotein Eε4 gene, and the second score of the classified object is smaller than the seventh threshold value, and the cases (5) to (7) refer to: (5) the first score of the classified object is smaller than the fifth threshold value, and the right hippocampal volume of the classified object is greater than the sixth threshold value, and the information of the classified object shows that it has the apolipoprotein Eε4 gene, and the second score of the classified object is smaller than the seventh threshold value. The case where the object of classification has the apolipoprotein Eε4 gene and the second score of the classification object is greater than the seventh threshold value; (6) the first score of the classification object is greater than the fifth threshold value, the right hippocampal volume of the classification object is greater than the sixth threshold value, and the information of the classification object shows that the object of classification has the apolipoprotein Eε4 gene and the second score of the classification object is greater than the seventh threshold value; (7) the first score of the classification object is less than the fifth threshold value, the right hippocampal volume of the classification object is greater than the sixth threshold value, and the information of the classification object shows that the object of classification does not have the apolipoprotein Eε4 gene.

[0079] Furthermore, the fifth threshold value may be 20.0, and the sixth threshold value may be 3.651 [cm 3 ], the 7th threshold is 0.111.

[0080] Furthermore, the multiple classification objects may be those who are positive in brain β-amyloid protein PET examination, the hippocampal volume of each of the multiple classification objects may be the left hippocampal volume of each of the multiple classification objects, and the clinical psychological test may be the Alzheimer's Disease Rating Scale-Cognitive Scale.

[0081] It may also be that in the classification step, for each of the multiple classification objects, when the score of the classification object is greater than the first threshold and the left hippocampus volume of the classification object is smaller than the second threshold, the classification object is classified into the first group, and when the score of the classification object is smaller than the first threshold and the left hippocampus volume of the classification object is greater than the second threshold, the classification object is classified into the second group.

[0082] Furthermore, the first threshold value may be 14.0, and the second threshold value may be 3.459 [cm 3 ].

[0083] Furthermore, the first threshold value may be 12.0, and the second threshold value may be 3.737 [cm 3 ].

[0084] Furthermore, the first threshold value may be 21.0, and the second threshold value may be 3.080 [cm 3 ].

[0085] Furthermore, the first threshold value may be 24.0, and the second threshold value may be 2.751 [cm 3 ].

[0086] Furthermore, in the classification step, for each of the multiple classification objects, a volume fraction value representing the ratio of the left hippocampal volume of the classification object to the score of the classification object is calculated, and the classification object is classified into one of the multiple groups based on the calculated volume fraction value.

[0087] Alternatively, the volume fraction value is the left hippocampal volume [mm 3 ] ratio, in the classification step, for each of the multiple classification objects, when the volume fraction value is less than 101, the classification object is classified into the first group.

[0088] It may also be that the respective hippocampal volumes of the multiple classification objects are the respective left hippocampal volumes of the multiple classification objects, the clinical psychological test is the Alzheimer's Disease Rating Scale-Cognitive Component Scale, and in the classification step, for each of the multiple classification objects, a volume score value representing the ratio of the left hippocampal volume of the classification object to the score of the classification object is calculated, and based on the calculated volume score value, the classification object is classified into one of the multiple groups.

[0089] Alternatively, the volume fraction value is the left hippocampal volume [mm 3 ] ratio, in the classification step, for each of the multiple classification objects, when the volume fraction value is less than 101, the classification object is classified into the first group.

[0090] A stratification device involved in one embodiment of the present invention comprises: an acquisition unit, which obtains, for each of a plurality of classification objects with mild cognitive impairment, a score of a result of a clinical psychological test conducted on the classification object and the hippocampal volume of the classification object; a classification unit, which classifies, for each of the plurality of classification objects, the classification object into one of a plurality of groups including at least a first group with a relatively high risk of developing Alzheimer's disease in the future and a second group with a relatively low risk of developing Alzheimer's disease in the future based on the score of the classification object and the hippocampal volume of the classification object; and an output unit, which outputs the classification result obtained by the classification unit.

[0091] The above-mentioned stratification device can classify each of a plurality of classification subjects with mild cognitive impairment into one of a plurality of groups corresponding to the risk of developing Alzheimer's disease in the future, using a method different from the conventional technology using brain β-amyloid protein PET examination results.

[0092] Hereinafter, specific examples of a layering method and the like according to one embodiment of the present invention will be described with reference to the drawings.

[0093] The embodiments shown here are all examples of the present invention. Therefore, the numerical values, shapes, components, configurations of components, connection methods, steps (processes), and the order of steps shown in the following embodiments are examples, and their purpose is not to limit the present invention. In addition, each figure is a schematic diagram, not a rigorous diagram. In each figure, the same number is given to substantially the same structure, and repeated descriptions are omitted or simplified.

[0094] In this specification, the stratification method is also referred to as a classification method, and the stratification device is also referred to as a classification device.

[0095] (Implementation Method 1)

[0096] The following is a description of a stratification device in Embodiment 1 for executing the stratification method involved in Embodiment 1. The stratification device is a device for classifying each of a plurality of classification objects having mild cognitive impairment into one of a plurality of groups corresponding to the risk of developing Alzheimer's disease in the future. The plurality of groups include at least a high-risk group, i.e., Group 1, having a relatively high risk of developing Alzheimer's disease in the future, and a low-risk group, i.e., Group 2, having a relatively low risk of developing Alzheimer's disease in the future.

[0097] Furthermore, the stratification device that executes the above-mentioned stratification method is an example of a device that executes a classification process in which the findings obtained by the inventors through a cohort study on a plurality of classification subjects with mild cognitive impairment are reflected.

[0098] <Composition>

[0099] Figure 2 This is a block diagram showing an example of the structure of the hierarchical device 10 that executes the hierarchical method according to the first embodiment.

[0100] The decomposition device 10 is implemented by, for example, a computer device. In this case, the decomposition device 10 is implemented by, for example, a processor in the computer device executing a program stored in a memory in the computer device.

[0101] like Figure 2 As shown, the stratification device 10 includes an acquisition unit 20 , a classification unit 30 , and an output unit 40 .

[0102] The acquisition unit 20 acquires, for each of a plurality of classification objects with mild cognitive impairment, a score obtained by performing a clinical psychological test on the classification object and a right hippocampal volume of the classification object. The right hippocampal volume can be measured by, for example, performing an MRI examination on the classification object and performing image processing on a head MRI image obtained by performing the MRI examination.

[0103] The clinical psychological test performed on the classified subjects to be described in the first embodiment is the Alzheimer's Disease Assessment Scale-cognitive subscale [ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale)].

[0104] The acquisition unit 20 may, for example, have a communication interface, through which the score (hereinafter also referred to as the "score of the Alzheimer's Disease Assessment Scale-Cognitive Component Scale") obtained by performing an Alzheimer's Disease Assessment Scale-Cognitive Component Scale test on the classification object and the right hippocampal volume of the classification object are obtained from an external device. It may also have a memory interface for reading data from a portable and removable memory (for example, a USB memory), through which the score of the Alzheimer's Disease Assessment Scale-Cognitive Component Scale and the right hippocampal volume are obtained from the portable and removable memory. It may also have an input-output interface for accepting operations performed by a user using the stratification device 10, through which the data input operations performed by the user are accepted, thereby obtaining the score of the Alzheimer's Disease Assessment Scale-Cognitive Component Scale and the right hippocampal volume.

[0105] The classification unit 30 classifies each of the plurality of classification objects into one of a plurality of groups including at least a first group having a relatively high risk of developing Alzheimer's disease in the future and a second group having a relatively low risk of developing Alzheimer's disease in the future, based on the score of the Alzheimer's Disease Rating Scale-Cognitive Component and the right hippocampal volume. In the first embodiment, the plurality of groups include a third group and a fourth group in addition to the first group and the second group, and the plurality of groups are described as four groups.

[0106] The classification unit 30 performs the above classification based on the findings obtained by the inventors through a cohort study on a plurality of classification subjects having mild cognitive impairment.

[0107] Specifically, the classification unit 30 performs the following classifications (1) to (4) for each of the multiple classification objects: (1) when the score of the Alzheimer's Disease Assessment Scale-Cognitive Component is greater than the first threshold and the right hippocampal volume is less than the second threshold, the classification object is classified into the first group; (2) when the score of the Alzheimer's Disease Assessment Scale-Cognitive Component is less than the first threshold and the right hippocampal volume is greater than the second threshold, the classification object is classified into the second group; (3) when the score of the Alzheimer's Disease Assessment Scale-Cognitive Component is greater than the first threshold and the right hippocampal volume is greater than the second threshold, the classification object is classified into the third group; (4) when the score of the Alzheimer's Disease Assessment Scale-Cognitive Component is less than the first threshold and the right hippocampal volume is less than the second threshold, the classification object is classified into the fourth group. Here, the classification unit 30 sets the first threshold to 20.0 and the second threshold to 3.651 [cm 3 ] to carry out the above classification.

[0108] The following is a description of findings obtained by the present inventors through a cohort study of subjects of multiple categories with mild cognitive impairment.

[0109] The present inventors conducted a cohort study on subjects of multiple categories with mild cognitive impairment and followed up the progression from mild cognitive impairment to Alzheimer's disease.

[0110] Figure 3 The results of the follow-up investigation conducted by the present inventors in the cohort study are shown (Kaplan-Meier survival curve).

[0111] exist Figure 3 In the Kaplan-Meier curve, the horizontal axis represents the time [years] since the start of the follow-up survey, and the vertical axis represents the cumulative conversion rate [%] of the subjects classified from mild cognitive impairment to Alzheimer's disease.

[0112] like Figure 3 As shown, in the cohort study, the inventors conducted a follow-up investigation of 325 subjects with mild cognitive impairment for about 5 years on the progression from mild cognitive impairment to Alzheimer's disease. During the approximately 5-year period, 104 subjects developed from mild cognitive impairment to Alzheimer's disease.

[0113] In the cohort study, the present inventors classified each of the multiple classification subjects into one of the following groups (1) to (4) at the beginning of the follow-up survey, and evaluated the Kaplan-Meier curves showing the results of the follow-up survey of each group after classification. The above-mentioned groups (1) to (4) are: (1) Group C (corresponding to Group 1) consisting of classification subjects whose scores on the Alzheimer's Disease Rating Scale-Cognitive Component Scale are greater than the first threshold and whose right hippocampal volume is smaller than the second threshold, (2) Group C (corresponding to Group 1) consisting of classification subjects whose scores on the Alzheimer's Disease Rating Scale-Cognitive Component Scale are greater than the first threshold and whose right hippocampal volume is smaller than the second threshold, (1) Group B (corresponding to the second group) is composed of classification objects whose scores on the Alzheimer's Disease Assessment Scale-Cognitive Component are lower than the first threshold and whose right hippocampal volume is higher than the second threshold, (2) Group D (corresponding to the third group) is composed of classification objects whose scores on the Alzheimer's Disease Assessment Scale-Cognitive Component are higher than the first threshold and whose right hippocampal volume is higher than the second threshold, and (3) Group A (corresponding to the fourth group) is composed of classification objects whose scores on the Alzheimer's Disease Assessment Scale-Cognitive Component are higher than the first threshold and whose right hippocampal volume is higher than the second threshold.

[0114] Figure 4 This is a Kaplan-Meier curve showing the results of a follow-up survey for each group conducted by the present inventors in a cohort study.

[0115] exist Figure 4 In the Kaplan-Meier curve shown, the horizontal axis represents the time [years] that has passed since the start of the follow-up survey, and the vertical axis represents the cumulative conversion rate [%] of the subjects classified from mild cognitive impairment to Alzheimer's disease.

[0116] from Figure 4 From the Kaplan-Meier curve shown, it can be seen that among Groups 1 to 4, Group 1 was the group with a relatively high risk of developing Alzheimer's disease in the future at the beginning of the follow-up survey, while Group 2 was the group with a relatively low risk of developing Alzheimer's disease in the future at the beginning of the follow-up survey.

[0117] Thus, the inventors obtained the following insights through cohort studies, namely, for each of a plurality of classification subjects with mild cognitive impairment, (1) when the score of the Alzheimer's Disease Assessment Scale-cognitive subscale is greater than the first threshold and the right hippocampal volume is less than the second threshold, the classification subject is classified into the first group; (2) when the score of the Alzheimer's Disease Assessment Scale-cognitive subscale is less than the first threshold and the right hippocampal volume is greater than the second threshold, the classification subject is classified into the second group; (3) when the score of the Alzheimer's Disease Assessment Scale-cognitive subscale is greater than the first threshold and the right hippocampal volume is greater than the second threshold, the classification subject is classified into the second group; (4) when the score of the Alzheimer's Disease Assessment Scale-Cognitive Component Scale is smaller than the first threshold value and the right hippocampal volume is smaller than the second threshold value, the classification object is classified into the fourth group. By performing the above classification, a plurality of classification objects with mild cognitive impairment can be classified into one of a plurality of groups (herein, four groups) including at least a first group with a relatively high risk of developing Alzheimer's disease in the future and a second group with a relatively low risk of developing Alzheimer's disease in the future.

[0118] Furthermore, the inventors of the present invention have obtained the following knowledge through cohort studies, that is, in the above classification, the first threshold is preferably 20.0±1SD, and the second threshold is preferably 3.651±1SD [cm 3 Here, the 1SD of the first threshold is 6.3, and the 1SD of the second threshold is 0.653 [cm 3 ].

[0119] Return to Figure 2 , the description of the layering device 10 is continued.

[0120] The output unit 40 outputs the classification result performed by the classification unit 30 .

[0121] The output unit 40 may, for example, have an output port, through which a display control signal including a classification result is output to an external display device, and the display control signal is used to cause the external display device to display an image representing the classification result. For example, it may also have a communication interface, through which classification result information including a classification result is sent.

[0122] <Work>

[0123] The operation of the layering device 10 having the above-mentioned structure will be described below with reference to the drawings.

[0124] Figure 5 1 is a flowchart of the first classification process performed by the stratification device 10. The first classification process is a process of classifying each of a plurality of classification objects into one of four groups including at least a first group having a relatively high risk of developing Alzheimer's disease in the future and a second group having a relatively low risk of developing Alzheimer's disease in the future, based on the score of the Alzheimer's Disease Rating Scale-Cognitive Component and the right hippocampal volume.

[0125] The first classification process is started, for example, when a user who uses the layer device 10 performs an operation on the layer device 10 to start the first classification process.

[0126] When the first classification process starts, the acquisition unit 20 obtains, for each of a plurality of classification objects with mild cognitive impairment, a score obtained as a result of performing the Alzheimer's Disease Assessment Scale-Cognitive Component Scale (ADAS-cog) on ​​the classification object (hereinafter also referred to as the "ADAS-cog score") and the right hippocampal volume of the classification object (step S5).

[0127] When ADAS-cog scores and right hippocampal volumes of multiple classification targets are obtained, the classification unit 30 selects one classification target from the multiple classification targets (step S10). Then, the classification unit 30 checks whether the ADAS-cog score of the selected classification target is 20.0 or more (step S15).

[0128] In the process of step S15 , when the ADAS-cog score is 20.0 or more (“Yes” in step S15 ), the classifying unit 30 checks whether the right hippocampal volume of the selected classification target is 3.651 or more (step S20 ).

[0129] In the process of step S20 , when the right hippocampal volume is not greater than 3.651 (“No” in step S20 ), the classification unit 30 classifies the classification target in the selected state into the first group (step S25 ).

[0130] In the process of step S20 , when the right hippocampal volume is 3.651 or more (“Yes” in step S20 ), the classification unit 30 classifies the classification target in the selected state into the third group (step S30 ).

[0131] In the process of step S15 , when the ADAS-cog score is not greater than 20.0 (No in step S15 ), the classifying unit 30 checks whether the right hippocampal volume of the selected classification target is greater than or equal to 3.651 (step S35 ).

[0132] In the process of step S35 , when the right hippocampal volume is not greater than 3.651 (“No” in step S35 ), the classification unit 30 classifies the classification target in the selected state into the fourth group (step S40 ).

[0133] In the process of step S35 , when the right hippocampal volume is equal to or greater than 3.651 (“Yes” in step S35 ), the classification unit 30 classifies the classification target in the selected state into the second group (step S45 ).

[0134] When the processing of step S25 is completed, the processing of step S30 is completed, the processing of step S40 is completed, and the processing of step S45 is completed, the classification unit 30 checks whether there is a classification object that has not been selected among the multiple classification objects (step S50). Here, the classification object that has not been selected refers to a classification object that has not been selected in the processing of step S10, and has not been selected in the processing of step S55 described later in the loop processing from the processing of step S15 to the "Yes" of step S50 and then the processing of step S15 is entered again.

[0135] In the process of step S50 , if there is an unselected classification target (“Yes” in step S50 ), the classification unit 30 selects one classification target from the unselected classification targets (step S55 ).

[0136] When the process of step S55 is completed, the process proceeds to step S15.

[0137] In the process of step S50 , when there is no unselected classification target (“No” in step S50 ), the output unit 40 outputs the classification result of each of the plurality of classification targets by the classification unit 30 (step S60 ).

[0138] When the process of step S60 is completed, the classifier 10 ends the above-mentioned first classification process.

[0139] <Inspection>

[0140] The stratification device 10 having the above-described structure can classify a plurality of classification subjects with mild cognitive impairment into one of a plurality of groups including at least a first group having a relatively high risk of developing Alzheimer's disease in the future and a second group having a relatively low risk of developing Alzheimer's disease in the future.

[0141] Therefore, by using the stratification device 10 to classify a plurality of classification subjects having mild cognitive impairment in advance, clinical trials etc. can be efficiently conducted with people who have developed Alzheimer's disease from mild cognitive impairment as research subjects.

[0142] Furthermore, the stratification device 10 having the above configuration can perform the above classification in a different method from the conventional technology. That is, the stratification device 10 does not utilize the relatively expensive brain β-amyloid protein PET examination results required in the conventional technology for the above classification.

[0143] Therefore, by using the stratification device 10, the above-mentioned classification can be performed at a low cost and with a better classification effect than when using the conventional technology.

[0144] (Implementation Method 2)

[0145] The following is a description of the stratification device in the second embodiment for executing the stratification method involved in the second embodiment. In the configuration of the second embodiment, a part of the function of the stratification device 10 involved in the first embodiment is changed. As shown in the description in the first embodiment, the stratification device 10 classifies a plurality of classification objects with mild cognitive impairment according to the score obtained as a result of performing the Alzheimer's Disease Rating Scale-Cognitive Component Scale and the right hippocampal volume. In this regard, in the stratification method involved in the second embodiment, in addition to the score obtained as a result of performing the Alzheimer's Disease Rating Scale-Cognitive Component Scale and the right hippocampal volume, a plurality of classification objects with mild cognitive impairment are classified according to whether or not the apolipoprotein Eε4 gene exists. Here, for the stratification device for executing the stratification method involved in the second embodiment, since the same components as the stratification device 10 have been described, the same numbers are assigned and the detailed description is omitted, and the following description focuses on the differences from the stratification device 10.

[0146] <Composition>

[0147] Figure 6 This is a block diagram showing an example of the configuration of a layering device 10A that executes the layering method according to the second embodiment.

[0148] like Figure 6 As shown, the delamination device 10A is different from the delamination device 10 according to the first embodiment in that the acquisition unit 20 is changed to an acquisition unit 20A, and the classification unit 30 is changed to a classification unit 30A.

[0149] The acquisition unit 20A obtains, for each of multiple classification objects with mild cognitive impairment, information indicating whether the classification object has the apolipoprotein Eε4 gene (hereinafter also referred to as "ApoE typing") in addition to the score obtained as a result of performing the Alzheimer's Disease Rating Scale-Cognitive Component Scale on the classification object and the right hippocampal volume of the classification object.

[0150] The classification unit 30A classifies each of the multiple classification objects into one of the multiple groups including at least a first group with a relatively high risk of developing Alzheimer's disease in the future and a second group with a relatively low risk of developing Alzheimer's disease in the future, based on the score of the Alzheimer's Disease Rating Scale-Cognitive Component, the right hippocampal volume, and the ApoE typing. In the second embodiment, the multiple groups include a third group, a fourth group, a fifth group, a sixth group, a seventh group, and an eighth group in addition to the first group and the second group. The multiple groups consisting of these eight groups are described below.

[0151] The classifying unit 30A performs the above-mentioned classification based on the findings obtained by the present inventors through a cohort study on a plurality of classification subjects having mild cognitive impairment.

[0152] More specifically, the classification unit 30A performs the following classifications (1) to (8) for each of the multiple classification objects: (1) when the ApoE typing shows that the classification object has the apolipoprotein Eε4 gene (hereinafter also referred to as "ApoE+"), and the score of the Alzheimer's Disease Assessment Scale-Cognitive Component is greater than the first threshold, and the right hippocampal volume is smaller than the second threshold, the classification object is classified into the first group; (2) when the ApoE typing shows that ApoE+, and the Alzheimer's Disease Assessment Scale-Cognitive Component is less than the second threshold, the classification object is classified into the first group; (3) When the ApoE typing shows ApoE+, the score of the Alzheimer's Disease Rating Scale-Cognitive Scale is greater than the first threshold, and the right hippocampal volume is greater than the second threshold, the classification object is classified into the second group. (4) When the ApoE typing shows ApoE+, the score of the Alzheimer's Disease Rating Scale-Cognitive Scale is less than the first threshold, and the right hippocampal volume is greater than the second threshold, the classification object is classified into the third group. (5) When the ApoE typing shows that the classification object does not have the apolipoprotein Eε4 gene (hereinafter also referred to as "ApoE-"), and the score of the Alzheimer's Disease Assessment Scale-Cognitive Component is greater than the first threshold value, and the right hippocampal volume is smaller than the second threshold value, the classification object is classified into the fifth group. (6) When the ApoE typing shows that ApoE-, and the score of the Alzheimer's Disease Assessment Scale-Cognitive Component is smaller than the first threshold value, and the right hippocampal volume is smaller than the second threshold value, the classification object is classified into the fifth group. When the second threshold is greater, the classification object is classified into the 6th group. (7) When the ApoE typing shows ApoE-, the score of the Alzheimer's Disease Rating Scale-Cognitive Component is greater than the first threshold, and the right hippocampal volume is greater than the second threshold, the classification object is classified into the 7th group. (8) When the ApoE typing shows ApoE-, the score of the Alzheimer's Disease Rating Scale-Cognitive Component is less than the first threshold, and the right hippocampal volume is less than the second threshold, the classification object is classified into the 8th group. Here, the classification unit 30A sets the first threshold to 20.0 and the second threshold to 3.651 [cm 3 ] and carry out the above classification.

[0153] The following is a description of findings obtained by the present inventors through a cohort study of subjects of multiple categories with mild cognitive impairment.

[0154] In the cohort study, the present inventors first classified each of a plurality of classification objects into (A) group α consisting of classification objects without the apolipoprotein Eε4 gene and (B) group β consisting of classification objects with the apolipoprotein Eε4 gene as the first stage classification at the beginning of the follow-up survey. Then, as the second stage classification, each of group α and group β was classified into one of the following groups (1) to (4), and the Kaplan-Meier curve showing the results of the follow-up survey of each group after classification was evaluated. The groups classified into (1) to (4) are: (1) group C consisting of classification objects whose scores on the Alzheimer's Disease Assessment Scale-Cognitive Subscale were greater than the first threshold and whose right hippocampal volume was less than the second threshold (corresponding to Group 1 in Group α and Group 5 in Group β); (2) Group B consisting of classification objects whose scores on the Alzheimer's Disease Rating Scale-Cognitive Component Scale are smaller than the first threshold and whose right hippocampal volume is larger than the second threshold (corresponding to Group 2 in Group α and Group 6 in Group β); (3) Group D consisting of classification objects whose scores on the Alzheimer's Disease Rating Scale-Cognitive Component Scale are larger than the first threshold and whose right hippocampal volume is larger than the second threshold (corresponding to Group 3 in Group α and Group 7 in Group β); (4) Group A consisting of classification objects whose scores on the Alzheimer's Disease Rating Scale-Cognitive Component Scale are smaller than the first threshold and whose right hippocampal volume is smaller than the second threshold (corresponding to Group 4 in Group α and Group 8 in Group β).

[0155] Fig. 7A as well as Figure 7B It is a Kaplan-Meier curve showing the results of follow-up investigation of each group conducted by the present inventors in the cohort study.

[0156] Fig. 7A is a Kaplan-Meier curve showing the results of the follow-up survey for each group conducted with group α as the object, Figure 7B β is a Kaplan-Meier curve showing the results of the follow-up survey for each group conducted with group β as the target.

[0157] exist Fig. 7A as well as Figure 7B In the Kaplan-Meier curve shown, the horizontal axis represents the time [years] that has passed since the start of the follow-up survey, and the vertical axis represents the cumulative conversion rate [%] of the subjects classified from mild cognitive impairment to Alzheimer's disease.

[0158] from Fig. 7A as well as Figure 7BFrom the Kaplan-Meier curve shown, it can be seen that among Group 1 to Group 8, Group 1 is a group with a relatively high risk of developing Alzheimer's disease in the future at the beginning of the follow-up survey, and Group 2 is a group with a relatively low risk of developing Alzheimer's disease in the future at the beginning of the follow-up survey.

[0159] Thus, the inventors of the present invention obtained the following insights through cohort studies, namely, for each of a plurality of classification subjects with mild cognitive impairment, the classification as shown in the following (1) to (8) was performed, (1) when the ApoE typing showed ApoE+, and the score of the Alzheimer's Disease Assessment Scale-Cognitive Component was greater than the first threshold, and the right hippocampal volume was less than the second threshold, the classification subject was classified into the first group, and (2) when the ApoE typing showed ApoE+, and the score of the Alzheimer's Disease Assessment Scale-Cognitive Component was less than the first threshold, and the right hippocampal volume was greater than the second threshold, the classification subject was classified into the second group. In the case where the ApoE typing shows ApoE+, the score of the Alzheimer's Disease Rating Scale-Cognitive Component is greater than the first threshold, and the right hippocampal volume is greater than the second threshold, the classification object is classified into the third group. (4) In the case where the ApoE typing shows ApoE+, the score of the Alzheimer's Disease Rating Scale-Cognitive Component is less than the first threshold, and the right hippocampal volume is less than the second threshold, the classification object is classified into the fourth group. (5) In the case where the ApoE typing shows that the classification object does not have the apolipoprotein Eε4 gene (hereinafter referred to as (also referred to as "ApoE-"), and the score of the cognitive subscale of the Alzheimer's Disease Rating Scale is greater than the first threshold, and the right hippocampal volume is smaller than the second threshold, the classification object is classified into the 5th group; (6) When the ApoE typing shows ApoE-, and the score of the cognitive subscale of the Alzheimer's Disease Rating Scale is smaller than the first threshold, and the right hippocampal volume is larger than the second threshold, the classification object is classified into the 6th group; (7) When the ApoE typing shows ApoE-, and the score of the cognitive subscale of the Alzheimer's Disease Rating Scale is greater than the first threshold, and the right hippocampal volume is larger than the second threshold, the classification object is classified into the 6th group. When the second threshold is large, the classification object is classified into the 7th group. (8) When the ApoE typing shows ApoE-, and the score of the Alzheimer's Disease Assessment Scale-cognitive subscale is smaller than the first threshold, and the right hippocampal volume is smaller than the second threshold, the classification object is classified into the 8th group. By performing the above classification, a plurality of classification objects with mild cognitive impairment can be classified into one of a plurality of groups (here 8 groups) including at least the 1st group with a relatively high risk of developing Alzheimer's disease in the future and the 2nd group with a relatively low risk of developing Alzheimer's disease in the future.

[0160] And, from Fig. 7A as well as Figure 7BFrom the Kaplan-Meier curve shown, it can be seen that, compared with the classification result obtained by performing the above-mentioned second-stage classification on group α composed of classification objects not having the apolipoprotein Eε4 gene, the classification result obtained by performing the above-mentioned second-stage classification on group α composed of classification objects not having the apolipoprotein Eε4 gene can more accurately classify a plurality of classification objects with mild cognitive impairment into one of a plurality of groups including at least a group with a relatively high risk of developing Alzheimer's disease in the future and a group with a relatively low risk of developing Alzheimer's disease in the future.

[0161] Thus, the inventors of the present invention have obtained the following insight through cohort studies, namely, in addition to the scores of the Alzheimer's Disease Assessment Scale-Cognitive Component and the right hippocampal volume, the ApoE typing can be used to more accurately classify the classification subjects into one of multiple groups including at least Group 1 with a relatively high risk of developing Alzheimer's disease in the future and Group 2 with a relatively low risk of developing Alzheimer's disease in the future.

[0162] <Work>

[0163] The operation of the layer separation device 10A having the above-described structure will be described below with reference to the drawings.

[0164] The delamination device 10A performs a second classification process in which a part of the first classification process performed by the delamination device 10 is changed.

[0165] Fig. 8A as well as Figure 8B This is a flowchart of the second classification process performed by the declassification device 10A.

[0166] like Fig. 8A as well as Figure 8B As shown, the second classification process includes additional processes of step S100 to step S180 compared to the first classification process.

[0167] Therefore, the following description will focus on the processing of step S100 to step S180.

[0168] When the second classification process starts, the acquisition unit 20A acquires the ADAS-cog score, the right hippocampal volume, and the ApoE typing of each of a plurality of classification targets having mild cognitive impairment (step S100 ).

[0169] When the process of step S100 is completed, the process proceeds to step S10.

[0170] When the process of step S10 is completed and the process of step S55 is completed, the classifying unit 30A checks whether the ApoE typing of the selected classification target indicates ApoE+ (step S110 ).

[0171] In the process of step S110 , if the ApoE typing of the classification target in the selected state does not indicate ApoE+ (“No” in step S110 ), the process proceeds to step S15 .

[0172] In the process of step S110 , when the ApoE typing of the selected classification target indicates ApoE+ (“Yes” in step S110 ), the classifier 30A checks whether the ADAS-cog score of the selected classification target is 20.0 or more (step S120 ).

[0173] In the process of step S120 , when the ADAS-cog score is 20.0 or more (“Yes” in step S120 ), the classifying unit 30A checks whether the right hippocampal volume of the selected classification target is 3.651 or more (step S130 ).

[0174] In the process of step S130 , when the right hippocampus volume is not greater than 3.651 (“No” in step S130 ), the classifying unit 30A classifies the classification target in the selected state into the fifth group (step S140 ).

[0175] In the process of step S130 , when the right hippocampal volume is 3.651 or more (“Yes” in step S130 ), the classification unit 30A classifies the classification target in the selected state into the seventh group (step S150 ).

[0176] In the process of step S120 , when the ADAS-cog score is not greater than 20.0 (No in step S120 ), the classifying unit 30A checks whether the right hippocampal volume of the selected classification target is greater than or equal to 3.651 (step S160 ).

[0177] In the process of step S160 , when the right hippocampal volume is not greater than 3.651 (“No” in step S160 ), the classifying unit 30A classifies the classification target in the selected state into the eighth group (step S170 ).

[0178] In the process of step S160 , when the right hippocampal volume is 3.651 or more (“Yes” in step S160 ), the classification unit 30A classifies the classification target in the selected state into the sixth group (step S180 ).

[0179] When the process of step S140 is completed, the process of step S150 is completed, the process of step S170 is completed, and the process of step S180 is completed, the process proceeds to step S50.

[0180] When the process of step S60 is completed, the layering device 10A ends the second classification process.

[0181] <Inspection>

[0182] The stratification device 10A having the above-mentioned structure categorizes a plurality of categorized subjects with mild cognitive impairment according to whether or not they have the apolipoprotein Eε4 gene in addition to the scores of the Alzheimer's Disease Rating Scale-Cognitive Component and the right hippocampal volume. Thus, the stratification device 10A can categorize the categorized subjects more accurately.

[0183] (Implementation method 3)

[0184] The following is a description of the stratification device in the third embodiment of the stratification method involved in the third embodiment. The structure of the stratification device involved in the third embodiment is that the function of a part of the stratification device 10 involved in the first embodiment is changed. As shown in the description of the first embodiment, the stratification device 10 classifies a plurality of classification objects with mild cognitive impairment according to the scores obtained as a result of the Alzheimer's Disease Rating Scale-Cognitive Component Scale, which is a clinical psychological test conducted on the classification object, and the right hippocampal volume. Here, the stratification method involved in the third embodiment classifies a plurality of classification objects with mild cognitive impairment according to the comprehensive score of the preclinical Alzheimer cognitive function test (PACC (Preclinical Alzheimer Cognitive Composit)) and the right hippocampal volume of the clinical psychological test conducted on the classification object. Here, with respect to the stratification device for executing the stratification method involved in the third embodiment, for the same components as the stratification device 10, since they have been described, the same numbers are given and detailed description is omitted, and the following description is centered on the differences from the stratification device 10.

[0185] <Composition>

[0186] Fig. 9 This is a block diagram showing an example of the configuration of a decomposition device 10B that executes the decomposition method according to the third embodiment.

[0187] like Fig. 9 As shown, the delamination device 10B is different from the delamination device 10 according to the first embodiment in that the acquisition unit 20 is changed to an acquisition unit 20B, and the classification unit 30 is changed to a classification unit 30B.

[0188] The obtaining unit 20B obtains, for each of the multiple classification subjects with mild cognitive impairment, a score obtained by combining the results of several preclinical Alzheimer's cognitive function tests conducted on the classification subject (hereinafter also referred to as "preclinical Alzheimer's cognitive function test comprehensive score") and the right hippocampal volume of the classification subject.

[0189] The classification unit 30B classifies each of the plurality of classification objects into one of a plurality of groups including at least a first group having a relatively high risk of developing Alzheimer's disease in the future and a second group having a relatively low risk of developing Alzheimer's disease in the future, based on the preclinical Alzheimer's cognitive function test comprehensive score and the right hippocampal volume. In the third embodiment, the plurality of groups includes a third group and a fourth group in addition to the first group and the second group, and the plurality of groups consisting of these four groups will be described.

[0190] The classifying unit 30B performs the above-mentioned classification based on the findings obtained by the present inventors through a cohort study on a plurality of classification subjects having mild cognitive impairment.

[0191] More specifically, the classification unit 30B performs the following classification for each of the multiple classification objects: (1) when the preclinical Alzheimer's cognitive function test comprehensive score is smaller than the third threshold value and the right hippocampal volume is smaller than the fourth threshold value, the classification object is classified into the first group; (2) when the preclinical Alzheimer's cognitive function test comprehensive score is larger than the third threshold value and the right hippocampal volume is larger than the fourth threshold value, the classification object is classified into the second group; (3) when the preclinical Alzheimer's cognitive function test comprehensive score is smaller than the third threshold value and the right hippocampal volume is larger than the fourth threshold value, the classification object is classified into the third group; (4) when the preclinical Alzheimer's cognitive function test comprehensive score is larger than the third threshold value and the right hippocampal volume is smaller than the fourth threshold value, the classification object is classified into the fourth group. Here, the classification unit 30B sets the fourth threshold value to 0.111 and the fourth threshold value to 3.651 [cm 3 ] to carry out the above classification.

[0192] The following describes findings obtained by the present inventors through a cohort study of subjects of multiple categories with mild cognitive impairment.

[0193] In the cohort study, the inventors first classified each of the multiple classification objects as the first stage, when starting the follow-up survey, (A) classified into group α composed of classification objects without apolipoprotein Eε4 gene; and (B) classified into group β composed of classification objects with apolipoprotein Eε4 gene, then performed the second stage classification for group α and group β classified in the first stage, and evaluated the Kaplan-Meier curve showing the results of the follow-up survey of each group after classification. The second stage classification refers to classification into one of the following groups (1) to (4): (1) classification with a preclinical Alzheimer cognitive function test comprehensive score smaller than the third threshold and a right hippocampal volume smaller than the fourth threshold (1) Group A consisting of subjects with a preclinical Alzheimer's cognitive function composite score greater than the third threshold and a right hippocampal volume greater than the fourth threshold (corresponding to Group 1 in Group α and Group 5 in Group β); (2) Group D consisting of subjects with a preclinical Alzheimer's cognitive function composite score greater than the third threshold and a right hippocampal volume greater than the fourth threshold (corresponding to Group 2 in Group α and Group 6 in Group β); (3) Group B consisting of subjects with a preclinical Alzheimer's cognitive function composite score less than the third threshold and a right hippocampal volume greater than the fourth threshold (corresponding to Group 3 in Group α and Group 7 in Group β); and (4) Group C consisting of subjects with a preclinical Alzheimer's cognitive function composite score greater than the third threshold and a right hippocampal volume less than the fourth threshold (corresponding to Group 4 in Group α and Group 8 in Group β).

[0194] Fig. 10A as well as Fig. 10B The figure is a Kaplan-Meier curve showing the results of the follow-up survey for each group conducted by the present inventors in the cohort study.

[0195] Fig. 10A is a Kaplan-Meier curve showing the results of the follow-up survey for each group, taking group α as the object. Fig. 10B This is a Kaplan-Meier curve showing the results of follow-up survey for each group, taking group β as the object.

[0196] exist Fig. 10A as well as Fig. 10B In the Kaplan-Meier curve shown, the horizontal axis represents the time [years] that has passed since the start of the follow-up survey, and the vertical axis represents the cumulative conversion rate [%] of the subjects classified from mild cognitive impairment to Alzheimer's disease.

[0197] from Fig. 10A as well as Fig. 10BFrom the Kaplan-Meier curve shown, it can be seen that among Groups 1 to 8, Groups 1 and 5 were the groups with relatively high risks of developing Alzheimer's disease in the future at the beginning of the follow-up survey, and Groups 2 and 6 were the groups with relatively low risks of developing Alzheimer's disease in the future at the beginning of the follow-up survey.

[0198] Thus, the inventors of the present invention have obtained the following insight through the cohort study, that is, for each of the multiple classified subjects with mild cognitive impairment, by performing the following classifications (1) to (4), the multiple classified subjects with mild cognitive impairment can be classified into one of multiple groups (herein, four groups) including at least a first group with a relatively high risk of developing Alzheimer's disease in the future and a second group with a relatively low risk of developing Alzheimer's disease in the future, wherein the classifications (1) to (4) refer to: (1) in the preclinical Alzheimer's cognitive function comprehensive score being less than the third threshold and the right hippocampus being (1) when the preclinical Alzheimer's cognitive function test comprehensive score is greater than the third threshold and the right hippocampal volume is greater than the fourth threshold, the classification object is classified into the first group; (2) when the preclinical Alzheimer's cognitive function test comprehensive score is greater than the third threshold and the right hippocampal volume is greater than the fourth threshold, the classification object is classified into the second group; (3) when the preclinical Alzheimer's cognitive function test comprehensive score is less than the third threshold and the right hippocampal volume is greater than the fourth threshold, the classification object is classified into the third group; (4) when the preclinical Alzheimer's cognitive function comprehensive score is greater than the third threshold and the right hippocampal volume is less than the fourth threshold, the classification object is classified into the fourth group.

[0199] Furthermore, the inventors of the present invention have obtained the following insights in the above classification through cohort studies, namely, the first threshold is preferably 0.111±1SD, and the second threshold is preferably 3.651±1SD [cm 3 Here, the 1SD of the first threshold is 2.630, and the 1SD of the second threshold is 0.653 [cm 3 ].

[0200] <Work>

[0201] The operation of the layer separation device 10B having the above-described structure will be described below with reference to the drawings.

[0202] Fig.11 1 is a flowchart of the third classification process performed by the stratification device 10B. The third classification process is to classify each of the plurality of classification objects into one of four groups including at least a first group having a relatively high risk of developing Alzheimer's disease in the future and a second group having a relatively low risk of developing Alzheimer's disease in the future, based on the preclinical Alzheimer's cognitive function test comprehensive score and the right hippocampal volume.

[0203] The third classification process is started, for example, when a user who uses the layer device 10B performs an operation to start the third classification process on the layer device 10B.

[0204] When the third classification process starts, the acquisition unit 20B obtains, for each of a plurality of classification objects with mild cognitive impairment, a score obtained from the results of the Preclinical Alzheimer's Cognitive Function Test (PACC) conducted on the classification object (hereinafter also referred to as the "PACC score") and the right hippocampal volume of the classification object (step S205).

[0205] When the PACC scores and right hippocampal volumes of multiple classification targets are obtained, the classification unit 30B selects one classification target from the multiple classification targets (step S210). Then, the classification unit 30B checks whether the PACC score of the selected classification target is 0.111 or more (step S215).

[0206] In the process of step S215 , when the PACC score is not equal to or greater than 0.111 (No in step S215 ), the classifying unit 30B checks whether the right hippocampal volume of the selected classification target is equal to or greater than 3.651 (step S220 ).

[0207] In the process of step S220 , when the right hippocampal volume is not greater than 3.651 (“No” in step S220 ), the classification unit 30B classifies the classification target in the selected state into the first group (step S225 ).

[0208] In the process of step S220 , when the right hippocampal volume is 3.651 or more (“Yes” in step S220 ), the classification unit 30B classifies the classification target in the selected state into the third group (step S230 ).

[0209] In the process of step S215 , when the PACC score is 0.111 or more (“Yes” in step S215 ), the classifying unit 30B checks whether the right hippocampal volume of the selected classification target is 3.651 or more (step S235 ).

[0210] In the process of step S235 , when the right hippocampal volume is not greater than 3.651 (“No” in step S235 ), the classification unit 30B classifies the classification target in the selected state into the fourth group (step S240 ).

[0211] In the process of step S235 , when the right hippocampal volume is 3.651 or more (“Yes” in step S235 ), the classification unit 30B classifies the classification target in the selected state into the second group (step S245 ).

[0212] When the processing of step S225 is completed, the processing of step S230 is completed, the processing of step S240 is completed, and the processing of step S245 is completed, the classification unit 30B checks whether there is a classification object that has not been selected among the multiple classification objects (step S250). Here, the classification object that has not been selected refers to the classification object that has not been selected in the processing of step S210, and the loop processing from the processing of step S215 to the processing of "Yes" in step S250 again enters the processing of step S215, and the classification object that has not been selected in the processing of step S255 described later.

[0213] In the process of step S250 , if there is an unselected classification target (“Yes” in step S250 ), the classification unit 30B selects one classification target from the unselected classification targets (step S255 ).

[0214] When the processing of step S255 is completed, the process proceeds to step S215.

[0215] In the process of step S250 , when there is no unselected classification target (“No” in step S250 ), the output unit 40 outputs the classification result performed by the classification unit 30B for each of the plurality of classification targets (step S260 ).

[0216] When the process of step S260 is completed, the layering device 10B ends the third classification process.

[0217] <Inspection>

[0218] The stratification device 10B having the above-described structure can classify a plurality of classification subjects with mild cognitive impairment into one of a plurality of groups including at least a first group having a relatively high risk of developing Alzheimer's disease in the future and a second group having a relatively low risk of developing Alzheimer's disease in the future.

[0219] Therefore, by using the stratification device 10B to classify a plurality of classification subjects having mild cognitive impairment in advance, clinical trials targeting people whose mild cognitive impairment has progressed to Alzheimer's disease can be efficiently performed.

[0220] Furthermore, the above-described classification can be performed by a different method from the conventional techniques using the above-described stratification device 10B. That is, the above-described classification performed by the stratification device 10B does not utilize the results of the relatively expensive brain β-amyloid PET examination required in the conventional techniques.

[0221] Therefore, by using the decomposition device 10B, the above-mentioned classification can be performed more efficiently and inexpensively compared with using the conventional technology.

[0222] (Implementation 4)

[0223] The following is a description of the stratification device in the fourth embodiment for executing the stratification method involved in the fourth embodiment. In the configuration of the fourth embodiment, a part of the function of the stratification device 10B involved in the third embodiment is changed. As shown in the description in the third embodiment, the stratification device 10B classifies a plurality of classification objects with mild cognitive impairment according to the preclinical Alzheimer's cognitive function test comprehensive score and the right hippocampal volume. Here, when the stratification method involved in the fourth embodiment classifies a plurality of classification objects with mild cognitive impairment, in addition to the preclinical Alzheimer's cognitive function test comprehensive score and the right hippocampal volume, the classification is also performed according to whether or not the apolipoprotein Eε4 gene is present. Here, regarding the stratification device for executing the stratification method involved in the fourth embodiment, since the same components as the stratification device 10B have been described, the same numbers are assigned and detailed descriptions are omitted, and the following description will focus on the differences from the stratification device 10B.

[0224] <Composition>

[0225] Fig.12 This is a block diagram showing an example of the configuration of a hierarchical device that executes the hierarchical method 10C according to the fourth embodiment.

[0226] like Fig.12 As shown, the configuration of the delamination device 10C is different from that of the delamination device 10B according to the third embodiment in that the acquisition unit 20B is changed to an acquisition unit 20C, and the classification unit 30B is changed to a classification unit 30C.

[0227] The obtaining unit 20C obtains, for each of a plurality of classification subjects having mild cognitive impairment, the ApoE typing in addition to the score obtained by integrating the results of the preclinical Alzheimer's cognitive function test for the classification subject and the right hippocampal volume of the classification subject.

[0228] The classification unit 30C classifies each of the multiple classification objects into one of the multiple groups including at least a first group with a relatively high risk of developing Alzheimer's disease in the future and a second group with a relatively low risk of developing Alzheimer's disease in the future, based on the preclinical Alzheimer's cognitive function test comprehensive score, the right hippocampal volume, and the ApoE typing. In the fourth embodiment, the multiple groups include a third group, a fourth group, a fifth group, a sixth group, a seventh group, and an eighth group in addition to the first group and the second group. The multiple groups consisting of these eight groups are described below.

[0229] The classifying unit 30C performs the above-mentioned classification based on findings obtained by conducting a cohort study on a plurality of classification targets having mild cognitive impairment by the present inventors.

[0230] More specifically, the classification unit 30C performs the following classifications (1) to (8) for each of the multiple classification objects: (1) when the ApoE typing shows ApoE+, the preclinical Alzheimer's cognitive function test comprehensive score is less than the third threshold, and the right hippocampal volume is less than the fourth threshold, the classification object is classified into the first group; (2) when the ApoE typing shows ApoE+, the preclinical Alzheimer's cognitive function test comprehensive score is greater than the third threshold, and the right hippocampal volume is greater than the fourth threshold, the classification object is classified into the second group; (3) when the ApoE typing shows ApoE+, the preclinical Alzheimer's cognitive function test comprehensive score is less than the third threshold, and the right hippocampal volume is greater than the fourth threshold, the classification object is classified into the third group; (4) when the ApoE typing shows ApoE+, the preclinical Alzheimer's cognitive function test comprehensive score is greater than the third threshold, and the right hippocampal volume is greater than the fourth threshold, the classification object is classified into the third group. When the threshold is small, the classification object is classified into the 4th group. (5) When the ApoE typing shows ApoE-, and the preclinical Alzheimer's cognitive function test comprehensive score is smaller than the third threshold, and the right hippocampal volume is smaller than the fourth threshold, the classification object is classified into the 5th group. (6) When the ApoE typing shows ApoE-, and the preclinical Alzheimer's cognitive function test comprehensive score is larger than the third threshold, and the right hippocampal volume is larger than the fourth threshold, the classification object is classified into the 6th group. (7) When the ApoE typing shows ApoE-, and the preclinical Alzheimer's cognitive function test comprehensive score is smaller than the third threshold, and the right hippocampal volume is larger than the fourth threshold, the classification object is classified into the 7th group. (8) When the ApoE typing shows ApoE-, and the preclinical Alzheimer's cognitive function test comprehensive score is larger than the third threshold, and the right hippocampal volume is smaller than the fourth threshold, the classification object is classified into the 8th group. Here, the classifying unit 30C sets the third threshold value to 0.111 and the fourth threshold value to 3.651 [cm 3 ] to carry out the above classification.

[0231] The following describes findings obtained by the present inventors through a cohort study involving subjects of multiple categories with mild cognitive impairment.

[0232] from Fig. 10A as well as Fig. 10B From the Kaplan-Meier curve shown, it can be seen that among Groups 1 to 8, Group 1 is a group with a relatively high risk of developing Alzheimer's disease in the future when the follow-up survey began, and Group 2 is a group with a relatively low risk of developing Alzheimer's disease in the future when the follow-up survey began.

[0233] Thus, the inventors of the present invention have obtained the following insight through cohort studies, namely, by performing the following classifications (1) to (8) for each of the multiple classification subjects with mild cognitive impairment, the multiple classification subjects with mild cognitive impairment can be classified into one of multiple groups (herein, 8 groups) including at least a first group with a relatively high risk of developing Alzheimer's disease in the future and a second group with a relatively low risk of developing Alzheimer's disease in the future. The above classifications (1) to (8) refer to: (1) ApoE+ in the ApoE typing and preclinical When the Alzheimer's cognitive function test composite score is less than the third threshold and the right hippocampal volume is less than the fourth threshold, the classification object is classified into the first group; (2) When the ApoE typing shows ApoE+, the preclinical Alzheimer's cognitive function test composite score is greater than the third threshold, and the right hippocampal volume is greater than the fourth threshold, the classification object is classified into the second group; (3) When the ApoE typing shows ApoE+, the preclinical Alzheimer's cognitive function test composite score is less than the third threshold, and the right hippocampal volume is greater than the fourth threshold, the classification object is classified into the second group. (4) when the ApoE typing shows ApoE+, the preclinical Alzheimer's cognitive function test comprehensive score is greater than the third threshold, and the right hippocampal volume is smaller than the fourth threshold, the classification object is classified into the fourth group; (5) when the ApoE typing shows ApoE-, the preclinical Alzheimer's cognitive function test comprehensive score is smaller than the third threshold, and the right hippocampal volume is smaller than the fourth threshold, the classification object is classified into the fifth group; (6) when the ApoE typing shows ApoE-, and the preclinical Alzheimer's cognitive function test comprehensive score is smaller than the third threshold, and the right hippocampal volume is smaller than the fourth threshold, the classification object is classified into the fifth group; (7) When the ApoE typing shows ApoE-, the preclinical Alzheimer's cognitive function test comprehensive score is smaller than the third threshold, and the right hippocampal volume is larger than the fourth threshold, the classification object is classified into the 6th group; (8) When the ApoE typing shows ApoE-, the preclinical Alzheimer's cognitive function test comprehensive score is larger than the third threshold, and the right hippocampal volume is smaller than the fourth threshold, the classification object is classified into the 8th group.

[0234] And, from Fig. 10A as well as Fig. 10BFrom the Kaplan-Meier curve shown, it can be seen that, compared with the classification result obtained by performing the above-mentioned second-stage classification on group α composed of classification objects consisting of classification objects not having the apolipoprotein Eε4 gene, the classification result obtained by performing the above-mentioned second-stage classification on group α composed of classification objects not having the apolipoprotein Eε4 gene can more accurately classify multiple classification objects with mild cognitive impairment into one of multiple groups including at least a group with a relatively high risk of developing Alzheimer's disease in the future and a group with a relatively low risk of developing Alzheimer's disease in the future.

[0235] In this way, the inventors obtained the following insight through cohort studies, that is, in addition to the preclinical Alzheimer's cognitive function test comprehensive score and the right hippocampal volume, further based on ApoE typing, it is possible to more accurately classify the classification objects into one of multiple groups including at least Group 1 with a relatively high risk of developing Alzheimer's disease in the future and Group 2 with a relatively low risk of developing Alzheimer's disease in the future.

[0236] <Work>

[0237] The operation of the layering device 10C having the above-described structure will be described below with reference to the drawings.

[0238] The delamination device 10C performs a fourth classification process in which a part of the third classification process performed by the delamination device 10B is changed.

[0239] Fig.13A as well as Fig. 13B This is a flowchart of the fourth classification process performed by the stratification device 10C.

[0240] like Fig.13A as well as Fig. 13B As shown, the fourth classification process adds the processes of step S300 to step S380 to the third classification process.

[0241] Therefore, the description here focuses on the processing from step S300 to step S380.

[0242] When the fourth classification process starts, the acquisition unit 20C acquires the PACC score, the right hippocampal volume of the classification target, and the ApoE typing for each of a plurality of classification targets having mild cognitive impairment (step S300 ).

[0243] When the process of step S300 is completed, the process proceeds to step S210.

[0244] When the process of step S210 is completed and the process of step S255 is completed, the classifying unit 30C checks whether the ApoE typing of the selected classification target indicates ApoE+ (step S310 ).

[0245] In the process of step S310, when the ApoE typing of the classification target in the selected state does not indicate ApoE+ ("No" in step S310), the process proceeds to step S215.

[0246] In the process of step S310 , when the ApoE typing of the selected classification target indicates ApoE+ (“Yes” in step S310 ), the classification unit 30C checks whether the PACC score of the selected classification target is greater than or equal to 0.111 (step S320 ).

[0247] In the process of step S320 , when the PACC score is not equal to or greater than 0.111 (No in step S320 ), the classifying unit 30C checks whether the right hippocampal volume of the selected classification target is equal to or greater than 3.651 (step S330 ).

[0248] In the process of step S330 , when the right hippocampus volume is not greater than 3.651 (“No” in step S330 ), the classification unit 30C classifies the classification target in the selected state into the fifth group (step S340 ).

[0249] In the process of step S330 , when the right hippocampal volume is 3.651 or more (“Yes” in step S330 ), the classification unit 30C classifies the classification target in the selected state into the seventh group (step S350 ).

[0250] In the process of step S320 , when the PACC score is 0.111 or more (“Yes” in step S320 ), the classifying unit 30C checks whether the right hippocampal volume of the selected classification target is 3.651 or more (step S360 ).

[0251] In the process of step S360 , when the right hippocampal volume is not greater than 3.651 (“No” in step S360 ), the classification unit 30C classifies the classification target in the selected state into the eighth group (step S370 ).

[0252] In the process of step S360 , when the right hippocampal volume is 3.651 or more (“Yes” in step S360 ), the classification unit 30C classifies the classification target in the selected state into the sixth group (step S380 ).

[0253] When the process of step S340 is completed, the process of step S350 is completed, the process of step S370 is completed, and the process of step S380 is completed, the process proceeds to step S250.

[0254] When the process of step S260 is completed, the declassification device 10C ends the fourth classification process.

[0255] <Inspection>

[0256] The stratification device 10C having the above configuration categorizes a plurality of categorized subjects with mild cognitive impairment not only based on the preclinical Alzheimer cognitive function test comprehensive score and the right hippocampal volume, but also based on whether or not the subjects have the apolipoprotein Eε4 gene. Thus, the stratification device 10C can categorize the categorized subjects more accurately.

[0257] (Implementation method 5)

[0258] The following is a description of the stratification device in the fifth embodiment for executing the stratification method involved in the fifth embodiment. The structure of the fifth embodiment is that a part of the function of the stratification device 10 involved in the first embodiment is changed. As shown in the description of the first embodiment, the stratification device 10 classifies a plurality of classification objects with mild cognitive impairment according to the score obtained as a result of performing the Alzheimer's Disease Rating Scale-Cognitive Component Scale and the right hippocampal volume. Here, when the stratification method involved in the fifth embodiment classifies a plurality of classification objects with mild cognitive impairment, in addition to the score obtained as a result of performing the Alzheimer's Disease Rating Scale-Cognitive Component Scale and the right hippocampal volume, the classification is also performed according to the score obtained by performing the comprehensive result of the preclinical Alzheimer's cognitive function test and whether or not the apolipoprotein Eε4 gene is present. Here, regarding the stratification device for executing the stratification method involved in the fifth embodiment, since the same components as the stratification device 10 have been described, the same numbers are given and detailed description is omitted, and the following description focuses on the differences from the stratification device 10.

[0259] <Composition>

[0260] Fig.14 This is a block diagram showing an example of the configuration of a delamination device 10D in the fifth embodiment that executes the delamination method according to the fifth embodiment.

[0261] like Fig.14 As shown, the configuration of the delamination device 10D is different from that of the delamination device 10 according to the first embodiment in that the acquisition unit 20 is changed to an acquisition unit 20D, and the classification unit 30 is changed to a classification unit 30D.

[0262] The acquisition unit 20D obtains, for each of multiple classification objects with mild cognitive impairment, a score obtained as a result of the Alzheimer's Disease Rating Scale-Cognitive Component Scale for the classification object and the right hippocampal volume of the classification object, as well as a score obtained as a result of the comprehensive result of the preclinical Alzheimer's cognitive function test for the classification object and information indicating whether the classification object has the apolipoprotein Eε4 gene (ApoE typing).

[0263] The classification unit 30D classifies each of the multiple classification objects into one of the multiple groups including at least Group 6, Group 7, and Group 8, which have a relatively high risk of developing Alzheimer's disease in the future, and Group 1 and Group 2, which have a relatively low risk of developing Alzheimer's disease in the future, based on the score of the Alzheimer's Disease Rating Scale-Cognitive Component, the right hippocampal volume, the ApoE typing, and the preclinical Alzheimer's cognitive function test comprehensive score. In Embodiment 5, the multiple groups include Group 3, Group 4, and Group 5 in addition to Group 1, Group 2, Group 6, Group 7, and Group 8, and the multiple groups consisting of these 8 groups are described.

[0264] The classifying unit 30D performs the above-mentioned classification based on the findings obtained by the present inventors through a cohort study on a plurality of classification targets having mild cognitive impairment.

[0265] More specifically, the classification unit 30D performs the following classifications (1) to (8) for each of the multiple classification objects: (1) when the score of the Alzheimer's Disease Assessment Scale-Cognitive Component is smaller than the 5th threshold, the right hippocampal volume is larger than the 6th threshold, and the ApoE typing shows ApoE-, the classification object is classified into the first group; (2) when the score of the Alzheimer's Disease Assessment Scale-Cognitive Component is larger than the 5th threshold, the right hippocampal volume is larger than the 6th threshold, the ApoE typing shows ApoE+, and the preclinical Alzheimer's cognitive function test comprehensive score is larger than the 7th threshold, and the score of the Alzheimer's Disease Assessment Scale-Cognitive Component is larger than the 7th threshold, the classification object is classified into the first group; 5 threshold is smaller, and the right hippocampal volume is larger than the 6th threshold, and the ApoE typing shows ApoE+, and the preclinical Alzheimer cognitive function test comprehensive score is larger than the 7th threshold, the classification object is classified as the 2nd group. (3) When the score of the Alzheimer's Disease Assessment Scale-Cognitive Subscale is smaller than the 5th threshold, and the right hippocampal volume is smaller than the 6th threshold, and the ApoE typing shows ApoE+, and the preclinical Alzheimer cognitive function test comprehensive score is larger than the 7th threshold, the classification object is classified as the 3rd group. (4) When the score of the Alzheimer's Disease Assessment Scale-Cognitive Subscale is smaller than the 5th threshold, and the right hippocampal volume is smaller than the 6th threshold, and the ApoE typing shows ApoE+, and the preclinical Alzheimer cognitive function test comprehensive score is larger than the 7th threshold, the classification object is classified as the 3rd group. When the E classification shows ApoE-, the classification object is classified into the 4th group. (5) When the score of the cognitive subscale of the Alzheimer's Disease Assessment Scale is greater than the 5th threshold, the right hippocampal volume is greater than the 6th threshold, and the ApoE classification shows ApoE-, the classification object is classified into the 5th group. (6) When the score of the cognitive subscale of the Alzheimer's Disease Assessment Scale is greater than the 5th threshold, the right hippocampal volume is greater than the 6th threshold, and the ApoE classification shows ApoE+, and the preclinical Alzheimer's cognitive function test comprehensive score is less than the 7th threshold, and the score of the cognitive subscale of the Alzheimer's Disease Assessment Scale is less than the 5th threshold, and the right hippocampal volume is greater than the 6th threshold, and the ApoE classification shows ApoE+, and the preclinical Alzheimer's cognitive function test comprehensive score is less than the 7th threshold, and the score of the cognitive subscale of the Alzheimer's Disease Assessment Scale is less than the 5th threshold, and the right hippocampal volume is greater than the 6th threshold, (7) when the score of the Alzheimer's Disease Assessment Scale-Cognitive Component Scale is greater than the 5th threshold value, and the right hippocampal volume is less than the 6th threshold value, the classification object is classified into the 6th group; (8) when the score of the Alzheimer's Disease Assessment Scale-Cognitive Component Scale is less than the 5th threshold value, and the right hippocampal volume is less than the 6th threshold value, and the ApoE typing shows ApoE+, and the preclinical Alzheimer's cognitive function test comprehensive score is less than the 7th threshold value, the classification object is classified into the 8th group. Here, the classification unit 30D sets the 5th threshold value to 20.0 and the 6th threshold value to 3.651 [cm 3 ], set the 7th threshold to 0.111 to perform the above classification.

[0266] The following is a description of findings obtained by the present inventors through a cohort study of subjects of multiple categories with mild cognitive impairment.

[0267] In the cohort study, the inventors classified each of a plurality of classified objects into one of the groups shown in (1) to (8) below, and evaluated the Kaplan-Meier curves showing the results of follow-up surveys of each group after classification, wherein the groups shown in (1) to (8) are: (1) Group 1 consisting of classified objects whose scores on the Alzheimer's Disease Assessment Scale-Cognitive Subscale are less than the fifth threshold, whose right hippocampal volume is greater than the sixth threshold, and whose ApoE typing shows ApoE-; (2) Group 1 consisting of classified objects whose scores on the Alzheimer's Disease Assessment Scale-Cognitive Subscale are greater than the fifth threshold, whose right hippocampal volume is greater than the sixth threshold, whose ApoE typing shows ApoE+, and whose clinical The second group was composed of subjects whose pre-bedside Alzheimer's cognitive function test score was greater than the 7th threshold, or subjects whose Alzheimer's Disease Assessment Scale-Cognitive Component score was less than the 5th threshold, whose right hippocampal volume was greater than the 6th threshold, whose ApoE typing showed ApoE+, and whose pre-clinical Alzheimer's cognitive function test score was greater than the 7th threshold; (3) the third group was composed of subjects whose Alzheimer's Disease Assessment Scale-Cognitive Component score was less than the 5th threshold, whose right hippocampal volume was less than the 6th threshold, whose ApoE typing showed ApoE+, and whose pre-clinical Alzheimer's cognitive function test score was greater than the 7th threshold; (4) subjects whose Alzheimer's Disease Assessment Scale-Cognitive Component score was less than the 5th threshold, whose right hippocampal volume was less than the 6th threshold, whose ApoE typing showed ApoE+, and whose pre-clinical Alzheimer's cognitive function test score was greater than the 7th threshold. The fourth group is composed of subjects whose scores on the cognitive subscale of the Alzheimer's Disease Assessment Scale are lower than the fifth threshold, whose right hippocampal volume is lower than the sixth threshold, and whose ApoE typing indicates ApoE-; (5) the fifth group is composed of subjects whose scores on the cognitive subscale of the Alzheimer's Disease Assessment Scale are higher than the fifth threshold, whose right hippocampal volume is higher than the sixth threshold, and whose ApoE typing indicates ApoE-; (6) the subjects whose scores on the cognitive subscale of the Alzheimer's Disease Assessment Scale are higher than the fifth threshold, whose right hippocampal volume is higher than the sixth threshold, whose ApoE typing indicates ApoE+, whose preclinical Alzheimer's cognitive function test comprehensive score is lower than the seventh threshold, or the subjects whose scores on the cognitive subscale of the Alzheimer's Disease Assessment Scale are higher than the sixth threshold, whose ApoE typing indicates ApoE+, whose preclinical Alzheimer's cognitive function test comprehensive score is lower than the seventh threshold, or the subjects whose scores on the cognitive subscale of the Alzheimer's Disease Assessment Scale are higher than the sixth threshold, whose ApoE typing indicates ApoE-. The sixth group is composed of subjects whose score on the cognitive subscale is lower than the fifth threshold, whose right hippocampal volume is higher than the sixth threshold, whose ApoE typing shows ApoE+, and whose preclinical Alzheimer's cognitive function test comprehensive score is lower than the seventh threshold; (7) the seventh group is composed of subjects whose score on the Alzheimer's Disease Assessment Scale-Cognitive Subscale is higher than the fifth threshold, and whose right hippocampal volume is lower than the sixth threshold; (8) the eighth group is composed of subjects whose score on the Alzheimer's Disease Assessment Scale-Cognitive Subscale is lower than the fifth threshold, whose right hippocampal volume is lower than the sixth threshold, whose ApoE typing shows ApoE+, and whose preclinical Alzheimer's cognitive function test comprehensive score is lower than the seventh threshold.

[0268] Fig.15A and Fig. 15B The figure is a Kaplan-Meier curve showing the results of the follow-up survey for each group conducted by the present inventors in the cohort study.

[0269] exist Fig.15A and Fig. 15B In the Kaplan-Meier curve shown, the horizontal axis represents the time [years] that has passed since the start of the follow-up survey, and the vertical axis represents the cumulative conversion rate [%] of the subjects classified from mild cognitive impairment to Alzheimer's disease.

[0270] from Fig.15A and Fig. 15B It is known that when the time elapsed after the start of the follow-up survey exceeds 3 years, the reliability of the cumulative conversion rate of the subjects who progressed from mild cognitive impairment to Alzheimer's disease decreases due to the decrease in the number of subjects who were classified. Therefore, the use of the cumulative conversion rate of the subjects who progressed from mild cognitive impairment to Alzheimer's disease in the cohort study was investigated when the time elapsed after the start of the follow-up survey exceeded 3 years.

[0271] from Fig.15A and Fig. 15B From the Kaplan-Meier curve shown, it can be seen that among Groups 1 to 8, Groups 6, 7, and 8 were the groups with relatively high risks of developing Alzheimer's disease in the future when the follow-up survey began, while Groups 1 and 2 were the groups with relatively low risks of developing Alzheimer's disease in the future when the follow-up survey began.

[0272] Thus, the inventors of the present invention have obtained the following insight through the cohort study, that is, by performing the following classifications (1) to (8) for each of the multiple classified subjects with mild cognitive impairment, the multiple classified subjects with mild cognitive impairment can be classified into one of the multiple groups (herein, 8 groups) including Group 6, Group 7, and Group 8 with relatively high risks of developing Alzheimer's disease in the future, and Group 1 and Group 2 with relatively low risks of developing Alzheimer's disease in the future, wherein the classifications (1) to (8) refer to: (1) the score of the Alzheimer's Disease Assessment Scale-Cognitive Subscale is smaller than the 5th threshold, the right hippocampal volume is larger than the 6th threshold, and the ApoE typing shows Apo E-, the classification object is classified into Group 1; (2) when the score of the Alzheimer's Disease Assessment Scale-Cognitive Subscale is greater than the 5th threshold, the right hippocampal volume is greater than the 6th threshold, the ApoE typing shows ApoE+, and the preclinical Alzheimer's cognitive function test comprehensive score is greater than the 7th threshold; and when the score of the Alzheimer's Disease Assessment Scale-Cognitive Subscale is less than the 5th threshold, the right hippocampal volume is greater than the 6th threshold, the ApoE typing shows ApoE+, and the preclinical Alzheimer's cognitive function test comprehensive score is greater than the 7th threshold, the classification object is classified into Group 2; (3) when the score of the Alzheimer's Disease Assessment Scale-Cognitive Subscale is greater than the 5th threshold (1) If the score of the cognitive subscale of the Alzheimer's Disease Assessment Scale is smaller than the fifth threshold, the right hippocampal volume is smaller than the sixth threshold, the ApoE typing shows ApoE+, and the preclinical Alzheimer's cognitive function test comprehensive score is larger than the seventh threshold, the classification object is classified as the third group; (2) If the score of the cognitive subscale of the Alzheimer's Disease Assessment Scale is smaller than the fifth threshold, the right hippocampal volume is smaller than the sixth threshold, and the ApoE typing shows ApoE-, the classification object is classified as the fourth group; (3) If the score of the cognitive subscale of the Alzheimer's Disease Assessment Scale is larger than the fifth threshold, the right hippocampal volume is larger than the sixth threshold, and the ApoE typing shows ApoE-, the classification object is classified as the fifth group; (4) If the score of the cognitive subscale of the Alzheimer's Disease Assessment Scale is larger than the fifth threshold, the right hippocampal volume is larger than the sixth threshold, and the ApoE typing shows ApoE-, the classification object is classified as the fifth group; (5) If the score of the cognitive subscale of the Alzheimer's Disease Assessment Scale is larger than the fifth threshold, the right hippocampal volume is larger than the sixth threshold, and the ApoE typing shows ApoE-, the classification object is classified as the fifth group; (6) In the case where the score of the cognitive subscale of the Alzheimer's Disease Assessment Scale is greater than the 5th threshold, the right hippocampal volume is greater than the 6th threshold, the ApoE typing shows ApoE+, and the preclinical Alzheimer's cognitive function test comprehensive score is less than the 7th threshold, and in the case where the score of the cognitive subscale of the Alzheimer's Disease Assessment Scale is less than the 5th threshold, the right hippocampal volume is greater than the 6th threshold, the ApoE typing shows ApoE+, and the preclinical Alzheimer's cognitive function test comprehensive score is less than the 7th threshold, the classification object is classified into the 6th group; (7) In the case where the score of the cognitive subscale of the Alzheimer's Disease Assessment Scale is greater than the 5th threshold, and the right hippocampal volume is less than the 6th threshold, the classification object is classified into the 7th group;(8) If the score of the Alzheimer's Disease Rating Scale-Cognitive Scale is smaller than the 5th threshold, the right hippocampal volume is smaller than the 6th threshold, the ApoE typing shows ApoE+, and the preclinical Alzheimer's cognitive function test comprehensive score is smaller than the 7th threshold, the classification object is classified into the 8th group. ;

[0273] Furthermore, the inventors of the present invention have obtained the following knowledge through cohort studies: in the above classification, the fifth threshold is preferably 20.0±1SD, and the sixth threshold is preferably 3.651±1SD [cm 3 ], and the seventh threshold is preferably 0.111±1SD. Here, the 1SD of the fifth threshold is 6.3, and the 1SD of the sixth threshold is 0.653 [cm 3 ], and the 1SD of the 7th threshold is 2.630.

[0274] <Work>

[0275] The operation of the delamination device 10D having the above-described structure will be described below with reference to the drawings.

[0276] Fig.16 : is a flowchart of the fifth classification process performed by the stratification device 10D. The fifth classification process is a process of classifying each of a plurality of classification objects into one of eight groups including at least Group 6, Group 7, and Group 8 having a relatively high risk of developing Alzheimer's disease in the future, and Group 1 and Group 2 having a relatively low risk of developing Alzheimer's disease in the future, based on the score of the Alzheimer's Disease Rating Scale-Cognitive Component Scale, the right hippocampal volume, the ApoE typing, and the preclinical Alzheimer's cognitive function test comprehensive score.

[0277] The fifth classification process is started, for example, when a user who uses the layer device 10D performs an operation on the layer device 10D to start the fifth classification process.

[0278] When the fifth classification process starts, the acquisition unit 20D obtains, for each of a plurality of classification objects with mild cognitive impairment, a score obtained as a result of performing the Alzheimer's Disease Assessment Scale-Cognitive Component Scale (ADAS-cog) on ​​the classification object (ADAS-cog score), a score obtained as a result of performing the Preclinical Alzheimer's Cognitive Function Test Comprehensive (PACC) on the classification object (PACC score), the right hippocampal volume of the classification object, and ApoE typing (step S405).

[0279] When the ADAS-cog scores, PACC scores, right hippocampal volumes, and ApoE typing of multiple classification objects are obtained, the classification unit 30D selects one classification object from the multiple classification objects (step S410). Then, the classification unit 30D investigates whether the ADAS-cog score of the classification object in the selected state is 20.0 or more (step S415).

[0280] In the process of step S415 , when the ADAS-cog score is not greater than 20.0 (No in step S415 ), the classifying unit 30D checks whether the right hippocampal volume of the selected classification target is greater than or equal to 3.651 (step S420 ).

[0281] In the process of step S420 , when the right hippocampal volume is 3.651 or more (“Yes” in step S420 ), the classifying unit 30D checks whether the ApoE typing of the selected classification target indicates ApoE+ (step S425 ).

[0282] In the process of step S425 , when the ApoE typing of the selected classification target does not indicate ApoE+ (“No” in step S425 ), the classifying unit 30D classifies the selected classification target into the first group (step S430 ).

[0283] In the process of step S420 , when the right hippocampal volume is not greater than 3.651 (“No” in step S420 ), the classifying unit 30D checks whether the ApoE typing of the selected classification target indicates ApoE+ (step S435 ).

[0284] In the process of step S435 , when the ApoE typing of the selected classification target does not indicate ApoE+ (“No” in step S435 ), the classification unit 30D classifies the selected classification target into the fourth group (step S440 ).

[0285] In the process of step S435 , when the ApoE typing of the selected classification target indicates ApoE+ (“Yes” in step S435 ), the classification unit 30D checks whether the PACC score of the selected classification target is 0.111 or more (step S445 ).

[0286] In the process of step S445 , when the PACC score is equal to or greater than 0.111 (“Yes” in step S445 ), the classifying unit 30D classifies the classification target in the selected state into the third group (step S450 ).

[0287] In the process of step S445 , when the PACC score is not equal to or greater than 0.111 (“No” in step S445 ), the classifying unit 30D classifies the classification target in the selected state into the eighth group (step S455 ).

[0288] In the process of step S415 , when the ADAS-cog score is 20.0 or more (“Yes” in step S415 ), the classifying unit 30D checks whether the right hippocampal volume of the selected classification target is 3.651 or more (step S460 ).

[0289] In the process of step S460 , when the right hippocampal volume is 3.651 or more (“Yes” in step S460 ), the classifying unit 30D checks whether the ApoE typing of the selected classification target indicates ApoE+ (step S465 ).

[0290] In the process of step S465 , when the ApoE typing of the selected classification target does not indicate ApoE+ (“Yes” in step S465 ), the classification unit 30D classifies the selected classification target into the fifth group (step S470 ).

[0291] In the processing of step S425, when the ApoE typing of the classification object in the selected state shows ApoE+ ("Yes" in step S425), and in the processing of step S465, when the ApoE typing of the classification object in the selected state shows ApoE+ ("Yes" in step S465), the classification unit 30D investigates whether the PACC score of the classification object in the selected state is greater than 0.111 (step S475).

[0292] In the process of step S475 , when the PACC score is equal to or greater than 0.111 (“Yes” in step S475 ), the classifying unit 30D classifies the classification target in the selected state into the second group (step S480 ).

[0293] In the process of step S475 , when the PACC score is not equal to or greater than 0.111 (No in step S475 ), the classifying unit 30D classifies the classification target in the selected state into the sixth group (step S485 ).

[0294] In the process of step S460 , when the right hippocampal volume is not greater than 3.651 (No in step S460 ), the classifying unit 30D classifies the classification target in the selected state into the seventh group (step S490 ).

[0295] When the processing of step S430 is completed, the processing of step S440 is completed, the processing of step S450 is completed, the processing of step S455 is completed, the processing of step S470 is completed, the processing of step S480 is completed, the processing of step S485 is completed, and the processing of step S490 is completed, the classification unit 30D checks whether there is a classification object that has not been selected among the multiple classification objects (step S495). Here, the classification object that has not been selected refers to a classification object that has not been selected in the processing of step S410, and after the processing of step S415 to the processing of "Yes" in step S495, the processing of step S415 is entered again, and the classification object has not been selected in the processing of step S496 described later.

[0296] In the process of step S495 , if there is any classification target that has not been selected (“Yes” in step S495 ), the classification unit 30D selects one classification target from the classification targets that have not been selected (step S496 ).

[0297] When the processing of step S496 is completed, the process proceeds to step S415.

[0298] In the process of step S495 , when there is no unselected classification target (“No” in step S495 ), the output unit 40 outputs the classification result performed by the classifying unit 30D for each of the plurality of classification targets (step S497 ).

[0299] When the processing of step S497 is completed, the layering device 10D ends the fifth classification processing.

[0300] <Inspection>

[0301] When classifying a plurality of classification objects with mild cognitive impairment, the classification device 10D having the above configuration classifies them based on the scores of the Alzheimer's Disease Rating Scale-Cognitive Component and the right hippocampal volume, as well as the preclinical Alzheimer's cognitive function test comprehensive score and the presence or absence of the apolipoprotein Eε4 gene. Thus, the classification device 10D can classify the classification objects more accurately.

[0302] (Implementation 6)

[0303] In order to more accurately obtain a stratification method for classifying each of a plurality of classification subjects with mild cognitive impairment into one of a plurality of groups corresponding to the risk of developing Alzheimer's disease in the future, the inventors evaluated the risk of developing from mild cognitive impairment to Alzheimer's disease by further taking various factors into consideration for those who were positive for brain β-amyloid PET examination. Here, a person whose score of the result of PET examination using AV45 as a marker showed a value greater than 1.11 was referred to as a person who was positive for brain β-amyloid PET examination.

[0304] Fig.17 This is a schematic diagram showing an example of the content of risk assessment based on various factors further conducted by the present inventors on subjects who tested positive for brain β-amyloid protein PET.

[0305] The present inventors aim at Fig.17 The content of the risk assessment shown has been continuously studied and researched, and as a result, a stratification method involved in Implementation Example 6 was conceived.

[0306] The following is an explanation of a stratification device for executing the stratification method involved in Embodiment 6. The structure of the stratification device involved in Embodiment 6 is compared with the stratification device 10 involved in Embodiment 1, and a part of the functions thereof are changed. The stratification device involved in Embodiment 6 is a device for classifying each of a plurality of classification objects, i.e., those who are positive in the brain β-amyloid protein PET test, i.e., those with mild cognitive impairment, into one of a plurality of groups corresponding to the risk of developing Alzheimer's disease in the future. The plurality of groups include at least a high-risk group, i.e., Group 1, which has a relatively high risk of developing Alzheimer's disease in the future, and a low-risk group, i.e., Group 2, which has a relatively low risk of developing Alzheimer's disease in the future.

[0307] The stratification device involved in embodiment 6 is an example of a device that performs classification processing, in which the insights obtained by the inventors through a cohort study of multiple classification subjects with positive brain β-amyloid protein PET test results, i.e., mild cognitive impairment, are reflected.

[0308] Here, the layering device involved in embodiment 6 has the same components as the layering device 10, the components that have been described are given the same symbols and their detailed descriptions are omitted, and the following description will focus on the differences from the layering device 10.

[0309] <Composition>

[0310] Fig.18 This is a block diagram showing an example of the structure of a layering device 10E that executes the layering method involved in the sixth embodiment.

[0311] like Fig.18 As shown, the structure of the delamination device 10E is different from that of the delamination device 10 according to the first embodiment in that the acquisition unit 20 is changed to an acquisition unit 20E, and the classification unit 30 is changed to a classification unit 30E.

[0312] The acquisition unit 20E obtains the score obtained by performing the Alzheimer's Disease Rating Scale-Cognitive Component Scale test on the classification object and the left hippocampal volume of the classification object for each of the multiple classification objects with mild cognitive impairment, i.e., the positive person of the brain beta-amyloid protein PET test. The left hippocampal volume can be measured by the following method, such as performing an MRI test on the classification object and performing image processing on the head MRI image obtained by the result of the MRI test.

[0313] The classifying unit 30E classifies each of the plurality of classification objects into one of a plurality of groups including at least a first group having a relatively high risk of developing Alzheimer's disease in the future and a second group having a relatively low risk of developing Alzheimer's disease in the future, based on the score of the Alzheimer's Disease Rating Scale-Cognitive Component and the volume of the left hippocampus. In Embodiment 6, the plurality of groups include a third group and a fourth group in addition to the first group and the second group, and the plurality of groups is described as four groups.

[0314] The classification unit 30E performs the above classification based on the findings obtained by the inventors through a cohort study of a plurality of classification subjects who are positive for brain β-amyloid protein PET test, that is, have mild cognitive impairment.

[0315] Specifically, the classification unit 30 performs the following classifications (1) to (4) for each of the multiple classification objects: (1) when the score of the Alzheimer's Disease Assessment Scale-Cognitive Component is greater than the first threshold and the left hippocampal volume is less than the second threshold, the classification object is classified into the first group; (2) when the score of the Alzheimer's Disease Assessment Scale-Cognitive Component is less than the first threshold and the left hippocampal volume is greater than the second threshold, the classification object is classified into the second group; (3) when the score of the Alzheimer's Disease Assessment Scale-Cognitive Component is greater than the first threshold and the left hippocampal volume is greater than the second threshold, the classification object is classified into the third group; (4) when the score of the Alzheimer's Disease Assessment Scale-Cognitive Component is less than the first threshold and the left hippocampal volume is less than the second threshold, the classification object is classified into the fourth group. Here, the classification unit 30E sets the first threshold to 14.0 and the second threshold to 3459 [mm 3 ] to carry out the above classification.

[0316] The following is a description of findings obtained by the inventors of the present invention through a cohort study of subjects who were positive for brain β-amyloid protein PET test, that is, subjects of multiple categories with mild cognitive impairment.

[0317] In a cohort study, the present inventors selected subjects who were positive for brain β-amyloid protein PET examination, that is, subjects of multiple categories with mild cognitive impairment, and conducted a follow-up investigation on the progression from mild cognitive impairment to Alzheimer's disease.

[0318] Fig.19 This is an example of survival prediction using the product limit method showing the results of follow-up investigation of each group conducted by the present inventors in the cohort study.

[0319] exist Fig.19 In the survival prediction by the product limit method shown in FIG. 1 , the horizontal axis represents the time [years] that has passed since the start of the follow-up survey, and the vertical axis represents the cumulative rate of subjects who will not progress from mild cognitive impairment to Alzheimer's disease.

[0320] like Fig.19 As shown, in the cohort study, the present inventors selected 220 subjects who were classified as those with mild cognitive impairment and tested positive for brain β-amyloid protein PET and conducted a follow-up investigation for about 5 years on the progression from mild cognitive impairment to Alzheimer's disease. During the approximately 5-year period, 70 subjects progressed from mild cognitive impairment to Alzheimer's disease.

[0321] In the cohort study, the present inventors classified each of the multiple classification subjects into one of the following groups (1) to (4) at the beginning of the follow-up survey, and evaluated the survival prediction by the product limit method showing the follow-up results of each group after classification. The above-mentioned groups (1) to (4) are: (1) Group A (corresponding to Group 1) consisting of subjects whose scores on the Alzheimer's Disease Rating Scale-Cognitive Component Scale are greater than the first threshold and whose left hippocampal volume is smaller than the second threshold; (2) Group B (corresponding to Group 1) consisting of subjects whose scores on the Alzheimer's Disease Rating Scale-Cognitive Component Scale are greater than the first threshold and whose left hippocampal volume is smaller than the second threshold; (1) Group B (corresponding to Group 2), which is composed of subjects whose scores on the Alzheimer's Disease Rating Scale-Cognitive Component Scale are lower than the first threshold and whose left hippocampal volume is larger than the second threshold; (2) Group C (corresponding to Group 3), which is composed of subjects whose scores on the Alzheimer's Disease Rating Scale-Cognitive Component Scale are higher than the first threshold and whose left hippocampal volume is larger than the second threshold; (3) Group D (corresponding to Group 4), which is composed of subjects whose scores on the Alzheimer's Disease Rating Scale-Cognitive Component Scale are lower than the first threshold and whose left hippocampal volume is smaller than the second threshold.

[0322] from Fig.19As shown in the survival prediction by the product limit method, among Groups 1 to 4, Group 1 was a group with a relatively high risk of developing Alzheimer's disease in the future when the follow-up survey began, while Group 2 was a group with a relatively low risk of developing Alzheimer's disease in the future when the follow-up survey began.

[0323] Furthermore, the inventors of the present invention have obtained the following findings in the above classification through cohort studies, namely, the first threshold is preferably 14.0±1SD, and the second threshold is preferably 3459 [mm 3 ]±1SD. Here, the 1SD of the first threshold is 6.9, and the 1SD of the second threshold is 543.5 [mm 3 ].

[0324] In particular, by setting the first threshold value and the second threshold value to the above values, it can be understood that the second group can be regarded as a group with no risk of developing Alzheimer's disease in the future.

[0325] <Work>

[0326] The operation of the layer separation device 10E having the above-described structure will be described below with reference to the drawings.

[0327] Fig. 20 1 is a flowchart of the sixth classification process performed by the stratification device 10E. The sixth classification process is a process of classifying each of a plurality of classification subjects, i.e., a positive person in the brain β-amyloid protein PET test, into one of four groups including at least a first group having a relatively high risk of developing Alzheimer's disease in the future and a second group having a relatively low risk of developing Alzheimer's disease in the future, based on the score of the cognitive subscale of the Alzheimer's Disease Rating Scale and the left hippocampal volume.

[0328] The sixth classification process is started, for example, when a user who uses the layer device 10E performs an operation on the layer device 10E to start the sixth classification process.

[0329] When the sixth classification process starts, the acquisition unit 20E obtains the score (ADAS-cog score) obtained as a result of performing the Alzheimer's Disease Assessment Scale-Cognitive Component Scale (ADAS-cog) on ​​each of the multiple classification objects who are positive for the brain β-amyloid protein PET test, i.e., those with mild cognitive impairment, and the left hippocampus volume of the classification object (step S605).

[0330] When ADAS-cog scores and left hippocampal volumes of multiple classification targets are obtained, the classification unit 30E selects one classification target from the multiple classification targets (step S610). Then, the classification unit 30E checks whether the ADAS-cog score of the selected classification target is 14.0 or more (step S615).

[0331] In the process of step S615 , when the ADAS-cog score is 14.0 or more (“Yes” in step S615 ), the classifier 30E checks whether the left hippocampal volume of the selected classification target is 3459 or more (step S620 ).

[0332] In the process of step S620 , when the left hippocampus volume is not greater than 3459 (“No” in step S620 ), the classification unit 30E classifies the classification target in the selected state into the first group (step S625 ).

[0333] In the process of step S620 , when the left hippocampus volume is greater than or equal to 3459 (“Yes” in step S620 ), the classification unit 30E classifies the classification target in the selected state into the third group (step S630 ).

[0334] In the process of step S615 , when the ADAS-cog score is not greater than 14.0 (No in step S615 ), the classifier 30E checks whether the left hippocampal volume of the selected classification target is greater than 3459 (step S635 ).

[0335] In the process of step S635 , when the left hippocampus volume is not greater than 3459 (“No” in step S635 ), the classification unit 30E classifies the classification target in the selected state into the fourth group (step S640 ).

[0336] In the process of step S35 , when the left hippocampus volume is greater than or equal to 3459 (“Yes” in step S635 ), the classification unit 30E classifies the classification target in the selected state into the second group (step S645 ).

[0337] When the processing of step S625 is completed, the processing of step S630 is completed, the processing of step S640 is completed, and the processing of step S645 is completed, the classifier 30E checks whether there is any classification object that has not been selected among the multiple classification objects (step S650). Here, the classification object that has not been selected refers to the classification object that has not been selected in the processing of step S610, and the classification object that has not been selected in the processing of step S655 described later in the loop processing of the processing of step S615 after entering the processing of "Yes" in step S650 again.

[0338] In the process of step S650 , if there is an unselected classification target (“Yes” in step S650 ), the classifying unit 30E selects one classification target from the unselected classification targets (step S655 ).

[0339] When the process of step S655 is completed, the process proceeds to step S615.

[0340] In the process of step S650 , when there is no unselected classification target (“No” in step S650 ), the output unit 40 outputs the classification result of each of the plurality of classification targets by the classifying unit 30E (step S660 ).

[0341] When the process of step S660 is completed, the classifier 10E ends the sixth classification process.

[0342] <Inspection>

[0343] The stratification device 10E of the above configuration selects those with positive brain beta-amyloid protein PET test from a plurality of classification objects with mild cognitive impairment, and classifies them according to the scores of the cognitive subscale of the Alzheimer's Disease Rating Scale and the left hippocampal volume. Accordingly, the stratification device 10E can classify the classification objects with higher accuracy.

[0344] (Variant 1)

[0345] The following is a description of the stratification device involved in the modification example 1. In the stratification device in the modification example 1, a part of the function of the stratification device 10E involved in the sixth embodiment is changed. As described in the sixth embodiment, the stratification device 10E sets the first threshold value to 14.0 and the second threshold value to 3459 [mm] based on the score of the cognitive subscale of the Alzheimer's Disease Rating Scale and the volume of the left hippocampus. 3 ], and classify multiple classification objects of those who are positive for brain β-amyloid protein PET examination, that is, those with mild cognitive impairment. In this regard, the stratification device involved in modification example 1 sets the first threshold to 12.0 and the second threshold to 3737 [mm 3 ], and classify a plurality of classification objects of a positive person with a brain beta-amyloid protein PET test, i.e., a person with mild cognitive impairment. That is, the structure of the stratification device involved in the modification example 1 is relative to the stratification device 10E, in the above classification, the first threshold is changed from 14.0 to 12.0, and the second threshold is changed from 3459 [mm 3 ] changed to 3737[mm 3 ].

[0346] Here, since the same components as those of the layering device 10E in the layering device according to the first modification have been described, the same reference numerals are given and detailed description is omitted, and the following description focuses on the differences from the layering device 10E.

[0347] <Composition>

[0348] Fig.21 This is a block diagram showing an example of the configuration of a hierarchical device 10F that executes the hierarchical method according to Modification 1.

[0349] like Fig.21 As shown in FIG. 1 , the structure of the delamination device 10F is different from that of the delamination device 10E according to the sixth embodiment in that the classifying unit 30E is changed to a classifying unit 30F.

[0350] The classification unit 30F is similar to the classification unit 30E. For each of the plurality of classification objects, the classification object is classified into one of the plurality of groups including at least the first group having a relatively high risk of developing Alzheimer's disease in the future and the second group having a relatively low risk of developing Alzheimer's disease in the future, based on the score of the Alzheimer's Disease Rating Scale-Cognitive Component Scale and the left hippocampal volume. In the first modification, as in the sixth embodiment, the plurality of groups include the third group and the fourth group in addition to the first group and the second group. The plurality of groups consisting of four groups will be described below.

[0351] Classification unit 30F, like classification unit 30E, performs the above classification based on the findings of the present inventors who conducted a cohort study on a plurality of classification targets who were positive for brain β-amyloid PET test, that is, had mild cognitive impairment.

[0352] Specifically, the classification unit 30F sets the first threshold value to 12.0 and the second threshold value to 3737 [mm 3 ], the same classification as the classification unit 30E is performed.

[0353] The following is a description of findings obtained by the present inventors through a cohort study of subjects of multiple categories with mild cognitive impairment.

[0354] In a cohort study, the present inventors selected subjects who were positive for brain β-amyloid protein PET examination, that is, subjects of multiple categories with mild cognitive impairment, and conducted a follow-up investigation on the progression from mild cognitive impairment to Alzheimer's disease.

[0355] Fig. 22 Another example of survival prediction using the product limit method is shown, which shows the results of follow-up investigation of each group conducted by the present inventors in a cohort study.

[0356] exist Fig. 22 In the survival prediction by the product limit method shown in Fig.19 The same survival prediction by the product limit method is shown, where the horizontal axis represents the time [years] that has passed since the start of the follow-up survey, and the vertical axis represents the rate of subjects classified from mild cognitive impairment who will not develop Alzheimer's disease.

[0357] In the cohort study, the present inventors classified each of a plurality of classified subjects into one of the following groups (1) to (4) at the beginning of the follow-up survey, and evaluated the survival prediction by the product limit method showing the follow-up results of each group after classification, (1) Group A (corresponding to the first group) consisting of classified subjects whose scores on the Alzheimer's Disease Assessment Scale-Cognitive Component Scale are greater than the first threshold and whose left hippocampal volume is less than the second threshold, (2) Group B (corresponding to the second group) consisting of classified subjects whose scores on the Alzheimer's Disease Assessment Scale-Cognitive Component Scale are less than the first threshold and whose left hippocampal volume is greater than the second threshold, (3) Group C (corresponding to the third group) consisting of classified subjects whose scores on the Alzheimer's Disease Assessment Scale-Cognitive Component Scale are greater than the first threshold and whose left hippocampal volume is greater than the second threshold, and (4) Group D (corresponding to the fourth group) consisting of classified subjects whose scores on the Alzheimer's Disease Assessment Scale-Cognitive Component Scale are less than the first threshold and whose left hippocampal volume is less than the second threshold.

[0358] from Fig. 22 As shown in the survival prediction by the product limit method, among Groups 1 to 4, Group 1 is a group with a relatively high risk of developing Alzheimer's disease in the future when the follow-up survey began, and Group 2 is a group with a relatively low risk of developing Alzheimer's disease in the future when the follow-up survey began.

[0359] Furthermore, the inventors of the present invention have also obtained the following knowledge through cohort studies, that is, in the above classification, the first threshold is preferably 12.0, and the second threshold is preferably 3737 [mm 3 ].

[0360] In particular, by setting the first threshold and the second threshold to the above-mentioned values, the second group can be regarded as a group with no risk of developing Alzheimer's disease in the future.

[0361] <Work>

[0362] The operation of the above-structured layering device 10E will be described below with reference to the drawings.

[0363] The delamination device 10F performs the seventh classification process instead of the sixth classification process performed by the delamination device 10E.

[0364] Fig.23 This is a flowchart of the seventh classification process performed by the classification device 10F.

[0365] In the seventh classification process, the processing of step S705 to step S710, the processing of step S725 to step S730, and the processing of step S740 to step S760 are the same as the processing of step S605 to step S610, the processing of step S625 to step S630, and the processing of step S640 to step S660 in the sixth classification process involved in the sixth embodiment, except that the classification unit 30E is replaced by the classification unit 30F and the stratification device 10E is replaced by the stratification device 10F. Therefore, since these processes have been explained, they are omitted here, and the following description will focus on the processing of step S715, the processing of step S720, and the processing of step S735.

[0366] When the process of step S710 is completed, the classifying unit 30F checks whether the ADAS-cog score of the selected classification target is 12.0 or more (step S715 ).

[0367] In the process of step S715 , when the ADAS-cog score is 12.0 or more (“Yes” in step S715 ), the classifier 30F checks whether the left hippocampal volume of the selected classification target is 3737 or more (step S720 ).

[0368] In the process of step S720 , when the volume of the left hippocampus is not greater than 3737 (“No” in step S720 ), the process proceeds to step S725 .

[0369] In the process of step S720 , when the left hippocampus volume is greater than or equal to 3737 (“Yes” in step S720 ), the process proceeds to step S730 .

[0370] In the process of step S715 , when the ADAS-cog score is not greater than 12.0 (No in step S715 ), the classifier 30F checks whether the left hippocampal volume of the selected classification target is greater than 3737 (step S735 ).

[0371] In the process of step S735 , when the left hippocampus volume is not greater than 3737 (“No” in step S735 ), the classification unit 30F classifies the classification target in the selected state into the fourth group (step S740 ).

[0372] In the process of step S735 , when the left hippocampus volume is greater than or equal to 3737 (“Yes” in step S735 ), the classification unit 30F classifies the classification target in the selected state into the second group (step S745 ).

[0373] When the process of step S760 is completed, the declassification device 10F ends the seventh classification process.

[0374] <Inspection>

[0375] The stratification device 10F of the above structure is the same as the stratification device 10E, and screens out the subjects with positive brain beta-amyloid protein PET test from a plurality of classification subjects with mild cognitive impairment, and classifies them according to the scores of the Alzheimer's Disease Rating Scale-Cognitive Component and the left hippocampal volume. Accordingly, the stratification device 10F is the same as the stratification device 10E, and can classify the classification subjects with higher accuracy.

[0376] (Variant 2)

[0377] The following is a description of the stratification device involved in the modification example 2. In the configuration of the stratification device involved in the modification example 2, a part of the function of the stratification device 10E involved in the sixth embodiment is changed. As described in the sixth embodiment, the stratification device 10E sets the first threshold value to 14.0 and the second threshold value to 3459 [mm] based on the score of the cognitive subscale of the Alzheimer's Disease Rating Scale and the volume of the left hippocampus. 3 ], classifying multiple classification objects of those who are positive for brain β-amyloid protein PET examination, that is, those with mild cognitive impairment. Based on this, the stratification device involved in the second variant sets the first threshold to 21.0 and the second threshold to 3080 [mm 3 ], a plurality of classification objects of positive brain β-amyloid protein PET test subjects, i.e., those with mild cognitive impairment, are classified. That is, the difference between the structure of the stratification device involved in the modification example 2 and the stratification device 10E is that in the above classification, the first threshold is changed from 14.0 to 21.0, and the second threshold is changed from 3459 [mm 3 ]changed to 3080[mm 3 ].

[0378] Here, since the components of the layering device involved in the modified example 2 that are the same as those of the layering device 10E have been described, they are given the same reference numerals and their detailed description is omitted. The following description will focus on the differences from the layering device 10E.

[0379] <Composition>

[0380] Fig.24 This is a block diagram showing an example of the configuration of a hierarchical device 10G that executes a hierarchical method according to Modification 2.

[0381] like Fig.24As shown in FIG. 1 , the structure of the delamination device 10G is different from that of the delamination device 10E according to the sixth embodiment in that the classifying unit 30E is changed to a classifying unit 30G.

[0382] Classification unit 30G, like classification unit 30E, classifies each of the plurality of classification objects into one of a plurality of groups including at least a first group having a relatively high risk of developing Alzheimer's disease in the future and a second group having a relatively low risk of developing Alzheimer's disease in the future, based on the score of the Alzheimer's Disease Rating Scale-Cognitive Component Scale and the volume of the left hippocampus. In modification 2, like implementation 6, the plurality of groups include a third group and a fourth group in addition to the first group and the second group, and these four groups are described below.

[0383] The classifying unit 30G, like the classifying unit 30E, performs the above-mentioned classification based on the findings obtained by the inventors from a cohort study of a plurality of classification targets who are positive for brain β-amyloid PET test, that is, have mild cognitive impairment.

[0384] Specifically, in the above classification performed by the classification unit 30G, the first threshold is set to 21.0 and the second threshold is set to 3080 [mm 3 ], the rest is the same as the classification performed by the classification unit 30E.

[0385] The following is a description of findings obtained by the present inventors through a cohort study of subjects of multiple categories with mild cognitive impairment.

[0386] In a cohort study, the present inventors selected subjects who were positive for brain β-amyloid protein PET examination, that is, subjects of multiple categories with mild cognitive impairment, and conducted a follow-up investigation on the progression from mild cognitive impairment to Alzheimer's disease.

[0387] Fig.25 Another example of survival prediction using the product limit method is shown, showing the results of follow-up investigation of each group in a cohort study conducted by the present inventors.

[0388] exist Fig.25 In the survival prediction by the product limit method shown in Fig.19 The same survival prediction by the product limit method is shown, where the horizontal axis represents the time [years] that has passed since the start of the follow-up survey, and the vertical axis represents the rate of subjects classified from mild cognitive impairment who will not develop Alzheimer's disease.

[0389] In the cohort study, the present inventors classified each of the multiple classification subjects into one of the following (1) to (4) groups at the beginning of the follow-up survey, and evaluated the survival prediction by the product limit method showing the follow-up results of each group after classification. The groups (1) to (4) are: (1) Group A (corresponding to Group 1) consisting of classification subjects whose scores on the Alzheimer's Disease Rating Scale-Cognitive Component Scale are greater than the first threshold and whose left hippocampal volume is smaller than the second threshold; (2) Group B (corresponding to Group 1) consisting of classification subjects whose scores on the Alzheimer's Disease Rating Scale-Cognitive Component Scale are greater than the first threshold and whose left hippocampal volume is smaller than the second threshold; (1) Group B (corresponding to Group 2), which is composed of classification objects whose scores on the Alzheimer's Disease Rating Scale-Cognitive Component Scale are lower than the first threshold and whose left hippocampal volume is higher than the second threshold; (2) Group C (corresponding to Group 3), which is composed of classification objects whose scores on the Alzheimer's Disease Rating Scale-Cognitive Component Scale are higher than the first threshold and whose left hippocampal volume is higher than the second threshold; (3) Group C (corresponding to Group 3); and (4) Group D (corresponding to Group 4), which is composed of classification objects whose scores on the Alzheimer's Disease Rating Scale-Cognitive Component Scale are lower than the first threshold and whose left hippocampal volume is lower than the second threshold.

[0390] from Fig.25 As shown in the survival prediction by the product limit method, among Groups 1 to 4, Group 1 was a group with a relatively high risk of developing Alzheimer's disease in the future when the follow-up survey began, and Group 2 was a group with a relatively low risk of developing Alzheimer's disease in the future when the follow-up survey began.

[0391] Furthermore, the inventors of the present invention have obtained the following knowledge through a cohort study: in the above classification, the first threshold is preferably 21.0, and the second threshold is preferably 3080 [mm 3 ].

[0392] In particular, by setting the first threshold and the second threshold to the above values, the first group can be regarded as a group with a very high risk of developing Alzheimer's disease in the future, with a rate of about 80%.

[0393] <Work>

[0394] The operation of the above-structured delamination device 10G will be described below with reference to the drawings.

[0395] The decomposition device 10G performs the eighth decomposition process instead of the sixth decomposition process performed by the decomposition device 10E.

[0396] Fig.26 This is a flowchart of the eighth classification process performed by the classification device 10G.

[0397] In the eighth classification process, the processing of step S805 to step S810, the processing of step S825 to step S830, and the processing of step S840 to step S860 are respectively the processing of step S605 to step S610, the processing of step S625 to step S630, and the processing of step S640 to step S660 in the sixth classification process involved in the sixth embodiment, except that the classification unit 30E is replaced by the classification unit 30G, and the stratification device 10E is replaced by the stratification device 10G, and the remaining processing is the same. Since these processes have been described here, their description is omitted, and the following description focuses on the processing of step S815, the processing of step S820, and the processing of step S835.

[0398] When the process of step S810 is completed, the classifying unit 30G checks whether the ADAS-cog score of the selected classification target is 21.0 or more (step S815 ).

[0399] In the process of step S815 , when the ADAS-cog score is 21.0 or more (“Yes” in step S815 ), the classifying unit 30G checks whether the left hippocampal volume of the selected classification target is 3080 or more (step S820 ).

[0400] In the process of step S820 , when the volume of the left hippocampus is not greater than 3080 (“No” in step S820 ), the process proceeds to step S825 .

[0401] In the process of step S820 , when the left hippocampus volume is greater than or equal to 3080 (“Yes” in step S820 ), the process proceeds to step S830 .

[0402] In the process of step S815 , when the ADAS-cog score is not greater than 21.0 (No in step S815 ), the classifying unit 30G checks whether the left hippocampal volume of the selected classification target is greater than 3080 (step S835 ).

[0403] In the process of step S835 , when the left hippocampus volume is not greater than 3080 (“No” in step S835 ), the classification unit 30G classifies the classification target in the selected state into the fourth group (step S840 ).

[0404] In the process of step S835 , when the left hippocampus volume is greater than or equal to 3080 (“Yes” in step S835 ), the classification unit 30G classifies the classification target in the selected state into the second group (step S845 ).

[0405] When the process of step S860 is completed, the declassification device 10G ends the eighth classification process.

[0406] <Inspection>

[0407] The stratification device 10G of the above configuration, like the stratification device 10E, selects those with positive brain β-amyloid protein PET test from a plurality of classification objects with mild cognitive impairment, and classifies them according to the score of the cognitive subscale of the Alzheimer's Disease Rating Scale and the volume of the left hippocampus. Thus, the stratification device 10G, like the stratification device 10E, can classify the classification objects with higher accuracy.

[0408] (Variant 3)

[0409] The following describes a layering device according to a third variant. In the configuration of the layering device according to the third variant, a portion of the functions of the layering device 10E according to the sixth embodiment are modified. As described in the sixth embodiment, the layering device 10E sets the first threshold value to 14.0 and the second threshold value to 3459 [mm 3 ], a plurality of classification objects with mild cognitive impairment are classified into those who are positive for brain β-amyloid protein PET examination. In the stratification device involved in variant example 3, the first threshold is set to 24.0 and the second threshold is set to 2751 [mm 3 ], a plurality of classification objects of positive brain β-amyloid protein PET test, i.e., mild cognitive impairment, are classified. That is, the structure of the stratification device involved in the modification example 2 is different from the stratification device 10E in that, in the above classification, the first threshold is changed from 14.0 to 24.0, and the second threshold is changed from 3459 [mm 3 ]changed to 2751[mm 3 ].

[0410] Here, since the same components as those of the layering device 10E have already been described, the same reference numerals are given to the layering device according to the third modification, and detailed description thereof is omitted, and the description will focus on the differences from the layering device 10E.

[0411] <Composition>

[0412] Fig. 27 1 is a block diagram showing an example of the configuration of a delamination device 10H that implements the delamination method according to the third modification.

[0413] like Fig. 27As shown in FIG. 1 , the structure of the delamination device 10H is different from that of the delamination device 10E according to the sixth embodiment in that the classifying unit 30E is changed to a classifying unit 30H.

[0414] The classification unit 30H is the same as the classification unit 30E, and for each of the plurality of classification objects, the classification object is classified into one of the plurality of groups including at least a first group having a relatively high risk of developing Alzheimer's disease in the future and a second group having a relatively low risk of developing Alzheimer's disease in the future, based on the score of the Alzheimer's Disease Rating Scale-Cognitive Component Scale and the left hippocampal volume. In the second modification, as in the sixth embodiment, the plurality of groups include a third group and a fourth group in addition to the first group and the second group, and these four groups are described.

[0415] The classifying unit 30H, like the classifying unit 30E, performs the above-mentioned classification based on the findings obtained by the inventors from a cohort study of a plurality of classification targets who are positive for brain β-amyloid PET test, that is, have mild cognitive impairment.

[0416] Specifically, in the above classification performed by the classification unit 30H, the first threshold is set to 24.0 and the second threshold is set to 2751 [mm 3 ], the rest is the same as the classification performed by the classification unit 30E.

[0417] The following is a description of findings obtained by the present inventors through a cohort study of subjects of multiple categories with mild cognitive impairment.

[0418] In a cohort study, the present inventors selected subjects who were positive for brain β-amyloid protein PET examination, that is, subjects of multiple categories with mild cognitive impairment, and conducted a follow-up investigation on the progression from mild cognitive impairment to Alzheimer's disease.

[0419] Fig.28 Another example of survival prediction using the product limit method is shown, showing the results of follow-up investigation of each group in a cohort study conducted by the present inventors.

[0420] exist Fig.28 In the survival prediction by the product limit method shown in Fig.19 The same survival prediction by the product limit method is shown, where the horizontal axis represents the time [years] that has passed since the start of the follow-up survey, and the vertical axis represents the rate of subjects classified from mild cognitive impairment who will not develop Alzheimer's disease.

[0421] In a cohort study, the present inventors classified each of a plurality of classified subjects into one of the following groups (1) to (4) at the beginning of a follow-up survey, and evaluated the survival prediction using the product limit method of the follow-up results for each classified group. The groups (1) to (4) are: (1) Group A (corresponding to Group 1) consisting of classified subjects whose scores on the Alzheimer's Disease Assessment Scale-Cognitive Component Scale are greater than the first threshold and whose left hippocampal volume is less than the second threshold; (2) Group B (corresponding to Group 1) consisting of classified subjects whose scores on the Alzheimer's Disease Assessment Scale-Cognitive Component Scale are greater than the first threshold and whose left hippocampal volume is less than the second threshold; and (3) Group C (corresponding to Group 1) consisting of classified subjects whose scores on the Alzheimer's Disease Assessment Scale-Cognitive Component Scale are greater than the first threshold and whose left hippocampal volume is less than the second threshold. (a) Group B (corresponding to Group 2), which is composed of subjects whose scores on the Alzheimer's Disease Assessment Scale-cognitive subscale are lower than the first threshold and whose left hippocampal volume is higher than the second threshold; (b) Group C (corresponding to Group 3), which is composed of subjects whose scores on the Alzheimer's Disease Assessment Scale-cognitive subscale are higher than the first threshold and whose left hippocampal volume is higher than the second threshold; and (c) Group D (corresponding to Group 4), which is composed of subjects whose scores on the Alzheimer's Disease Assessment Scale-cognitive subscale are lower than the first threshold and whose left hippocampal volume is lower than the second threshold.

[0422] from Fig.28 As shown in the survival prediction by the product limit method, among Groups 1 to 4, Group 1 was a group with a relatively high risk of developing Alzheimer's disease in the future when the follow-up survey began, while Group 2 was a group with a relatively low risk of developing Alzheimer's disease in the future when the follow-up survey began.

[0423] Furthermore, the inventors of the present invention have obtained the following knowledge through a cohort study: in the above classification, the first threshold is preferably 24.0, and the second threshold is preferably 2751 [mm 3 ].

[0424] In particular, by setting the first threshold and the second threshold to the above values, the first group can be regarded as a group with a very high risk of developing Alzheimer's disease in the future, that is, about 91%.

[0425] <Work>

[0426] The operation of the above-configured delamination device 10H will be described below with reference to the drawings.

[0427] The delamination device 10H performs the ninth classification process instead of the sixth classification process performed by the delamination device 10E.

[0428] Fig.29 This is a flowchart of the ninth classification process performed by the classifier 10H.

[0429] In the ninth classification process, the processing of step S905 to step S910, the processing of step S925 to step S930, and the processing of step S940 to step S960 are the same as the processing of step S605 to step S610, the processing of step S625 to step S630, and the processing of step S640 to step S660 in the sixth classification process involved in the sixth embodiment, except that the classification unit 30E is replaced by the classification unit 30H and the stratification device 10E is replaced by the stratification device 10H. Therefore, since these processes have been explained, they are omitted here, and the following description will focus on the processing of step S915, the processing of step S920, and the processing of step S935.

[0430] When the process of step S910 is completed, the classifying unit 30H checks whether the ADAS-cog score of the selected classification target is 24.0 or more (step S915 ).

[0431] In the process of step S915 , when the ADAS-cog score is 24.0 or more (Yes in step S915 ), the classifying unit 30H checks whether the left hippocampal volume of the selected classification target is 2751 or more (step S920 ).

[0432] In the process of step S920 , when the left hippocampus volume is not greater than 2751 (“No” in step S920 ), the process proceeds to step S925 .

[0433] In the process of step S920 , when the left hippocampus volume is greater than or equal to 2751 (“Yes” in step S920 ), the process proceeds to step S930 .

[0434] In the process of step S915 , when the ADAS-cog score is not greater than 24.0 (No in step S915 ), the classifying unit 30H checks whether the left hippocampal volume of the selected classification target is greater than 2751 (step S935 ).

[0435] In the process of step S935 , when the left hippocampus volume is not greater than 2751 (No in step S935 ), the classification unit 30H classifies the classification target in the selected state into the fourth group (step S940 ).

[0436] In the process of step S935 , when the left hippocampus volume is equal to or greater than 2751 (“Yes” in step S935 ), the classification unit 30H classifies the classification target in the selected state into the second group (step S945 ).

[0437] When the process of step S960 is completed, the declassification device 10H ends the ninth classification process.

[0438] <Inspection>

[0439] The stratification device 10H of the above configuration is the same as the stratification device 10E, which selects the subjects with positive brain beta-amyloid protein PET test from a plurality of classification subjects with mild cognitive impairment, and classifies them according to the scores of the Alzheimer's Disease Rating Scale-Cognitive Component and the left hippocampal volume. Based on this, the stratification device 10H can classify the classification subjects with higher accuracy, just like the stratification device 10E.

[0440] (Implementation 7)

[0441] The present inventors aim at Fig.17 The contents of the risk assessment shown above were further studied, and a new variable was found for classifying each of a plurality of classification subjects with mild cognitive impairment into one of a plurality of groups corresponding to the risk of developing Alzheimer's disease in the future.

[0442] That is, the present inventors were able to perform the above classification with higher accuracy by performing the above classification using a volume fraction value (Cog_Vol) indicating a ratio between the volume of the left hippocampus of the classification target and the ADAS-cog score of the classification target.

[0443] The following example uses the volume fraction value (Cog_Vol) as the left hippocampal volume [mm 3 ] relative to the ADAS-cog score, that is, the volume score value (Cog_Vol) is regarded as the left hippocampal volume [mm 3 ] is divided by the ADAS-cog score of the classification object.

[0444] Specifically, the volume fraction value (Cog_Vol) can be calculated by the following formula.

[0445] Cog_Vol = left hippocampal volume [mm 3 ] / ADAS-cog score

[0446] The following is a description of a stratification device that performs the stratification method involved in Embodiment 7. The stratification device involved in Embodiment 7 is configured by changing a portion of the functions of the stratification device 10E involved in Embodiment 6. The stratification device involved in Embodiment 7, like the stratification device 10E, classifies each of a plurality of classification objects, i.e., those who are positive for brain β-amyloid protein PET examination, i.e., those with mild cognitive impairment, into one of a plurality of groups corresponding to the risk of developing Alzheimer's disease in the future. The plurality of groups include at least a high-risk group, i.e., Group 1, having a relatively high risk of developing Alzheimer's disease in the future, and a low-risk group, i.e., Group 2, having a relatively low risk of developing Alzheimer's disease in the future.

[0447] The stratification device according to the seventh embodiment is an example of a device that performs classification processing using the volume fraction value (Cog_Vol) discovered by the inventors of the present invention.

[0448] Here, the same components of the layering device according to Embodiment 7 as those of the layering device 10E are given the same reference numerals as the components already described and are described in detail. The following description will focus on the differences from the layering device 10E.

[0449] <Composition>

[0450] Fig.30 This is a block diagram showing an example of the structure of a hierarchical device 10I that executes the hierarchical method involved in the seventh embodiment.

[0451] like Fig.30 As shown in FIG. 1 , the structure of the delamination device 10I is different from that of the delamination device 10E according to the sixth embodiment in that the classifying unit 30E is changed to a classifying unit 30I.

[0452] The classification unit 30I is the same as the classification unit 30E, and for each of the plurality of classification objects, the classification object is classified into one of a plurality of groups including at least a first group having a relatively high risk of developing Alzheimer's disease in the future and a second group having a relatively low risk of developing Alzheimer's disease in the future, based on the score of the Alzheimer's Disease Rating Scale-Cognitive Component and the left hippocampal volume. In Embodiment 7, the case where the plurality of groups are the two groups consisting of the first group and the second group is described.

[0453] The classification unit 30I performs the above classification based on the findings obtained by the present inventors through a cohort study of a plurality of classification targets who are subjects of positive brain β-amyloid protein PET test, that is, subjects with mild cognitive impairment.

[0454] Specifically, the classifier 30I performs the above classification for each of the multiple classification objects according to the volume fraction value (Cog_Vol) newly discovered by the present inventors through cohort research. Here, the classifier 30I classifies the classification object into the first group when the volume fraction value (Cog_Vol) is less than 101, and classifies the classification object into the second group when the volume fraction value (Cog_Vol) is not less than 101.

[0455] The volume fraction value (Cog_Vol) newly discovered by the inventors through a cohort study is described below.

[0456] Fig.31 This is a correspondence table showing the relationship between the volume fraction value (Cog_Vol) and the number of subjects classified as having progressed from mild cognitive impairment to Alzheimer's disease.

[0457] Fig.32 This is a correlation diagram showing the relationship between the volume fraction value (Cog_Vol) and the period from the calculation of the volume fraction value (Cog_Vol) to the development of Alzheimer's disease in patients who were positive for brain β-amyloid PET examination.

[0458] exist Fig.32 In the correlation diagram shown, the horizontal axis represents the volume fraction value (Cog_Vol), and the vertical axis represents the period [years] from when the volume fraction value (Cog_Vol) is calculated until the development of Alzheimer's disease.

[0459] like Fig.31 , Fig.32 As shown, 16 out of 17 subjects with a positive brain β-amyloid protein PET test with a volume score value (Cog_Vol) less than 101, that is, subjects with mild cognitive impairment, developed from mild cognitive impairment to Alzheimer's disease, that is, 94.14% of the 17 subjects with a volume score value (Cog_Vol) less than 101 developed from mild cognitive impairment to Alzheimer's disease.

[0460] And if Fig.32 As shown, 13 of the 17 subjects in this classification developed from mild cognitive impairment to Alzheimer's disease within 1 year.

[0461] As described above, the inventors have discovered a new variable, volume fraction value (Cog_Vol), which can classify multiple categories of subjects with mild cognitive impairment who are positive for brain β-amyloid PET examination into a group with a very high risk of developing Alzheimer's disease in the future, with a rate of about 94%.

[0462] Through further research, the inventors of the present invention have obtained the following insight, namely, by setting multiple thresholds for the volume fraction value (Cog_Vol), it is possible to further classify each of the multiple classification subjects of those who test positive for brain β-amyloid protein PET, i.e., those with mild cognitive impairment, into one of the multiple groups corresponding to the risk of developing Alzheimer's disease in the future.

[0463] Fig.33 This is a correspondence table showing the relationship between the volume fraction value (Cog_Vol), multiple thresholds discovered by the inventors, and the number of classified subjects who progress from mild cognitive impairment to Alzheimer's disease, for those who tested positive for brain β-amyloid protein PET among classified subjects with mild cognitive impairment.

[0464] Fig.34 This is a correlation diagram showing the following relationship, that is, showing the relationship between the volume fraction value (Cog_Vol) and the period from the calculation of the volume fraction value (Cog_Vol) to the development of Alzheimer's disease or the period that does not develop Alzheimer's disease in those who have a positive brain β-amyloid protein PET test.

[0465] exist Fig.34 In the correlation diagram shown, the horizontal axis is the volume fraction value (Cog_Vol), and the vertical axis is the period [years] from when the volume fraction value (Cog_Vol) is calculated until the disease develops into Alzheimer's disease, or the period [years] that does not develop into Alzheimer's disease.

[0466] Fig.35 This is a correspondence table showing the relationship between the volume fraction value (Cog_Vol) and multiple thresholds discovered by the inventors, and the ratio of the classified subjects who progress from mild cognitive impairment to Alzheimer's disease, for those who test positive for brain β-amyloid protein PET among the classified subjects with mild cognitive impairment.

[0467] like Figure 33 to Figure 35As shown, the present inventors have obtained the knowledge that the following classification can be performed for each of the subjects with mild cognitive impairment who tested positive for brain β-amyloid protein PET examination, namely, by performing the classifications (1) to (5), (1) when the volume fraction value (Cog_Vol) is less than 101 as the first threshold value, the classification subject is classified into the first group; (2) when the volume fraction value (Cog_Vol) is greater than 101 as the first threshold value and less than 142 as the second threshold value, the classification subject is classified into the second group; (3) when the volume fraction value (Cog_Vol) is greater than 142 as the second threshold value and less than 266 as the third threshold value, the classification subject is classified into the third group; (4) when the volume fraction value (Cog_Vol) is greater than 142 as the second threshold value and less than 266 as the third threshold value, the classification subject is classified into the third group; When the integral value (Cog_Vol) is greater than 266, which is the third threshold value, and is less than 340, which is the fourth threshold value, the classification object is classified into the fourth group. (5) When the volume fraction value (Cog_Vol) is greater than 340, which is the fourth threshold value, the classification object is classified into the fifth group, so that the first group can be regarded as a group with a rate of 94.1% developing into Alzheimer's disease in the future, the second group can be regarded as a group with a rate of 60.0% developing into Alzheimer's disease in the future, the third group can be regarded as a group with a rate of 32.6% developing into Alzheimer's disease in the future, the fourth group can be regarded as a group with a rate of 10.4% developing into Alzheimer's disease in the future, and the fifth group can be regarded as a group with a rate of 0% developing into Alzheimer's disease in the future.

[0468] At this time, the inventors obtained the following insights: the incidence of Alzheimer's disease within 1 year was 70.5% for the subjects classified as Group 1, the incidence of Alzheimer's disease within 2 years was 88.2%, and the incidence of Alzheimer's disease within 3 years was 94.1%. The incidence of Alzheimer's disease within 1 year was 10.0%, within 2 years was 26.6%, within 3 years was 60.0%, and within 4 years was 60.0%. For subjects classified as Group 3, the incidence rate of Alzheimer's disease within 1 year was 5.9%, within 2 years was 13.9%, within 3 years was 28.7%, and within 4 years was 32.7%. For subjects classified as Group 4 or Group 5, the incidence rate of Alzheimer's disease within 1 year was 1.4%, within 2 years was 1.4%, within 3 years was 1.4%, and within 4 years was 4.16%.

[0469] As described above, it can be seen that the larger the volume fraction value (Cog_Vol), the lower the incidence of Alzheimer's disease.

[0470] The inventors of the present invention conducted further research and obtained the following insight, that is, regardless of whether the classification object is a positive brain β-amyloid protein PET test, by setting multiple thresholds for the volume score value (Cog_Vol), each of the multiple classification objects with mild cognitive impairment can be classified into one of the multiple groups corresponding to the risk of developing Alzheimer's disease in the future.

[0471] Fig.36 This is a correspondence table, which shows the relationship between the volume score value (Cog_Vol) of the classified subjects with mild cognitive impairment, the multiple thresholds discovered by the inventors, and the number of classified subjects who develop from mild cognitive impairment to Alzheimer's disease, regardless of whether the subject is positive for brain β-amyloid protein PET examination.

[0472] Fig.37 This is a correlation diagram that shows the relationship between the volume fraction value (Cog_Vol) and the period from the calculation of the volume fraction value (Cog_Vol) to the development of Alzheimer's disease, or the period without developing Alzheimer's disease, regardless of whether the patient is positive for brain β-amyloid protein PET examination.

[0473] exist Fig.37 In the correlation diagram shown, the horizontal axis is the volume fraction value (Cog_Vol), and the vertical axis is the period [years] from the calculation of the volume fraction value (Cog_Vol) until the development of Alzheimer's disease or the period [years] that does not develop Alzheimer's disease.

[0474] like Fig.36 , Fig.37As shown, the present inventors were able to further group the classification objects with mild cognitive impairment by performing the following classifications (1) to (5) for each of the classification objects without considering whether the object was a positive person in the brain β-amyloid protein PET examination. The classifications (1) to (5) are as follows: (1) when the volume fraction value (Cog_Vol) is less than the first threshold value, i.e., less than 101, the classification object is classified into the first group; (2) when the volume fraction value (Cog_Vol) is greater than the first threshold value, i.e., 101, and less than the second threshold value, i.e., 142, the classification object is classified into the second group; (3) when the volume fraction value (Cog_Vol) is greater than the second threshold value, i.e., greater than 142, and less than the third threshold value, i.e., 266, the classification object is classified into the second group. The classification object is group 3. (4) when the volume fraction value (Cog_Vol) is greater than the third threshold value, i.e., greater than 266, and less than the fourth threshold value, i.e., 340, the classification object is classified into group 4. (5) when the volume fraction value (Cog_Vol) is greater than the fourth threshold value, i.e., 340, the classification object is classified into group 5. The grouping is as follows: group 1 is regarded as a group with a rate of 78.1% developing into Alzheimer's disease in the future, group 2 is regarded as a group with a rate of 60.3% developing into Alzheimer's disease in the future, group 3 is regarded as a group with a rate of 34.6% developing into Alzheimer's disease in the future, group 4 is regarded as a group with a rate of 10.3% developing into Alzheimer's disease in the future, and group 5 is regarded as a group with a rate of 3.2% developing into Alzheimer's disease in the future.

[0475] The inventors of the present invention conducted further research and obtained the following insight, namely, by setting multiple thresholds for the volume fraction value (Cog_Vol) for subjects classified as positive, negative, and subjects with no positive or negative information in the brain β-amyloid protein PET test, each of the multiple classified subjects with mild cognitive impairment can be classified into one of the multiple groups corresponding to the risk of developing Alzheimer's disease in the future.

[0476] Fig.38 This is a correspondence table for the classification subjects with positive and negative results of brain β-amyloid protein PET examination, as well as the classification subjects with no positive or negative information, i.e., the classification subjects with mild cognitive impairment. The correspondence table shows the relationship between the volume fraction value (Cog_Vol), multiple thresholds discovered by the inventors, and the transition of the ratio of the classification subjects who progress from mild cognitive impairment to Alzheimer's disease.

[0477] like Fig.38As shown, the inventors of the present invention have obtained the following knowledge, that is, by performing the following classifications (1) to (5) on each of the classification objects with positive, negative, and classification objects with no positive or negative information in the brain β-amyloid protein PET examination, it is possible to further group them, wherein the classifications (1) to (5) are as follows: (1) when the volume fraction value (Cog_Vol) is less than the first threshold value, i.e., less than 101, the classification object is classified into the first group; (2) when the volume fraction value (Cog_Vol) is greater than the first threshold value, i.e., greater than 101, and less than the second threshold value, i.e., 142, the classification object is classified into the second group; (3) when the volume fraction value (Cog_Vol) is greater than the second threshold value, i.e., greater than 142, and less than the third threshold value, i.e., 266, the classification object is classified into the second group; (4) when the volume fraction value (Cog_Vol) is greater than the third threshold value, i.e., greater than 266, and less than the fourth threshold value, i.e., 340, the classification object is classified into the fourth group; (5) when the volume fraction value (Cog_Vol) is greater than the fourth threshold value and greater than 340, the classification object is classified into the fifth group. The further grouping is as follows: Group 1 is regarded as a group with a rate of 79.4% developing into Alzheimer's disease in the future, Group 2 is regarded as a group with a rate of 61.6% developing into Alzheimer's disease in the future, Group 3 is regarded as a group with a rate of 36.4% developing into Alzheimer's disease in the future, Group 4 is regarded as a group with a rate of 10.8% developing into Alzheimer's disease in the future, and Group 5 is regarded as a group with a rate of 0.6% developing into Alzheimer's disease in the future.

[0478] At this time, the inventors obtained the following findings: the incidence of Alzheimer's disease within 1 year for the subjects classified as Group 1 was 34.9%, within 2 years was 55.5%, within 3 years was 60.3%, within 4 years was 63.5%, within 5 years was 68.3%, within 6 years was 79.4%, and the incidence of Alzheimer's disease within 1 year for the subjects classified as Group 2 was The incidence of Alzheimer's disease within 2 years was 15.0%, the incidence of Alzheimer's disease within 2 years was 30.1%, the incidence of Alzheimer's disease within 3 years was 45.9%, the incidence of Alzheimer's disease within 4 years was 53.4%, the incidence of Alzheimer's disease within 5 years was 54.9%, and the incidence of Alzheimer's disease within 6 years was 61.6%. The incidence of Alzheimer's disease within 1 year and within 2 years for those classified as Group 3 was 6.4%, 16.0%, and 16.9%. %, within 3 years the incidence of Alzheimer's disease was 25.4%, within 4 years the incidence of Alzheimer's disease was 29.3%, within 5 years the incidence of Alzheimer's disease was 31.5%, within 6 years the incidence of Alzheimer's disease was 36.4%, and those classified as Group 4 had an incidence of Alzheimer's disease within 1 year of 3.2%, within 2 years of 5.4%, within 3 years of 6.5%, and within 4 years of 6.9%. The incidence rates of Alzheimer's disease within 1 year were 0%, the incidence rates of Alzheimer's disease within 2 years were 0%, the incidence rates of Alzheimer's disease within 3 years were 0.6%, the incidence rates of Alzheimer's disease within 4 years were 0.6%, the incidence rates of Alzheimer's disease within 5 years were 1.7%, and the incidence rates of Alzheimer's disease within 6 years were 3.4%.

[0479] As described above, it can be seen that the larger the volume fraction value (Cog_Vol), the lower the incidence of Alzheimer's disease.

[0480] The present inventors further conducted a cohort study on subjects with mild cognitive impairment whose brain β-amyloid protein PET test results were positive or negative.

[0481] As a result, the inventors have obtained the following knowledge, that is, using Fig.33The different threshold values ​​shown can classify each of the classification objects whose results of the brain β-amyloid protein PET examination are judged to be positive or negative, that is, multiple classification objects with mild cognitive impairment, into one of multiple groups corresponding to the risk of developing Alzheimer's disease in the future with higher accuracy.

[0482] Fig.39 This is a correspondence table for classification subjects with mild cognitive impairment whose brain β-amyloid protein PET test results are judged to be positive or negative. The correspondence table shows the relationship between the volume fraction value (Cog_Vol_ab), multiple thresholds discovered by the inventors, and the transition of the ratio of classification subjects progressing from mild cognitive impairment to Alzheimer's disease.

[0483] exist Fig.39 In the figure, the volume fraction value (Cog_Vol_ab) is similar to Fig.33 The volume fraction value (Cog_Vol) in is calculated in the same way as above, except Fig.33 In addition to the two parameters of volume fraction value (Cog_Vol) in the above, the third parameter is whether the result of brain beta-amyloid PET examination is confirmed, and the calculation is performed by limiting the people whose results of brain beta-amyloid PET examination are confirmed as the classification objects. Fig.39 The volume fraction value (Cog_Vol_ab) in Fig.33 The threshold values ​​shown are different from the threshold values ​​used for classification, so in order to Fig.33 The volume fraction value (Cog_Vol) in the formula (A) is used to distinguish the volume fraction value (Cog_Vol) and is expressed as a volume fraction value (Cog_Vol_ab).

[0484] like Fig.39As shown, the inventors of the present invention have obtained the following knowledge, that is, by performing the following classifications (1) to (5) for each of the classification subjects with mild cognitive impairment for which the result of the brain β-amyloid protein PET examination is determined to be either positive or negative, it is possible to further group them, wherein the classifications (1) to (5) are: (1) when the volume fraction value (Cog_Vol_ab) is less than the first threshold value, i.e., less than 67, the classification subject is classified into the first group; (2) when the volume fraction value (Cog_Vol_ab) is greater than the first threshold value, i.e., greater than 67, and less than the second threshold value, i.e., 135, the classification subject is classified into the second group; (3) when the volume fraction value (Cog_Vol_ab) is greater than the second threshold value, i.e., greater than 135, and less than the third threshold value, i.e., 177, the classification subject is classified into the second group. In the above case, the classification object is classified into the third group; (4) when the volume fraction value (Cog_Vol_ab) is greater than the third threshold value, i.e., greater than 177, and less than the fourth threshold value, i.e., 392, the classification object is classified into the fourth group; (5) when the volume fraction value (Cog_Vol_ab) is greater than the fourth threshold value, i.e., 392, the classification object is classified into the fifth group. The further grouping is as follows: Group 1 is regarded as a group with a rate of 94.1% developing into Alzheimer's disease in the future, Group 2 is regarded as a group with a rate of 43.3% developing into Alzheimer's disease in the future, Group 3 is regarded as a group with a rate of 27.8% developing into Alzheimer's disease in the future, Group 4 is regarded as a group with a rate of 5.1% developing into Alzheimer's disease in the future, and Group 5 is regarded as a group with a rate of 0% developing into Alzheimer's disease in the future.

[0485] At this time, the inventors obtained the following findings: the incidence of Alzheimer's disease within 1 year was 64.7% for the subjects classified into the first group, the incidence of Alzheimer's disease within 2 years was 82.4% for the subjects classified into the second group, the incidence of Alzheimer's disease within 1 year was 11.1% for the subjects classified into the second group, the incidence of Alzheimer's disease within 2 years was 13.3% for the subjects classified into the third group, the incidence of Alzheimer's disease within 1 year was 34.4% for the subjects classified into the third group, the incidence of Alzheimer's disease within 1 year was 38.8% for the subjects classified into the third group, and the incidence of Alzheimer's disease within 1 year was 43.3%. The incidence rate is 7.4%, the incidence rate of Alzheimer's disease within 2 years is 13.0%, the incidence rate of Alzheimer's disease within 3 years is 24.0%, the incidence rate of Alzheimer's disease within 4 years is 25.9%, the incidence rate of Alzheimer's disease within 5 years is 25.9%, and the incidence rate of Alzheimer's disease within 6 years is 27.8%. The subjects classified into Group 4 have an incidence rate of Alzheimer's disease within 1 year of 1.3%, an incidence rate of Alzheimer's disease within 2 years of 2.5%, an incidence rate of Alzheimer's disease within 3 years of 3.2%, an incidence rate of Alzheimer's disease within 4 years of 3.2%, an incidence rate of Alzheimer's disease within 5 years of 3.8%, and an incidence rate of Alzheimer's disease within 6 years of 5.1%. The subjects classified into Group 5 have an incidence rate of Alzheimer's disease within 6 years of 0%.

[0486] As described above, it can be seen that the larger the volume fraction value (Cog_Vol_ab), the lower the incidence of Alzheimer's disease.

[0487] <Work>

[0488] The operation of the above-structured layering device 10I will be described below with reference to the drawings.

[0489] The declassification device 10I performs the tenth classification process instead of the sixth classification process performed by the declassification device 10E.

[0490] Fig.40 This is a flowchart of the tenth classification process performed by the stratification device 10I.

[0491] In the 10th classification process, the processes of step S1005 to step S1010 and the processes of step S1050 to step S1060 are respectively the same as the processes of step S605 to step S610 and the processes of step S650 to step S660 in the 6th classification process involved in the 6th embodiment, except that the classifier 30E is replaced by the classifier 30I and the stratification device 10E is replaced by the stratification device 10I. Here, the description of the processes that have been described will be omitted, and the following description will focus on the processes of step S1015 to step S1040.

[0492] When the process of step S1010 is completed, the classifier 30I calculates a volume score value (Cog_Vol) by dividing the left hippocampus volume of the selected classification target by the ADAS-cog score of the classification target (step S1015 ).

[0493] Then, the classifying unit 30I checks whether the calculated volume fraction value (Cog_Vol) is smaller than 101 (step S1020).

[0494] In the process of step S1020 , when the volume fraction value (Cog_Vol) is smaller than 101 (“Yes” in step S1020 ), the classifying unit 30I classifies the classification target in the selected state into the first group (step S1030 ).

[0495] In the process of step S1020 , when the volume fraction value (Cog_Vol) is not less than 101 (No in step S1020 ), the classifying unit 30I classifies the classification target in the selected state into the second group (step S1040 ).

[0496] When the process of step S1030 is completed or the process of step S1040 is completed, the process proceeds to step S1050.

[0497] When the processing of step S1060 is completed, the decomposition device 10I ends the tenth classification processing.

[0498] <Inspection>

[0499] The stratification device 10I of the above configuration, like the stratification device 10E, screens out those with positive brain β-amyloid protein PET test from a plurality of classification objects with mild cognitive impairment, and classifies them according to the score of the Alzheimer's Disease Rating Scale-Cognitive Component and the volume of the left hippocampus. Thus, the stratification device 10I, like the stratification device 10E, can classify the classification objects with higher accuracy.

[0500] (Replenish)

[0501] As shown above, as an example of the technology disclosed in this application, the description is based on embodiments 1 to 7 and variations 1 to 3. However, the present invention is not limited to these embodiments and variations. Without departing from the scope of the present invention, various modifications that can be thought of by those skilled in the art are performed on the present embodiment to obtain a form, or a form constructed by combining constituent elements in different embodiments can be included in the scope of one or more forms of the present invention.

[0502] One embodiment of the present invention may be not only the layering devices 10 to 10I, but also a layering method that uses the characteristic components included in the layering devices 10 to 10I as steps. Furthermore, one embodiment of the present invention may be a computer program that causes a computer to execute the characteristic steps included in the layering method. Furthermore, one embodiment of the present invention may be a computer-readable non-transitory recording medium that records the above-mentioned computer program.

[0503] In addition, the stratification method according to one embodiment of the present invention is effectively utilized in the development of prevention of Alzheimer's disease.

[0504] Industrial Applicability

[0505] The present invention can be widely used in a stratification method for classifying each of a plurality of classification subjects having mild cognitive impairment into one of a plurality of groups corresponding to the risk of developing Alzheimer's disease in the future.

[0506] Explanation of symbols

[0507] 10, 10A, 10B, 10C, 10D, 10E, 10F, 10G, 10H, 10I layered device

[0508] 20, 20A, 20B, 20C, 20D, 20E obtain the

[0509] 30, 30A, 30B, 30C, 30D, 30E, 30F, 30G, 30H, 30I classification department

[0510] 40 Output unit

Claims

1. A layered method, wherein include: An obtaining step of obtaining, for each of a plurality of classified subjects with mild cognitive impairment, a score of a result of a clinical psychological test conducted on the classified subject and a hippocampal volume of the classified subject; a classification step of classifying, for each of the plurality of classification objects, the classification object into one of a plurality of groups including at least a first group having a relatively high risk of developing Alzheimer's disease in the future and a second group having a relatively low risk of developing Alzheimer's disease in the future, based on the score of the classification object and the hippocampal volume of the classification object; as well as An output step, outputting the classification result through the classification step, The hippocampal volumes of the plurality of classified objects are the right hippocampal volumes of the plurality of classified objects. The clinical psychological test is the Alzheimer's Disease Rating Scale-Cognitive Subscale, In the classification step, for each of the multiple classification objects, when the score of the classification object is greater than the first threshold and the right hippocampal volume of the classification object is smaller than the second threshold, the classification object is classified into the first group; when the score of the classification object is smaller than the first threshold and the right hippocampal volume of the classification object is larger than the second threshold, the classification object is classified into the second group, The first threshold is 20.0±1SD, The second threshold is 3.651±1SD[cm 3 ], The 1SD of the first threshold is 6.3, The 1SD of the second threshold is 0.653 [cm 3 ].

2. A layered method, wherein include: An obtaining step of obtaining, for each of a plurality of classified subjects with mild cognitive impairment, a score of a result of a clinical psychological test conducted on the classified subject and a hippocampal volume of the classified subject; a classification step of classifying, for each of the plurality of classification objects, the classification object into one of a plurality of groups including at least a first group having a relatively high risk of developing Alzheimer's disease in the future and a second group having a relatively low risk of developing Alzheimer's disease in the future, based on the score of the classification object and the hippocampal volume of the classification object; as well as an output step, outputting the classification result obtained through the classification step, The hippocampal volumes of the plurality of classified objects are the right hippocampal volumes of the plurality of classified objects. The clinical psychological test is a comprehensive score of preclinical Alzheimer cognitive function test, In the classification step, for each of the multiple classification objects, when the score of the classification object is smaller than the third threshold value and the right hippocampal volume of the classification object is smaller than the fourth threshold value, the classification object is classified into the first group; when the score of the classification object is larger than the third threshold value and the right hippocampal volume of the classification object is larger than the fourth threshold value, the classification object is classified into the second group, The third threshold is 0.111±1SD, The fourth threshold is 3.651±1SD[cm 3 ], The 1SD of the third threshold is 2.630, The 1SD of the fourth threshold is 0.653 [cm 3 ].

3. The layering method according to claim 1 or 2, In the obtaining step, for each of the plurality of classification objects, information indicating whether the classification object has the apolipoprotein Eε4 gene is further obtained. In the classification step, for each of the plurality of classification objects, the classification object is classified into one of the plurality of groups based on the information.

4. A layered method, wherein include: An obtaining step of obtaining, for each of a plurality of classified subjects with mild cognitive impairment, a score of a result of a clinical psychological test conducted on the classified subject and a hippocampal volume of the classified subject; a classification step of classifying, for each of the plurality of classification objects, the classification object into one of a plurality of groups including at least a first group having a relatively high risk of developing Alzheimer's disease in the future and a second group having a relatively low risk of developing Alzheimer's disease in the future, based on the score of the classification object and the hippocampal volume of the classification object; as well as an output step, outputting the classification result obtained through the classification step, The hippocampal volumes of the plurality of classified objects are the right hippocampal volumes of the plurality of classified objects. The clinical psychological test includes the Alzheimer's Disease Rating Scale-Cognitive Scale and the Preclinical Alzheimer's Cognitive Function Test Comprehensive Score, In the obtaining step, for each of the plurality of classification objects, information indicating whether the classification object has the apolipoprotein Eε4 gene is further obtained. In the classification step, for each of the plurality of classification objects, in the following cases (1) to (4), the classification object is classified into the first group, and in the following cases (5) to (7), the classification object is classified into the second group, wherein the cases (1) to (4) refer to: (1) the first score of the classification object is smaller than the fifth threshold value, the right hippocampal volume of the classification object is larger than the sixth threshold value, and the information of the classification object shows that it has the apolipoprotein Eε4 gene, and the second score of the classification object is smaller than the seventh threshold value, and the first score is used as the classification object for the classification The first score of the subject is greater than the fifth threshold, the right hippocampal volume of the subject is greater than the sixth threshold, the information of the subject shows that the subject has the apolipoprotein Eε4 gene, and the second score of the subject is less than the seventh threshold; (3) the first score of the subject is greater than the fifth threshold, and the subject (4) the first score of the classified object is smaller than the fifth threshold, the right hippocampal volume of the classified object is smaller than the sixth threshold, and the information of the classified object shows that it has apolipoprotein Eε4 gene, and the second score of the classified object is smaller than the seventh threshold, the situations (5) to (7) refer to: (5) the first score of the classified object is smaller than the fifth threshold, the right hippocampal volume of the classified object is larger than the sixth threshold, and the information of the classified object shows that it has apolipoprotein Eε4 gene 4 genes, and the second score of the classification object is greater than the seventh threshold; (6) the first score of the classification object is greater than the fifth threshold, and the right hippocampal volume of the classification object is greater than the sixth threshold, and the information of the classification object shows that the apolipoprotein Eε4 gene is present, and the second score of the classification object is greater than the seventh threshold; (7) the first score of the classification object is less than the fifth threshold, and the right hippocampal volume of the classification object is greater than the sixth threshold, and the information of the classification object shows that the apolipoprotein Eε4 gene is not present, The fifth threshold is 20.0±1SD, The sixth threshold is 3.651±1SD[cm 3 ], The 7th threshold is 0.111±1SD, The 1SD of the fifth threshold is 6.3, The 1SD of the sixth threshold is 0.653 [cm 3 ], 1SD of the 7th threshold is 2.

630.

5. A stratification device, comprising: an obtaining unit that obtains, for each of a plurality of classified subjects having mild cognitive impairment, a score of a result of a clinical psychological test performed on the classified subject and a hippocampal volume of the classified subject; a classification unit that classifies, for each of the plurality of classification objects, the classification object into one of a plurality of groups including at least a first group having a relatively high risk of developing Alzheimer's disease in the future and a second group having a relatively low risk of developing Alzheimer's disease in the future, based on the score of the classification object and the hippocampal volume of the classification object; as well as an output unit, outputting the classification result obtained by the classification unit, The hippocampal volumes of the plurality of classified objects are the right hippocampal volumes of the plurality of classified objects. The clinical psychological test is the Alzheimer's Disease Rating Scale-Cognitive Subscale, The classification unit classifies, for each of the plurality of classification objects, the classification object into the first group when the score of the classification object is greater than the first threshold and the right hippocampal volume of the classification object is smaller than the second threshold, and classifies the classification object into the second group when the score of the classification object is smaller than the first threshold and the right hippocampal volume of the classification object is greater than the second threshold, The first threshold is 20.0±1SD, The second threshold is 3.651±1SD[cm 3 ], The 1SD of the first threshold is 6.3, The 1SD of the second threshold is 0.653 [cm 3 ].

6. A stratification device, comprising: an obtaining unit that obtains, for each of a plurality of classified subjects having mild cognitive impairment, a score of a result of a clinical psychological test performed on the classified subject and a hippocampal volume of the classified subject; a classification unit that classifies, for each of the plurality of classification objects, the classification object into one of a plurality of groups including at least a first group having a relatively high risk of developing Alzheimer's disease in the future and a second group having a relatively low risk of developing Alzheimer's disease in the future, based on the score of the classification object and the hippocampal volume of the classification object; as well as an output unit, outputting the classification result obtained by the classification unit, The clinical psychological test is a comprehensive score of preclinical Alzheimer cognitive function test, The classification unit classifies, for each of the plurality of classification objects, the classification object into the first group when the score of the classification object is smaller than a third threshold value and the right hippocampal volume of the classification object is smaller than a fourth threshold value, and classifies the classification object into the second group when the score of the classification object is larger than the third threshold value and the right hippocampal volume of the classification object is larger than the fourth threshold value, The third threshold is 0.111±1SD, The fourth threshold is 3.651±1SD[cm 3 ], The 1SD of the third threshold is 2.630, The 1SD of the fourth threshold is 0.653 [cm 3 ].

7. The layering device according to claim 5 or 6, The obtaining unit further obtains, for each of the plurality of classification objects, information indicating whether the classification object has an apolipoprotein Eε4 gene, The classification unit further classifies each of the plurality of classification targets into one of the plurality of groups based on the information.

8. A stratification device, comprising: an obtaining unit that obtains, for each of a plurality of classified subjects having mild cognitive impairment, a score of a result of a clinical psychological test performed on the classified subject and a hippocampal volume of the classified subject; a classification unit that classifies, for each of the plurality of classification objects, the classification object into one of a plurality of groups including at least a first group having a relatively high risk of developing Alzheimer's disease in the future and a second group having a relatively low risk of developing Alzheimer's disease in the future, based on the score of the classification object and the hippocampal volume of the classification object; as well as an output unit, outputting the classification result obtained by the classification unit, The hippocampal volumes of the plurality of classified objects are the right hippocampal volumes of the plurality of classified objects. The clinical psychological test includes the Alzheimer's Disease Rating Scale-Cognitive Scale and the Preclinical Alzheimer's Cognitive Function Test Comprehensive Score, The obtaining unit further obtains, for each of the plurality of classification objects, information indicating whether the classification object has an apolipoprotein Eε4 gene, The classification unit classifies each of the multiple classification objects into the first group in the following cases (1) to (4), and classifies the classification object into the second group in the following cases (5) to (7), wherein the cases (1) to (4) refer to: (1) the first score of the classification object is smaller than the fifth threshold, the right hippocampal volume of the classification object is larger than the sixth threshold, and the information of the classification object shows that it has the apolipoprotein Eε4 gene, and the second score of the classification object is smaller than the seventh threshold, and the first score is used as the classification object for classification; The first score of the classification object is greater than the fifth threshold, and the right hippocampal volume of the classification object is greater than the sixth threshold, and the information of the classification object shows that the apolipoprotein Eε4 gene is present, and the second score of the classification object is less than the seventh threshold; (3) the first score of the classification object is greater than the fifth threshold, and the classification object (4) the first score of the classified object is smaller than the fifth threshold, the right hippocampal volume of the classified object is smaller than the sixth threshold, and the information of the classified object shows that it has the apolipoprotein Eε4 gene, and the second score of the classified object is smaller than the seventh threshold, the situations (5) to (7) refer to: (5) the first score of the classified object is smaller than the fifth threshold, the right hippocampal volume of the classified object is larger than the sixth threshold, and the information of the classified object shows that it has the apolipoprotein Eε4 gene gene, and the second score of the classification object is greater than the seventh threshold; (6) the first score of the classification object is greater than the fifth threshold, and the right hippocampal volume of the classification object is greater than the sixth threshold, and the information of the classification object shows that it has the apolipoprotein Eε4 gene, and the second score of the classification object is greater than the seventh threshold; (7) the first score of the classification object is less than the fifth threshold, and the right hippocampal volume of the classification object is greater than the sixth threshold, and the information of the classification object shows that it does not have the apolipoprotein Eε4 gene, The fifth threshold is 20.0±1SD, The sixth threshold is 3.651±1SD[cm 3 ], The 7th threshold is 0.111±1SD, The 1SD of the fifth threshold is 6.3, The 1SD of the sixth threshold is 0.653 [cm 3 ], 1SD of the 7th threshold is 2.630.

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