Method for evaluating status of mild cognitive impairment and application of same

Abstract

A method for evaluating an aMCI status of an individual comprises: (1) delivering an evaluation scheme having one or more tests to an individual; (2) obtaining the individual's responses to the one or more tests; (3) generating an evaluation score of the individual based on the individual's responses; and (4) generating an aMCI status of the individual based on the evaluation score of the individuals.

Description

[0001] Attorney Docket No. 626986.100014 METHOD FOR EVALUATING STATUS OF MILD COGNITIVE IMPAIRMENT AND APPLICATION OF SAME

[0002] FIELD OF THE INVENTION

[0003] The present disclosure relates to the technical field of evaluating status of mild cognitive impairment, and more particular to a test administered verbally to a patient for evaluating the patient’s status of mild cognitive impairment.

[0004] BACKGROUND OF THE INVENTION

[0005] The background description provided herein is for the purpose of generally presenting the context of the present invention. The subject matter discussed in the background of the invention section should not be assumed to be prior art merely as a result of its mention in the background of the invention section. Similarly, a problem mentioned in the background of the invention section or associated with the subject matter of the background of the invention section should not be assumed to have been previously recognized in the prior art. The subject matter in the background of the invention section merely represents different approaches, which in and of themselves may also be inventions.

[0006] As global population ages, the prevalence of dementia continues to rise worldwide, negatively impacting families, the economy, and healthcare services. In recent years, clinical research has increasingly focused on early detection of dementia. Patients with mild cognitive impairment (MCI) are considered to be in a transitional stage between healthy aging and dementia, such as AD (Chang et al., 2010). As such, global research has concentrated on screening patients with MCI and distinguishing them from healthy individual undergoing normal aging.

[0007] Neuropsychological cognitive assessment plays a crucial role in screening for MCI. Numerous scientific studies have shown that neuropsychological tests can effectively detect early signs of cognitive dysfunction (Belleville et al., 2017; Chang et al., 2020), enabling earlier treatment and intervention, which may delay or prevent further cognitive decline and improve patients' quality of life. Early screening also helps distinguish between normal aging and potential pathological changes. While mild cognitive changes are common among older adults, these do not necessarily indicate MCI or neurodegenerative diseases. By using quantitative andAttorney Docket No. 626986.100014

[0008] objective methods to measure cognitive function, early signs of cognitive impairment can be detected, and the risk of progressing to dementia over several years can be predicted.

[0009] Neuropsychological assessments can also identify an individual's cognitive strengths and weaknesses, aiding in personalized and precise intervention for future health management.

[0010] MCI represents a group of individuals at higher risk of developing dementia. Due to the heterogeneity of its clinical presentation, MCI is categorized into four subtypes based on two dimensions: amnestic and non-amnestic, and single or multiple cognitive domain impairments. Amnestic MCI (aMCI), with either single or multiple cognitive domain impairments, is particularly associated with the progression to Alzheimer's disease (AD). Individuals with aMCI affecting multiple domains, including language, are more likely to develop AD-type dementia than those with memory impairment alone. Thus, for aMCI individuals, clinical assessment should extend beyond episodic memory impairment to evaluate other cognitive domains to determine dementia risk.

[0011] Although previous research has provided ample evidence that neuropsychological tests can effectively differentiate normal from abnormal aging, a highly sensitive and time-efficient assessment scheme is still lacking. Take the commonly used MMSE tool as an example: it is the most prevalent screening tool in clinical settings and only takes ten minutes to administer, yet its sensitivity in detecting aMCI is less than 50% (Arevalo-Rodriguez et al., 2021), especially in early-stage patients. This limitation arises because the MMSE is a brief, general cognitive assessment tool that was not originally designed for the aMCI population, making it insufficient to capture all the changes associated with aMCI. While detailed neuropsychological assessments significantly increase the accuracy of identifying MCI, they often take several hours, making them impractical for widespread use. Therefore, developing a sensitive and practical assessment scheme would better distinguish abnormal cognitive changes associated with aging, identify individuals with aMCI earlier, and provide the healthcare system with more time and resources for treatment and support plans, ultimately reducing medical costs and increasing efficiency. Additionally, it is essential to have an assessment test that accommodates aging patients with reduced or impaired vision. Society would be better equipped to address the challenges of an aging population by providing appropriate social support and health management for those with MCI.

[0012] Therefore, a method for predicting cognitive outcomes of MCI under ChEI treatmentAttorney Docket No. 626986.100014

[0013] using brain age is imperatively needed.

[0014] SUMMARY OF THE INVENTION

[0015] These and other aspects of the present invention will become apparent from the following description of the preferred embodiment taken in conjunction with the following drawings, although variations and modifications therein may be effected without departing from the spirit and scope of the novel concepts of the disclosure.

[0016] In one aspect of the invention, the present application discloses a method for evaluating an aMCI status of an individual. The method comprises delivering an evaluation scheme having one or more tests to an individual; obtaining the individual’s responses to the one or more tests; generating an evaluation score of the individual based on the individual’s responses; and generating an aMCI status of the individual based on the evaluation score of the individual.

[0017] In one embodiment, each of the one or more tests comprises at least one question; and wherein the at least one question is delivered to the individual verbally or textually.

[0018] In one embodiment, the individual’s responses comprise at least one answer in verbal. In one embodiment, the evaluation scheme comprises a cognitive test function section. In one embodiment, the cognitive test function section comprises at least one of a verbal listing learning test, a semantic verbal fluency test, an attribute verification test, a digit span sequencing test, a Hayling sentence completion test, and a time orientation test.

[0019] In one embodiment, the evaluation score is generated at least partially based on the individual’s responses to the at least one of the verbal listing learning test, the semantic verbal fluency test, the attribute verification test, the digit span sequencing test, the Hayling sentence completion test, and the time orientation test.

[0020] In one embodiment, the evaluation score is generated at least partially based on an individual’s reaction time to the at least one of the verbal listing learning test, the semantic verbal fluency test, the attribute verification test, the digit span sequencing test, the Hayling sentence completion test, and the time orientation test.

[0021] In one embodiment, the cognitive test function section comprises the verbal listing learning test, and the semantic verbal fluency test; wherein the verbal listing learning test comprises at least one verbal listing learning question requesting the individual to memorize a group of words delivery to the individual and then repeat the memorized group of wordsAttorney Docket No. 626986.100014

[0022] verbally; wherein the semantic verbal fluency test comprises at least one semantic verbal fluency question requesting the individual to verbally provide words within at least one semantic category within a certain time period.

[0023] In one embodiment, the cognitive test function section comprises one of the Hayling sentence completion test and the attribute verification test; wherein the Hayling sentence completion test comprises at least one sentence completion question requesting the individual to complete a sentence with an omission having at least one omitted word using at least one word which is different from the omitted word; wherein the attribute verification test comprises at least one attribute verification question requesting the individual to determine if an attribute statement is correct.

[0024] In one embodiment, the cognitive test function section comprises both the Hayling sentence completion test and the attribute verification test.

[0025] In one embodiment, the cognitive test function section comprises at least one of the digit span sequencing test and the time orientation test; wherein the digit span sequencing test comprises at least one digit span sequencing question requesting the individual to arrange multiple elements in an ascending or descending order verbally; and wherein the time orientation test comprises at least one time orientation question requesting the individual to verbally provide a date or a time.

[0026] In one embodiment, the evaluation scheme further comprises a subjective testing section. In one embodiment, the subjective testing section comprises at least one of a subjective cognitive decline test, an emotional screening test, and a lifestyle test.

[0027] In one embodiment, the evaluation score is generated at least partially based on the individual’s responses to the at least one of the subjective cognitive decline test, the emotional screening test, and the lifestyle test.

[0028] In one embodiment, the subjective cognitive decline (SCD) test comprises at least one SCD question requesting the individual to provide an evaluation of at least one status of individual’s memory, attention, and cognitive function.

[0029] In one embodiment, the emotional screening test comprises at least one emotional status question requesting the individual to provide an evaluation of the individual’s emotional status, and wherein an emotional status score is generated based on the evaluation of the individual’s emotional status provided by the individual.Attorney Docket No. 626986.100014

[0030] In one embodiment, the lifestyle test comprises at least one sleep status question requesting the individual to provide an evaluation of the individual’s sleep status.

[0031] In one embodiment, the lifestyle test comprises at least one exercise status question requesting the individual to provide an evaluation of the individual’s exercise status.

[0032] In one embodiment, step (1) and step (2) of the evaluation scheme are conducted using an electronic device.

[0033] In one embodiment, the electronic device comprises at least one voice module, wherein the at least voice module delivers the one or more test to the individual, and obtains the individual’s responses to the one or more test.

[0034] In one embodiment, the electronic device comprises an interactive screen, wherein the interactive screen displays the one or more tests to the individual.

[0035] In another aspect of the invention, a method for evaluating an aMCI status of an individual comprises delivering an evaluation scheme having a cognitive test function section and a subjective testing section to an individual; obtaining the individual’s responses to the evaluation scheme; generating an evaluation score of the individual based on the individual’s responses; and generating an aMCI status of the individual based on the evaluation score of the individual, wherein the cognitive test function section comprises a verbal listing learning test, a semantic verbal fluency test, an attribute verification test, a digit span sequencing test, a Hayling sentence completion test, and a time orientation test; wherein the subjective testing section comprises at least one of an emotional screening test, and a lifestyle test;wherein the individual’s response to the evaluation scheme includes answers provided by the individual in response to questions in the tests of the evaluation scheme and a time period for the individual to complete at least one of the answers for at least one of the questions.

[0036] BRIEF DESCRIPTION OF THE DRAWINGS

[0037] The accompanying drawings illustrate one or more embodiments of the invention and together with the written description, serve to explain the principles of the invention. Wherever possible, the same reference numbers are used throughout the drawings to refer to the same or like elements of an embodiment.

[0038] FIG. 1 shows a chart reflecting CoBA total scores of HC and aMCI groups.

[0039] FIG. 2 shows a chart reflecting MMSE total score of HC and aMCI groups.Attorney Docket No. 626986.100014

[0040] DETAILED DESCRIPTION OF THE INVENTION

[0041] The invention will now be described more fully hereinafter with reference to the accompanying drawings, in which exemplary embodiments of the invention are shown. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. Like reference numerals refer to like elements throughout.

[0042] The terms used in this specification generally have their ordinary meanings in the art, within the context of the invention, and in the specific context where each term is used. Certain terms that are used to describe the invention are discussed below, or elsewhere in the specification, to provide additional guidance to the practitioner regarding the description of the invention. For convenience, certain terms may be highlighted, for example using italics and / or quotation marks. The use of highlighting has no influence on the scope and meaning of a term; the scope and meaning of a term is the same, in the same context, whether or not it is highlighted. It will be appreciated that same thing can be said in more than one way.

[0043] Consequently, alternative language and synonyms may be used for any one or more of the terms discussed herein, nor is any special significance to be placed upon whether or not a term is elaborated or discussed herein. Synonyms for certain terms are provided. A recital of one or more synonyms does not exclude the use of other synonyms. The use of examples anywhere in this specification including examples of any terms discussed herein is illustrative only, and in no way limits the scope and meaning of the invention or of any exemplified term. Likewise, the invention is not limited to various embodiments given in this specification.

[0044] It will be understood that, as used in the description herein and throughout the claims that follow, the meaning of “a”, “an”, and “the” includes plural reference unless the context clearly dictates otherwise. Also, it will be understood that when an element is referred to as being “on” another element, it can be directly on the other element or intervening elements may be present therebetween. In contrast, when an element is referred to as being “directly on” another element, there are no intervening elements present. As used herein, the term “and / or” includes any and all combinations of one or more of the associated listed items.Attorney Docket No. 626986.100014

[0045] It will be understood that, although the terms first, second, third etc. may be used herein to describe various elements, components, regions, layers and / or sections, these elements, components, regions, layers and / or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer or section from another element, component, region, layer or section. Thus, a first element, component, region, layer or section discussed below could be termed a second element, component, region, layer or section without departing from the teachings of the invention.

[0046] Further more, when being used in association with the term “beyond a threshold score”, the relative terms “greater than” or “smaller than” can be used interchangeable.

[0047] It will be further understood that the terms “comprises” and / or “comprising,” or “includes” and / or “including” or “has” and / or “having”, or “carry” and / or “carrying,” or “contain” and / or “containing,” or “involve” and / or “involving, and the like are to be open-ended, i.e., to mean including but not limited to. When used in this disclosure, they specify the presence of stated features, regions, integers, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, regions, integers, steps, operations, elements, components, and / or groups thereof.

[0048] Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and the present disclosure, and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.

[0049] As used in this disclosure, “around”, “about”, “approximately” or “substantially” shall generally mean within 20 percent, preferably within 10 percent, and more preferably within 5 percent of a given value or range. Numerical quantities given herein are approximate, meaning that the term “around”, “about”, “approximately” or “substantially” can be inferred if not expressly stated.

[0050] As used in this disclosure, the phrase “at least one of A, B, and C” should be construed to mean a logical (A or B or C), using a non-exclusive logical OR. As used herein, the term “and / or” includes any and all combinations of one or more of the associated listed items.

[0051] As used in this disclosure, “verbal” or “verbally” refers to delivery and / or communicationAttorney Docket No. 626986.100014

[0052] of information via the use of words in a voice-based spoken form, which refers specifically to something expressed orally rather than in writing.

[0053] As used in this disclosure, “textual” or “textually” refers to delivery and / or communication of information via the use of words in a text-based form, which refers specifically to something expressed in writing rather than in verbal.

[0054] Embodiments of the invention are illustrated in detail hereinafter with reference to accompanying drawings. The description below is merely illustrative in nature and is in no way intended to limit the invention, its application, or uses. The broad teachings of the invention can be implemented in a variety of forms. Therefore, while this invention includes particular examples, the true scope of the invention should not be so limited since other modifications will become apparent upon a study of the drawings, the specification, and the following claims. For purposes of clarity, the same reference numbers will be used in the drawings to identify similar elements. It should be understood that one or more steps within a method may be executed in different order (or concurrently) without altering the principles of the invention.

[0055] The description will be made as to the embodiments of the present invention in conjunction with the accompanying drawings in FIGs. 1-2. In accordance with the purposes of this invention, as embodied and broadly described herein, this invention, in one aspect, relates to a method for evaluating a status of MCI for an individual.

[0056] In certain embodiments, the present invention discloses an evaluation scheme focusing on specific cognitive domains, including episodic memory, semantic knowledge, and frontal executive function. This evaluation scheme provides an evaluation result regarding an individual test taker’s aMCI status, and effectively differentiates aMCI individuals from the control group, which undergoes normal aging.

[0057] In certain embodiments, the evaluation scheme of the present invention is complemented by subjective cognitive questions and / or emotional screening questions.

[0058] In certain embodiments, the evaluation is designed to be completed within about 15 minutes, and be accomplished via verbal administration, without relying on visual function of an individual taking the evaluation.

[0059] The evaluation scheme has several advantages. First, it covers a more comprehensive range of language aspects and features a simplified scoring system, making it a valuable clinical tool for identifying users at high risk for aMCI. Second, it takes significantly less time than aAttorney Docket No. 626986.100014

[0060] detailed neuropsychological assessment which often take several hours and making the detailed neuropsychological assessment impractical for widespread use, while maintains a high sensitivity in detecting aMCI as compared to MMSE assessment which has a sensitivity of less than 50% of detecting aMCI. Most importantly, the evaluation scheme of the present invention can be conducted solely in verbal, which completely eliminates the reliance of a patient’s visual function.

[0061] In certain embodiments, the evaluation is designed to be completed between about 12-18 minutes. In certain embodiments, the evaluation is designed to be completed between about 10-20 minutes. In certain embodiments, the evaluation is designed to be completed between about 5-30 minutes. In certain embodiments, the evaluation is designed to be completed within 45 minutes. In certain embodiments, the evaluation is designed to be completed within 60 minutes.

[0062] In certain embodiments, the evaluation includes a cognitive function testing section. In certain embodiments, the cognitive function testing section includes multiple tests which are presented to an individual test taker.

[0063] In certain embodiments, each of the multiple tests in the cognitive function testing section include one or more questions. Each of the questions has one or more objectively correct answers.

[0064] In certain embodiments, the multiple tests include one or more of the following tests: Semantic Verbal Fluency Test, Attribute Verification Test, Digit Span Sequencing Test, Hayling Sentence Completion Test For Response Inhibition, Verbal List Learning Test with Semantic Categories, and Time-Orientation Test.

[0065] In certain embodiments, the cognitive function testing section includes two tests selected from the following tests: Semantic Verbal Fluency Test, Attribute Verification Test, Digit Span Sequencing Test, Hayling Sentence Completion Test For Response Inhibition, Verbal List Learning Test with Semantic Categories, and Time-Orientation Test.

[0066] In certain embodiments, the cognitive function testing section includes three tests selected from the following tests: Semantic Verbal Fluency Test, Attribute Verification Test, Digit Span Sequencing Test, Hayling Sentence Completion Test For Response Inhibition, Verbal List Learning Test with Semantic Categories, and Time-Orientation Test.

[0067] In certain embodiments, the cognitive function testing section includes four tests selected from the following tests: Semantic Verbal Fluency Test, Attribute Verification Test, Digit SpanAttorney Docket No. 626986.100014

[0068] Sequencing Test, Hayling Sentence Completion Test For Response Inhibition, Verbal List Learning Test with Semantic Categories, and Time-Orientation Test.

[0069] In certain embodiments, the cognitive function testing section includes five tests selected from the following tests: Semantic Verbal Fluency Test, Attribute Verification Test, Digit Span Sequencing Test, Hayling Sentence Completion Test For Response Inhibition, Verbal List Learning Test with Semantic Categories, and Time-Orientation Test.

[0070] In certain embodiments, the cognitive function testing section includes six tests: Semantic Verbal Fluency Test, Attribute Verification Test, Digit Span Sequencing Test, Hayling Sentence Completion Test For Response Inhibition, Verbal List Learning Test with Semantic Categories, and Time-Orientation Test.

[0071] In certain embodiments, the cognitive function testing section includes six tests selected from Semantic Verbal Fluency Test, Attribute Verification Test, Digit Span Sequencing Test, Hayling Sentence Completion Test For Response Inhibition, Verbal List Learning Test with Semantic Categories, and Time-Orientation Test, together with one or more additional tests. Each of the additional tests includes one or more questions having one or more objectively correct answers.

[0072] In certain embodiments, the cognitive function testing section includes Verbal List Learning Test with Semantic Categories and Semantic Verbal Fluency Test.

[0073] In certain embodiments, the cognitive function testing section includes Verbal List Learning Test with Semantic Categories and Semantic Verbal Fluency Test, and one or more tests selected from Attribute Verification Test, Digit Span Sequencing Test, Hayling Sentence Completion Test For Response Inhibition, and Time-Orientation Test.

[0074] In certain embodiments, the evaluation includes a subj ective testing section. The subjective test section includes one or more tests selected from Subjective Cognitive Decline (SCD) Test, Emotional Screening Test, and Lifestyle Screening Test.

[0075] In certain embodiments, each of the tests in the subjective testing section includes one or more questions. Each of the questions focuses on the individual’s evaluation of his or her own mental or physiological status.

[0076] In certain embodiments, the evaluation scheme of the present invention includes only the cognitive function testing section. In certain embodiments, the evaluation scheme of the present invention includes only the subject testing section. In certain embodiments, the evaluationAttorney Docket No. 626986.100014

[0077] scheme of the present invention includes both the cognitive function testing section and the subject testing section.

[0078] In certain embodiments, all the questions in the cognitive function testing section are delivered to the individual taking the tests verbally. In certain embodiments, answers of all the questions in the cognitive function testing section are presented by the individual test taker verbally.

[0079] In certain embodiments, all the questions in the cognitive function testing section are delivered to the individual taking the tests by words, either verbally, textually or in combination. In certain embodiments, all the questions in the cognitive function testing section are answered by the individual taking the tests either verbally, textually, or inputs through equipment e.g. keyboard, mouse, laser pen, etc.

[0080] In certain embodiments, all the questions in the cognitive function testing section are delivered to the individual taking the tests by words without using graphics, such that individual’s with impaired visual function is capable of taking the cognitive function tests, the individual can take the cognitive function tests over the phones or other telecommunication methods remotely without physically presenting at a test center / doctor’s office / medical facility, and / or the individual can take an automated or semi-automated test utilizing large language models.

[0081] In certain embodiments, all the questions in the subjective testing section are delivered to the individual taking the tests by words, either verbally, textually or in combination. In certain embodiments, all the questions in the subjective testing section are answered by the individual taking the tests either verbally, textually, or inputs through equipment e.g. keyboard, mouse, laser pen, etc.

[0082] In certain embodiments, all the questions in the subjective testing section are delivered to the individual taking the tests by words without using graphics, such that individual’s with impaired visual function is capable of taking the cognitive function tests, the individual can take the subjective testing section over the phones or other telecommunication methods remotely without physically presenting at a test center / doctor’s office / medical facility, and / or the individual can take an automated or semi-automated test utilizing large language models.Attorney Docket No. 626986.100014

[0083] Cognitive Function Testing Section

[0084] In certain embodiments, an evaluation scheme of the present invention includes a cognitive function testing section.

[0085] In certain embodiments, the cognitive function testing section includes one or more of a semantic verbal fluency test, an attribute verification test, a digit span sequencing test, aHayling sentence completion test for response inhibition, a verbal list learning test with semantic categories, and a time-orientation test.

[0086] In certain embodiments, each of the one or more of the semantic verbal fluency test, the attribute verification test, the digit span sequencing test, the Hayling sentence completion test for response inhibition, the verbal list learning test with semantic categories, and the time-orientation test taken by the individual test taker produces a score based on the individual test taker’s responses to the particular test.

[0087] In certain embodiments, a cognitive function testing score is generated based on partial or all scores obtained by the individual test taker taking the one or more tests of the cognitive function testing section.

[0088] In certain embodiments, the aMCI status of the individual test taker is determined based on part or all of the scores generated based on the individual test taker’s responses to the one or more tests.

[0089] In certain embodiments, the aMCI status of the individual test taker is determined based on the cognitive function testing score.

[0090] Semantic Verbal Fluency Test

[0091] Patients with Alzheimer's disease (AD) often exhibit impairments in verbal fluency, semantic knowledge, and connected speech processing. Similar patterns have been observed in aMCI patients, whose language dysfunction is primarily reflected in vocabulary and semantic aspects, including deficits in verbal fluency and confrontation naming. Additionally, aMCI individuals are more prone to making semantically related errors in naming tasks, such as saying "bear" instead of "tiger," compared to other types of naming errors. These lexical-semantic deficits in aMCI may stem from difficulties in word retrieval and semantic processing, which could be related to damage in brain networks involving the temporal and frontal lobes and reduced volume in the perirhinal cortex, a region crucial for integrating cross-modal objectAttorney Docket No. 626986.100014

[0092] representations.

[0093] Overall, in naming tests, the aMCI group tends to fail more frequently in biological categories (e.g., vegetables, fruits, animals) than in non-biological categories (e.g., tools, clothing), indicating that aMCI individuals struggle with semantic categories that share more common attributes and fewer unique features. Therefore, this assessment scheme includes a semantic verbal fluency test to evaluate language generation, semantic memory, executive function, and attention. It measures how many words a participant can generate within a specific semantic category (e.g., "animals," "fruits," or "city names") in a limited time frame, such as one minute, reflecting the participant's ability to rapidly retrieve and organize language information from memory. A lower score may indicate cognitive impairment, particularly in language generation, memory retrieval, or executive function. An example of this test question is: "You have one minute to name as many fruits as you can. Try to list as many as possible without repeating."

[0094] Research has extensively explored language impairments at the lexical-semantic level in MCI, such as in naming and fluency tests, while also observing deficits beyond these areas. Studies using comprehensive language testing tools have shown that aMCI patients exhibit deficits in language tasks that extend beyond lexical-semantic processing, such as sentence comprehension. Other research focusing on non-lexical and non-semantic language processing has found that older aMCI patients perform significantly worse compared to healthy controls. These poorer performances may be partially due to diminished executive control and reduced working memory capacity, negatively impacting the ability to comprehend various syntactic structures and temporarily store different words.

[0095] In certain embodiments, a semantic category in a semantic verbal fluency test of the present invention is a group of words or concepts that share related meanings or belong to a similar class based on common features or functions. These categories help to organize knowledge and language by grouping concepts that have something in common. For example, in language and cognitive sciences, semantic categories allow us to understand and process information by linking related ideas together.

[0096] Some examples include:

[0097] Animals - words like "dog," "cat," "lion," and "bird."

[0098] Colors - words like "red," "blue," "green," and "yellow."Attorney Docket No. 626986.100014

[0099] Furniture - words like "chair," "table," "bed," and "sofa."

[0100] Emotions - words like "happy," "sad," "angry," and "excited."

[0101] In certain embodiments, an individual is asked to verbally generate / name words within one specific semantic category within a limited time frame in a semantic verbal fluency test of the present invention.

[0102] In certain embodiments, an individual is asked to verbally generate / name words within multiple semantic categories within a limited time frame in a semantic verbal fluency test of the present invention.

[0103] In certain embodiments, the semantic category comprises one or more subcategories of biological terms. In certain embodiments, the semantic category comprises one or more subcategories of non-biological terms.

[0104] In certain embodiments, the semantic category comprises one or more of the following subcategories: nouns, functional words, predicates, and others.

[0105] In certain embodiments, the semantic category comprises one or more of the following subcategories: household, food, drinks, clothing, body parts, animals, plants, vehicles, articles, commodities, toys, tools, furniture, rooms, outside features / items, people, routines, games, time words, sounds, places, action words, description words, adverbs, adjectives, question words, pronouns, connecting words, quantifiers, locations, helping verbs, prepositions, states, final particles, directions, classifiers, articles, and verb endings.

[0106] In certain embodiments, the semantic category comprises one or more of the following subcategories: living things including animals, plants, insects, humans, bacteria / microorganisms; nature and the environment including weather phenomena (e.g. rain, sun, wind, snow), bodies of water (e.g. oceans, lakes, rivers), landforms (e.g. mountains, valleys, hills, deserts), natural resources (e.g. minerals, water, plants); people and roles including family members (e g. mother, father, sister), occupations (e.g. teacher, doctor, engineer, artist), nationalities / ethnic groups, social roles (e.g. leader, friend, citizen); physical objects including furniture (e.g. chair, table, sofa, bed), appliances (e.g. refrigerator, oven, washing machine), vehicles (e.g. car, bicycle, airplane, train), tools (e.g. hammer, saw, drill); food and beverages including fruits (e.g. apple, banana, orange), vegetables (e.g. carrot, lettuce, tomato), beverages (e.g. water, juice, coffee, tea), grains and cereals (e.g. wheat, rice, corn), proteins (e.g. meat, fish, eggs, beans); body parts and functions including external body parts (e.g. arm, leg, head), internal organs (e.g. heart,Attorney Docket No. 626986.100014

[0107] brain, liver), sensory organs (e.g. eyes, ears, nose, skin), bodily functions (e g. breathing, digestion, circulation); places and locations including buildings (e.g. house, school, hospital), geographic locations (e.g. continent, country, city), natural settings (e.g. beach, forest, desert), commercial places (e.g. store, restaurant, office); time including days of the week (e.g. Monday, Tuesday), months (e.g. January, February), seasons (e.g. spring, summer, fall, winter), times of day (e.g. morning, afternoon, night), units of time e.g. (minute, hour, day, year); events and activities including holidays (e.g. Christmas, new year, diwali), life events (e.g. birthday, wedding, graduation), celebrations (e.g. party, festival, gathering), daily routines (e.g. eating, sleeping, working), hobbies (e.g. reading, painting, hiking); actions and verbs including physical actions (e.g. run, jump, swim, lift), communication actions (e.g. speak, write, listen), cognitive actions (e.g. think, remember, plan), emotional actions (e.g. smile, cry, laugh); colors including basic colors (e.g. red, blue, green, yellow), shades (e.g. light blue, dark green, pastel pink); shapes and patterns including geometric shapes (e.g. circle, square, triangle), patterns (e.g. striped, polka-dotted, plaid); numbers and mathematics including cardinal numbers (e.g. one, two, three), mathematical operations (e.g. addition, subtraction), fractions and percentages (e.g. half, quarter, 75%); materials and textures including materials (e.g. wood, metal, glass, fabric), textures (e.g. smooth, rough, soft, hard); measurement and quantities including length (e.g. meter, kilometer, inch), weight (e.g. kilogram, pound, gram), volume (e.g. liter, gallon, ounce), temperature (e.g. hot, cold, warm, freezing); emotions and states including positive emotions (e.g. happiness, excitement, love), negative emotions (e.g. anger, sadness, fear), mental states (e.g. calm, anxious, focused); technology and electronics including devices (e.g. computer, smartphone, tablet), communication tools (e.g. email, messaging, call), digital platforms (e.g. social media, websites, apps); transportation and travel including modes of transport (e.g. car, train, airplane, boat), travel types (e.g. business, leisure, adventure), infrastructure (e.g. airport, station, port); health and medicine including illnesses and conditions (e.g. flu, cancer, diabetes), medical practices (e.g. surgery, therapy, check-up), medications and treatments (e.g. antibiotic, vaccine); science and education including scientific fields (e g. biology, chemistry, physics), academic disciplines (e.g. math, literature, art), school-related items (e.g. notebook, pen, desk); money and finance including currency (e.g. dollar, euro, yen), financial concepts (e.g. loan, savings, interest), payment methods (e.g. credit card, cash, check); moral and social concepts including values (e.g. honesty, respect, loyalty), rights and freedoms (e.g. freedom of speech,Attorney Docket No. 626986.100014

[0108] privacy), laws and ethics (e.g. justice, fairness, duty); literature and arts including literary genres (e.g. fiction, poetry, mystery), art forms (e.g. painting, sculpture, dance), music genres (e.g. classical, rock,jazz, pop); religion and beliefs including world religions (e.g. Christianity, islam, buddhism), religious practices (e.g. prayer, meditation, fasting), symbols (e.g. cross, crescent, star of david).

[0109] In certain embodiments, the semantic category comprises terms commonly known and / or used by an individual test taker in his or her daily life, regardless of his or her education level.

[0110] In certain embodiments, the specific semantic category in which an individual test taker is requested to generate / name words is determined according to the individual’s education level.

[0111] In certain embodiments, the limited time frame for an individual to verbally generate words is about 30 seconds. In certain embodiments, the limited time frame for an individual to verbally generate words is about 45 seconds. In certain embodiments, the limited time frame for an individual to verbally generate words is about 60 seconds. In certain embodiments, the limited time frame for an individual to verbally generate words is about 75 seconds. In certain embodiments, the limited time frame for an individual to verbally generate words is about 90 seconds. In certain embodiments, the limited time frame for an individual to verbally generate words is about 105 seconds. In certain embodiments, the limited time frame for an individual to verbally generate words is about 120 seconds.

[0112] In certain embodiments, one or more of the questions in the semantic verbal fluency test are single choice questions.

[0113] In certain embodiments, one or more of the questions in the semantic verbal fluency test are multiple choice questions.

[0114] In certain embodiments, one or more of the questions in the semantic verbal fluency test are answered by a narrative answer provided by the individual test taker.

[0115] In certain embodiments, an aMCI status result produced by the evaluation scheme of the present invention partially depends on the time spent by the individual test taker for answering the one or more of the questions in the semantic verbal fluency test.

[0116] In certain embodiments, the individual test taker receives a score based on his or her answers in the semantic verbal fluency test, on which the aMCI status result partially or fully depends.Attorney Docket No. 626986.100014

[0117] Attribute Verification Test

[0118] In the auditory and comprehension domain, prior studies have found that individuals with aMCI perform worse on attribute verification tests compared to healthy controls. The results suggest that aMCI individuals struggle to retrieve attributes from the semantic network, consistent with evidence of volume reduction in the anterior temporal and inferior frontal cortices, regions crucial for semantic storage and the proper utilization of semantic representations. Furthermore, one study reported that statement accuracy could influence AD patients' performance on this task. The cognitive demands may differ between false and true statements, with false statements requiring the retrieval of more potential attributes, making them more challenging for AD patients to verify.

[0119] Consequently, this assessment scheme includes an attribute verification test with false statements. An example of this test question is: "Please judge whether these sentences are true or false, and respond as quickly as possible by saying 'true' or 'false.' For example, 'The sun is green (true / false) — what would you say?' Great, now let's begin. 'Sparrows are purple (true / false)."' In certain embodiments, the attribute verification test of the present invention includes one or more true or false questions delivered to an individual test taker.

[0120] In certain embodiments, each of the true or false questions of the attribute verification test includes one statement, and the individual test taker is asked to determine whether the statement is true or false.

[0121] In certain embodiments, the statement in each of the true or false questions is fact based. In certain embodiments, the statement in each of the true or false questions is based on one or more facts which is commonly and / or widely known by the public.

[0122] In certain embodiments, the statement in each of the true or false questions is based on one or more facts which is commonly and / or widely known by the individual test taker regardless of the individual test taker’s education level.

[0123] In certain embodiments, each of the true or false questions has a single correct answer, which is either true or false.

[0124] In certain embodiments, one or more true or false questions of the attribute verification test is selected from an attribute verification test question database.

[0125] In certain embodiments, one or more true or false questions in the question database are designed by a medical professional / experts.Attorney Docket No. 626986.100014

[0126] In certain embodiments, one or more true or false questions in the question database are generated by a large language model and reviewed by a medical professional / experts.

[0127] In certain embodiments, each of the true or false questions of the attribute verification test is delivered to the individual test taker verbally, and the individual test taker provides the answer verbally.

[0128] In certain embodiments, an aMCI status result produced by the evaluation scheme of the present invention partially depends on the time spent by the individual test taker for answering the one or more of the questions in the attribute verification test.

[0129] In certain embodiments, the individual test taker receives a score based on his or her answers in the attribute verification test, on which the aMCI status result partially or fully depends.

[0130] Digit Span Sequencing Test

[0131] To evaluate working memory and executive function, this assessment scheme includes a digit span sequencing test. Individual test takers hear or see a series of random digits and are asked to repeat them in ascending or descending order. This task assesses verbal working memory, attention, cognitive control, and executive function. An example of this test question is: "I will now give you a set of numbers. Please arrange them from smallest to largest and say them back to me. For example, if I say '5-2' (one number per second), you would say '2-5.' First set: 3-7-2 ; second set: 2-8-5-6 ; third set: 9-4-6-2-5 ."

[0132] In certain embodiments, the digit span sequencing test of the present invention includes one or more sequencing questions delivered to an individual test taker.

[0133] In certain embodiments, each of the sequencing questions including a request to an individual test taker to arrange multiple elements by an order commonly known / understood by the public.

[0134] In certain embodiments, the multiple elements are numbers. In certain embodiments, the multiple elements are letters. In certain embodiments, the multiple elements can be any set of elements having an order commonly known / understood by the public. In certain embodiments, the multiple elements can be any set of elements having an order understood by the individual test taker regardless of his or ger education level.

[0135] In certain embodiments, the multiple elements include two elements. In certainAttorney Docket No. 626986.100014

[0136] embodiments, the multiple elements include three elements. In certain embodiments, the multiple elements include four elements. In certain embodiments, the multiple elements include five elements. In certain embodiments, the multiple elements include six elements. In certain embodiments, the multiple elements include seven elements. In certain embodiments, the multiple elements include eight elements. In certain embodiments, the multiple elements include night elements. In certain embodiments, the multiple elements include ten elements.

[0137] In certain embodiments, in each of the sequencing questions, the individual test taker is requested to arrange the multiple elements either in an ascending order or descending order.

[0138] In certain embodiments, each of the sequencing questions of the digit span sequencing test is delivered to the individual test taker verbally, and the individual test taker provides the answer verbally.

[0139] In certain embodiments, one or more of the sequencing questions are single choice questions.

[0140] In certain embodiments, one or more of the sequencing questions are multiple choice questions.

[0141] In certain embodiments, one or more of the sequencing questions are answered by a narrative answer provided by the individual test taker.

[0142] In certain embodiments, the aMCI status result produced by the evaluation scheme of the present invention partially depends on the time spent by the individual test taker for answering the one or more of the questions in the digit span sequencing test.

[0143] In certain embodiments, the individual test taker receives a score based on his or her answers in the digit span sequencing test, on which the aMCI status result partially or fully depends.

[0144] Hayling Sentence Completion Test for Response Inhibition

[0145] Previous studies have found that aMCI groups, compared to healthy controls (HC), exhibit deficits on standardized neuropsychological tests involving switching and inhibition abilities. Therefore, this assessment scheme includes the Hayling Sentence Completion Test focused on response inhibition. The Hayling Sentence Completion Test is a neuropsychological tool used to evaluate executive function, particularly inhibitory control, language generation, response inhibition, and attention. It measures an individual test taker's ability to adapt andAttorney Docket No. 626986.100014

[0146] suppress inappropriate responses in the context of language and sentence completion. This test is often used to detect frontal lobe dysfunction, as the frontal lobe plays a crucial role in executive functioning and inhibitory control.

[0147] During the test, the test administrator reads a series of sentences that are missing the final word, and the individual test taker is asked to provide an answer based on specific instructions. For the response inhibition version, the individual test taker is instructed to deliberately avoid providing a word that makes sense in context, instead offering an unrelated word. For example, if the sentence is "The captain wants to stay with the sinking ," the individual test taker might respond with words like "lightbulb" or "apple," intentionally choosing something unrelated to the context, but not a word like "ship." The participant must suppress a strongly activated response and generate a new one, with the ability to provide completely unrelated words reflecting effective inhibitory control. Failure to inhibit a natural response (e g., providing a reasonable answer) indicates weaknesses in inhibitory function.

[0148] In certain embodiments, the hayling sentence completion test of the present invention includes one or more sentence completion questions delivered to an individual test taker.

[0149] In certain embodiments, each of the sentence completion questions of the hayling sentence completion test includes one statement with an omission in the statement.

[0150] In certain embodiments, the omission in the statement includes one omitted word. In certain embodiments, the omitted word can be determined by the individual test taker according to one or more facts commonly / widely known or understood by the public, or one or more facts understood by the individual text taker regardless of his or her education level.

[0151] In certain embodiments, the individual test taker is asked to respond to the sentence completion question by completing the sentence using one or more words which are different from the omitted word.

[0152] In certain embodiments, the omission in the statement includes multiple omitted words. In certain embodiments, the omitted words can be determined by the individual test taker according to one or more facts commonly / widely known or understood by the public, or one or more facts understood by the individual text taker regardless of his or her education level.

[0153] In certain embodiments, the individual test taker is asked to respond to the sentence completion question by completing the sentence using one or more words, and at least one of the words used by the individual test taker is expected to be different from the multiple omittedAttorney Docket No. 626986.100014

[0154] words.

[0155] In certain embodiments, for each of the sentence completion questions of the hayling sentence completion test, the individual test taker is requested to complete the statement having the omission, and the completed sentence provided by the individual test taker is expected to be in contradictory to one or more facts commonly / widely known or understood by the public, or one or more facts understood by the individual text taker regardless of his or her education level.

[0156] In certain embodiments, one or more sentence completion questions of the hayling sentence completion test is selected from an hayling sentence completion test question database.

[0157] In certain embodiments, one or more sentence completion questions in the question database are designed by a medical professional / experts.

[0158] In certain embodiments, one or more sentence completion questions in the question database are generated by a large language model and reviewed by a medical professional / experts.

[0159] In certain embodiments, each of the sentence completion questions of the hayling sentence completion test is delivered to the individual test taker verbally, and the individual test taker provides the answer verbally.

[0160] In certain embodiments, one or more of the sentence completion questions are single choice questions.

[0161] In certain embodiments, one or more of the sentence completion questions are multiple choice questions.

[0162] In certain embodiments, one or more of the sentence completion questions are answered by a narrative answer provided by the individual test taker.

[0163] In certain embodiments, the aMCI status result produced by the evaluation scheme of the present invention partially depends on the time spent by the individual test taker for answering the one or more of the questions in the haying sentence completion test.

[0164] In certain embodiments, the individual test taker receives a score based on his or her answers in the haying sentence completion test, on which the aMCI status result partially or fully depends.

[0165] Verbal List Learning Test with Semantic Categories

[0166] The Verbal List Learning Test is a valuable tool for assessing language memory andAttorney Docket No. 626986.100014

[0167] learning capabilities, specifically short-term memory, long-term memory, and recall abilities. It typically involves remembering a list of words and testing the participant's retention and ability to learn new information. During the test, the administrator reads a list of words (e.g., "tooth," "yarn," "chrysanthemum," "red," "school"), and the participant is asked to recall as many words as possible immediately after hearing them. The process is repeated multiple times (e.g., twice) to evaluate the participant's ability to gradually learn and remember more words over time. This portion of the test reveals the participant's immediate memory capacity and the progression of word learning.

[0168] After a delay (e.g., 10 minutes), during which the participant may engage in other tasks to distract them, they are asked to recall the original list of words to test long-term memory retention. A modified version of the Verbal List Learning Test, the Semantic Category Verbal List Learning Test, assesses how participants use semantic relationships (i.e., word meanings) to organize and remember information. This test not only evaluates short-term and long-term memory but also examines how semantic cues aid learning and recall.

[0169] The administrator provides a list of words that belong to different semantic categories, such as "horse," "apple," "table," "tiger," and "sofa." The participant hears the list and must remember and recall as many words as possible. Unlike the traditional VLLT, these words are categorized semantically, allowing participants to use these associations to aid memory.

[0170] Participants might recall words by category, listing all animals first, followed by fruits, and so on. After a delay, the test measures how many words from the original list the participant can remember, assessing long-term memory retention. If participants struggle to recall, categorybased prompts may be used, such as "What animals were there?" or "What fruits?" to facilitate memory retrieval. The Semantic Category Verbal List Learning Test is effective for assessing semantic memory deficits and evaluating the use of learning strategies, making it a useful tool for aMCI assessment.

[0171] In certain embodiments, a verbal list learning test with semantic categories includes one or more memorizing questions which require an individual test taker to memorize a group of words. In certain embodiments, one or more memorizing questions is delivered to the individual test taker with a group of words and an instruction to the individual test taker to memorize the group of words. The individual test taker is then requested to repeat the group of words delivered to him or her.Attorney Docket No. 626986.100014

[0172] In certain embodiments, the individual test taker is not requested to repeat the group of words in the same order as to the words being delivered to him or her. In certain embodiments, the individual test taker is requested to repeat the group of words in the same order as to the words being delivered to him or her.

[0173] In certain embodiments, the individual test taker is requested to repeat the group of words immediately after the group of words being delivered. In certain embodiments, the individual test taker is requested to repeat the group of words after a waiting period following the delivery of the group of words.

[0174] In certain embodiments, the individual test taker is requested to repeat the group of words for one time. In certain embodiments, the individual test taker is requested to repeat the group of words for more than one time. In certain embodiments, the individual test taker is requested to repeat the group of words for a first time immediately after the group of words delivered, and for s second time after a waiting period following the delivery of the group of words. In certain embodiments, the individual test taker is requested to repeat the group of words for a first time immediately after a first waiting period following the delivery of the group of words, and for s second time after a second waiting period following the delivery of the group of words.

[0175] In certain embodiments, the waiting period is about 30 seconds. In certain embodiments, the waiting period ranges between about 30 seconds to 60 seconds. In certain embodiments, the waiting period ranges between about 1 minute to 3 minutes. In certain embodiments, the waiting period ranges between about 3 minutes to 5 minutes. In certain embodiments, the waiting period ranges between about 5 minutes to 10 minutes. In certain embodiments, the waiting period ranges between about 10 minutes to 30 minutes. In certain embodiments, the waiting period ranges between about 30 minutes to 60 minutes. In certain embodiments, the waiting period ranges between about 60 minutes to 120 minutes.

[0176] In certain embodiments, the group of words includes words from one semantic category. In certain embodiments, the group of words includes words from multiple semantic categories.

[0177] In certain embodiments, the semantic category comprises one or more of the following subcategories: nouns, functional words, predicates, and others.

[0178] In certain embodiments, the semantic category comprises one or more of the following subcategories: household, food, drinks, clothing, body parts, animals, plants, vehicles, articles, commodities, toys, tools, furniture, rooms, outside features / items, people, routines, games, timeAttorney Docket No. 626986.100014

[0179] words, sounds, places, action words, description words, adverbs, adjectives, question words, pronouns, connecting words, quantifiers, locations, helping verbs, prepositions, states, final particles, directions, classifiers, articles, and verb endings.

[0180] In certain embodiments, the semantic category comprises one or more of the following subcategories: living things including animals, plants, insects, humans, bacteria / microorganisms; nature and the environment including weather phenomena (e.g. rain, sun, wind, snow), bodies of water (e.g. oceans, lakes, rivers), landforms (e.g. mountains, valleys, hills, deserts), natural resources (e.g. minerals, water, plants); people and roles including family members (e g. mother, father, sister), occupations (e.g. teacher, doctor, engineer, artist), nationalities / ethnic groups, social roles (e.g. leader, friend, citizen); physical objects including furniture (e.g. chair, table, sofa, bed), appliances (e.g. refrigerator, oven, washing machine), vehicles (e.g. car, bicycle, airplane, train), tools (e.g. hammer, saw, drill); food and beverages including fruits (e.g. apple, banana, orange), vegetables (e.g. carrot, lettuce, tomato), beverages (e.g. water, juice, coffee, tea), grains and cereals (e.g. wheat, rice, corn), proteins (e.g. meat, fish, eggs, beans); body parts and functions including external body parts (e.g. arm, leg, head), internal organs (e.g. heart, brain, liver), sensory organs (e.g. eyes, ears, nose, skin), bodily functions (e.g. breathing, digestion, circulation); places and locations including buildings (e.g. house, school, hospital), geographic locations (e.g. continent, country, city), natural settings (e.g. beach, forest, desert), commercial places (e.g. store, restaurant, office); time including days of the week (e.g. Monday, Tuesday), months (e.g. January, February), seasons (e.g. spring, summer, fall, winter), times of day (e.g. morning, afternoon, night), units of time e.g. (minute, hour, day, year); events and activities including holidays (e.g. Christmas, new year, diwali), life events (e.g. birthday, wedding, graduation), celebrations (e.g. party, festival, gathering), daily routines (e.g. eating, sleeping, working), hobbies (e.g. reading, painting, hiking); actions and verbs including physical actions (e.g. run,jump, swim, lift), communication actions (e.g. speak, write, listen), cognitive actions (e.g. think, remember, plan), emotional actions (e.g. smile, cry, laugh); colors including basic colors (e.g. red, blue, green, yellow), shades (e.g. light blue, dark green, pastel pink); shapes and patterns including geometric shapes (e.g. circle, square, triangle), patterns (e.g. striped, polka-dotted, plaid); numbers and mathematics including cardinal numbers (e.g. one, two, three), mathematical operations (e.g. addition, subtraction), fractions and percentages (e.g. half, quarter, 75%); materials and textures including materials (e.g. wood, metal, glass, fabric),Attorney Docket No. 626986.100014

[0181] textures (e.g. smooth, rough, soft, hard); measurement and quantities including length (e.g. meter, kilometer, inch), weight (e.g. kilogram, pound, gram), volume (e.g. liter, gallon, ounce), temperature (e.g. hot, cold, warm, freezing); emotions and states including positive emotions (e.g. happiness, excitement, love), negative emotions (e.g. anger, sadness, fear), mental states (e.g. calm, anxious, focused); technology and electronics including devices (e.g. computer, smartphone, tablet), communication tools (e.g. email, messaging, call), digital platforms (e.g. social media, websites, apps); transportation and travel including modes of transport (e.g. car, train, airplane, boat), travel types (e.g. business, leisure, adventure), infrastructure (e.g. airport, station, port); health and medicine including illnesses and conditions (e.g. flu, cancer, diabetes), medical practices (e.g. surgery, therapy, check-up), medications and treatments (e.g. antibiotic, vaccine); science and education including scientific fields (e.g. biology, chemistry, physics), academic disciplines (e.g. math, literature, art), school-related items (e.g. notebook, pen, desk); money and finance including currency (e.g. dollar, euro, yen), financial concepts (e.g. loan, savings, interest), payment methods (e.g. credit card, cash, check); moral and social concepts including values (e.g. honesty, respect, loyalty), rights and freedoms (e.g. freedom of speech, privacy), laws and ethics (e.g. justice, fairness, duty); literature and arts including literary genres (e.g. fiction, poetry, mystery), art forms (e.g. painting, sculpture, dance), music genres (e.g. classical, rock, jazz, pop); religion and beliefs including world religions (e.g. Christianity, islam, buddhism), religious practices (e.g. prayer, meditation, fasting), symbols (e.g. cross, crescent, star of david).

[0182] In certain embodiments, the semantic category comprises terms commonly known and / or used by an individual test taker in his or her daily life, regardless of his or her education level.

[0183] In certain embodiments, the semantic category in which an individual test taker is requested to repeat the group of words is determined according to the individual’s education level.

[0184] In certain embodiments, one or more memorizing questions of the verbal list learning test with semantic categories is selected from a verbal list learning test with semantic categories question database.

[0185] In certain embodiments, one or more memorizing questions in the question database are designed by a medical professional / experts.

[0186] In certain embodiments, one or more memorizing questions in the question database areAttorney Docket No. 626986.100014

[0187] generated by a large language model and reviewed by a medical professional / experts.

[0188] In certain embodiments, each of the memorizing questions of the verbal list learning test with semantic categories is delivered to the individual test taker verbally, and the individual test taker provides the answer verbally.

[0189] In certain embodiments, one or more of the memorizing questions are single choice questions.

[0190] In certain embodiments, one or more of the memorizing questions are multiple choice questions.

[0191] In certain embodiments, one or more of the memorizing questions are answered by a narrative answer provided by the individual test taker.

[0192] In certain embodiments, the aMCI status result produced by the evaluation scheme of the present invention partially depends on the time spent by the individual test taker for answering the one or more of the questions in the verbal list learning test.

[0193] In certain embodiments, the individual test taker receives a score based on his or her answers in the verbal list learning test, on which the aMCI status result partially or fully depends.

[0194] Time-Orientation Test

[0195] Time disorientation is often one of the earliest symptoms of dementia. The Time-Orientation Test is a simple yet effective neuropsychological assessment tool used to evaluate an individual's awareness and orientation to time. It tests whether the participant can accurately recall and recognize the current date, month, year, day of the week, and time. For example, the administrator may ask, "What is today’s date? What time is it now?" The Time-Orientation Test reflects the participant's understanding and judgment of temporal information, assessing memory and attention related to time.

[0196] In certain embodiments, a time-orientation test of the present invention includes one or more time-orientation questions.

[0197] In certain embodiments, each of the one or more time-orientation questions requests the individual test taker to provide an answer regarding the date and / or the time.

[0198] In certain embodiments, each of the one or more time-orientation questions focuses the current date and / or the current time. In certain embodiments, each of the one or more timeorientation questions focuses the date and / or time in the past. In certain embodiments, each ofAttorney Docket No. 626986.100014

[0199] the one or more time-orientation questions focuses the date and / or time in the future.

[0200] In certain embodiments, each of the time-orientation questions is delivered to the individual test taker verbally, and the individual test taker provides the answer verbally.

[0201] In certain embodiments, the aMCI status result produced by the evaluation scheme of the present invention partially depends on the time spent by the individual test taker for answering the one or more of the questions in the time-orientation test.

[0202] In certain embodiments, the individual test taker receives a score based on his or her answers in the time-orientation test, on which the aMCI status result partially or fully depends.

[0203] Subjective Testing Section

[0204] In certain embodiments, in addition to the cognitive function testing section, an evaluation scheme of the present invention also includes a subjective testing section.

[0205] In certain embodiments, the subjective testing section includes one or more of a subjective cognitive decline test, an emotional screening test, and a lifestyle test.

[0206] In certain embodiments, each of the one or more of the subjective cognitive decline test, the emotional screening test, and the lifestyle test taken by the individual test taker produces a score based on the individual test taker’s responses to the particular test.

[0207] In certain embodiments, the aMCI status of the individual test taker is determined based on the scores generated based on the individual test taker’s responses to the one or more tests.

[0208] In certain embodiments, a subjective testing score is generated based on partial or all scores obtained by the individual test taker taking the one or more tests of the cognitive function testing section.

[0209] In certain embodiments, the aMCI status of the individual test taker is determined based on the subjective testing score.

[0210] Subjective Cognitive Decline (SCD) Test

[0211] In clinical practice, there is a group of individuals who subjectively feel that their memory, attention, or other cognitive functions have declined, such as frequently forgetting daily events, struggling to find the right words, or having difficulty maintaining focus. However, objective cognitive tests, such as standardized neuropsychological assessments, may not show significant abnormalities. This group is classified as having Subjective Cognitive Decline (SCD).Attorney Docket No. 626986.100014

[0212] Research indicates that SCD could be one of the earliest clinical signs of Alzheimer's disease. Although objective testing cannot detect abnormalities at this stage, over time, these individuals may progress to Mild Cognitive Impairment (MCI) and eventually develop Alzheimer's disease. Hence, SCD is considered a potential risk signal associated with neurodegenerative diseases and is seen as a precursor state to MCI.

[0213] While MCI patients exhibit objective cognitive impairment that does not significantly impact daily life, SCD refers to a stage where individuals subjectively sense cognitive decline that has yet to be detected by tests. This evaluation scheme includes questions to evaluate subjective cognitive decline, such as:

[0214] 1. Do you feel you have memory problems? > Yes > No (Score: 1)

[0215] 2. How long ago did you start noticing memory decline? years (^ 5 years scores 1 point)

[0216] 3. Are you worried about your memory problems? > Yes > No (Score: 1)

[0217] 4. Compared to people of a similar age, do you feel your memory is worse? > Yes > No (Score: 1)

[0218] 5. Do your family members think your memory has worsened? > Yes > No (Score: 1) > I Don’t know

[0219] These questions aim to differentiate whether subjective memory concerns are longstanding or more recent. The former may have weaker predictive power for progressing to MCI, as it could reflect a habitual tendency rather than pathological change.

[0220] In certain embodiments, the subjective testing section of the present invention includes a SCD test.

[0221] In certain embodiments, the SCD test of the Subjective Testing Section includes one or more SCD questions.

[0222] In certain embodiments, one or more of the SCD questions requests the individual test taker to provide a subjective evaluation of his or her own memory, attention, or other cognitive functions.

[0223] In certain embodiments, one or more of the SCD questions requests the individual test taker to provide a subjective evaluation of his or her own short-term memory, attention, or other cognitive functions.Attorney Docket No. 626986.100014

[0224] In certain embodiments, one or more of the SCD questions requests the individual test taker to provide a subjective evaluation of his or her own long-term memory, attention, or other cognitive functions.

[0225] In certain embodiments, one or more of the SCD questions requests the individual test taker to provide a comparison of his or her memory, attention, or other cognitive functions with another individual.

[0226] In certain embodiments, one or more of the SCD questions requests the individual test taker to provide a comparison of his or her memory, attention, or other cognitive functions at one time point with his or her memory, attention, or other cognitive functions at a second time point.

[0227] In certain embodiments, one or more of the SCD questions requests the individual test taker to provide a third party’s opinion regarding his or her memory, attention, or other cognitive functions, e.g., the individual test taker’s family members’ or friends’ evaluation of the individual test taker’s memory, attention, or other cognitive functions.

[0228] In certain embodiments, an individual test taker’s short-term memory, attention, or other cognitive functions refers to his or her memory, attention, or other cognitive functions within recent 1 year. In certain embodiments, an individual test taker’s short-term memory, attention, or other cognitive functions refers to his or her memory, attention, or other cognitive functions within recent 9 months. In certain embodiments, an individual test taker’s short-term memory, attention, or other cognitive functions refers to his or her memory, attention, or other cognitive functions within recent 6 months. In certain embodiments, an individual test taker’s short-term memory, attention, or other cognitive functions refers to his or her memory, attention, or other cognitive functions within recent 3 months. In certain embodiments, an individual test taker’s short-term memory, attention, or other cognitive functions refers to his or her memory, attention, or other cognitive functions within recent 1 month.

[0229] In certain embodiments, an individual test taker’s long-term memory, attention, or other cognitive functions refers to his or her memory, attention, or other cognitive functions within recent 2 years. In certain embodiments, an individual test taker’s long-term memory, attention, or other cognitive functions refers to his or her memory, attention, or other cognitive functions within recent 5 years. In certain embodiments, an individual test taker’s long-term memory, attention, or other cognitive functions refers to his or her memory, attention, or other cognitive functions within recent 10 years.Attorney Docket No. 626986.100014

[0230] In certain embodiments, one or more of the SCD questions are single choice questions. In certain embodiments, one or more of the SCD questions are multiple choice questions. In certain embodiments, one or more of the SCD questions are answered by a narrative answer provided by the individual test taker.

[0231] In certain embodiments, each of the SCD questions is delivered to the individual test taker verbally, and the individual test taker provides the answer verbally.

[0232] In certain embodiments, the aMCI status result produced by the evaluation scheme of the present invention partially depends on the time spent by the individual test taker for answering the one or more of the questions in the SCD test.

[0233] In certain embodiments, the individual test taker receives a SCD score based on his or her answers in the SCD test, on which the aMCI status result partially or fully depends.

[0234] Emotional Screening Questions Test

[0235] Emotional problems, such as depression and anxiety, are closely linked to cognitive impairment. Short-term depression and anxiety can affect brain function, leading to declines in memory, attention, and executive function, and may increase the rate of subjective memory complaints, raising the risk of misdiagnosis as pre-dementia in clinical settings. Additionally, long-term emotional disorders like depression may indicate an increased risk of developing cognitive impairment or dementia in the future.

[0236] Therefore, the evaluation scheme includes an emotional screening test having questions for screening depression and emotional issues, providing a stronger basis for distinguishing between cognitive impairment and emotional problems in clinical practice. An example of the screening questions is:

[0237] In the past two weeks, how often have you experienced the following:

[0238] - Difficulty getting motivated or enjoying activities. Your feelings could be: never, fewer than seven days, seven to ten days, almost every day.

[0239] (Each question is scored as follows: Never: 3, Fewer than seven days: 2, Seven to ten days: 1, Almost every day: 0)

[0240] 1. (Score ) Feeling tense, anxious, or uneasy: > Never > Fewer than seven days Seven to ten days > Almost every day

[0241] 2. (Score ) Unable to stop or control worrying: > Never > Fewer than seven daysAttorney Docket No. 626986.100014

[0242] > Seven to ten days > Almost every day

[0243] 3. (Score ) Feeling down, depressed, or hopeless: > Never > Fewer than seven days > Seven to ten days > Almost every day

[0244] 4. (Score ) Lack of interest or pleasure in things: > Never > Fewer than seven days > Seven to ten days > Almost every day

[0245] These questions help assess the impact of emotional issues on cognitive functions and aid in identifying whether cognitive complaints are linked to mood disorders.

[0246] In certain embodiments, the subjective testing section includes an emotional screening test.

[0247] In certain embodiments, the emotional screening test of the subjective testing section includes one or more emotional screening questions.

[0248] In certain embodiments, one or more of the emotional screening questions requests the individual test taker to provide an evaluation of his or her emotional status, e.g. depression and anxiety.

[0249] In certain embodiments, one or more of the emotional screening questions requests the individual test taker to provide an evaluation of his or her own short-term emotional status, e.g. depression and anxiety.

[0250] In certain embodiments, one or more of the emotional screening questions requests the individual test taker to provide an evaluation of his or her own long-term emotional status, e.g. depression and anxiety.

[0251] In certain embodiments, one or more of the emotional screening questions requests the individual test taker to provide a comparison of his or her emotional status with another individual.

[0252] In certain embodiments, one or more of the emotional screening questions requests the individual test taker to provide a comparison of his or her emotional status at one time point with his or her emotional status at a second time point.

[0253] In certain embodiments, one or more of the emotional screening questions requests the individual test taker to provide a third party’s opinion regarding his or her emotional status, e g., the individual test taker’s family members’ or friends’ evaluation of the individual test taker’s emotional status.

[0254] In certain embodiments, an individual test taker’s short-term emotional status refers to hisAttorney Docket No. 626986.100014

[0255] or her emotional status within recent 1 month. In certain embodiments, an individual test taker’s short-term emotional status refers to his or her emotional status within recent 20 days. In certain embodiments, an individual test taker’s short-term emotional status refers to his or her emotional status within recent 15 days. In certain embodiments, an individual test taker’s short-term emotional status refers to his or her emotional status within recent 10 days. In certain embodiments, an individual test taker’s short-term emotional status refers to his or her emotional status within recent 7 days. In certain embodiments, an individual test taker’s short-term emotional status refers to his or her emotional status within recent 5 days.

[0256] In certain embodiments, an individual test taker’s long-term emotional status refers to his or her emotional status within recent 3 months. In certain embodiments, an individual test taker’s long-term emotional status refers to his or her emotional status within recent 6 months. In certain embodiments, an individual test taker’s long-term emotional status refers to his or her emotional status within recent 9 months. In certain embodiments, an individual test taker’s long-term emotional status refers to his or her emotional status within recent 12 months. In certain embodiments, an individual test taker’s long-term emotional status refers to his or her emotional status within recent 3 years.

[0257] In certain embodiments, one or more of the emotional status questions are single choice questions.

[0258] In certain embodiments, one or more of the emotional status questions are multiple choice questions.

[0259] In certain embodiments, one or more of the emotional status questions are answered by a narrative answer provided by the individual test taker.

[0260] In certain embodiments, the aMCI status result produced by the evaluation scheme of the present invention partially depends on the time spent by the individual test taker for answering the one or more of the questions in the emotional screening test.

[0261] In certain embodiments, the individual test taker receives an emotional screening score based on his or her answers in the emotional screening test, on which the aMCI status result partially or fully depends.

[0262] In certain embodiments, the emotional screening score is compared with an emotional screening threshold score. And when the individual’s cognitive function testing score shows that the individual has aMCI or is at a high risk of aMCI, and the emotional screening score isAttorney Docket No. 626986.100014

[0263] beyond the emotional screening threshold score, one can determine that the aMCI or high risk in aMCI is caused by the individual emotion status.

[0264] Lifestyle Test

[0265] In certain embodiments, the subjective testing section of the present invention includes a lifestyle test which contains one or more lifestyle questions asking about an individual test taker’s lifestyle such as sleep, exercise, etc.

[0266] Sleep Status Question

[0267] There is a strong link between sleep quality and cognitive function. Sleep plays a crucial role in memory consolidation. During sleep, the brain converts short-term memories into longterm ones and strengthens the learning process, with slow-wave sleep (deep sleep) being particularly important for this. Sleep deprivation disrupts this process, leading to memory decline. Chronic sleep deprivation or insomnia can result in difficulties with concentration, slower thinking, longer reaction times, and impaired decision-making and creativity. Over time, these cognitive problems can accumulate and affect daily life. Furthermore, research suggests that poor sleep quality or insufficient sleep may increase the accumulation of beta-amyloid in the brain, a hallmark of Alzheimer's disease. Sleep deprivation hampers the brain’s ability to clear these proteins, raising the risk of dementia. Thus, the evaluation scheme includes questions about sleep, such as: "Overall, how would you rate your sleep quality in the past month? > Very good > Fairly good > Somewhat poor > Very poor," to assess the risk of aMCI.

[0268] In certain embodiments, the lifestyle test of the subjective testing section includes one or more sleep status questions.

[0269] In certain embodiments, one or more of the sleep status questions request the individual test taker to provide an evaluation of his or her sleep status.

[0270] In certain embodiments, one or more of the sleep status questions request the individual test taker to provide an evaluation of his or her own short-term sleep status.

[0271] In certain embodiments, one or more of the sleep status questions request the individual test taker to provide an evaluation of his or her own long-term sleep status.

[0272] In certain embodiments, one or more of the sleep status questions request the individual test taker to provide a comparison of his or her sleep status with another individual.

[0273] In certain embodiments, one or more of the sleep status questions request the individualAttorney Docket No. 626986.100014

[0274] test taker to provide a comparison of his or her sleep status at one time point with his or her sleep status at a second time point.

[0275] In certain embodiments, one or more of the sleep status questions request the individual test taker to provide a third party’s opinion regarding his or her sleep status, e.g., the individual test taker’s family members’ or friends’ evaluation of the individual test taker’s sleep status.

[0276] In certain embodiments, one or more of the sleep status questions request the individual test taker to provide objective answers to the questions, e.g., hours of sleep per day.

[0277] In certain embodiments, one or more of the sleep status questions request the individual test taker to provide subjective answers to the questions, e.g., my sleep is very good, good, fairly good, somewhat poor, very poor.

[0278] In certain embodiments, an individual test taker’s short-term sleep status refers to his or her sleep status within recent 1 month. In certain embodiments, an individual test taker’s shortterm sleep status refers to his or her sleep status within recent 20 days. In certain embodiments, an individual test taker’s short-term sleep status refers to his or her sleep status within recent 15 days. In certain embodiments, an individual test taker’s short-term sleep status refers to his or her sleep status within recent 10 days. In certain embodiments, an individual test taker’s short-term sleep status refers to his or her sleep status within recent 7 days. In certain embodiments, an individual test taker’s short-term sleep status refers to his or her sleep status within recent 5 days.

[0279] In certain embodiments, an individual test taker’s long-term sleep status refers to his or her sleep status within recent 3 months. In certain embodiments, an individual test taker’s longterm sleep status refers to his or her sleep status within recent 6 months. In certain embodiments, an individual test taker’s long-term sleep status refers to his or her sleep status within recent 9 months. In certain embodiments, an individual test taker’s long-term sleep status refers to his or her sleep status within recent 12 months. In certain embodiments, an individual test taker’s longterm sleep status refers to his or her sleep status within recent 3 years.

[0280] In certain embodiments, one or more of the sleep status questions are single choice questions.

[0281] In certain embodiments, one or more of the sleep status questions are multiple choice questions.

[0282] In certain embodiments, one or more of the sleep status questions are answered by a narrative answer provided by the individual test taker.Attorney Docket No. 626986.100014

[0283] In certain embodiments, the aMCI status result produced by the evaluation scheme of the present invention partially depends on the time spent by the individual test taker for answering the one or more of the sleep status questions.

[0284] In certain embodiments, the individual test taker receives a score based on his or her answers to the one or more of the sleep status questions, on which the aMCI status result partially or fully depends.

[0285] Exercise Status Question

[0286] Regular physical activity is crucial for brain health. Exercise enhances executive function, attention, planning skills, and memory. It promotes the release of neurotransmitters and increases the production of brain-derived neurotrophic factor (BDNF), which supports neuron growth and connectivity, boosting brain plasticity and learning abilities. Studies have shown that aerobic exercise (such as brisk walking, running, or swimming) significantly benefits brain function by improving blood flow to the brain, increasing oxygen supply, and reducing age-related brain tissue shrinkage. These effects help prevent or slow down cognitive decline. In addition to aerobic exercise, resistance training (such as weightlifting, yoga, or core strength training) also benefits cognitive function, enhancing memory and executive function and reducing age-related cognitive decline.

[0287] Moreover, numerous studies confirm that regular exercise can lower the risk of cognitive impairment and dementia. Physical activity reduces the accumulation of beta-amyloid, associated with Alzheimer's pathology, and promotes vascular health in the brain, lowering the risk of vascular cognitive impairment. Consequently, this assessment scheme includes exercise-related questions, such as: "In the past seven days, how many days did you engage in vigorous physical activities such as running, hiking, aerobic sports (like tennis, basketball, or soccer), or weight training for at least 10 minutes, making you breathe much harder than usual? > 0 days (Score: 0) > 1 day (Score: 1) > 2 days (Score: 2) > 3 or more days (Score: 3)," to evaluate the risk of aMCI.

[0288] In certain embodiments, the lifestyle test of the subjective testing section includes one or more exercise status questions.

[0289] In certain embodiments, one or more of the exercise status questions request the individual test taker to provide an evaluation of his or her exercise status.Attorney Docket No. 626986.100014

[0290] In certain embodiments, one or more of the exercise status questions request the individual test taker to provide an evaluation of his or her own short-term exercise status.

[0291] In certain embodiments, one or more of the exercise status questions request the individual test taker to provide an evaluation of his or her own long-term exercise status.

[0292] In certain embodiments, one or more of the exercise status questions request the individual test taker to provide a comparison of his or her exercise status with another individual.

[0293] In certain embodiments, one or more of the exercise status questions request the individual test taker to provide a comparison of his or her exercise status at one time point with his or her exercise status at a second time point.

[0294] In certain embodiments, one or more of the exercise status questions request the individual test taker to provide a third party’s opinion regarding his or her exercise status, e.g., the individual test taker’s family members’ or friends’ evaluation of the individual test taker’s exercise status.

[0295] In certain embodiments, one or more of the exercise status questions directly focus on the individual test taker’s exercise status, e.g., exercise time duration and / or frequency per day, week, or month, type of exercises performed(cardio exercise, strength exercise, ), intensity of exercises performed, etc.

[0296] In certain embodiments, one or more of the exercise status questions focus on the effects of exercise on the individual test taker, e.g., the individual test taker’s physiological vitals such as breath rate, heart rate, blood oxygen level, and etc before, during, and / or after the exercise.

[0297] In certain embodiments, one or more of the exercise status questions request the individual test taker to provide objective answers to the questions.

[0298] In certain embodiments, one or more of the exercise status questions request the individual test taker to provide subjective answers to the questions.

[0299] In certain embodiments, an individual test taker’s short-term exercise status refers to his or her exercise status within recent 1 month. In certain embodiments, an individual test taker’s short-term exercise status refers to his or her exercise status within recent 20 days. In certain embodiments, an individual test taker’s short-term exercise status refers to his or her exercise status within recent 15 days. In certain embodiments, an individual test taker’s short-term exercise status refers to his or her exercise status within recent 10 days. In certain embodiments, an individual test taker’s short-term exercise status refers to his or her exercise status withinAttorney Docket No. 626986.100014

[0300] recent 7 days. In certain embodiments, an individual test taker’s short-term exercise status refers to his or her exercise status within recent 5 days.

[0301] In certain embodiments, an individual test taker’s long-term exercise status refers to his or her exercise status within recent 3 months. In certain embodiments, an individual test taker’s long-term exercise status refers to his or her exercise status within recent 6 months. In certain embodiments, an individual test taker’s long-term exercise status refers to his or her exercise status within recent 9 months. In certain embodiments, an individual test taker’s long-term exercise status refers to his or her exercise status within recent 12 months. In certain embodiments, an individual test taker’s long-term exercise status refers to his or her exercise status within recent 3 years.

[0302] In certain embodiments, one or more of the exercise status questions are single choice questions.

[0303] In certain embodiments, one or more of the exercise status questions are multiple choice questions.

[0304] In certain embodiments, one or more of the exercise status questions are answered by a narrative answer provided by the individual test taker.

[0305] In certain embodiments, the aMCI status result produced by the evaluation scheme of the present invention partially depends on the time spent by the individual test taker for answering the one or more of the exercise status questions.

[0306] In certain embodiments, the individual test taker receives a score based on his or her answers to the one or more of the exercise status questions, on which the aMCI status result partially or fully depends.

[0307] Scoring System

[0308] In certain embodiments, each of the one or more of the semantic verbal fluency test, the attribute verification test, the digit span sequencing test, the Hayling sentence completion test for response inhibition, the verbal list learning test with semantic categories, and the time-orientation test taken by the individual test taker produces a score based on the individual test taker’s responses to the particular test.

[0309] In certain embodiments, a cognitive function testing score is generated based on partial or all scores obtained by the individual test taker taking the one or more tests of the cognitiveAttorney Docket No. 626986.100014

[0310] function testing section.

[0311] In certain embodiments, the aMCI status of the individual test taker is determined based on part or all of the scores generated based on the individual test taker’s responses to the one or more tests.

[0312] In certain embodiments, the aMCI status of the individual test taker is determined based on the cognitive function testing score.

[0313] In certain embodiments, each of the one or more of the subjective cognitive decline test, the emotional screening test, and the lifestyle test taken by the individual test taker produces a score based on the individual test taker’s responses to the particular test.

[0314] In certain embodiments, the aMCI status of the individual test taker is determined based on the scores generated based on the individual test taker’s responses to the one or more tests.

[0315] In certain embodiments, a subjective testing score is generated based on partial or all scores obtained by the individual test taker taking the one or more tests of the cognitive function testing section.

[0316] In certain embodiments, the aMCI status of the individual test taker is determined based on the subjective testing score.

[0317] In certain embodiments, the individual test taker is determined to have aMCI or is at high risk of having aMCI when a sum of the individual test taker’s cognitive function testing score and the subjective testing score is beyond aMCI threshold score.

[0318] In certain embodiments, the individual test taker is determined to have aMCI or is at high risk of having aMCI when a sum of the individual test taker’s cognitive function testing score and at least one of the SCD score, the emotional status score, and the lifestyle score is beyond aMCI threshold score.

[0319] Al Component

[0320] The evaluation scheme of the present invention is designed to be administered verbally, which simplifies implementation. In recent years, with advances in speech recognition and artificial intelligence (Al) conversational technologies (e.g., ChatGPT), it has become feasible to conduct cognitive assessments through a voice-based user interface (UI).

[0321] In certain embodiments, the evaluation scheme of the present invention includes options for both human testers and automated administration using computing devices such as computersAttorney Docket No. 626986.100014

[0322] or smartphones.

[0323] In certain embodiments, an app developed with speech recognition and conversational Al functionality is used to administer the tests. This technology enables large-scale cognitive testing, allowing both healthy individuals and those concerned about cognitive impairment to participate without needing trained professionals, significantly increasing the likelihood of identifying high-risk individuals with mild cognitive impairment.

[0324] User Interface (UI) Component

[0325] The primary goal of the evaluation scheme of the present invention is to screen for individuals at high risk of mild cognitive impairment. Given that many individuals with MCI are older and may have hearing issues, the app, which relies on a voice-based interface, is also designed to display questions on the screen. This way, as the test questions are read aloud, they are simultaneously displayed, enabling individuals with hearing difficulties to read and understand the questions, ensuring effective participation in the assessment.

[0326] EXAMPLE 1

[0327] Below is a complete implementation example of the evaluation scheme.

[0328] Statements in quotation marks are delivered verbally to an individual test taker.

[0329] Introduction

[0330] "Today, we will go through some tasks together. Some of them will be easy, and some may be a bit more challenging, but let's give it a try together. Please avoid looking at your phone or watch during the process. Do you have any questions? Alright, let's get started."

[0331] (Record the current time: hours minutes, and start the first stopwatch)

[0332] Question 1. Memory Recall Task

[0333] "I am going to read you a list of nouns. After I read each noun, please repeat it back to me. Once I have read the entire list, I will ask you to recall as many nouns as you can. Are you ready?"

[0334] (Read one word per second, with brief pauses between words. Only say the list once, no repetitions.)

[0335] Words: "suit, guitar, black vinegar, moon lute, rain boots, oyster sauce."Attorney Docket No. 626986.100014

[0336] "Alright, now please tell me the nouns you remember. The order does not matter." (Score correct recalled nouns; order does not have to match. Record the recalled order and mark © for recording. All participants get two learning and recall attempts.)

[0337] First Attempt:

[0338] - Suit - Guitar - Black vinegar - Moon lute - Rain boots - Oyster sauce Second Attempt:

[0339] - Suit - Guitar - Black vinegar - Moon lute - Rain boots - Oyster sauce

[0340] Question 2. Time-Orientation Question

[0341] "What is today’s date, and what time is it?"

[0342] (★ Within 1 hour counts as correct; © record response)

[0343] Question 3. Number Sequencing Task

[0344] "I will give you a set of numbers. Please arrange them from smallest to largest and say them back to me. For example, if I say '5-2' (★ say one number per second), you would say '2-5.' Any questions?" © Record response.

[0345] Number: "372" -*■ Expected response: 237

[0346] Question 4. Hayling Sentence Completion Task

[0347] "Next, we will do a sentence completion game. I will say a sentence that is missing a word. Your task is to fill in the blank with a word, but avoid giving the correct word. The less related the word is, the better. For example: 'On a rainy day, remember to bring (pause for a second)... what?' The correct answer would be 'umbrella,' but you need to avoid saying 'umbrella.' Instead, say something unrelated, like 'vacuum' or 'lamp' — something like 'raincoat' is too similar because it belongs to the same category. Ready? Remember, the quicker and more unrelated your answer, the better."

[0348] (★ Record each response and reaction time (RT))

[0349] "To travel abroad, you must go to the airport to take a

[0350] (Incorrect answer: airplane; Scoring: 2 / 1 / 0) RT:Attorney Docket No. 626986.100014

[0351] Question 5. True / False Statement Test

[0352] "I will now read some sentences to you. Please say 'true' if the sentence is correct or 'false' if it is incorrect, as quickly as possible. For example, 'The sun is green (true / false)' — what would you say? Good, let's start."

[0353] (★ Underlined answers are correct; record reaction time (RT))

[0354] - "Sparrows are purple (true / false)" RT:

[0355] Question 6: Emotional Screening Questions

[0356] "In the past two weeks, how often have you experienced the following feelings, such as a lack of motivation or interest in doing things? Your options are: never, fewer than seven days, seven to ten days, almost every day."

[0357] (★ Scoring: Never: 3, Fewer than seven days: 2, Seven to ten days: 1, Almost every day: 0)

[0358] 1. (Score ) Feeling tense, anxious, or uneasy: > Never > Fewer than seven days Seven to ten days > Almost every day

[0359] 2. (Score ) Unable to stop or control worrying: > Never > Fewer than seven days Seven to ten days > Almost every day

[0360] 3. (Score ) Feeling down, depressed, or hopeless: > Never > Fewer than seven days > Seven to ten days > Almost every day

[0361] 4. (Score ) Lack of interest or pleasure in things: > Never > Fewer than seven days > Seven to ten days > Almost every day

[0362] Question 7. Sleep Quality Question

[0363] "In the past month, overall, how would you rate your sleep quality?"

[0364] > Very good (Score: 3) > Fairly good (Score: 2) > Somewhat poor (Score: 1) > Very poor (Score: 0)

[0365] (★ Record the score)

[0366] Belows are some other examples of questions of the evaluation scheme.Attorney Docket No. 626986.100014

[0367] Additional Implementation Example

[0368] Question 8. Subjective Cognitive Decline Questions

[0369] 8-1. "Do you feel you have memory problems?"

[0370] > Yes (Score: 1) > No

[0371] 8-2. "How long ago did you start noticing memory decline?"

[0372] > years (Score: 1 if 5= 5 years)

[0373] 8-3. "Are you worried about your memory problems?"

[0374] > Yes (Score: 1) > No

[0375] 8-4. "Compared to people of a similar age, do you feel your memory is worse?"

[0376] > Yes (Score: 1) > No

[0377] 8-5. "Do your family members think your memory has worsened?"

[0378] > Yes (Score: 1) > No > Don’ t know

[0379] Question 9. Physical Activity Question

[0380] "In the past seven days, how many days did you engage in vigorous physical activities, such as running, hiking, aerobic sports (like singles tennis, basketball, soccer), or weight training, for at least 10 minutes that made you breathe much harder than usual?"

[0381] (★ Record the actual number of days and activities performed, then select the corresponding score)

[0382] Participant engaged in vigorous physical activity for days, doing

[0383] >

[0384] > 0 days (Score: 0) > 1 day (Score: 1) > 2 days (Score: 2) > 3 or more days (Score: 3)

[0385] Question 10. Semantic Verbal Fluency Task

[0386] "You have one minute to name as many fruits as you can without repeating any. Ready? Go!"

[0387] (★ Record the participant's responses © Recording)

[0388] Participant’ s Responses © Recording:

[0389] **0-15 seconds:**Attorney Docket No. 626986.100014

[0390] **16-30 seconds:**

[0391] **31-45 seconds:**

[0392] **46-60 seconds:**

[0393] Number of fruits named:

[0394] **0-15 seconds:**

[0395] **16-30 seconds:**

[0396] **31-45 seconds:**

[0397] **46-60 seconds:**

[0398] **Total number:**

[0399] Question 11. Recall Tasks

[0400] 11-1. Recall Phase

[0401] "I previously read a list of nouns and had you repeat them. Do you still remember any of those nouns? The order doesn't matter."

[0402] - Suit

[0403] - Guitar

[0404] - Black vinegar

[0405] - Moon lute

[0406] - Rain boots

[0407] - Oyster sauce

[0408] (★ If the participant recalls all items correctly, skip to Recognition. If not, proceed to Cued Recall.)

[0409] 11-2. Cued Recall Phase

[0410] (★ Score 1 point for each correct answer and circle participant's response © Recording)

[0411] "Do you remember any items in the clothing category?"

[0412] - (Suit, Rain boots)

[0413] "Do you remember any condiments?"

[0414] - (Black vinegar, Oyster sauce)

[0415] "Do you remember any musical instruments?"Attorney Docket No. 626986.100014

[0416] - (Guitar, Moon lute)

[0417] (★ If Cued Recall is fully correct, skip Recognition.)

[0418] EXAMPLE 2

[0419] Experimental results of the evaluation scheme taken by individual test takers.

[0420] Participants

[0421] This study included 28 aMCI patients (age: M ± SD = 73.79 ± 4.69; 23 females and 5 males) and 37 healthy controls (HC) (age: M ± SD = 70.70 ± 5.71; 22 females and 15 males). The aMCI patients were recruited from a local hospital’s memory clinic, and the HC participants were recruited from nearby community residents. All participants were Asian and native Mandarin speakers. Individuals with neurological disorders (e.g., epilepsy, stroke, and head injury), psychiatric illnesses, substance abuse (e.g., alcohol and illegal drugs), or clinically significant sensory impairments (e.g., blindness or severe hearing loss) were excluded.

[0422] Additionally, individuals with developmental or acquired language disorders, such as developmental language disorder, learning disability, or post-stroke aphasia, were excluded through a thorough interview covering developmental and medical histories.

[0423] Mild cognitive impairment (MCI) was diagnosed based on criteria proposed by the International Working Group, requiring participants to meet the following conditions: 1) neither normal nor demented, 2) intact activities of daily living and unimpaired or only mildly impaired instrumental functions, and 3) objective cognitive impairment on neuropsychological tests. Objective cognitive impairment was defined as performance at least 1 standard deviation below age-adjusted norms on at least two neuropsychological tests within the same cognitive domain. Memory-impaired individuals were categorized as having amnestic MCI (aMCI). Each participant completed the Chinese version of the Mini-Mental State Examination (MMSE).

[0424] Neuropsychological Testing (NPT)

[0425] To assess baseline cognitive function, participants underwent a comprehensive battery of neuropsychological tests covering four domains: attention and processing speed, learning and memory, language, and executive function. Attention and processing speed were measured using the Digit Span subtest (forward and backward) from the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) and the Word condition of the Color-Word Interference Test (CWIT) fromAttorney Docket No. 626986.100014

[0426] the Delis-Kaplan Executive Function System (D-KEFS). Learning and memory were assessed with the Logical Memory subtest (immediate and delayed recall) from the Wechsler Memory Scale-Third Edition (WMS-III), the total learning and delayed recall scores from the California Verbal Learning Test, and the immediate and delayed recall conditions from the Rey Complex Figure Test (RCFT). Language ability was evaluated using the Vocabulary subtest from the WAIS-III and the 30-item Boston Naming Test. Executive function was assessed using the reaction time difference between Part 2 and Part 1 of the Color Trails Test (CTT) and the inhibition and switching conditions of the CWIT. Depression status was evaluated using the short form of the Geriatric Depression Scale (GDS).

[0427] Scoring

[0428] The scoring method for the assessment follows the implementation example:

[0429] 1) CoBA-cognition: Includes only the cognitive function tests from the example, specifically Questions 1-5, 10, and 11.

[0430] 2) CoBA-behavior: Includes only the subjective cognition, emotional, and lifestyle questions from the example, specifically Questions 6-9.

[0431] 3) CoBA-total: The combined score of CoBA-cognition and CoBA-behavior.

[0432] Each question has its own scoring system, with the final score being the sum of all individual question scores. The maximum score for CoBA-cognition is 50, for CoBA-behavior is 23, and for CoBA-total is 73. The MMSE, used as a comparison tool, has a maximum score of 30.

[0433] Statistical Analysis

[0434] Since there were significant demographic differences between the aMCI and HC groups, ANCOVA tests (controlling for age, education, and gender) were used to analyze the MMSE and CoBA scores, yielding F values, p-values, partial eta squared values, and estimated power. The Mean ± SD values represent the raw data statistics.

[0435] Results

[0436] FIG. 1 shows a chart reflecting CoBA total scores of HC and aMCI groups.

[0437] FIG. 2 shows a chart reflecting MMSE total score of HC and aMCI groups.Attorney Docket No. 626986.100014

[0438] Table 1 shows the demographic, clinical, and cognitive data for the aMCI and HC groups. The aMCI group scored significantly lower on CoBA-cognition, CoBA-behavior, and CoBA-total compared to the HC group. However, there was no significant difference in MMSE scores between the aMCI and HC groups.

[0439] Table 1. Demographic, clinical, and cognitive data for the aMCI and HC groups.

[0440] <

[0441]

[0442] # indicates that the statistical analysis results reported here have been adjusted for age, education, and sex variables.

[0443] The foregoing description of the exemplary embodiments of the invention has been presented only for the purposes of illustration and description and is not intended to be exhaustive or to limit the invention to the precise forms disclosed. Many modifications and variations are possible in light of the above teaching.

[0444] While there has been shown several and alternate embodiments of the present invention, it is to be understood that certain changes can be made as would be known to one skilled in the art without departing from the underlying scope of the invention as is discussed and set forth above and below including claims and drawings. Furthermore, the embodiments described above and claims set forth below are only intended to illustrate the principles of the present invention and are not intended to limit the scope of the invention to the disclosed elements.

[0445] References cited in the instant application, which may include patents, patent applications and various publications, are cited and discussed in the description of this invention. The citationAttorney Docket No. 626986.100014

[0446] and / or discussion of such references is provided merely to clarify the description of the present invention and is not an admission that any such reference is “prior art” to the invention described herein. All references cited and discussed in the description of this invention, are incorporated herein by reference in their entireties and to the same extent as if each reference was individually incorporated by reference.

Claims

1. Attorney Docket No. 626986.100014CLAIMSWhat is claimed is:

1. A method for evaluating an aMCI status of an individual, the method comprising:(1) delivering an evaluation scheme having one or more tests to an individual;(2) obtaining the individual’s responses to the one or more tests;(3) generating an evaluation score of the individual based on the individual’s responses; and(4) generating an aMCI status of the individual based on the evaluation score of the individual.

2. The method according to claim 1, wherein each of the one or more tests comprises at least one question; and wherein the at least one question is delivered to the individual verbally or textually.

3. The method according to claim 2, wherein the individual’s responses comprise at least one answer in verbal.

4. The method according to claim 1, wherein the evaluation scheme comprises a cognitive test function section.

5. The method according to claim 4, wherein the cognitive test function section comprises at least one of a verbal listing learning test, a semantic verbal fluency test, an attribute verification test, a digit span sequencing test, a Hayling sentence completion test, and a time orientation test.

6. The method according to claim 5, wherein the evaluation score is generated at least partially based on the individual’s responses to the at least one of the verbal listing learning test, the semantic verbal fluency test, the attribute verification test, the digit span sequencing test, the Hayling sentence completion test, and the time orientation test.Attorney Docket No. 626986.1000147. The method according to claim 6, wherein the evaluation score is generated at least partially based on an individual’s reaction time to the at least one of the verbal listing learning test, the semantic verbal fluency test, the attribute verification test, the digit span sequencing test, the Hayling sentence completion test, and the time orientation test.

8. The method according to claim 5, wherein the cognitive test function section comprises the verbal listing learning test, and the semantic verbal fluency test;wherein the verbal listing learning test comprises at least one verbal listing learning question requesting the individual to memorize a group of words delivery to the individual and then repeat the memorized group of words verbally;wherein the semantic verbal fluency test comprises at least one semantic verbal fluency question requesting the individual to verbally provide words within at least one semantic category within a certain time period.

9. The method according to claim 5, wherein the cognitive test function section comprises one of the Hayling sentence completion test and the attribute verification test;wherein the Hayling sentence completion test comprises at least one sentence completion question requesting the individual to complete a sentence with an omission having at least one omitted word using at least one word which is different from the omitted word;wherein the attribute verification test comprises at least one attribute verification question requesting the individual to determine if an attribute statement is correct.

10. The method according to claim 9, wherein the cognitive test function section comprises both the Hayling sentence completion test and the attribute verification test.

11. The method according to claim 5, wherein the cognitive test function section comprises at least one of the digit span sequencing test and the time orientation test; wherein the digit span sequencing test comprises at least one digit span sequencingAttorney Docket No. 626986.100014question requesting the individual to arrange multiple elements in an ascending or descending order verbally; andwherein the time orientation test comprises at least one time orientation question requesting the individual to verbally provide a date or a time.

12. The method according to claim 4, wherein the evaluation scheme further comprises a subjective testing section.

13. The method according to claim 12, wherein the subjective testing section comprises at least one of a subjective cognitive decline test, an emotional screening test, and a lifestyle test.

14. The method according to claim 12, wherein the evaluation score is generated at least partially based on the individual’s responses to the at least one of the subjective cognitive decline test, the emotional screening test, and the lifestyle test.

15. The method according to claim 13, wherein the subjective cognitive decline (SCD) test comprises at least one SCD question requesting the individual to provide an evaluation of at least one status of individual’s memory, attention, and cognitive function.

16. The method according to claim 13, wherein the emotional screening test comprises at least one emotional status question requesting the individual to provide an evaluation of the individual’s emotional status, and wherein an emotional status score is generated based on the evaluation of the individual’s emotional status provided by the individual.

17. The method according to claim 13, wherein the lifestyle test comprises at least one sleep status question requesting the individual to provide an evaluation of the individual’s sleep status.

18. The method according to claim 13, wherein the lifestyle test comprises at leastAttorney Docket No. 626986.100014one exercise status question requesting the individual to provide an evaluation of the individual’s exercise status.

19. The method according to claim 3, wherein step (1) and step (2) of the evaluation scheme are conducted using an electronic device.

20. The method according to claim 19, wherein the electronic device comprises at least one voice module, wherein the at least voice module delivers the one or more test to the individual, and obtains the individual’s responses to the one or more test.

21. The method according to claim 20, wherein the electronic device comprises an interactive screen, wherein the interactive screen displays the one or more tests to the individual.

22. A method for evaluating an aMCI status of an individual, the method comprising:(1) delivering an evaluation scheme having a cognitive test function section and a subjective testing section to an individual;(2) obtaining the individual’s responses to the evaluation scheme;(3) generating an evaluation score of the individual based on the individual’s responses; and(4) generating an aMCI status of the individual based on the evaluation score of the individual,wherein the cognitive test function section comprises a verbal listing learning test, a semantic verbal fluency test, an attribute verification test, a digit span sequencing test, a Hayling sentence completion test, and a time orientation test;wherein the subjective testing section comprises at least one of an emotional screening test, and a lifestyle test;wherein the individual’s response to the evaluation scheme includes answers provided by the individual in response to questions in the tests of the evaluation scheme and a time period for the individual to complete at least one of the answers for at leastAttorney Docket No. 626986.100014one of the questions.

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