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Method for predicting risk of cognitive deterioration

A risk, level technology, applied in the field of prognosis and treatment, genetic vulnerability, indicators of brain iron levels, can solve problems such as not

Inactive Publication Date: 2018-01-26
CRC FOR MENTAL HEALTH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Autopsy studies have found brain tau accumulation in normal aging, and while elevated CSF tau is one of the best available prognostic biomarkers, it is still not clinically useful

Method used

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  • Method for predicting risk of cognitive deterioration
  • Method for predicting risk of cognitive deterioration
  • Method for predicting risk of cognitive deterioration

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0160] Example 1: Ferritin levels in cerebrospinal fluid predict Alzheimer's disease outcome and are regulated by APOE

[0161] Ferritin is the body's major iron storage protein; the effect of brain iron status on longitudinal outcomes was investigated in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort by using cerebrospinal fluid (CSF) levels of ferritin as an indicator.

[0162] This example shows the association of baseline CSF-ferritin data with 7-year biomarker, cognitive, anatomical and diagnostic outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) prospective clinical cohort. It shows that CSF ferritin levels are comparable to the more established AD CSF biomarkers tau / Ab in predicting various outcomes in AD. 1–42 Ratio and Apolipoprotein E (ApoE) level comparison serve a similar purpose.

[0163] (i) method

[0164] ADNI description. Data were downloaded from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc....

Embodiment 2

[0207] Example 2: Cerebrospinal ferritin determines the risk of cognitive decline in preclinical APOE-ε4 carriers

[0208] The ε4 allele of apolipoprotein E (ApoE) confers the greatest risk of Alzheimer's disease (AD) and increases cerebrospinal fluid (CSF) ferritin by approximately 20% due to ε4 carriage (Ayton S et al (2015)) , recent data implicate brain iron accumulation as a risk vector. CSF ferritin levels predict longitudinal cognitive performance and risk of transition to AD in subjects with mild cognitive impairment (MCI). This example shows that CSF ferritin correlates with established AD risk variables APOE-ε4, CSF tau / Aβ in predicting 7-year cognitive decline in normal population 1-42 Binds to ApoE.

[0209] (i) method

[0210] This example uses data obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu; July 15, 2014).

[0211] Aβ 1-42 Baseline CSF levels of , tau (Luminex), ApoE, ferritin (Myriad Rules Based Medicin...

Embodiment 3

[0222] Example 3: Assessing a Patient's Risk of Cognitive Degeneration

[0223] In practicing the methods of the invention, it is contemplated that the patient's level of cognitive ability will be assessed. This level will provide the basis for determining whether they will degrade over time. The patient may have shown signs of cognitive impairment following the assessment.

[0224] CSF samples can be obtained and CSF ferritin levels determined by methods such as immunoassays and the like. This sample can then be compared to predetermined samples from CN patients processed in the same manner.

[0225] Differences in CSF ferritin levels between the patients and CN patients will be determined. Based on the magnitude of the difference, the degree of cognitive decline can be determined. If the difference is large and the patient's CSF ferritin level is high relative to the CN patient level, the assessed patient would show a higher risk of cognitive decline. If the difference ...

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Abstract

The present invention relates to methods for predicting a risk of cognitive deterioration, monitoring progression of cognitive deterioration and diagnosing cognitive deterioration in a patient. The present invention further relates to methods for diminishing progression rate of cognitive deterioration in a patient by lowering brain iron levels in the patient or lowering CSF ferritin levels in thepatient.

Description

technical field [0001] The present invention relates to a method for predicting the risk of cognitive degeneration in the field of dementia, cognitive and / or affective and / or behavioral disorders, Alzheimer's disease and related dementias. More particularly, it relates to genetic vulnerabilities, methods of prognosis and methods of treatment. It involves a correlation between brain iron and cognitive decline. Preferably, the present invention relates to the use of ferritin, or more preferably cerebrospinal fluid (CSF) ferritin, as a method for diagnosing, prognosing and / or monitoring the progression of cognitive degeneration and classifying individuals into more than one category according to the diagnosis or prognosis of cognitive degeneration Methods for indicators of brain iron levels. More specifically, the present invention relates to the diagnosis, prognosis and monitoring of Alzheimer's disease (AD) in subjects or individuals who will suffer from the disease through t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/68G01N24/08G01N29/04A61B5/055A61K31/4412A61P25/28
CPCA61K31/4412A61B5/0055A61B5/14507A61B5/4064A61B5/4088A61B5/7275G01N2800/2814G01N2800/50G01N2800/52A61B5/055A61B5/4842G16H50/30G01N33/84A61P25/28C12Q1/6883G01N33/6896G01N2333/775G01N2800/2821
Inventor S·艾顿N·福克斯A·I·布什
Owner CRC FOR MENTAL HEALTH
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