Cognitive Decline in Alzheimer's Disease Is Not Associated with APOE.

Aged, 80 and over Alleles Alzheimer Disease / genetics Apolipoproteins E / genetics Cognitive Dysfunction / psychology Cohort Studies Female Genotype Humans Longitudinal Studies Male Mental Status and Dementia Tests / statistics & numerical data

APOE Alzheimer’s disease cognitive decline dementia genetics

Journal

Journal of Alzheimer's disease : JAD

ISSN: 1875-8908

Titre abrégé: J Alzheimers Dis

Pays: Netherlands

ID NLM: 9814863

Informations de publication

Date de publication:
2021

Historique:

pubmed: 7 9 2021

medline: 5 1 2022

entrez: 6 9 2021

Statut: ppublish

Résumé

The rate of cognitive decline in Alzheimer's disease (AD) has been found to vary widely between individuals, with numerous factors driving this heterogeneity. This study aimed to compute a measure of cognitive decline in patients with AD based on clinical information and to utilize this measure to explore the genetic architecture of cognitive decline in AD. An in-house cohort of 616 individuals, hereby termed the Cardiff Genetic Resource for AD, as well as a subset of 577 individuals from the publicly available ADNI dataset, that have been assessed at multiple timepoints, were used in this study. Measures of cognitive decline were computed using various mixed effect linear models of Mini-Mental State Examination (MMSE). After an optimal model was selected, a metric of cognitive decline for each individual was estimated as the random slope derived from this model. This metric was subsequently used for testing the association of cognitive decline with apolipoprotein E (APOE) genotype. No association was found between the number of APOEɛ2 or ɛ4 alleles and the rate of cognitive decline in either of the datasets examined. Further exploration is required to uncover possible genetic variants that affect the rate of decline in patients with AD.

Sections du résumé

BACKGROUND

The rate of cognitive decline in Alzheimer's disease (AD) has been found to vary widely between individuals, with numerous factors driving this heterogeneity.

OBJECTIVE

This study aimed to compute a measure of cognitive decline in patients with AD based on clinical information and to utilize this measure to explore the genetic architecture of cognitive decline in AD.

METHODS

An in-house cohort of 616 individuals, hereby termed the Cardiff Genetic Resource for AD, as well as a subset of 577 individuals from the publicly available ADNI dataset, that have been assessed at multiple timepoints, were used in this study. Measures of cognitive decline were computed using various mixed effect linear models of Mini-Mental State Examination (MMSE). After an optimal model was selected, a metric of cognitive decline for each individual was estimated as the random slope derived from this model. This metric was subsequently used for testing the association of cognitive decline with apolipoprotein E (APOE) genotype.

RESULTS

No association was found between the number of APOEɛ2 or ɛ4 alleles and the rate of cognitive decline in either of the datasets examined.

CONCLUSION

Further exploration is required to uncover possible genetic variants that affect the rate of decline in patients with AD.

Identifiants

DOI: 10.3233/JAD-210685 PMID: 34487047

pubmed: 34487047

pii: JAD210685

doi: 10.3233/JAD-210685

doi:

Substances chimiques

Apolipoproteins E 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng