The role of Alzheimer's disease polygenic risk scores in changes of cognitive function in older adults: A longitudinal cohort study: Genetics/genetics of cognitive aging. (7th December 2020)

• Record Type: Journal Article
• Authors: Pan, Gongbu; King, Anna E.; Bindoff, Aidan; Summers, Mathew J.; Vickers, James C.
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 3
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.037853
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Previous studies show evidence that more than 21 genetic variants and polygenic risk were associated with Alzheimer's disease (AD). But the relationship between AD polygenic risk scores (ADPRS) and cognitive function/decline was unclear due to the lack of longitudinal data. This study investigated the potential association between ADPRS and changes in cognitive function. Method: The TBHP is an ongoing longitudinal prospective study of 459 healthy older adults. Participants with available genotype data (N = 325) were included in analysis. ADPRS was calculated by using sets of AD susceptibility variants identified by a meta‐analysis of GWAS data. The cognitive function domain scores at baseline and year 1, 2, 3 and 5 were calculated using factor analysis (principal components extraction method). Single factor scores for episodic memory, working memory, executive function, and language processing domains were combined by using factor coefficients via regression analysis. Linear mixed‐effects model analysis was performed to investigate the association between ADPRS and cognitive function longitudinally. Result: The ADPRS was significantly associated with an increase of working memory and executive function over 60 months, particularly in APOE ε4 carriers. In BDNF met carriers, ADPRS was associated with the decline of executive function. There were no direct associations between ADPRS and longitudinal changes in cognitive function. Conclusion: The relationship between ADPRS and changes in specific cognitive domains were highly being driven by APOE and BDNF status. These findings strongly support the potential role of common variants in predicting the changes in cognitive function before AD.