Andrews, S.J., McFall, G.P., Booth, A. orcid.org/0000-0003-4808-3880 et al. (2 more authors) (2019) Association of Alzheimer's disease genetic risk loci with cognitive performance and decline: A systematic review. Journal of Alzheimer's Disease, 69 (4). pp. 1109-1136. ISSN 1387-2877
Abstract
The association of Apolipoprotein E (APOE) with late-onset Alzheimer's disease (LOAD) and cognitive endophenotypes of aging has been widely investigated. There is increasing interest in evaluating the association of other LOAD risk loci with cognitive performance and decline. The results of these studies have been inconsistent and inconclusive. We conducted a systematic review of studies investigating the association of non-APOE LOAD risk loci with cognitive performance in older adults. Studies published from January 2009 to April 2018 were identified through a PubMed database search using keywords and by scanning reference lists. Studies were included if they were either cross-sectional or longitudinal in design, included at least one genome-wide significant LOAD risk loci or a genetic risk score, and had one objective measure of cognition. Quality assessment of the studies was conducted using the quality of genetic studies (Q-Genie) tool. Of 2,466 studies reviewed, 49 met inclusion criteria. Fifteen percent of the associations between non-APOE LOAD risk loci and cognition were significant. However, these associations were not replicated across studies, and the majority were rendered non-significant when adjusting for multiple testing. One-third of the studies included genetic risk scores, and these were typically significant only when APOE was included. The findings of this systematic review do not support a consistent association between individual non-APOE LOAD risk and cognitive performance or decline. However, evidence suggests that aggregate LOAD genetic risk exerts deleterious effects on decline in episodic memory and global cognition.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 IOS Press. This is an author-produced version of a paper subsequently published in Journal of Alzheimer's Disease. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Alzheimer’s disease; cognition; genetic predisposition to disease; single nucleotide polymorphism |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Health and Related Research (Sheffield) > ScHARR - Sheffield Centre for Health and Related Research |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 18 Jun 2019 15:54 |
Last Modified: | 13 Dec 2021 01:58 |
Status: | Published |
Publisher: | IOS Press |
Refereed: | Yes |
Identification Number: | 10.3233/JAD-190342 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:147522 |