TY - JOUR
T1 - Memory Resilience to Alzheimer's Genetic Risk
T2 - Sex Effects in Predictor Profiles
AU - McDermott, Kirstie L.
AU - McFall, G. Peggy
AU - Andrews, Shea J.
AU - Anstey, Kaarin J.
AU - Dixon, Roger A.
N1 - Publisher Copyright:
© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - Objectives Apolipoprotein E (APOE) ϵ 4 and Clusterin (CLU) C alleles are risk factors for Alzheimer's disease (AD) and episodic memory (EM) decline. Memory resilience occurs when genetically at-risk adults perform at high and sustained levels. We investigated whether (a) memory resilience to AD genetic risk is predicted by biological and other risk markers and (b) the prediction profiles vary by sex and AD risk variant. Method Using a longitudinal sample of nondemented adults (n = 642, aged 53-95) we focused on memory resilience (over 9 years) to 2 AD risk variants (APOE, CLU). Growth mixture models classified resilience. Random forest analysis, stratified by sex, tested the predictive importance of 22 nongenetic risk factors from 5 domains (n = 24-112). Results For both sexes, younger age, higher education, stronger grip, and everyday novel cognitive activity predicted memory resilience. For women, 9 factors from functional, health, mobility, and lifestyle domains were also predictive. For men, only fewer depressive symptoms was an additional important predictor. The prediction profiles were similar for APOE and CLU. Discussion Although several factors predicted resilience in both sexes, a greater number applied only to women. Sex-specific mechanisms and intervention targets are implied.
AB - Objectives Apolipoprotein E (APOE) ϵ 4 and Clusterin (CLU) C alleles are risk factors for Alzheimer's disease (AD) and episodic memory (EM) decline. Memory resilience occurs when genetically at-risk adults perform at high and sustained levels. We investigated whether (a) memory resilience to AD genetic risk is predicted by biological and other risk markers and (b) the prediction profiles vary by sex and AD risk variant. Method Using a longitudinal sample of nondemented adults (n = 642, aged 53-95) we focused on memory resilience (over 9 years) to 2 AD risk variants (APOE, CLU). Growth mixture models classified resilience. Random forest analysis, stratified by sex, tested the predictive importance of 22 nongenetic risk factors from 5 domains (n = 24-112). Results For both sexes, younger age, higher education, stronger grip, and everyday novel cognitive activity predicted memory resilience. For women, 9 factors from functional, health, mobility, and lifestyle domains were also predictive. For men, only fewer depressive symptoms was an additional important predictor. The prediction profiles were similar for APOE and CLU. Discussion Although several factors predicted resilience in both sexes, a greater number applied only to women. Sex-specific mechanisms and intervention targets are implied.
KW - Alzheimer's risk factors
KW - Apolipoprotein E
KW - Clusterin
KW - Random forest analysis
KW - Victoria Longitudinal Study
UR - http://www.scopus.com/inward/record.url?scp=85031946581&partnerID=8YFLogxK
U2 - 10.1093/geronb/gbw161
DO - 10.1093/geronb/gbw161
M3 - Article
C2 - 28025282
AN - SCOPUS:85031946581
SN - 1079-5014
VL - 72
SP - 937
EP - 946
JO - Journals of Gerontology - Series B Psychological Sciences and Social Sciences
JF - Journals of Gerontology - Series B Psychological Sciences and Social Sciences
IS - 6
ER -