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Sex effects in predictors of memory resilience for carriers of Alzheimer’s genetic risk Open Access


Other title
memory resilience
Alzheimer's genetic risk
Victoria Longitudinal Study
random forest analysis
Apolipoprotein E
sex differences
Type of item
Degree grantor
University of Alberta
Author or creator
McDermott, Kirstie L
Supervisor and department
Dixon, Roger (Psychology)
Examining committee member and department
Fujiwara, Esther (Psychiatry)
Camicioli, Richard (Medicine)
Singhal, Anthony (Psychology)
Centre for Neuroscience

Date accepted
Graduation date
2016-06:Fall 2016
Master of Science
Degree level
Apolipoprotein E (APOE) ɛ4 and Clusterin (CLU) C alleles are risk factors for Alzheimer’s disease (AD) and preclinical cognitive and memory decline in older adults. We investigated whether memory resilience to genetic risk (i.e., Apolipoprotein E [APOE] ɛ4, Clusterin [CLU] CC, and a high additive genetic risk score [GRS]) is predicted by factors that are sex-specific and genetically robust. Using a longitudinal sample of cognitively normal adults (n = 642, aged 53-95) we defined memory resilience as possessing specified genetic risk while sustaining high episodic memory (EM) function over time. Random forest analysis, stratified by sex, tested the predictive importance of 22 risk factors derived from five documented AD risk domains: (a) demographic (e.g., education), (b) functional biomarker (e.g., pulse pressure), (c) health (e.g., diabetes), (d) mobility (e.g., walking time), and (e) lifestyle (e.g., everyday physical activity). For both sexes, younger age, higher education, stronger grip, and everyday novel cognitive activity predicted memory resilience. For females, demographic, functional, health, mobility, and lifestyle factors predicted resilience. For males, fewer depressive symptoms was an important predictor. Prediction patterns were similar for the two variants and the GRS. Long-term memory resilience in non-demented aging is predicted by risk and protective factors that are both common and unique to females and males. The greater number and wider breadth identified for females may enhance opportunities for sex-specific multi-factorial interventions to promote functional maintenance and delay cognitive decline. Promoting memory and cognitive resilience is especially crucial for aging adults with unmodifiable AD genetic risk.
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