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

• Author / Creator

  McDermott, Kirstie L

• 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.

• Subjects / Keywords

  • Apolipoprotein E
  • Random forest analysis
  • Victoria Longitudinal Study
  • Biomarkers
  • Aging
  • Alzheimer's genetic risk
  • Memory resilience
  • Clusterin
  • Sex differences

• Graduation date

  Fall 2016

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3ST7F49F

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.