Sex-specific protective effects of cognitive reserve on age-related cognitive decline: A 5-Year prospective cohort study

Background and objectives: Females have higher age-adjusted incidence of Alzheimer's disease than males but the reasons for this remain unclear. One proposed contributing factor is that, historically, women had less access to education and therefore may accumulate less cognitive reserve. However, educational attainment is confounded by IQ, which in itself is a component of cognitive reserve and does not differ between sexes. Steeper age-related cognitive declines are associated with increased risk of dementia. We therefore evaluated the moderating effects of two proxies for cognitive reserve, education and IQ, on the steepness of age-related declining cognitive trajectories in unimpaired older males and females.

Methods: The Tasmania Healthy Brain Project, a long-term cohort study, recruited healthy Australians aged 50-80 years without cognitive impairment. Baseline cognitive reserve was measured using educational history and IQ, measured by the Wechsler Test of Adult Reading, Full Scale Predicted IQ (WTAR-FSIQ). Cognitive trajectories for language, executive function, episodic and working memory over 5 years were extracted from neuropsychological assessments. The adjusted effects of education, estimated IQ, and APOE polymorphisms on cognitive trajectories were compared between males and females.

Results: 562 individuals (mean [SD] age 60 [6.7] years; 68% male; 33% APOE ε4+) were followed up over five years with 1,924 assessments and 24,946 cognitive test scores (annualized attrition rate 6.6% per year). Estimated IQ correlated with years of education (p < .001). Estimated IQ interacted with sex to moderate age-related cognitive trajectories (p = .03; adjusted for education); lower IQ males experienced steeper declining trajectories than higher IQ males, but lower IQ females had similar steepness of declining trajectories to higher IQ females. Education was not associated with rate of cognitive decline (p = .67; adjusted for WTAR-FSIQ). There were no significant differences in age-related cognitive trajectories between APOE genotypes in either sex.

Discussion: IQ, a measure of cognitive reserve, predicted the steepness of declining cognitive trajectories in males only. Education did not explain as much variation in cognitive trajectories as IQ. Our findings do not support the hypothesis that historical sex- disparities in access to education contribute to the higher female incidence of Alzheimer's disease.