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Abstract
Background and Objectives Females have a higher age-adjusted incidence of Alzheimer disease than males but the reasons for this remain unclear. One proposed contributing factor is that, historically, females 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 2 proxies for cognitive reserve, education and IQ, on the steepness of age-related declining cognitive trajectories in unimpaired older males and females.
Methods The Tasmanian 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, and episodic and working memory over 5 years were extracted from neuropsychological assessments. The adjusted effects of education, estimated IQ, and APOE allelic variant on cognitive trajectories were compared between males and females.
Results Five hundred sixty-two individuals (mean [SD] age 60 [6.7] years; 68% male; 33% APOE ε4+) were followed up over 5 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 < 0.001). Estimated IQ interacted with sex to moderate age-related cognitive trajectories (p = 0.03; 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 = 0.67; 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 disease.
Glossary
- BNT=
- Boston Naming Test;
- COWAT=
- Controlled Oral Word Association Test;
- MCI=
- mild cognitive impairment;
- NHMRC=
- National Health and Medical Research Council of Australia;
- PAL=
- Paired Associates Learning;
- RAVLT=
- Rey Auditory Verbal Learning Test;
- SWM=
- Spatial Working Memory;
- THBP=
- Tasmanian Healthy Brain Project;
- TMT-B=
- Trail Making Test Part B;
- WAIS-III=
- Wechsler Adult Intelligence Scale-third edition
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
Submitted and externally peer reviewed. The handling editor was Linda Hershey, MD, PhD, FAAN.
- Received March 23, 2022.
- Accepted in final form August 22, 2022.
- © 2022 American Academy of Neurology
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