# Sex differences in the association between episodic memory residual reserve index and change in executive function

## TL;DR

The study found that women benefit more than men from cognitive reserve in protecting executive function, especially when brain integrity is low, and this effect is not influenced by beta-amyloid levels.

## Contribution

This study reveals sex-specific protective effects of cognitive reserve on executive function decline, independent of brain beta-amyloid.

## Key findings

- Females showed greater protection from cognitive reserve at low brain integrity compared to males.
- The protective effect of cognitive reserve on executive function was not influenced by beta-amyloid burden.
- A three-way interaction was observed between cognitive reserve, brain integrity, and sex affecting executive function decline.

## Abstract

Sex differences in cognitive reserve might contribute to females being disproportionately affected by Alzheimer’s disease (AD). We investigated sex differences in the protective effects of cognitive reserve, and whether brain beta-amyloid accounts for differences. Older adults (n = 997 from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing) diagnosed as Cognitively Normal, Mild Cognitive Impairment, or AD at baseline were assessed every 18 months for up to a maximum of seven visits. Cognitive reserve was calculated from the variance in episodic memory not explained by demographic or brain measures. Executive functioning (EF) intercept and slope were regressed onto the main and interaction effects of cognitive reserve x brain integrity x sex, plus covariates (age, number of APOE ε4 alleles). A three-way interaction was observed between cognitive reserve, brain integrity, and sex on the EF slope. Females benefitted more than males from the protective effects of cognitive reserve at low levels of brain integrity. Sex differences in the protective effect of cognitive reserve were not moderated by brain beta-amyloid burden.