LAUSR

Background: Cognitive reserve aims to explain individual differences in the susceptibility to the functional impact of dementia in the presence of equal amount of neuropathological damage. It is thought to be shaped by a combination of innate individual differences and lifetime exposures. Which determinants are associated with cognitive reserve remains unknown. Objective: The objective of this study was to investigate the associations of sociodemographic, lifestyle, physical, and psychosocial determinants with cognitive reserve, and potential sex differences. Methods: This cross-sectional study included 4,309 participants from the Rotterdam Study (mean age 63.9±10.7) between 2006–2016. Participants completed five cognitive tests and a brain MRI-scan. Cognitive reserve was defined as a latent variable that captures variance common across five cognitive tests, while adjusting for demographic and MRI-inferred neuropathological factors. The associations of potential determinants and cognitive reserve, adjusted for relevant confounders, were assessed with structural equation models. Results: Current smoking (adjusted mean difference: –0.31, 95%confidence interval –0.42; –0.19), diabetes mellitus (–0.25, –0.40; –0.10) and depressive symptoms (–0.07/SD, –0.12; –0.03) were associated with a lower cognitive reserve whereas alcohol use (0.07/SD, 0.03; 0.12) was associated with higher cognitive reserve. Only smoking was associated with cognitive reserve in both men and women. Employment, alcohol use, diabetes, history of cancer, COPD, and depressive symptoms were only associated with cognitive reserve in women. Conclusion: Our study found that current smoking, diabetes mellitus, and depressive symptoms were associated with a lower cognitive reserve, whereas more alcohol use was associated with a higher cognitive reserve, but with clear differences between men and women.