Cognitive reserve (CR) partly explains cognitive variability in the presence of pathological brain aging. We investigated the interplay of lifelong CR with age, sex, and brain aging markers in cognitive phenotypes among older adults with very limited education. This population-based cross-sectional study included 179 dementia-free participants (age ≥65 years; 39.7% women; 67.0% had no or elementary education) examined in 2014-2016. We assessed lacunes and volumes of hippocampus, ventricles, grey matter, white matter (WM), and white matter hyperintensities. Lifelong CR score was generated from six lifespan intellectual factors (e.g., education and social support). We used Mini-Mental State Examination (MMSE) score to assess cognition and Petersen's criteria to define mild cognitive impairment (MCI). Data were analyzed using general linear and logistic models. The association of higher lifelong CR score (range: -4.0-5.0) with higher MMSE score was stronger in women (multivariable-adjusted β-coefficient and 95% CI: 1.75;0.99-2.51) than in men (0.68;0.33-1.03) (pinteraction = 0.006). The association of higher CR with MCI (multivariable-adjusted odds ratio and 95% CI: 0.77;0.60-0.99) did not vary by age or sex. Among participants with low CR (<1.4[median]), greater hippocampal and WM volumes were related to higher MMSE scores with multivariable-adjusted β-coefficients being 1.77(0.41-3.13) and 0.44(0.15-0.74); the corresponding figures in those with high CR were 0.15(-0.76-1.07) and -0.17(-0.41-0.07) (pinteraction <0.01). There was no statistical interaction of CR with MRI markers on MCI. Greater lifelong CR capacity is associated with better late-life cognition among people with limited education, possibly by compensating for impact of neurodegeneration.
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