Background Cognitive reserve (CR), typically measured through socio-behavioral proxies, can partially explain better cognitive performance despite underlying brain aging or neuropathology. Objective To examine the associations of CR with mild cognitive impairment (MCI) and cognitive function while considering Alzheimer's disease (AD)-related plasma biomarkers. Methods This population-based cross-sectional study included 4706 dementia-free individuals from MIND-China. Data on AD-related plasma biomarkers were available for 1204 individuals. A composite CR score was generated by integrating education, occupational complexity, mental activity, and social support, using structural equation modeling. A neuropsychological test battery was used to assess the function of episodic memory, executive function, attention, and verbal fluency. MCI and subtypes of MCI were defined according to the Petersen's criteria. Data were analyzed using general linear and logistic regression models. Results Controlling for AD-related plasma biomarkers, higher educational attainment was associated with better performance in all four examined cognitive domains (p &lt; 0.001) and with lower likelihoods of MCI, amnestic MCI (aMCI), and non-aMCI (p &lt; 0.05); late-life mental activity was significantly related to lower likelihoods of MCI and aMCI (p &lt; 0.05). Midlife occupation and late-life social support were not significantly associated with MCI or subtypes (p &gt; 0.05). Higher composite CR scores were related to better performance in all the examined cognitive domains as well as lower likelihoods of MCI, aMCI, and non-aMCI (p &lt; 0.05). Conclusions Greater composite CR, derived from the CR indicators across different stages of the lifespan, is associated with better cognitive function independent of AD-related plasma biomarkers, driven mainly by early-life educational attainment.

Associations between lifelong cognitive reserve, Alzheimer's disease-related plasma biomarkers, and cognitive function in dementia-free older adults: A population-based study