With the aging of the U.S. population, the number of cognitively disabled persons is expected to substantially increase in coming decades, underscoring the urgent need for effective interventions. Here, we review the current evidence linking psychosocial factors to late-life cognitive loss and consider the study design needed to illuminate the biologic bases of the associations. We then examine an ongoing study that includes several of the key design elements, the Rush Memory and Aging Project. In this longitudinal clinical-pathological cohort study, indicators of personality, social connectedness, and psychological well-being were shown to predict late-life cognitive outcomes. Participants who died underwent a uniform neuropathologic examination to quantify common dementia-related pathologies. Some psychosocial indicators were associated with cerebral infarction; some indicators modified the association of neurodegenerative pathologies with cognitive loss; and the association of some indicators with cognitive outcomes appears to be independent of the pathologies traditionally associated with late-life dementia. These findings suggest that psychosocial behavior influences late-life cognitive health through multiple neurobiologic mechanisms. A better understanding of these mechanisms may lead to novel strategies for preserving cognitive health in old age.
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