Abstract
CONTEXT: Purpose in life is associated with a substantially reduced risk of Alzheimer disease (AD), but the neurobiologic basis of this protective effect remains unknown. OBJECTIVE: To test the hypothesis that purpose in life reduces the deleterious effects of AD pathologic changes on cognition in advanced age. DESIGN: A longitudinal, epidemiologic, clinicopathologic study of aging was conducted that included detailed annual clinical evaluations and brain autopsy. PARTICIPANTS: Two hundred forty-six community-based older persons from the Rush Memory and Aging Project participated. MAIN OUTCOME MEASURES: Purpose in life was assessed via structured interview, and cognitive function was evaluated annually and proximate to death. On postmortem examination, 3 indexes of AD pathologic features were quantified: global AD pathologic changes, amyloid, and tangles. The associations of disease pathologic changes and purpose in life with cognition were examined using linear regression and mixed models. RESULTS: Purpose in life modified the association between the global measure of AD pathologic changes and cognition (mean [SE] parameter estimate, 0.532 [0.211]; P = .01), such that participants who reported higher levels of purpose in life exhibited better cognitive function despite the burden of the disease. Purpose in life also reduced the association of tangles with cognition (parameter estimate, 0.042 [0.019]; P = .03), and the protective effect of purpose in life persisted even after controlling for several potentially confounding variables. Furthermore, in analyses examining whether purpose in life modified the association between AD pathologic effects and the rate of cognitive decline, we found that higher levels of purpose in life reduced the effect of AD pathologic changes on cognitive decline (parameter estimate, 0.085 [0.039]; P = .03). CONCLUSION: Higher levels of purpose in life reduce the deleterious effects of AD pathologic changes on cognition in advanced age.