Proneness to psychological distress is associated with risk of Alzheimer's disease

Background: Chronic stress is associated with hippocampal damage and impaired memory in animals and humans. Objective: To examine this relationship with clinical and pathologic data from the Religious Orders Study. Methods: Older Catholic clergy members underwent annual clinical evaluations, which included clinical classification of Alzheimer's disease ( AD) and detailed cognitive function testing from which composite measures of global cognition and specific cognitive functions were derived. At the baseline evaluation, participants completed a measure of the tendency to experience psychological distress, a stable personality trait that served as an indicator of susceptibility to negative emotional states across the life span. More than 90% of participants who died underwent a uniform postmortem examination of the brain from which summary measures of AD pathology were derived. The association of distress proneness with incident AD and cognitive decline and with measures of AD pathology was examined in analyses adjusted for selected demographic and clinical variables. Results: During a mean of 4.9 years of follow- up, 140 persons developed AD. Those high in distress proneness ( 90th percentile) had twice the risk of developing AD than those low in distress proneness ( 10th percentile). Distress proneness was related to decline in episodic memory but not in other cognitive domains, with a > 10- fold increase in episodic memory decline in those high in distress proneness compared with those low in the trait. Among those who died, however, distress proneness was not related to common measures of AD pathology. Conclusion: Proneness to experience psychological distress is a risk factor for AD, an effect independent of AD pathologic markers such as cortical plaques and tangles.