Clinical and pathological data from the Rush Memory and Aging Project were used 
to test the hypothesis that distress proneness is associated with increased risk 
of Alzheimer's disease (AD). More than 600 older persons without dementia 
completed a 6-item measure of neuroticism, a stable indicator of proneness to 
psychological distress. At annual intervals thereafter, they underwent uniform 
evaluations that included clinical classification of AD and administration of 18 
cognitive tests. Those who died underwent brain autopsy from which composite 
measures of AD pathology were derived. During a mean of about 3 years of 
follow-up, 55 people were clinically diagnosed with AD. In analyses that 
controlled for age, sex, and education, persons with a high level of distress 
proneness (score = 24, 90th percentile) were 2.7 times more likely to develop AD 
than those not prone to distress (score = 6, 10th percentile). Adjustment for 
depressive symptomatology or frequency of cognitive, social, and physical 
activity did not substantially change this effect. Distress proneness was also 
associated with more rapid cognitive decline. Among 45 participants who died and 
underwent brain autopsy, distress proneness was unrelated to diverse measures of 
AD pathology and was inversely related to cognition after controlling for AD 
pathology. The results support the hypothesis that distress proneness is 
associated with increased risk of dementia and suggest that neurobiologic 
mechanisms other than AD pathology may underlie the association.