OBJECTIVE: To identify the components of the neuroticism trait most responsible for its association with cognitive decline and dementia in old age. DESIGN: Longitudinal clinical-pathologic cohort study. SETTING: Chicago metropolitan area. PARTICIPANTS: A total of 785 older persons without dementia completed standard self-report measures of six components of neuroticism and then had annual clinical evaluations for a mean of 3.4 years and brain autopsy in the event of death. MEASUREMENTS: Incidence of clinically diagnosed Alzheimer disease (AD), change in global and specific cognitive functions, and postmortem measures of plaques and tangles, cerebral infarction, and Lewy bodies. RESULTS: During follow-up, 94 individuals developed AD. Higher levels of anxiety and vulnerability to stress were associated with increased risk of AD and more rapid decline in global cognition, with no effects for the other four trait components. In analyses of specific cognitive systems, neuroticism subscales were related to decline in episodic memory, working memory, and perceptual speed, but not in semantic memory or visuospatial ability. No component of neuroticism was related to the neuropathologic lesions most commonly associated with late-life dementia. CONCLUSIONS: Neuroticism's association with late-life dementia mainly reflects vulnerability to stress and anxiety and their correlation with decline in the ability to process and retain new information.
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