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.