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Harm Avoidance and Risk of Alzheimer's Disease

Objective: To test the hypothesis that harm avoidance, a trait associated with behavioral inhibition, is associated with the risk of developing Alzheimer's disease (AD). Methods: A total of 791 adults 55 years and older without dementia completed a standard self-report measure of harm avoidance. They then underwent annual evaluations that included detailed cognitive testing and clinical classification of mild cognitive impairment (MCI), dementia, and AD. In a uniform neuropathologic examination of those who died, counts of neuritic plaques, diffuse plaques, and neurofibrillary tangles were standardized and combined to yield a pathologic measure of disease. The relation of harm avoidance to incidence of AD and related outcomes was estimated in analyses adjusted for age, sex, and education. Results: During a mean of 3.5 years of annual observation, 98 people (12.4%) developed incident AD. A high level of harm avoidance (90th percentile) was associated with a more than two-fold increase in risk of AD compared with a low score (10th percentile). Higher harm avoidance was also associated with increased incidence of MCI and more rapid decline in episodic memory, working memory, and perceptual speed (but not semantic memory or visuospatial ability). In 116 participants who died and underwent brain autopsy, harm avoidance was not related to a composite measure of plaques and tangles. Conclusions: A high level of the harm avoidance trait, indicating a tendency toward behavioral inhibition, is related to the risk of developing AD and its precursor, MCI.AD = Alzheimer's disease; MCI = mild cognitive impairment; SD = standard deviation; SE = standard error