OBJECTIVE:: High neuroticism has been associated with a greater risk of dementia, and an active/socially integrated lifestyle with a lower risk of dementia. The aim of the current study was to explore the separate and combined effects of neuroticism and extraversion on the risk of dementia, and to examine whether lifestyle factors may modify this association. METHODS:: A population-based cohort of 506 older people with no dementia from the Kungsholmen Project, Stockholm, Sweden, was followed up for an average of 6 years. Personality traits were assessed using the Eysenck Personality Inventory. Dementia was diagnosed by specialists according to DSM-III-R criteria. RESULTS:: Neither high neuroticism nor low extraversion alone was related to significantly higher incidence of dementia. However, among people with an inactive or socially isolated lifestyle, low neuroticism was associated with a decreased dementia risk (hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.27-0.96). When compared to ersons with high neuroticism and high extraversion, a decreased risk of dementia was detected in individuals with low neuroticism and high extraversion (HR = 0.51, 95% CI = 0.28-0.94), but not among persons with low neuroticism and low extraversion (HR = 0.95, 95% CI = 0.57-1.60), nor high neuroticism and low extraversion (HR = 0.97 95% CI = 0.57-1.65). Stratified analysis by lifestyle showed that the inverse association of low neuroticism and high extraversion in combination was present only among the inactive or socially isolated persons. CONCLUSION:: Low neuroticism in combination with high extraversion is the personality trait associated with the lowest dementia risk; however, among socially isolated individuals even low neuroticism alone seems to decrease dementia risk. Copyright © 2009 by AAN Enterprises, Inc.