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Objective: To investigate the cross-sectional association between personality characteristics and hypothalamic-pituitary-adrenal (HPA) axis regulation in older persons. Methods: The study sample consisted of 1,150 participants (mean age 74.8 ± 7.1 years, 48% male) from the population-based Longitudinal Aging Study Amsterdam. HPA axis activity was measured with salivary cortisol collected after awakening and late in the evening. Outcome measures were awakening and evening cortisol levels (natural log transformed) and the diurnal pattern of cortisol. Determinants were scores on questionnaires assessing neuroticism, mastery, and self-esteem. Results: Multiple linear regression analyses adjusted for potential confounders did not show significant associations between any of the personality characteristics and any of the cortisol measures. On evening cortisol, a significant interaction was observed between neuroticism and age (B = -0.001; T = -2.50, df = 1,139;p value = 0.01). After stratification in two age groups, the authors observed that high levels of neuroticism were associated with elevated levels of evening cortisol in subjects aged <75 years (B = 0.02; 95% confidence interval: 0.010-0.03; T = 2.15, df = 630, p 0.03) but not in subjects aged 75 years or older. Conclusions: The findings of this large population-based study of older persons suggest that the personality characteristics mastery and self-esteem are not associated with HPA axis regulation as measured with salivary awakening and evening cortisol. However, high neuroticism may be associated with elevated levels of evening cortisol in the younger old but not in the older old. [ABSTRACT FROM AUTHOR]