ELEVATED MIDLIFE CORTISOL IS ASSOCIATED WITH MCI SIX YEARS LATER

Stress and hypothalamic-pituitary-adrenal (HPA) axis dysregulation have been associated with increased Aβ, tau, and Alzheimer's disease (AD) progression. These have also been associated with hippocampal reduction or dysfunction that is mediated by elevated cortisol. Little is known, however, about how cortisol is related to earlier stages of the AD continuum. We hypothesized that elevated cortisol levels in middle-aged adults would be associated with mild cognitive impairment (MCI) at a follow-up. Salivary cortisol was obtained from 599 men during wave 1 of the Vietnam Era Twin Study of Aging (VETSA). Average age was 56 (51-60) at wave 1 and 62 (56-66) at wave 2. Cortisol was obtained at awakening, 30 minutes post-awakening, 3 PM, and bedtime on 2 non-consecutive days at home and 1 in-lab day. We calculated area under the curve (AUC) and cortisol awakening response (CAR=increase from awakening to 30 minutes post-awakening) averaged over the 3 days. In mixed linear models we examined the association between cortisol at wave 1 and MCI status (MCI vs. cognitively normal [CN]) at wave 2, controlling for age, SES, corticosteroid medication, and APOE status (ε4+ vs. ε4-). MCI was based on the Jak/Bondi approach. Both higher CAR and AUC cortisol at wave 1 were higher in MCI compared with CN participants (CAR: 11.41, p