Cortisol reactivity to a psychosocial stressor significantly increases the risk of developing Cognitive Impairment no Dementia five years later.

Alzheimer's disease (AD) patients show high cortisol levels suggesting that biological mediators of stress may play a role in the neurodegenerative process of cognitive disorders. However, there is no consensus as to whether cortisol concentrations represent a risk factor for the development of cognitive impairment. We analyzed the potential association between the incidence of cognitive impairment and cortisol concentrations under basal and acute stress conditions in 129 individuals aged 50 years or older, with preserved cognitive and functional abilities. All participants were recruited in 2011 for assessment of cognitive performance and cortisol levels. Cortisol was analyzed in saliva samples collected during two typical and consecutive days, in the morning, afternoon, and night, and also during exposure to an acute psychosocial stressor (Trier Social Stress Test - TSST). After a five-year follow-up, 69 of these volunteers were reassessed for cognitive performance, functional evaluation, memory complaints, and depression. The incidence of cognitive impairment not dementia (CIND) was 26.1 %, and was positively associated with greater TSST-induced cortisol release (responsiveness) [(95 % CI = 1.001-1.011; B = 0.006), p = 0.023]. Moreover, five years before diagnosis, participants who later developed CIND had greater responsiveness to TSST (p = 0.019) and lower cortisol awakening response (CAR: p = 0.018), as compared to those who did not develop CIND. These findings suggest that higher psychosocial stress responsiveness profiles may represent a preclinical sign of cognitive impairment.