Intranasal insulin decreases circulating cortisol concentrations during early sleep in elderly humans

Aging is associated with increases in hypothalamic-pituitary-adrenal (HPA) axis activity that can predispose to metabolic and cognitive impairments. We investigated in elderly and young subjects whether intranasal insulin administration to the human brain reduces early-sleep nadir concentrations of adrenocorticotropin and cortisol, that is, indicators of baseline HPA axis activity. In within-subject comparisons, intranasal insulin (160 IU) or placebo was administered to 14 elderly (mean age 70.0 years) and 30 young (23.6 years) healthy subjects before bedtime. Sleep was polysomno-graphically assessed and blood samples were repeatedly collected. Elderly compared with young participants displayed increased early-sleep cortisol concentrations (p < 0.04) and reductions in slow wave and REM sleep (p < 0.001). Insulin administration reduced cortisol levels between 2300 hours and 0020 hours in the elderly (p = 0.03) but not young participants (p = 0.56; p = 0.003 for interaction). Findings indicate that central nervous insulin acts as an inhibitory signal in basal HPA axis activity regulation and suggest that intranasal insulin may normalize sleep-associated stress axis activity in older age. (C) 2017 The Author(s). Published by Elsevier Inc.