Blunted diurnal cortisol pattern is associated with frailty: A cross-sectional study of 745 participants aged 65 to 90 years

Background: The role of neuroendocrine alterations in the etiology of frailty syndrome is still poorly understood. Hypothalamic-pituitary-adrenal axis dysregulation is a plausible candidate pathway contributing to frailty. Thus, we sought to examine the associations of diurnal cortisol secretion with frailty in older adults. Methods: A cross-sectional analysis was conducted among 745 study participants (age 65-90 years, mean age 75.1 years) of the population-based KORA Age study. Associations between salivary cortisol measures at awakening (morning 1 [M1]), 30 minutes after awakening (M2), and evening (E) and frailty criteria were determined. Results: Lower cortisol levels in the first morning sample (M1) (P = .18) and M2 (P = .14) and increased E levels (P = .004) were observed in prefrail (35.17%, n = 262) and frail (3.36%, n = 25) individuals, in a dose-response manner. Frailty was strongly associated with smaller ratios of morning to evening levels; M1 to E ratio (P = .02) and M2 to E ratio (P = .003). Higher evening cortisol levels were associated with a 24% increased risk of a prefrail state (odds ratio, 1.22; 95% confidence interval, 1.03-1.44). A smaller morning to evening ratio was associated with an increased risk of low grip strength (1.42, 1.09-1.86) and gait speed (1.31, 1.02-1.68). Conclusion: Frailty status is associated with blunted cortisol reactivity as demonstrated by lower morning and higher evening salivary cortisol levels.