Sleep impairments in healthy seniors: Roles of stress, cortisol, and interleukin-1 beta

Study Objectives: Increased stress responsivity and a longer-lasting glucoc orticoid increase are common findings in aging studies. Increased cortisol levels at the circadian nadir also accompany aging. We used 24h free urine cortisol to assess these age changes in healthy seniors. We hypothesized th at free cortisol levels would explain individual differences in age-related sleep impairments. Design: The study compared sleep, cortisol, and sleep-c ortisol correlations under baseline and "stress" conditions in men and wome n. Setting: Subjects were studied in the General Clinical Research Center u nder baseline conditions and a mildly stressful procedure (24h indwelling i ntravenous catheter placement). Participants: Eighty-eight healthy, nonobes e subjects (60 women and 28 men) from a large study of successful aging par ticipated in the study. Mean ages were 70.6 (+/-6.2) and 72.3 (+/-5.7) year s for women and men, respectively. Measurements: The 24h urines were collec ted for cortisol assay (radioimmunoassay [RIA]); blood was sampled at three diurnal time points for assay (enzyme-linked immunosorbent assay [ELISA]) of interleukin-1 (IL-1) beta; sleep architecture and sleep electroencephalo grams (EEGs) were analyzed (after an adaptation and screening night) on bas eline and stress nights via polysomnography and EEG power spectral analysis . Results: Healthy older women and men with higher levels of free cortisol (24h urine level) under a mild stress condition had impaired sleep (lower s leep efficiency; fewer minutes of stages 2, 3, and 4 sleep; more EEG beta a ctivity during non-rapid eye movement sleep [NREM] sleep). Similar results were obtained when stress reactivity measures were used (cortisol and sleep values adjusted for baseline values), but not when baseline values alone w ere used. Gender differences were apparent: Men had higher levels of free u rine cortisol in both baseline and mild stress conditions. Cortisol and sle ep correlated most strongly in men; cortisol stress response levels explain ed 36% of the variance in NREM sleep stress responses. In women, but not me n, higher cortisol was also associated with earlier time of arising and les s REM sleep. Higher cortisol response to stress was associated with increas ed circulating levels of IL-1 beta, explaining 24% of the variance in a sub set of women. Conclusion: These results indicate that free cortisol (ns ind exed by 24h urine values) can index responses to mild stress in healthy sen ior adults, revealing functional correlations (impaired sleep, earlier time s of arising, more EEG beta activity during sleep, more IL-1 beta) and gend er differences.