title: Sleep impairments in healthy seniors: roles of stress, cortisol, and interleukin-1 beta.
abstract: OBJECTIVE
  Increased stress responsivity and a longer-lasting glucocorticoid increase are common findings in aging studies. Increased cortisol levels at the circadian nadir also accompany aging. We used 24 h free urine cortisol to assess these age changes in healthy seniors. We hypothesized that free cortisol levels would explain individual differences in age-related sleep impairments.
  
  
  METHODS
  The study compared sleep, cortisol, and sleep-cortisol correlations under baseline and "stress" conditions in men and women.
  
  
  METHODS
  Subjects were studied in the General Clinical Research Center under baseline conditions and a mildly stressful procedure (24 h indwelling intravenous catheter placement).
  
  
  METHODS
  Eighty-eight healthy, nonobese subjects (60 women and 28 men) from a large study of successful aging participated in the study. Mean ages were 70.6 (+/-6.2) and 72.3 (+/-5.7) years for women and men, respectively.
  
  
  METHODS
  The 24 h urines were collected 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 electroencephalograms (EEGs) were analyzed (after an adaptation and screening night) on baseline and stress nights via polysomnography and EEG power spectral analysis.
  
  
  RESULTS
  Healthy older women and men with higher levels of free cortisol (24 h urine level) under a mild stress condition had impaired sleep (lower sleep efficiency; fewer minutes of stages 2, 3, and 4 sleep; more EEG beta activity 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 were used. Gender differences were apparent: Men had higher levels of free urine cortisol in both baseline and mild stress conditions. Cortisol and sleep correlated most strongly in men; cortisol stress response levels explained 36% of the variance in NREM sleep stress responses. In women, but not men, higher cortisol was also associated with earlier time of arising and less REM sleep. Higher cortisol response to stress was associated with increased circulating levels of IL-1beta, explaining 24% of the variance in a subset of women.
  
  
  CONCLUSIONS
  These results indicate that free cortisol (as indexed by 24 h urine values) can index responses to mild stress in healthy senior adults, revealing functional correlations (impaired sleep, earlier times of arising, more EEG beta activity during sleep, more IL-1beta) and gender differences.
authors.affiliation: Department of Biobehavioral Nursing and Health Systems, University of Washington, Seattle, USA. prinz@u.washington.edu
authors.forename: P N
authors.initials: PN
authors.lastname: Prinz
authors.forename: S L
authors.initials: SL
authors.lastname: Bailey
authors.forename: D L
authors.initials: DL
authors.lastname: Woods
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology; D004569:Electroencephalography; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000502:physiology* / Q000652:urine; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D007375:Interleukin-1 / Q000097:blood / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D017286:Polysomnography; D012894:Sleep Stages / Q000502:physiology; D012893:Sleep Wake Disorders / Q000209:etiology* / Q000503:physiopathology*; D013312:Stress, Physiological / Q000150:complications* / Q000503:physiopathology*
chemical_list: D007375:Interleukin-1; D006854:Hydrocortisone