title: Higher levels and blunted diurnal variation of cortisol in frail older women.
abstract: BACKGROUND
  Frailty is an important geriatric condition with increased vulnerability to stressors (e.g., infection and injury) and for developing functional dependence and mortality. Impairments in signaling pathways, including neuroendocrine alterations, are thought to be involved in the etiology of frailty, but have not been well characterized to date. We evaluated whether higher levels and blunted diurnal variation of salivary cortisol are cross-sectionally associated with frailty burden.
  
  
  METHODS
  Two hundred fourteen community-dwelling women, 80-90 years old, from the Women's Health and Aging Study participated in this study between 2004 and 2005. Seven saliva samples were collected for cortisol measurement over a 24-hour period. Main outcomes were awakening, evening, and overall mean cortisol; diurnal amplitude; and rate of decline of cortisol level during morning hours. All cortisol concentrations were log-transformed. Frailty burden was calculated, based on a previously validated tool, as the number (0-5) of the following criteria present: weakness, exhaustion, weight loss, slowness, and inactivity.
  
  
  RESULTS
  Significant positive associations were found between frailty burden and evening cortisol (beta = 0.11, p =.04), and between frailty burden and 24-hour mean cortisol (beta = 0.07, p =.03). Increasing frailty burden was significantly associated with smaller declines in cortisol during morning hours (beta = 0.04, p =.02). Frailty burden of > or =2 was associated with a smaller diurnal amplitude (beta = -0.34, p =.03). Awakening cortisol was not significantly associated with frailty burden (beta = 0.01, p =.8). All analyses included adjustments for several important confounders.
  
  
  CONCLUSIONS
  Our findings provide the first epidemiological evidence that higher levels and blunted diurnal variation of cortisol may be involved in the vulnerability and clinical presentation observed in frail older women.
authors.affiliation: Division of Geriatric Medicine and Gerontology, School of Medicine, John Hopkins University, Baltimore, MD, USA. rvaradhan@jhmi.edu
authors.forename: Ravi
authors.initials: R
authors.lastname: Varadhan
authors.forename: Jeremy
authors.initials: J
authors.lastname: Walston
authors.forename: Anne R
authors.initials: AR
authors.lastname: Cappola
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Carlson
authors.forename: Gary S
authors.initials: GS
authors.lastname: Wand
authors.forename: Linda P
authors.initials: LP
authors.lastname: Fried
mesh_terms: D000369:Aged, 80 and over; D002940:Circadian Rhythm; D003430:Cross-Sectional Studies; D005260:Female; D016330:Frail Elderly; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis*; D012044:Regression Analysis; D012463:Saliva / Q000737:chemistry; D018709:Statistics, Nonparametric
chemical_list: D006854:Hydrocortisone