Nonlinear multisystem physiological dysregulation associated with frailty in older women: Implications for etiology and treatment

Abstract

Background. Frailty in older adults, defined as a constellation of signs and symptoms, is associated with abnormal levels in individual physiological systems. We tested the hypothesis that it is the critical mass of physiological systems abnormal that is associated with frailty, over and above the status of each individual system, and that the relationship is nonlinear. Methods. Using data on women aged 70-79 years from the Women's Health and Aging Studies I and II, multiple analytic approaches assessed the cross-sectional association of frailty with eight physiological measures. Results. Abnormality in each system (anemia, inflammation, insulin-like growth factor-1, dehydroepiandrosterone- sulfate, hemoglobin A1c, micronutrients, adiposity, and fine motor speed) was significantly associated with frailty status. However, adjusting for the level of each system measure, the mean number of systems impaired significantly and nonlinearly predicted frailty. Those with three or more systems impaired were most likely to be frail, with odds of frailty increasing with number of systems at abnormal level, from odds ratios (ORs) of 4.8 to 11 to 26 for those with one to two, three to four, and five or more systems abnormal (p