Derivation of a measure of physiological multisystem dysregulation: Results from WHAS and health ABC

Alden L. Gross, Michelle C. Carlson, Nadia M. Chu, Mara A. McAdams-DeMarco, Dan Mungas, Eleanor M. Simonsick, Ravi Varadhan, Qian Li Xue, Jeremy Walston, Karen Bandeen-Roche

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Introduction: Multifactorial biological processes underpin dysregulation over several individual physiological systems. However, it is challenging to characterize and model this multisystemic dysregulation and its relationship with individual physiologic systems. We operationalized a theory-driven measure of multisystem dysregulation and empirically tested for measurement differences by key characteristics. Methods: We used the Women's Health and Aging Studies (WHAS) I and II (N = 649), and the Health ABC study (N = 1515). Twelve biomarkers representing multiple systems including stress response (e.g., inflammation), endocrine system, and energy regulation were identified. A series of confirmatory factor analyses (CFA) were conducted to evaluate the interplay between physiological systems and underlying multisystem dysregulation. We evaluated convergent criterion validity of a score for multisystem dysregulation against the physical frailty phenotype, and predictive criterion validity with incidence of walking difficulty and mortality. Results: A bifactor CFA, a model in which dysregulation of individual systems proceeds independently of generalized dysregulation, fit data well in WHAS (RMSEA: 0.019; CFI: 0.977; TLI: 0.961) and Health ABC (RMSEA: 0.047; CFI: 0.874; TLI: 0.787). The general dysregulation factor was associated with frailty (OR: 2.2, 95 % CI: 1.4, 3.5), and elevated risk of incident walking difficulty and mortality. Findings were replicated in Health ABC. Discussion: Biomarker data from two epidemiologic studies support the construct of multisystem physiological dysregulation. Results further suggest system-specific and system-wide processes have unique and non-overlapping contributions to dysregulation in biological markers.

Original languageEnglish (US)
Article number111258
JournalMechanisms of Ageing and Development
StatePublished - Jun 2020


  • Biomarkers
  • Frailty
  • Psychometrics

ASJC Scopus subject areas

  • Aging
  • Developmental Biology


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