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. 2025;71(7):564-575.
doi: 10.1159/000546250. Epub 2025 May 5.

Decoding Precision Aging: The Intersection of Cognitive Decline, Frailty, and Hormonal Biomarkers

J Ray Runyon  1   2 , Mohammad Dehghan Rouzi  3 , Myeounggon Lee  3 , Cole Babbitt  1 , David W Tano  1 , Diezel Cochenour  1 , Esther M Sternberg  1 , Terrill Yuhas  4 , Lisa White  4 , Bijan Najafi  3 , Bonnie J LaFleur  4   5
Affiliations

Decoding Precision Aging: The Intersection of Cognitive Decline, Frailty, and Hormonal Biomarkers

J Ray Runyon et al. Gerontology. 2025.

Abstract

Introduction: Cognitive frailty, characterized by the coexistence of cognitive impairment and physical frailty, is a significant predictor of cognitive decline. However, few studies integrate both cognitive and physical assessments alongside hormonal markers, such as cortisol, that may influence frailty and cognitive function. To address this gap, our study combines noninvasive physical, cognitive, and cortisol markers to assess frailty in aging adults.

Methods: Data were collected from four sites as part of the Healthy Minds for Life (HML) longitudinal cohort, a project within the Precision Aging Network. Baseline data included cognitive evaluation using the Montreal Cognitive Assessment (MoCA); frailty assessment using a validated 20-s elbow flexion-extension test analyzed by AI under single-task (ST) and dual-task (DT) conditions; cortisol measurement in eccrine sweat samples via direct analysis in real-time mass spectrometry (DART-MS); and demographic information.

Results: Of 202 participants completing all assessments, 60 were identified with mild cognitive impairment (MCI). The dual-task frailty index (FI) derived from the 20-s test significantly differentiated individuals with MCI from cognitively robust participants and correlated strongly with MoCA scores (p = 0.015). The dual-task FI showed superior model fit compared to the single-task FI when predicting cognitive function. A significant correlation between the dual-task FI and cortisol by age interaction was observed (p = 0.0042) highlighting the potential impact of cortisol to moderate the relationship between frailty and age in an otherwise healthy aging population. By contrast, no significant correlation was found between dual-task FI and aging outside of the presence of cortisol (p = 0.116) in this study.

Conclusions: This study highlights practical and efficient methods for assessing frailty emphasizing the value of DT testing and cortisol measures in identifying individuals at higher risk for cognitive and physical decline. The findings underscore the importance of integrating hormonal markers with cognitive and physical assessments to enhance risk stratification and intervention planning in aging populations.

Keywords: Cognitive frailty; Digital biomarker; Digital health; Hormonal biomarkers; Precision aging.

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Conflict of interest statement

Conflict of Interest Statement

BN is a co-inventor of a patent owned by the University of Arizona, which may have some overlap with the frailty algorithm described in this study. Additionally, he has served as a consultant for BioSensics LLC on projects unrelated to the specific aims of this study. B.J.L. is a consultant with Linshom, LLC and INanoBio, Inc., neither is related to any PAN related activities. The other authors declare no conflicts of interest relevant to the scope of this study. B.N. was a member of the journal’s Editorial Board at the time of submission

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