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Updated: Dec 5, 2025

Frailty Assessment in an Aging Mouse Model
Published on: September 23, 2025
Physical Frailty Phenotype Criteria and Their Synergistic Association on Cognitive Functioning
Nadia M Chu1,2, Karen Bandeen-Roche3,4, Qian-Li Xue3,5
1Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Background:
Frailty (physical frailty phenotype [PFP]) and its criteria (slow gait, weakness, weight loss, low activity, and exhaustion) are each associated with cognitive dysfunction. The extent to which the PFP is associated with cognition beyond that expected from its component parts remains uncertain.
Method:
We used the National Health and Aging Trends Study to quantify associations between PFP criteria and cognitive performance (level/change) using adjusted mixed effects models. We tested whether frailty was associated with excess cognitive vulnerability (synergistic/excess effects, Cohen's d) beyond criteria contributions by assessing interactions between each criterion and frailty.
Results:
Among 7439 community-dwelling older adults (mean age = 75.2 years) followed for a mean of 3.2 years (SE = 0.03), 14.1% were frail. The PFP and PFP criteria were all associated with lower baseline cognitive performance, among which slow gait (-0.31 SD, SE = 0.02) and frailty (-0.23 SD, SE = 0.02) were strongest. Only slow gait (-0.03 SD/year, SE = 0.01), frailty (-0.02 SD/year, SE = 0.01), weight loss (-0.02 SD/year, SE = 0.01), and weakness (-0.02 SD/year, SE = 0.01) were associated with cognitive decline. Frailty was associated with cognitive performance above and beyond each criterion (excess effects ranging from -0.07 SD [SE = -0.05] for slow gait to -0.23 SD [SE = 0.03] for weakness); the same was not true for cognitive decline. Slow gait was the only criterion associated with cognitive change among both frail and nonfrail participants (frail: Cohen's d/year = -0.03, SE = 0.01; nonfrail: Cohen's d/year = -0.02, SE = 0.01).
Conclusions:
PFP is an important frailty measure that is cross-sectionally associated with lower cognitive performance, but not with subsequent cognitive decline, above and beyond its criteria contributions. Further research into the construct of frailty as a "syndrome" correlated with cognition and other adverse outcomes is needed.
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