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Updated: Apr 4, 2026

Frailty Assessment in an Aging Mouse Model
Published on: September 23, 2025
Physical frailty in late-life depression is associated with deficits in speed-dependent executive functions
Guy G Potter1, Douglas R McQuoid1, Heather E Whitson2,3
1Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.
Objective:
The aim of this study was to examine the association between physical frailty and neurocognitive performance in late-life depression (LLD).
Methods:
Cross-sectional design using baseline data from a treatment study of late-life depression was used in this study. Individuals aged 60 years and older were diagnosed with major depressive disorder at time of assessment (N = 173). All participants received clinical assessment of depression and completed neuropsychological testing during a depressive episode. Physical frailty was assessed using an adaptation of the FRAIL scale. Neuropsychological domains were derived from a factor analysis that yielded three factors: (i) speeded executive and fluency, (ii) episodic memory, and (iii) working memory. Associations were examined with bivariate tests and multivariate models.
Results:
Depressed individuals with a FRAIL score >1 had worse performance than nonfrail depressed across all three factors; however, speeded executive and fluency was the only factor that remained significant after controlling for depression symptom severity and demographic characteristics.
Conclusions:
Although physical frailty is associated with broad neurocognitive deficits in LLD, it is most robustly associated with deficits in speeded executive functions and verbal fluency. Causal inferences are limited by the cross-sectional design, and future research would benefit from a comparison group of nondepressed older adults with similar levels of frailty. Research is needed to understand the mechanisms underlying associations among depression symptoms, physical frailty, and executive dysfunction and how they are related to the cognitive and symptomatic course of LLD.
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