Relationship Between Physical Frailty and Low‐Grade Inflammation in Late‐Life Depression

Objectives To determine whether physical frailty is associated with low‐grade inflammation in older adults with depression, because late‐life depression is associated with physical frailty and low‐grade inflammation. Design Baseline data of a cohort study. Setting Primary care and specialized mental health care. Participants Individuals aged 60 and older with depression according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition , criteria (N = 366). Measurements The physical frailty phenotype, defined as three out of five criteria (weight loss, weakness, exhaustion, slowness, low physical activity level), and three inflammatory markers (C‐reactive protein ( CRP ), interleukin‐6 ( IL ‐6), and neutrophil gelatinase–associated lipocalin ( NGAL )) were assessed. Results The physical frailty phenotype was not associated with inflammatory markers in linear regression models adjusted for sociodemographic characteristics, lifestyle characteristics, and somatic morbidity. Of the individual criteria, handgrip strength was associated with CRP ( β  = −0.21, P  = .002) and IL ‐6 ( β  = −0.25, P  < .001), and gait speed was associated with NGAL ( β  = 0.15, P  = .02). Principal component analysis identified two dimensions within the physical frailty phenotype: performance‐based physical frailty (encompassing gait speed, handgrip strength, and low physical activity) and vitality‐based physical frailty (encompassing weight loss and exhaustion). Only performance‐based physical frailty was associated with higher levels of inflammatory markers ( CRP : β  = 0.14, P  = .03; IL ‐6: β  = 0.13, P  = .06; NGAL : β  = 0.14, P  = .03). Conclusion The physical frailty phenotype is not a unidimensional construct in individuals with depression. Only performance‐based physical frailty is associated with low‐grade inflammation in late‐life depression, which might point to a specific depressive subtype.