Physical frailty is an age-associated syndrome of decreased reserve leading to vulnerability to physiological stressors and associated with negative outcomes. The underlying structural brain abnormalities of physical frailty are unclear. We investigated the association between brain volume, cortical brain infarcts, and physical frailty. In this multicenter study, 214 nondemented participants were classified as frail (n = 32), prefrail (n = 107), or nonfrail (n = 75) based on the Fried frailty phenotype. The associations between frailty and brain volumes and cortical brain infarcts were investigated by linear or logistic regression analyses. Participants in the frail group showed a lower total brain volume (-19.67 mL [95% confidence interval -37.84 to -1.50]) and lower gray matter volume (-12.19 mL [95% confidence interval -23.84 to -0.54]) compared to nonfrail participants. Frailty was associated with cortical brain infarcts [frail 16% [n = 5], prefrail 11% [n = 12], and nonfrail 3% [n = 2]). Reduced total brain volume and gray matter volume and increased cortical brain infarcts seem therefore to be part of the structural substrate of the physical frailty phenotype.

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