Association of the prefrailty with global brain atrophy and white matter lesions among cognitively unimpaired older adults: the Nakajima study

Physical frailty has been associated with adverse outcomes such as dementia. However, the underlying structural brain abnormalities of physical frailty are unclear. We investigated the relationship between physical frailty and structural brain abnormalities in 670 cognitively unimpaired individuals (mean age 70.1 years). Total brain volume (TBV), hippocampal volume (HV), total white matter hypointensities volume (WMHV), and estimated total intracranial volume (eTIV) on the 3D T1-weighted images were automatically computed using FreeSurfer software. Participants were divided into two states of physical frailty (robust vs. prefrail) based on the revised Japanese version of the Cardiovascular Health Study criteria. The multivariable-adjusted mean values of the TBV-to-eTIV ratio was significantly decreased, whereas that of the WMHV-to-eTIV ratio was significantly increased in the prefrail group compared with the robust group. Slowness, one of the components of physical frailty, was significantly associated with reduced TBV-to-eTIV and HV-to-eTIV ratios, and slowness and weakness were significantly associated with an increased WMHV-to-eTIV ratio. Our results suggest that the prefrail state is significantly associated with global brain atrophy and white matter hypointensities. Furthermore, slowness was significantly associated with hippocampal atrophy.