Abstract
BACKGROUND: Impaired cerebrospinal fluid (CSF) dynamics may affect brain health in older adults and contribute to age-related changes in brain structure. Disproportionately enlarged subarachnoid-space hydrocephalus (DESH) is a neuroimaging finding associated with impaired CSF dynamics. However, the association between frailty-a condition characterised by increased vulnerability in late life-and DESH-related CSF space volumes remains poorly understood. Therefore, in this study, we aimed to investigate this association. METHODS: This cross-sectional study was conducted using data from 1,395 community-dwelling Japanese adults aged ≥ 65 years without dementia. Frailty was assessed using the Japanese version of the Fried criteria, comprising slowness, weakness, low activity, shrinking, and exhaustion. Volumes of regions of interest (ROIs) were measured by magnetic resonance imaging, and DESH-related regions (ventricular system [VS], Sylvian fissures [SF], and the subarachnoid space at the high convexity and midline [SHM]) were quantified using voxel-based morphometry. RESULTS: Ordinal logistic regression analysis was conducted with frailty status (robust [reference], prefrail, or frail) as the dependent variable and each ROI volume as independent variables. The results showed positive associations of VS volume (odds ratio [OR] 1.21; 95% confidence interval [CI] 1.06-1.37) and SF volume (OR 1.81, 95% CI 1.09-3.02) with frailty, whereas SHM volume was negatively associated (OR 0.84, 95% CI 0.72-0.97). Logistic regression analyses of each frailty component and ROIs showed that slowness (slow gait speed) was consistently associated with all three DESH-related regions (false-discovery rate-adjusted q < 0.05). CONCLUSIONS: DESH-related CSF space volumes, reflecting impaired CSF dynamics, were significantly associated with frailty in community-dwelling older adults. These findings highlight the potential role of CSF dynamics as a neural mechanism underlying frailty and suggest a novel target for preventive strategies.