Free water changes and their correlations with multimodal biomarkers in frontotemporal dementia.

INTRODUCTION

The alterations of free water (FW) in behavioral variant frontotemporal dementia (bvFTD) and its clinical correlations remain unclear.

METHODS

FW levels in the whole brain and specific white matter fiber tract was evaluated in 112 bvFTD patients and 103 normal controls.

RESULTS

BvFTD patients exhibited elevated FW in the whole brain and regional white matter tracts, especially in the uncinate fasciculus and cingulum hippocampus. FW was correlated with perivascular spaces (PVSs) and diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index. FW was also correlated with clinical scales, gray matter volume, and glucose metabolism. Additionally, FW was correlated with plasma glial fibrillary acidic protein and total tau. Mediation analyses showed that FW mediated the association between PVS and ALPS, and brain neurodegeneration mediated the association between FW and clinical scores.

DISCUSSION: Elevated FW is involved in bvFTD and contributes to glymphatic dysfunction and neurodegeneration.