White Matter Free Water is a Composite Marker of Cerebral Small Vessel Degeneration

To investigate the association between white matter free water (FW) and common imaging markers of cerebral small vessel diseases (CSVD) in two groups of subjects with different clinical status. One hundred and forty-four community subjects (mean age 60.5) and 84 CSVD subjects (mean age 61.2) were retrospectively included in the present study. All subjects received multi-modal magnetic resonance imaging and clinical assessments. The association between white matter FW and common CSVD imaging markers, including white matter hyperintensities (WMH), dilated perivascular space (PVS), lacunes, and microbleeds, were assessed using simple and multiple regression analysis. The association between FW and cognitive scores were also investigated. White matter FW was positively associated with WMH volume (β = 0.270, p = 0.001), PVS volume (β = 0.290, p < 0.001), number of microbleeds (β = 0.148, p = 0.043), and age (β = 0.170, p = 0.036) in the community cohort. In the CSVD cohort, FW was positively associated with WMH volume (β = 0.648, p < 0.001), PVS score (β = 0.224, p < 0.001), number of lacunes (β = 0.140, p = 0.046), and sex (β = 0.125, p = 0.036). The associations between FW and cognitive scores were stronger than conventional CSVD markers in both datasets. White matter FW is a potential composite marker that can sensitively detect cerebral small vessel degeneration and also reflect cognitive impairments.