Reduced coupling between the global blood-oxygen-level-dependent signal and cerebrospinal fluid inflow is associated with the severity of small vessel disease

Small vessel disease (SVD) is highly prevalent in the elderly and associated with an increased risk of dementia and stroke. SVD may have disturbed cerebrospinal fluid (CSF) flow, which can compromise waste clearance and accelerate disease progression.We retrospectively included 146 SVD patients from a prospectively collected dataset, with one- or two-year follow-up data in 61 patients. The coupling strength between the global blood-oxygen-level-dependent (gBOLD) signal and CSF inflow was used to reflect CSF dynamics. We performed regression analyses to investigate the association between the gBOLD-CSF coupling index and the severity of SVD and vascular risk factors. Longitudinal analysis was carried out to investigate causal relationships.Patients with severe SVD had significantly decreased gBOLD-CSF coupling (β = -0.180, p = 0.032). Dilation of perivascular spaces in the basal ganglia area (β = -0.172, p = 0.033) and diabetes (β = -0.204, p = 0.014) were associated with reduced gBOLD-CSF coupling. In longitudinal analyses, diabetes was associated with faster decline in gBOLD-CSF coupling (β = 0.20, p = 0.039), while perivascular space (PVS) dilation in the centrum semiovale showed a opposite relationship (β = -0.20, p = 0.041). The gBOLD-CSF coupling could not predict SVD progression.Altered CSF flow is associated with the severity of SVD.