Glymphatic-mediated Pathway Pinking Neurovascular Dysfunction to Cognitive-sleep Impairment in Cerebral Small Vessel...

Cerebral small vessel disease (CSVD) is a major contributor to vascular cognitive impairment, with respective changes in neurovascular coupling (NVC) and glymphatic function, but the association between them has not been illustrated. This study aimed to investigate the relationship between NVC and glymphatic function in patients with CSVD coexisting cognitive impairment.

We prospectively enrolled 78 patients with CSVD with cognitive impairment (CSVD-CI) and 57 with normal cognition (CSVD-NC). NVC metrics were assessed by calculating correlation coefficients and ratios between cerebral blood flow (CBF) and voxel-wise concordance (VWC) maps. Glymphatic function was evaluated using the diffusion tensor image along the perivascular space (DTI-ALPS) index, choroid plexus volume (CPV), and perivascular space (PVS) volume fraction. Partial correlation and mediation analyses were performed to investigate the relationships among imaging metrics and clinical parameters.

Patients with CSVD-CI exhibited reduced global NVC coefficients and lower CBF/VWC ratios in multiple cortical regions, including the left inferior frontal gyrus, paracentral lobule, inferior temporal gyrus, middle occipital gyrus, and middle temporal gyrus. The ALPS-index was significantly lower in CSVD-CI compared to CSVD-NC, while PVS volume fraction and CPV were increased. ROC analyses demonstrated that the NVC and glymphatic function metrics effectively distinguished between patients with CSVD-CI and CSVD-NC. Mediation analysis revealed that the ALPS-index significantly mediated the relationship between NVC metrics and cognitive function and sleep.

Our findings suggest that NVC leading to glymphatic dysfunction may underlie the mechanisms responsible for the decline in cognitive performance and sleep quality in patients with CSVD.