Impact of neurovascular coupling and glymphatic function on cognitive function in asymptomatic cerebral small vessel disease.

INTRODUCTION: Cognitive impairment ties to neurovascular coupling (NVC) dysfunction, which may interact with the glymphatic pathway. This study examined the relationships between NVC, glymphatic clearance, and cognitive function in asymptomatic cerebral small vessel disease (CSVD). METHODS: In 231 asymptomatic CSVD patients, whole-brain NVC was assessed via voxel-wise ratios of cerebral blood flow to fractional amplitude of low-frequency fluctuations (CBF/fALFF) and spatial correlation; glymphatic function via the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index. Partial correlation, linear regression (with covariates), and mediation analyses were used to explore associations with cognitive function. RESULTS: CBF/fALFF ratio in precuneus and bilateral angular gyrus linked to DTI-ALPS index. Precuneus CBF/fALFF ratio correlated positively with episodic memory; CBF/fALFF correlation coefficients associated with executive function. DTI-ALPS index mediated the latter association (adjusted for demographics, vascular risks, and CSVD neuroimaging markers). DISCUSSION: NVC may be a potential biomarker for cognitive dysfunction in asymptomatic CSVD. Optimizing NVC and glymphatic function could help prevent cognitive impairment in asymptomatic CSVD.