Abstract
Hypertension is the primary risk factor for cerebral small vessel disease (CSVD). However, its mechanistic links are yet to be completely understood. Advancements in diffusion-weighted magnetic resonance imaging (dMRI) increased sensitivity in detecting subtle white matter (WM) structural integrity changes. 44 hypertension patients without symptomatic CSVD underwent multi-modal evaluation of cerebral structure and function, including dMRI, neuropsychological tests and transcranial Doppler monitoring of the right middle cerebral artery (MCA) and left posterior cerebral artery (PCA) to assess neurovascular coupling (NVC). In the PCA, the modeled NVC curve was studied. We examined the cross-sectional relationship of WM integrity with NVC and cognitive performance, using correlational tractography. Diffusion measures from two dMRI models were used: fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity from diffusion tensor imaging, and quantitative anisotropy (QA) and isotropy from q-space diffeomorphic reconstruction. Regarding the NVC in the PCA, vascular elastic properties and initial response speed markers indicated better functional hyperemia with better WM integrity. However, the amplitude suggested increased NVC with worse WM integrity. In the MCA, increased NVC was associated with lower WM integrity. Better cognitive performance associated with preserved WM integrity. Increased functional hyperemia despite worse WM integrity may reflect less efficient NVC in hypertensive patients, potentially arising from (mal)adaptive mechanisms and brain network reorganization in response to CSVD. This observational study highlights the potential of transcranial Doppler and QA as susceptibility markers of pre-symptomatic CSVD.