Long-term impact of white matter hyperintensities and amyloid beta on thalamic subregions in cerebral small vessel disease: A prospective cohort study.

INTRODUCTION

Cerebral small vessel disease (CSVD) contributes to cognitive decline, yet the impact of white matter hyperintensity (WMH) distribution and plasma amyloid beta (Aβ) on thalamic subregions remains unclear.

METHODS

In this prospective study, 175 patients with CSVD and matched controls underwent high-resolution magnetic resonance imaging (MRI), plasma biomarker assessment, and cognitive testing. WMHs were segmented and categorized by spatial patterns. Thalamic subregions were parcellated using the THalamus Optimized Multi-Atlas Segmentation (THOMAS) framework. Mixed-effects models evaluated the longitudinal effects of WMH progression and plasma Aβ on thalamic subregional volumes.

RESULTS

CSVD patients exhibited selective atrophy in left medial geniculate nucleus (MGN), mediodorsal-parafascicular (MD-Pf), and lateral geniculate nucleus (LGN), with volumes associated with processing speed and attentional control. Thalamic and basal ganglia WMH burden significantly predicted subregional atrophy. In CSVD, WMH progression dominated longitudinal thalamic degeneration.

DISCUSSION: Distinct WMH spatial patterns and vascular factors drive thalamic subregional atrophy in CSVD, contributing to cognitive decline.

HIGHLIGHTS: Patients with cerebral small vessel disease (CSVD) exhibit selective atrophy in thalamic subregions compared to healthy controls (HCs). Thalamic white matter hyperintensity (WMH) burden strongly predicts mediodorsal-parafascicular and lateral geniculate nucleus atrophy in patients with CSVD. Plasma amyloid beta dynamics differentially influence thalamic integrity in CSVD compared to HCs.