Subcortical volumes and cognition in CADASIL - A pilot study

Background: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) represents the most common heritable cause of vascular dementia. Subcortical volumes might be proxies of brain reserve capacity and reflective of cognitive function. We explored the impact of subcortical volumes on cognition in CADASIL patients.

Methods: We included 90 patients with pathogenic NOTCH3 variants from the Taiwan Associated Genetic and Nongenetic Small Vessel Disease cohort. They underwent MRI sessions at baseline. The volumes of the putamen, caudate, pallidum, thalamus, cerebellum, cortical gray matter and brain parenchymal fraction (BPF) were calculated by using FreeSurfer. We tested the association of the subcortical volumes, cortical gray matter volume and BPF with scores of the Mini-mental state examination (MMSE), cognitive domains, and the diagnosis of vascular cognitive impairment (VCI) which was defined as MMSE score <24.

Results: The thalamus and putamen were consistently associated with the MMSE (thalamus adjusted beta per SD decrement -1.41 [95 % CI -2.68-(-0.14)], p = 0.03; R²=0.25; putamen -1.93 [95 % CI -2.99-(-0.86)], p < 0.001; R²=0.36) and VCI (thalamus OR per SD-decrement 3.66 [95 % CI 1.38-9.72], p = 0.009), putamen (OR 3.06 [95 % CI 1.21-7.73], p = 0.02). A larger thalamus volume was also associated with better executive function and visuospatial perception. The cortical gray matter volume and the BPF showed associations with various cognitive outcomes in all analyses.

Conclusion: Although cortical gray matter volume and the BPF still appear to be robust markers of cognitive performance in CADASIL, the volumes of the thalamus and the putamen might also be promising regions of interest for future research.