Multimodal imaging analyses in patients with genetic and sporadic forms of small vessel disease

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is thought to be a pure genetic form of subcortical vascular cognitive impairment (SVCI). The aim of this study was to compare white matter integrity and cortical thickness between typical CADASIL, a genetic form, and two sporadic forms of SVCI (with NOTCH3 and without NOTCH3 variants). We enrolled typical CADASIL patients (N = 11) and SVCI patients [with NOTCH3 variants (N = 15), without NOTCH3 variants (N = 101)]. To adjust the age difference, which reflects the known difference in clinical and radiologic courses between typical CADASIL patients and SVCI patients, we constructed a W-score of measurement for diffusion tensor image and cortical thickness. Typical CADASIL patients showed more frequent white matter hyperintensities in the bilateral posterior temporal region compared to SVCI patients (p < 0.001, uncorrected). We found that SVCI patients, regardless of the presence of NOTCH3 variants, showed significantly greater microstructural alterations (W-score, p < 0.05, FWE-corrected) and cortical thinning (W-score, p < 0.05, FDR-corrected) than typical CADASIL patients. In this study, typical CADASIL and SVCI showed distinct anatomic vulnerabilities in the cortical and subcortical structures. However, there was no difference between SVCI with NOTCH3 variants and SVCI without NOTCH3 variants.

Comparison of Longitudinal Changes of Cerebral Small Vessel Disease Markers and Cognitive Function Between Subcortical Vascular Mild Cognitive Impairment With and Without NOTCH3 Variant: A 5-Year Follow-Up Study

“…However, we previously reported that approximately 13% of consecutive patients with SVCI had NOTCH3 variants, although they were of advanced age and frequently had a history of HTN ( 4 ). In our previous cross-sectional studies, these atypical SVCI patients with NOTCH3 variant have shown no significant differences in clinical and imaging features compared to patients without NOTCH3 variant ( 4 , 5 ). However, cross-sectional comparison, a snapshot of a single moment in time, has interpretative limitations.…”

Genetic Factors of Cerebral Small Vessel Disease and Their Potential Clinical Outcome

“…The third type of lesions were the cerebral microbleeds (CMBs) [39]. Affected brain areas were the thalamus, central semivovale, basal ganglia, temporal lobes or pons [37,40]. The imaging data of a typical CADASIL (A1), the atypical form of CADASIL with (A2) and without genetic mutations (A3), were summarized in Figure 2.…”

“…In adults, NOTCH3 could be essential for the development, remodeling and differentiation of vascular system. A recent study revealed that patients with typical CADASIL with NOTCH3 variants showed distinct anatomic vulnerabilities in both grey and white matter structures [40] (Figure 2).…”

“…SVD were known as complex disorders [1,22,42]. SVD disorders have several subtypes (such as CARASIL, CADASIL, HDLS, Fabry disease), and the exact molecular mechanisms of these diseases remain incompletely understood [1,22,40,42]. Several risk factors that could play a role in SVD have been identified, such as aging, head injury or stroke.…”

“…( B - 1,B - 2 ) Typical CADASIL cases reveal significantly prevalent WMH distribution in the bilateral posterior temporal region compared with SVCI patients with and without NOTCH3 variants. Reprinted with permission from ref [40]. Copyright under a CC BY license (Creative Commons Attribution 4.0 International License).…”