Incidental DWI-Positive Lesions in 2 Cohorts of CAA and CADASIL

BACKGROUND AND OBJECTIVES: Incidental hyperintense lesions on diffusion-weighted imaging (DWI) are suggested as emerging marker of cerebral small vessel disease (SVD). To further determine their role in SVD, we aimed to describe their prevalence on high-resolution DWI in 2 distinct SVD types. Second, in each SVD type, we aimed to assess incidental DWI-positive lesion distribution and associations with clinical variables. METHODS: Data from 2 hospital-based prospective cohorts in the Netherlands and Germany were used, which included patients meeting the modified Boston criteria for probable cerebral amyloid angiopathy (CAA, BIONIC study) and patients with a confirmed diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL, VASCAMY study). In case of a stroke history, patients ≤3 months poststroke were excluded. 3T high-resolution baseline MRIs of patients with probable CAA and baseline, 18-month, and 36-month MRIs of patients with CADASIL were included. All MRI markers were rated following STRIVE-2. Within patient groups, we explored in univariable analyses the association between cardiovascular risk factors and MRI markers and incidental DWI-positive lesions and in multiple regression the association between fluid biomarkers and incidental DWI-positive lesions. RESULTS: Baseline data were available for 43 CAA patients (mean baseline age 71 ± 6 years, 44% female) and 75 CADASIL patients (mean baseline age 53 ± 9.9 years, 62% female). Cross-sectionally, incidental DWI-positive lesions were detected in 24/43 (56% [95% CI 41%-70%]) CAA patients and 16/75 (21% [95% CI 14%-32%]) CADASIL patients. In CAA, 65% of lesions were located in the cortex, whereas in CADASIL, 95% of lesions were located in the subcortical white or gray matter. In CAA patients, DWI-positive lesions were significantly associated with increased neurofilament light chain (NfL) in serum and CSF, but not with other CSF, MRI, or cardiovascular risk factors. In CADASIL patients, DWI-positive lesions were significantly associated with increased serum NfL, increased white matter hyperintensity volume and lacune presence. DISCUSSION: In CAA and CADASIL, the prevalence of incidental DWI-positive lesions is high, and lesions have disease-specific distribution, and associations with serum, CSF, and MRI biomarkers, suggesting that incidental DWI-positive lesions are a feature of SVD. Future studies should investigate their prognostic value.