Distinct characteristics and risk factors of symptomatic and incidental DWI lesions in cerebral amyloid angiopathy

Cerebral amyloid angiopathy (CAA) has long been regarded as a hemorrhagic age-related small vessel disease (SVD). However, cerebral ischemia, indicated by symptomatic and incidental diffusion-weighted imaging (sDWI and iDWI) hyperintensities, remains controversial regarding its clinical relevance and pathological mechanisms. This study aimed to investigate the prevalence, distributing characteristics, and risk factors of sDWI and iDWI lesions in patients with CAA.

Participants meeting the criteria for probable CAA (Boston criteria version 1.5) were recruited from a prospective cohort of cerebral small vessel disease at Peking Union Medical College Hospital between March 2017 and February 2026. Baseline clinical data and neuroimaging markers of SVD were collected. sDWI lesions and iDWI lesions were recorded at any MRI time point, with topography showing via lesion probability maps. Cumulative incidence was estimated using Kaplan-Meier method. The characteristics were compared between patients with sDWI lesions or iDWI lesions and those without any DWI lesion at baseline. The prospective Cox regression analyses were performed to identify risk factors for sDWI lesions and iDWI lesions, respectively.

We enrolled 185 patients with probable CAA, of whom 99 underwent follow-up MRI with a total of 163 scans. sDWI lesions were detected in 29 patients and iDWI lesions in 49 patients. sDWI lesions predominantly involved deep regions (72.7%), whereas iDWI lesions were mainly located in cortical-juxtacortical regions (62.5%). In the prospective analysis, the 3-year cumulative incidence was 9.45% (95% CI: 0.67%-17.46%) for sDWI lesions and 25.74% (95% CI:15.2%-34.97%) for iDWI lesions, respectively. Cox analysis of 99 patients with follow-up MRI identified that the number of traditional vascular risk factors (hypertension, diabetes mellitus, coronary artery disease, and smoking) (HR: 2.968; P = 0.013) and lacunes (HR: 1.187; P = 0.016) were independent predictors for sDWI lesions after adjusting for age, sex. The independent predictive values of iDWI lesions were lacunes (HR: 1.158; P < 0.001), disseminated cSS (HR: 2.994; P = 0.014), and lobar CMB grade (HR: 2.059; P = 0.019), after adjusting for age, sex, number of traditional vascular risk factors, and focal cSS.

Cerebral ischemia was not uncommon in CAA. sDWI and iDWI lesions had distinct topographical distributions and risk factor profiles, suggesting potentially different underlying mechanisms. DWI-positive lesions may provide a useful imaging marker of SVD activity and injury in future longitudinal studies and clinical trials of CAA.