Distinct ocular microvascular alterations in Alzheimer's disease and cerebral small vessel disease

INTRODUCTION: While both Alzheimer's disease (AD) and cerebral small vessel disease (CSVD) involve vascular dysfunction, the ocular microvascular differences between them remain largely underinvestigated. METHODS: This cross-sectional study included 650 participants (149 AD, 276 CSVD, and 225 cognitively unimpaired individuals). Optical coherence tomography angiography (OCTA) metrics were analyzed to characterize ocular microvascular alterations. RESULTS: CSVD patients exhibited a higher burden of retinal ischemic perivascular lesions (RIPLs) than AD patients (all p < 0.05), whereas AD patients showed reduced choriocapillaris (CC) density (p = 0.031). In the CSVD group, RIPLs were associated with total CSVD score (p = 0.049), while reduced CC density was associated with elevated phosphorylated tau 181 in the AD group (p = 0.001). Machine learning models integrating OCTA metrics effectively differentiated AD from CSVD (area under the curve = 0.86). DISCUSSION: AD and CSVD exhibit distinct ocular microvascular alterations, supporting OCTA-derived measures as potential non-invasive biomarkers. TRIAL REGISTRATION NUMBER: ChiCTR2000041386.