AD and CSVD exhibit distinct ocular microvascular alterations, supporting OCTA-derived measures as potential non-invasive biomarkers for differentiating these two conditions.
CSVD patients exhibited a higher burden of retinal ischemic perivascular lesions (RIPLs) compared to AD patients.
AD patients showed reduced choriocapillaris (CC) density compared to other groups.
In the CSVD group, RIPLs were associated with total CSVD score, indicating a relationship between retinal and cerebral small vessel pathology.
Reduced choriocapillaris density in the AD group was associated with elevated phosphorylated tau 181 levels.
Machine learning models integrating OCTA metrics effectively differentiated AD from CSVD with an area under the curve of 0.86.
Both AD and CSVD involve vascular dysfunction, but the ocular microvascular alterations differ distinctly between the two conditions.
This research suggests that two brain diseases — Alzheimer's disease (AD) and cerebral small vessel disease (CSVD) — leave different fingerprints in the blood vessels of the eye, which can be detected using a non-invasive imaging technology called optical coherence tomography angiography (OCTA). In a study of 650 people (149 with AD, 276 with CSVD, and 225 without cognitive impairment), researchers found that patients with CSVD had more retinal lesions caused by poor blood flow (called retinal ischemic perivascular lesions), while patients with AD had reduced density of the tiny blood vessels beneath the retina (called the choriocapillaris). These differences were linked to known disease markers: the retinal lesions in CSVD correlated with overall disease severity in the brain, and the reduced choriocapillaris density in AD was linked to higher levels of phosphorylated tau, a protein associated with Alzheimer's pathology. Using these eye-based measurements in a machine learning model, researchers were able to distinguish between AD and CSVD with an accuracy reflected by an area under the curve of 0.86, which indicates good performance. This matters because AD and CSVD can be difficult to tell apart clinically, yet they may require different treatments. Currently, distinguishing between them often requires expensive or invasive tests. This research suggests that eye imaging with OCTA could serve as a practical, non-invasive tool to help differentiate AD from CSVD. Because the eye shares biological origins with the brain, changes in retinal blood vessels may provide a window into what is happening in the brain. If confirmed in larger studies, this approach could make diagnosis faster, cheaper, and less burdensome for patients.
Zhang Z, Cao L, Liu P, Yang S, Yan Y, Kwapong W, et al.. (2026). Distinct ocular microvascular alterations in Alzheimer's disease and cerebral small vessel disease.. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.71809