Quantitative Swept-Source Optical Coherence Tomography Angiography Indicators of Neurovascular Dysfunction in Alzheimer Disease

Importance: Alzheimer disease (AD) affects millions globally, but current diagnostic approaches typically can be costly and invasive. Accessible, noninvasive screening tools for early detection of cognitive impairment are needed. Objective: To determine whether optical coherence tomography angiography (OCTA)-based biomarkers of the retina, choroid, and choriocapillaris differ across cognitive states and whether these biomarkers might discriminate among normal cognition, mild cognitive impairment (MCI), and AD dementia. Design, Setting, and Participants: This cross-sectional study enrolled 103 individuals referred from the University of Washington Alzheimer's Disease Research Center (ADRC) between April 2022 and September 2024. Participants included 49 cognitively normal controls, 29 with MCI, and 25 with AD dementia per ADRC research-criteria evaluations. All participants underwent swept-source OCTA (SS-OCTA). These data were analyzed from February 2025 to March 2026. Main Outcomes and Measures: Cognitive status, retinal vessel skeleton density (VSD), choriocapillaris flow deficit (CCFD), and ganglion cell complex (GCC) thickness. Results: Among 103 participants (mean [SD] age, 74.8 [6.72] years; 50 [48.5%] female and 53 male [51.5%]), the adjusted mean GCC was thinner in AD dementia (63.31 μm) vs controls (67.93 μm) (difference, -4.62 μm; 95% CI, -8.92 to -0.31 μm; P = .03). Adjusted mean CCFD was lower in MCI (8.12%) than AD dementia (9.07%) (difference, -0.95%; 95% CI, -1.71 to -0.19; P = .01) but higher in AD dementia than controls (8.33%) (difference, 0.74%; 95% CI, 0.02-1.46; P = .04). In multivariable models, VSD (MCI: odds ratio [OR], 0.79; 95% CI, 0.77-0.81; AD dementia: OR, 0.66; 95% CI, 0.65-0.68; P < .001) and CCFD (MCI: OR, 0.66; 95% CI, 0.65-0.67; AD dementia: OR, 1.50; 95% CI, 1.49-1.52; P < .001) were significantly associated with cognitive status, with an area under the curve of 0.72 to 0.87 in a 21-participant test set (10 controls, 6 MCI, 5 AD dementia). Conclusions and Relevance: In a relatively small cohort study, OCTA revealed distinct microvascular signatures across cognitive stages. VSD decreased, and CCFD showed a biphasic pattern across cognitive stages in multivariable models, which may suggest early compensatory choriocapillaris hyperperfusion followed by perfusion failure in AD dementia. These findings suggest OCTA biomarkers may serve as accessible, noninvasive indicators of cognitive neurodegeneration, warranting larger longitudinal validation.