To investigate the utility of retinal imaging with optical coherence tomography angiography (OCTA) metrics as noninvasive biomarkers of small vessel disease and amyloid burden in the brain.

OCTA allows visualization and density measurements of the capillaries at various levels of the retina. Vascular changes and amyloid deposition associated with Alzheimer’s Disease (AD) and other dementias may be reflected as density changes in the retinal capillaries, making OCTA a noninvasive preclinical biomarker of small vessel disease and dementia.

We investigated associations between OCTA and neuroimaging metrics in 47 cognitively unimpaired participants from the Mayo Clinic Study of Aging. OCTA metrics were used as predictors and included superficial and deep capillary density of the fovea, parafovea, and macula as well as the foveal avascular zone (FAZ) area from both eyes. Neuroimaging metrics included a high burden of white matter hyperintensity (WMH), presence of cerebral microbleeds, presence of lacunar infarcts, and the presence of amyloid deposition as evidenced on positron emission tomography (PET).  We used linear models to test associations between OCT predictors and neuroimaging outcomes while controlling for age and sex.

Associations between neuroimaging metrics were restricted to the fovea, showing decreased capillary density with increased burden of WMH in both the superficial (p = 0.014) and deep (p = 0.013) fovea but not the parafovea or whole macula. Similarly, participants with amyloid deposition had decreased capillary density in the superficial (p=0.012) and deep (p = 0.015) fovea but not the parafovea or macula. Participants with amyloid deposition also had a significantly larger FAZ (p = 0.029). No associations were found between OCT metrics and presence of cerebral microbleeds or presence of lacunar infarcts.

The foveal capillary density associations observed suggest a possible common mechanism of disease between small vessel disease and Alzheimer’s disease pathologies.