Optical Coherence Tomography Angiography Retinal Imaging Associations With Burden of Small Vessel Disease and Amyloid Positivity in the Brain

Background: Alzheimer disease (AD) and other dementias are associated with vascular changes and amyloid deposition, which may be reflected as density changes in the retinal capillaries. These changes may can be directly visualized and quantified with optical coherence tomography angiography (OCTA), making OCTA a potential noninvasive preclinical biomarker of small vessel disease and amyloid positivity. Our objective was to investigate the feasibility of retinal imaging metrics as noninvasive biomarkers of small vessel disease and amyloid positivity in the brain. Methods: We investigated associations between OCTA and neuroimaging and cognitive metrics in 41 participants without dementia from the Mayo Clinic Study of Aging and Alzheimer’s Disease Research Center. OCTA metrics included superficial, deep, and full retina capillary density of the fovea, parafovea, and macula as well as the area of the foveal avascular zone (FAZ). Neuroimaging metrics included a high burden of white matter hyperintensity (WMH), presence of cerebral microbleeds (CMB), lacunar infarcts, and amyloid positivity as evidenced on positron emission tomography (PET), whereas cognitive metrics included mini-mental status examination (MMSE) score. We performed generalized estimating equations to account for measurements in each eye while controlling for age and sex to estimate associations between OCTA metrics and neuroimaging and cognitive scores. Results: Associations between OCTA and neuroimaging metrics were restricted to the fovea. OCTA showed decreased capillary density with high burden of WMH in both the superficial ( P = 0.003), deep ( P = 0.004), and full retina ( P = 0.01) in the fovea but not the parafovea or whole macula. Similarly, participants with amyloid PET positivity had significantly decreased capillary density in the superficial fovea ( P = 0.027) and deep fovea ( P = 0.03) but higher density in the superficial parafovea ( P = 0.038). Participants with amyloid PET positivity also had a significantly larger FAZ ( P = 0.031), whereas in those with high WMH burden the difference did not reach statistical significance ( P = 0.075). There was also a positive association between MMSE and capillary density of the full retina within the fovea ( P = 0.037) and in the superficial parafovea ( P = 0.046). No associations were found between OCTA metrics and presence of CMB or presence of lacunar infarcts. Conclusions: The associations of lower foveal capillary density with cerebral WMH and amyloid positivity suggest that further research is warranted to evaluate for shared mechanisms of disease between small vessel disease and AD pathologies.