Bermudez Camilo, Lesnick Timothy G, More Swati S, Ramanan Vijay K, Knopman David S, Rabinstein Alejandro A, Cogswell Petrice M, Jack Clifford R, Vemuri Prashanthi, Petersen Ronald C, Graff-Radford Jonathan, Chen John J
Department of Neurology (CB, VKR, DSK, AAR, RCP, JG-R, JJC), Mayo Clinic, Rochester, Minnesota; Center for Drug Design (SSM), College of Pharmacy, University of Minnesota, Minneapolis, Minnesota; Departments of Radiology (PMC, CRJ, PV) and Ophthalmology (JJC), Mayo Clinic, Rochester, Minnesota; and Department of Quantitative Health Sciences (TGL), Mayo Clinic, Rochester, Minnesota.
J Neuroophthalmol. 2025 Mar 1;45(1):63-70. doi: 10.1097/WNO.0000000000002230. Epub 2024 Aug 1.
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.
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.
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.
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.
阿尔茨海默病（AD）和其他痴呆症与血管变化和淀粉样蛋白沉积有关，这可能表现为视网膜毛细血管密度的变化。这些变化可通过光学相干断层扫描血管造影（OCTA）直接可视化和量化，使OCTA成为小血管疾病和淀粉样蛋白阳性的潜在非侵入性临床前生物标志物。我们的目的是研究视网膜成像指标作为大脑中小血管疾病和淀粉样蛋白阳性的非侵入性生物标志物的可行性。
我们在梅奥诊所衰老与阿尔茨海默病研究中心的41名无痴呆症参与者中，研究了OCTA与神经影像学及认知指标之间的关联。OCTA指标包括中央凹、旁中央凹和黄斑的浅层、深层及全视网膜毛细血管密度，以及中央凹无血管区（FAZ）的面积。神经影像学指标包括高负担的白质高信号（WMH）、脑微出血（CMB）的存在、腔隙性梗死，以及正电子发射断层扫描（PET）显示的淀粉样蛋白阳性，而认知指标包括简易精神状态检查（MMSE）评分。我们进行了广义估计方程分析，以考虑每只眼睛的测量数据，同时控制年龄和性别，以估计OCTA指标与神经影像学及认知评分之间的关联。
OCTA与神经影像学指标之间的关联仅限于中央凹。OCTA显示，中央凹浅层（P = 0.003）、深层（P = 0.004）和全视网膜（P = 0.01）的毛细血管密度随着WMH高负担而降低，但旁中央凹或整个黄斑区未出现这种情况。同样，淀粉样蛋白PET阳性的参与者中央凹浅层（P = 0.027）和深层（P = 0.03）的毛细血管密度显著降低，但旁中央凹浅层的密度较高（P = 0.038）。淀粉样蛋白PET阳性的参与者的FAZ也显著更大（P = 0.031），而WMH负担高的参与者之间的差异未达到统计学显著性（P = 0.075）。MMSE与中央凹内全视网膜（P = 0.037）和旁中央凹浅层（P = 0.046）的毛细血管密度之间也存在正相关。未发现OCTA指标与CMB的存在或腔隙性梗死的存在之间存在关联。
中央凹较低的毛细血管密度与脑WMH和淀粉样蛋白阳性之间的关联表明，有必要进一步研究以评估小血管疾病和AD病理之间疾病的共同机制。
