Retinal microvasculature dysfunction is associated with Alzheimer's disease and mild cognitive impairment

Abstract

Background: The retina and brain share many neuronal and vasculature characteristics. We investigated the retinal microvasculature in Alzheimer's disease (AD) and mild cognitive impairment (MCI) using optical coherence tomography angiography (OCTA).

Methods: In this cross-sectional study, 24 AD participants, 37 MCI participants, and 29 controls were diagnosed according to internationally accepted criteria. OCTA images of the superficial and deep capillary plexus (SCP, DCP) of the retinal microvasculature were obtained using a commercial OCTA system (Zeiss Cirrus HD-5000 with AngioPlex, Carl Zeiss Meditec, Dublin, CA). The main outcome measures were vessel density (VD) and fractal dimension (FD) in the SCP and DCP within a 2.5-mm ring around the fovea which were compared between groups. Perfusion density of large vessels and foveal avascular zone (FAZ) area were additional outcome parameters.

Results: Age, gender, and race did not differ among groups. However, there was a significant difference in diabetes status (P = 0.039) and systolic blood pressure (P = 0.008) among the groups. After adjusting for confounders, AD participants showed significantly decreased VD in SCP and DCP (P = 0.006 and P = 0.015, respectively) and decreased FD in SCP (P = 0.006), compared to controls. MCI participants showed significantly decreased VD and FD only in SCP (P = 0.006 and P < 0.001, respectively) and not the DCP (P > 0.05) compared with controls. There was no difference in the OCTA variables between AD and MCI (P > 0.05). Perfusion density of large vessels and FAZ area did not differ significantly between groups (P > 0.05).

Conclusions and relevance: Eyes of patients with AD have significantly reduced macular VD in both plexuses whereas MCI participants only showed reduction in the superficial plexus. Changes in the retinal microvasculature and capillary network may offer a valuable insight on the brain in AD.

Keywords: Alzheimer’s disease; Mild cognitive impairment; Optical coherence tomography angiography.

Fig. 1

The framework of optical coherence tomography angiography (OCTA) image post-processing. a, b Raw images were extracted from the OCTA machines. c, d The images were binarized to obtain the large vessel densities. e An annulus centered at FAZ center with inner diameter of 1 mm and outer diameter 2.5 mm was generated as a mask to the 3 × 3 mm image. f Larger vessels were automatically detected in the superficial capillary plexus. g, h The FAZs were manually delineated from both plexuses. i, j The vessel densities were calculated in the annulus

Fig. 2

Distribution of a superficial vessel density, b deep vessel density, c superficial fractal dimension, and d deep fractal dimension stratified by participants having with Alzheimer’s disease (AD), mild cognitive impairment (MCI), and controls. Data and P values shown are after adjustment for age, gender, race, diabetes, and blood pressure (systolic and diastolic levels). The asterisk symbol (*) indicates a statistical significance of P < 0.05 when compared to the controls

Fig. 3

Optical coherence tomography angiography (OCTA) images of the superficial (a–c) and deep (g–i) capillary plexuses were extracted from the OCTA machines. d–f, j–l Vessel density maps of the macular annulus region showing retinal microvasculature of participants with Alzheimer’s disease (AD; d, j), mild cognitive impairment (MCI; e, k), and controls (f, l). AD participants showed a decrease in vessel densities in both plexuses compared to controls. MCI participants showed a decrease vessel density only in superficial capillary plexus and not the deep capillary plexus