Retinal Microvascular and Neurodegenerative Changes in Alzheimer’s Disease and Mild Cognitive Impairment Compared with Control Participants

Published:March 11, 2019DOI:


      Evaluate and compare the retinal microvasculature in the superficial capillary plexus (SCP) in Alzheimer’s disease (AD), mild cognitive impairment (MCI), and cognitively intact controls using OCT angiography. OCT parameters were also compared.


      Cross-sectional study.


      Seventy eyes from 39 AD participants, 72 eyes from 37 MCI participants, and 254 eyes from 133 control participants were enrolled.


      Participants were imaged using Zeiss Cirrus HD-5000 with AngioPlex (Carl Zeiss Meditec, Dublin, CA) and underwent cognitive evaluation with Mini-Mental State Examination.

      Main Outcome Measures

      Vessel density (VD) and perfusion density (PD) in the SCP within the Early Treatment Diabetic Retinopathy Study 6-mm circle, 3-mm circle, and 3-mm ring were compared between groups. Foveal avascular zone (FAZ) area, central subfield thickness (CST), macular ganglion cell-inner plexiform layer (GC-IPL) thickness, and peripapillary retinal nerve fiber layer (RNFL) thickness were also compared.


      Alzheimer’s participants showed significantly decreased SCP VD and PD in the 3-mm ring (P = 0.001 and P = 0.002, respectively) and 3-mm circle (P = 0.003 and P = 0.004, respectively) and decreased SCP VD in the 6-mm circle (P = 0.047) compared with MCI and significantly decreased SCP VD and PD in the 3-mm ring (P = 0.008 and P = 0.004, respectively) and 3-mm circle (P = 0.015 and P = 0.009, respectively) and SCP PD in the 6-mm circle (P = 0.033) when compared with cognitively intact controls. There was no difference in SCP VD or PD between MCI and controls (P > 0.05). FAZ area and CST did not differ significantly between groups (P > 0.05). Alzheimer’s participants showed significantly decreased GC-IPL thickness over the inferior (P = 0.032) and inferonasal (P = 0.025) sectors compared with MCI and significantly decreased GC-IPL thickness over the entire (P = 0.012), superonasal (P = 0.041), inferior (P = 0.004), and inferonasal (P = 0.006) sectors compared to controls. MCI participants showed significantly decreased temporal RNFL thickness (P = 0.04) compared with controls.


      Alzheimer’s participants showed significantly reduced macular VD, PD, and GC-IPL thickness compared with MCI and controls. Changes in the retinal microvasculature may mirror small vessel cerebrovascular changes in AD.

      Abbreviations and Acronyms:

      AD (Alzheimer’s disease), CST (central subfield thickness), ETDRS (Early Treatment Diabetic Retinopathy Study), FAZ (foveal avascular zone), GC-IPL (ganglion cell–inner plexiform layer), logMAR (logarithm of the minimum angle of resolution), MCI (mild cognitive impairment), MMSE (Mini-Mental State Examination), OCTA (OCT angiography), PD (perfusion density), PET (positron emission tomography), RNFL (retinal nerve fiber layer), SCP (superficial capillary plexus), VD (vessel density)
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