Longitudinal Analysis of the Retina and Choroid in Cognitively Normal Individuals at Higher Genetic Risk of Alzheimer Disease

Ophthalmol Retina. 2022 Jul;6(7):607-619. doi: 10.1016/j.oret.2022.03.001. Epub 2022 Mar 11.

Abstract

Purpose: To assess the baseline differences and longitudinal rate of change in retinal and choroidal imaging parameters between apolipoprotein ε4 (APOE ε4) carriers and noncarriers with normal cognition.

Design: Prospective study.

Subjects: Four hundred thirteen eyes of 218 individuals with normal cognition aged ≥ 55 years with known APOE status (98 APOE ε4 carriers and 120 noncarriers). The exclusion criteria included diabetes mellitus, uncontrolled hypertension, glaucoma, and vitreoretinal or neurodegenerative disease.

Methods: OCT and OCT angiography (OCTA) were performed at baseline and 2 years (Zeiss Cirrus HD-OCT 5000 with AngioPlex; Zeiss Meditec). The groups were compared using sex- and age-adjusted generalized estimating equations.

Main outcome measures: OCT parameters: retinal nerve fiber layer thickness, macular ganglion cell-inner plexiform layer thickness, central subfield thickness (CST), and choroidal vascularity index. OCT angiography parameters: foveal avascular zone area, perfusion density (PD), vessel density, peripapillary capillary PD (CPD), and capillary flux index (CFI). The rate of change per year was calculated.

Results: At the baseline, the APOE ε4 carriers had lower CST (P = 0.018), PD in the 6-mm ETDRS circle (P = 0.049), and temporal CFI (P = 0.047). Seventy-one APOE ε4 carriers and 78 noncarriers returned at 2 years; at follow-up, the 6-mm ETDRS circle (P = 0.05) and outer ring (P = 0.049) showed lower PD in the APOE ε4 carriers, with no differences in the rates of change between the groups (all P > 0.05).

Conclusions: There was exploratory evidence of differences in the CST, PD, and peripapillary CFI between the APOE ε4 carriers and noncarriers with normal cognition. Larger and longer-term studies may help further elucidate the potential prognostic value of these findings.

Keywords: Apoliporroteinε4; Imaging; OCT; OCTA; Preclinical Alzheimer disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / genetics
  • Apolipoprotein E4 / genetics
  • Choroid
  • Humans
  • Neurodegenerative Diseases*
  • Prospective Studies
  • Retina / diagnostic imaging

Substances

  • Apolipoprotein E4