Outer Retinal Thickness is Associated with Cognitive Function in Normal Aging to Intermediate Age-related Macular Degeneration (AMD)

Abstract

Purpose : Research on Alzheimer’s disease (AD), mild cognitive impairment, and pre-clinical AD has demonstrated a thinner retinal nerve fiber layer (NFL) as compared to age-similar controls. Because AD and AMD both impact older adults, a question is whether this is true for persons with AMD. In a cross-sectional study in persons on the AMD trajectory up to intermediate AMD, we examined associations between retinal thickness using spectral domain optical coherence tomography (OCT) and cognition.

Methods : Persons ≥70 years were recruited from UAB Ophthalmology and Visual Sciences and classified as normal aging, early AMD, and intermediate AMD using the AREDS 9-step system for color fundus photography. Cognitive status was assessed by the NIH Toolbox® cognitive battery generating uncorrected and age-corrected scores for fluid and crystallized cognition. We acquired OCT volumes (Spectralis HRA+OCT). An 11-line segmentation in the HEYEX software was exported in .xml format for review; adjustment was performed by a trained operator with HEYEX. Thicknesses were combined to reflect the vertical organization of retinal neurons and two vascular watersheds: NFL, GC complex (GCL-IPL), inner retina (NFL + GCL + IPL + INL), outer retina (OPLtoELM, ELMtoPR1 + PR1toRPE + RPEtoBrM), Retina (Inner Retina + Outer Retina). Thicknesses were combined in an area-weighted manner to achieve mean thickness across the 6-mm-diameter ETDRS grid. Spearman partial correlations estimated associations between cognitive scores and retinal thickness variables adjusting for age.

Results : From 63 persons with 21 per group of normal aging, early AMD, and intermediate AMD, thinning of the outer retina significantly correlated with lower cognition scores (p<0.05). Of note, no other retinal thickness variables were associated with cognition scores.

Conclusions : Only outer retina thickness, i.e. photoreceptors and supporting glia and retinal pigment epithelium, is associated with cognition in the aging to intermediate AMD transition, and not the NFL as previously reported for AD-associated conditions. Early and intermediate AMD constitute a retinal disease whose earliest and primary impact is in outer retinal cells and their supporting microvasculature. Our finding hints at a unique impact on brain from outer retina in persons with AMD.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Age-adjusted correlations: cognition and retinal thickness