Thinning of outer retina is associated with decreased hippocampal volume and cortical thinning in Alzheimer’s disease related areas

Abstract

Purpose : Retinal nerve fiber layer (RNFL) thinning is a potential biomarker of Alzheimer’s disease (AD) and related dementias. The purpose of this study is to explore associations of brain atrophy with retinal layer assessments in the Alabama Study on Early Macular Degeneration supplement cohort.

Methods : Participants with early, and intermediate age-related macular degeneration (AMD) and controls underwent retinal and brain imaging. Retinal measures included optical coherence tomography (OCT)-based layer thickness measures (RNFL, ganglion cell layer, inner retina, outer retina, and total retina) in each of three Early Treatment of Diabetic Retinopathy Study (ETDRS) subfields. MRI measures included total volume of brain, cortex, cortical white matter, gray matter, and hippocampus, occipital cortical thickness, and combined cortical thickness of AD-affected areas. Linear regression was used to evaluate associations between retinal variables and brain measures adjusting for age, sex, and education level. LASSO regression was used to identify the most relevant retinal measures at each subfield for each MRI measure. Cross-validation was used to select the penalty parameter that led to the best model.

Results : Sixty-two subjects (26% male) aged 70 to 87 were included (Table 1). No retinal thickness measures were associated with brain, cortex, white matter, or gray matter volume. Significantly smaller hippocampus (β=0.02, p=0.013) and thinner cortex in the AD-affected areas (β=4.51, p=0.00089) were associated with thinner outer retina. Significant positive associations were observed between total retina thickness and occipital cortical thickness (β=1.89, p=0.037) and thickness of AD-related cortical regions (β=2.37, p=0.0077). Outer retinal thickness in the outer ETDRS ring was the most frequently reported retinal variable in LASSO regression (Table 2).

Conclusions : We observed associations between outer retina thinning and both hippocampal volume loss and cortical thinning in AD-related brain regions. Further studies are needed to validate whether the outer retina in AMD may serve as a potential biomarker for brain atrophy and clinical monitoring of dementia.

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

 

Table 1. Demographics and descriptive of MRI brain and OCT measures

 

Table 2. The estimated coefficients for LASSO model with the optimal penalty between brain assessments and retinal layer thickness by ETDRS subfields