The Association of APOE ε4 Allele with Retinal Layer Thickness and Microvasculature in Older Adults: Optic Nerve Decline and Cognitive Change Study

Abstract

Purpose: To investigate the relationship between the apolipoprotein E (APOE) ε4 allele and retinal structural and vascular characteristics in older adult participants from several research studies. We also studied the relationship between these structural and vascular characteristics with multifocal visual evoked potential (mfVEP) indices, neuropsychological parameters and MRI brain volumes in these participants. Methods: In this study, 109 participants with a mean (SD) age of 67.1 (9.0) years were recruited. Participants were classified as APOE ε4 carriers or non-carriers based on the presence or absence of the ε4 allele. Baseline measurements included peripapillary retinal nerve fibre layer optical coherence tomography (RNFL OCT), and OCT–angiography (OCT-A) for evaluation of the retinal layer thickness and vessel density (VD) parameters. A multifocal visual evoked potential (mfVEP) test, including amplitude and latency, was used to assess the visual pathway function. Finally, cognitive function was evaluated using a battery of neuropsychological tests. OCT-A images were analysed in ImageJ to quantify VD in the superficial and deep vascular plexus and the size of the foveal avascular zone (FAZ). The relationship between carriers of APOE ε4 allele and these ocular parameters was analysed using generalised estimating equation (GEE) models and data adjusted for age, sex and inter-eye differences as within-subject variables (p < 0.05). Results: Twenty-four participants were APOE ε4 carriers. Temporal RNFL thickness was decreased in APOE ε4 carriers (p < 0.01). Vessel density between carriers and non-carriers was not significantly different at either the superficial or deep level. The FAZ area was significantly smaller in ε4 carriers in both superficial (p < 0.01) and deep layers (p < 0.003). Conclusions: Retinal abnormalities were present in participants with increased genetic risk of dementia due to presence of the ε4 allele. These findings provide preliminary evidence for their potential role in the diagnosis of dementia.

Brain-Derived Neurotrophic Factor Val66Met is Associated with Variation in Cortical Structure in Healthy Aging Subjects

“…All subjects underwent optical coherence tomography (OCT) peripapillary circular scans at approximately 3.4 mm diameter for retinal nerve fibre layer (RNFL) thickness measures and macular posterior pole scan for ganglion cell-inner plexiform layer (GCIPL) thickness (Spectralis HRA + OCT; Heidelberg Engineering, Heidelberg, Germany, Version 4.0) [27]. Scans with a quality score of <15 were excluded from the analysis as recommended by the Heidelberg guideline.…”

“…Scans were assessed and automatic segmentation of the RNFL, GCL and IPL were reviewed by two assessors (TS and SS) for OCT and by (AS and DS) for OCTA, and poor-quality images or those with artefacts were excluded from statistical analysis. An internal 6 × 6 grid was analysed from the posterior pole macular thickness map, as described previously [27,28]. The vessel density (VD) and vascular feature analyses were conducted utilising ImageJ software (National Institutes of Health, available at https://imagej.net/Fiji/Downloads) with a method adapted from Elfarnawany et al [21,29,30].…”