The Association of APOE 4 Allele with Retinal Layer Thickness and Microvasculature in Older Adults: Optic Nerve Decline and Cognitive Change Study

Purpose: To investigate the relationship between the apolipoprotein E (APOE) epsilon 4 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 epsilon 4 carriers or non-carriers based on the presence or absence of the epsilon 4 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 epsilon 4 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 epsilon 4 carriers. Temporal RNFL thickness was decreased in APOE epsilon 4 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 epsilon 4 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 epsilon 4 allele. These findings provide preliminary evidence for their potential role in the diagnosis of dementia.