## 4 Discussion
### Comparisons to Previous Literature  
Recent studies that have explored the retinal microvasculature in AD patients have found differences between the FAZ of healthy controls and clinically diagnosed AD patients [11; 35], whilst others have found differences in both the superficial and deeper layers of the FAZ [36]. The APOE \(\varepsilon 4\) allele has also been associated with faster rates of GCIPL (ganglion cell inner plexiform layer) thinning in eyes of normal-tension glaucoma, further solidifying its potential influence across neurodegenerative diseases [37]. With our cohort being comprised of community-dwelling aging participants, the FAZ results should be interpreted with caution. Whilst our results show a decreased FAZ in the carrier cohort, the results are the opposite of what one would expect. We attribute this primarily to statistical chance and the nature of the cohort. The carrier cohort were classified as normal aging participants, with the \(\varepsilon 4\) allele expecting to show features of very early dysfunction. It may be possible that some individuals were at an early preclinical stage of early MCI (mild cognitive impairment). Another possible explanation found to explain this inverse association is the role of subretinal inflammatory changes. These changes, found in an AMD mouse model, have been shown to be isoform-dependent, with the APOE \(\varepsilon 2\) isoform a risk factor and the \(\varepsilon 4\) isoform protective. A growing number of studies have implicated a link between AD and retinal neurodegenerative disease that share several pathological events and risk factors. APOE \(\varepsilon 4\) is the strongest genetic risk factor for AD, whereas APOE \(\varepsilon 2\) is considered a protective factor; however, in retinal neurodegenerative diseases, paradoxically APOE \(\varepsilon 4\) is a protective factor and APOE \(\varepsilon 2\) is a risk factor [38]. Although there are many reports on the effects of APOE isoforms on AD initiation and progression, data about their role in retinal neurodegenerative diseases are limited and further studies are needed to reveal their differential effects on pathogenesis of these diseases. In our dataset, we only found one neuropsychological domain that showed a significant difference between APOE \(\varepsilon 4\) genotypes. A major risk factor for AD is the presence of the APOE \(\varepsilon 4\) allele; however, few studies have simultaneously investigated its role with respect to cognitive decline,specifically logical memory. [PERSON] et al. [39] reported that the presence of the APOE \(\epsilon\)4 allele revealed greater decline in amyloid beta-positive/APOE \(\epsilon\)4\({}^{+}\) participants, with minimal decline in other groups. The results in our study are similar to those of [PERSON] et al. (2014), with APOE \(\epsilon\)4\({}^{+}\) carrier status showing a greater decline in logical memory immediate recall. Again, contrary to expectations, we found no significant associations between the genotype groups with regard to MRI volumetric variables or mfVEP. The most probable explanation for this is that our cohort was comprised of aging participants, with little to no global alterations in the brain and visual pathway. The association between RNFL thickness measurements and brain structural volumes is well known and established [40]. There is a direct correlation between RNFL thickness located in the temporal quadrant and hippocampal volume [41], with a reduced thickness of the retinal ganglion layer reported in both AD and mild-MCI subjects [42; 43]. Although these associations have been reported previously, they offer the possibility for RNFL changes to be a potential early diagnostic marker for AD-related atrophy. The current study did not find any significant changes in the sectoral regions of the RNFL except for the temporal quadrant. Thinner RNFL, particularly in the temporal region, has previously been shown to correlate with older age in OCT analysis, especially in glaucoma [44; 45; 46].