## 1 Introduction  
Dementia and cognitive decline due to aging continue to be a major public health burden worldwide. The current prevalence of dementia among those aged over 60 is 5-7%, with the number of individuals diagnosed with dementia likely to double as a result of the aging population if current trends continue [1]. Cognitive decline remains a key feature of neurodegenerative diseases and is often a major complaint of participants with disorders such as Alzheimer's disease (AD). Early and definitive diagnosis of AD remains a key challenge and the subject of current research. With the development of disease-modifying treatments, there is a need for early and definitive diagnosis, which may rely on clinical biomarkers. Currently available biomarkers for AD include positron emission tomography (PET) imaging and cerebral spinal fluid (CSF) examination. Whilst useful, both are highly expensive, not readily available, and invasive. This makes them unsuitable for large-scale population screening. The retina is often considered a window to the brain and offers an opportunity to potentially function as a biomarker. The retina is physically connected to the brain via axons that form the optic nerve, which allow both anterograde and retrograde forms of communication between the two structures. The close relationship between the brain and retina, including their anatomical substructures, provides a form of non-invasive imaging that can allow for a better understanding of processes that occur in both organs, for both AD and healthy aging. An individual's genetic predisposition may also serve as a biomarker for the development of AD. A familial history of AD increases the risk of developing the condition, as does having at least one copy of the apolipoprotein E (APOE) \(\epsilon\)4 allele. Pathological features of AD are the deposition of amyloid \(\beta\) (A\(\beta\)) peptide and hyperphosphorylation of tau protein; however, recently, vascular factors have also been considered to be involved in the pathophysiology of AD [2]. The APOE \(\epsilon\)4 allele is one of the strongest genetic risk factors for sporadic forms of AD. The \(\epsilon\)4 allele is estimated to be expressed in more than 50% of AD patients. Having one copy of the \(\epsilon\)4 allele increases the risk of developing AD two- to threefold, whilst being homozygous for \(\epsilon\)4 increases the risk tenfold. [3]. Apolipoprotein E regulates cholesterol metabolism and modulates the clearance of amyloid \(\beta\). The precise biological mechanisms linking the APOE genotype and AD, however, are not well understood. Cross-sectional studies in older adults without dementia have suggested that APOE \(\epsilon\)4 is associated with impairment in memory, executive function, processing speed and global cognitive function [4; 5]. Additionally, neuroimaging studies have utilised PET scanning to investigate the involvement of the APOE \(\epsilon\)2 allele in episodic memory decline and AD disease progression [4; 5]. An individual's APOE \(\epsilon\)4 carrier status could thus be used as a marker of increased risk of the development of AD in an aging cohort and to examine relationships with potential biomarkers in the eye. Although not currently used clinically for AD progression or diagnosis, retinal examination may offer valuable insights into understanding the complex nature of this condition. Due to the similarities between the retinal and cerebral vasculature, which share embryological origin as well as physiological and anatomical properties, it is logical to use the retinal vascular network to understand the characteristics of vascular cerebral pathologies such as AD [2; 6; 7]. MRI studies have revealed notable differences in cerebral microvasculature and vascular features between APOE \(\epsilon\)4-positive and \(\epsilon\)4-negative individuals.