Recent Advances in Retinal Biomarkers for Diagnosis of Early Alzheimer’s Disease

Abstract

The burden of Alzheimer’s disease (AD) is rapidly increasing worldwide. Developments towards early diagnosis and prevention of AD have been impeded by challenges in detection of the disease in its prodromal preclinical phase, when patients are clinically asymptomatic or exhibit mild cognitive impairments using specialized neuropsychological testing. Further, the current diagnostic processes are invasive, costly, and challenging for access. In addition, clinical testing is often initiated once the disease has progressed to late-stage, when irreversible pathological changes to the brain have occurred. As an extension of the central nervous system (CNS), the retina shares similar morphological and physiological properties. However, unlike the rest of the CNS, retinal tissue can be directly and non-invasively visualized using common ophthalmologic techniques, making this an attractive biomarker for AD. Technological advances in ocular imaging instrumentation have enabled the exploration of retinal biomarkers for detection of early AD with mild cognitive impairment (MCI). With cerebral amyloid aggregation likely occurring as early as 20 years prior to the onset of clinical dementia, it is imperative to develop a feasible, large-scale screening protocol for at-risk populations that is affordable, accessible, and non-invasive. In this review, we highlight novel ophthalmologic instrumentation used to identify and characterize retinal biomarkers in AD, such as optical coherence tomography (OCT), fundus photography, OCT angiography, and confocal scanning laser ophthalmoscopy (cSLO).