Retinal Biomarkers in Detection of Alzheimer’s Disease

Abstract

Research Question: Are retinal biomarkers predictive of preclinical, prodromal, and clinical Alzheimer’s disease (AD) in patients 60 and older of different ethnicities in primary care settings in comparison to current primary care protocols? Specifically, how do the following biomarkers relate to AD: (1) retinal amyloid inclusion body surface area, (2) retinal nerve fiber layer (RNFL) thickness, and (3) retinal ganglion cell layer (RGCL) thickness?

Background, Significance, and Rationale for the Question: AD is a prevalent neurodegenerative disease. However, AD remains poorly detected, especially in primary care settings. In addition, while current neurodiagnostic procedures are accurate, they are invasive, costly, and have limited accessibility. Studies have shown a relationship between retinal biomarkers and AD, yet their overall utility, including primary care, has not been determined. Research also suggests that African American and Hispanic populations may be more subject to development of AD because of additional risk factors. This study provides a robust preliminary dataset exploring the relationship between AD and retinal biomarkers of a multiethnic population with varying degrees of AD in a primary care setting.

Materials and Methods: Recruited patients underwent a clinical dementia AD examination including: an interview, medical evaluation, neuropsychological testing, blood work, brain MRI, and brain ß-amyloid PET scan. Inclusion and exclusion criteria were met. Patients’ eyes were dilated then scanned using spectral-domain optical coherence tomography (SD-OCT) and blue-peak autofluorescence (BAF) fundus imaging. Layer segmentation with SD-OCT was used to examine the thickness of the RNFL and RGCL. Results, Conclusions, and Impact: Retinal biomarkers were assessed on 91 individuals testing for association with AD or mild cognitive impairment (MCI). The areas of the retina associated with cognitive changes were the inferior quadrant of the outer retinal layers, all four quadrants of the peripapillary retinal nerve fiber layer (pRNFL), and the inferior portion of the macular retinal nerve fiber layer (mRNFL). This evidence coincides with previous studies that suggest AD is associated with significant retinal biomarkers and support utility of retinal AD biomarkers for detecting AD. Retinal biomarkers of AD could prove valuable as a non-invasive, inexpensive, and widely available screening step in the AD neurodiagnostic process as well as allow opportunity to determine the efficacy of intervention once available.