Abstract

Inner retina in Alzheimer's Disease (AD) may experience neuroinflammation resulting in atrophy. The objective of our study was to determine whether retinal GCIPL (ganglion cell-inner plexiform layer) or nerve fiber layer (NFL) thickness may serve as noninvasive biomarkers to diagnose AD. This cross-sectional case-control study enrolled 15 mild cognitive impairment (MCI) patients, 15 mild-moderate AD patients, and 18 cognitively normal adults. NFL and GCIPL thicknesses on optical coherence tomography (OCT) were measured using Duke Optical Coherence Tomography Retinal Analysis Program (DOCTRAP) and Spectralis software. We demonstrated that regional thicknesses of NFL or GCIPL on macular or nerve OCTs did not differ between groups. However, a multi-variate regression analysis identified macular areas with a significant thickening or thinning in NFL and GCIPL in MCI and AD patients. Our primary findings controvert previous reports of thinner NFL in moderate-to-severe AD. The areas of thickening of GCIPL and NFL in the macula adjacent to areas of thinning, as revealed by a more complex statistical model, suggest that NFL and GCIPL may undergo dynamic changes during AD progression.

Highlights

  • Alzheimer’s disease (AD) is the only one of America’s top 10 leading causes of death that has no proven preventive or curative interventions

  • Current diagnostic modalities for AD are limited by cost, invasiveness, or suboptimal specificity and sensitivity [1]

  • All clinical, imaging, and laboratory data were reviewed by one neurologist (JRB) and one clinical neuropsychologist (GGP) from the Duke Alzheimer’s Disease Research Center (ADRC) to arrive at a consensus decision regarding assignment to cognitive diagnostic group

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Summary

Introduction

Alzheimer’s disease (AD) is the only one of America’s top 10 leading causes of death that has no proven preventive or curative interventions. And cost effective diagnosis is crucial to the stage of treatment and drug development. Current diagnostic modalities for AD are limited by cost (magnetic resonance imaging [MRI] or positron emission tomography [PET]), invasiveness (cerebrospinal fluid [CSF] biomarkers), or suboptimal specificity and sensitivity (genetic markers, serum amyloid) [1]. Neuropsychological evaluation is the “gold standard” for pre-mortem diagnosis of AD [2], but the testing is time-intensive, and may require multiple evaluations or access to specialists.

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