Application of Structural Retinal Biomarkers to Detect Cognitive Impairment in a Primary Care Setting




Nyalakonda, Ramyashree
Petersen, Melissa
Zhang, Fan
Johnson, Leigh
Tolman, Alex
Gutierrez, Alejandra
O'Bryant, Sid
Mozdbar, Sima


0000-0002-6255-1807 (Nyalakonda, Ramyashree)

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Alzheimer’s Disease (AD) is the most prevalent form of dementia and a leading cause of death in the elderly. The detection of AD remains poor in primary care despite the advancement of neurodiagnostic procedures. There are no rapid and cost-effective tools available to primary care providers to conduct cognitive examinations to diagnose AD. The goal of this study is to determine the predictive ability of structural retinal biomarkers to identify cognitive impairment in a primary care setting.


Participants were recruited from Alzheimer’s Disease in Primary Care (ADPC) study. As part of the ADPC Retinal Biomarker Study (ADPC RBS), visual acuity, an ocular history questionnaire, eye pressure, optical coherence tomography (OCT) imaging and fundus imaging was performed. Exclusion criteria included high intraocular pressure defines as greater than or equal to 30 mmHg in either eye, history of adverse effects with pupillary relation, known hypersensitivity to tropicamide or any ingredient in the formulation, active ocular infection or inflammation, history of angle closure glaucoma, or having undergone ocular surgery within the last 6 months. Cognitive diagnoses were assigned algorithmically and verified at consensus review by an expert in the field of dementia.


Data were examined on a total of 91 participants (59 cognitively unimpaired, 32 cognitively impaired (26 mild cognitive impairment (MCI), 6 AD)). The top biomarkers for predicting cognitive impairment included the inferior quadrant of the outer retinal layers, all four quadrants of the peripapillary retinal nerve fiber layer (pRNFL), and the inferior quadrant of the macular retinal nerve fiber layer. While all four quadrants of the pRNFL are highly important biomarkers for identifying those with cognitive impairment, the inferior and superior quadrants displayed higher relative importance compared to the temporal and nasal quadrants.


This study was the first to examine the utility of retinal biomarkers in diagnosis cognitive impairment in a primary care setting with models reflecting how it could be employed as a screening tool in practice. The current data provides strong support for continued investigation into structural retinal biomarkers, particularly the retinal nerve fiber layer, as screening tools for AD. In prior studies, preferential thinning of the inner retinal layers is found in AD compared to healthy controls. This study can help distinguish those with cognitive impairment from those cognitively unimpaired. The availability of such a biomarker could increase access to disease modifying treatments once available.