The Atlas of Retinal Imaging in Alzheimer’s Study (ARIAS): Study design and objectives

Abstract

AbstractBackgroundThe development of widely accessible, minimally invasive, cost‐effective Alzheimer’s disease (AD) biomarkers is a global public health imperative. There is a definite need for a multi‐stage neurodiagnostic screening system that is sensitive and specific to identify high risk individuals prior to cognitive decline. There is rapidly growing evidence that retinal biomarkers have the potential to serve as diagnostic or prognostic AD biomarkers. However, some results have been discordant due to variations in methodology, equipment, and study populations. Moreover, longitudinal data is sparse, and there is lack of insight as to which retinal biomarkers are relevant for each disease stage. Finally, the field needs to understand how structural, functional/metabolic, and angiographic retinal biomarkers interact in the AD process, and whether or not these interactions reflect cerebral pathophysiology. We propose a multi‐site longitudinal, prospective, observational study evaluating the natural history of retinal imaging biomarkers associated with AD disease risk, disease burden, and disease progression. The study objective is to create a ‘gold standard’ reference database of structural anatomic and functional imaging of the retina, in order to enable the identification and development of both sensitive and reliable markers of disease risk and/or disease progression.MethodParticipants (N=330 aged 55‐80; 50 CN– low AD risk, 200 CN – high AD risk, 50 MCI, and 30 mild AD) will be examined 4 times over 5 years. Exams will include neuropsychological testing, blood draw, APOE E4 genotyping, medical/functional assessment, gait assessment, and sleep analysis for 14 days post‐visit. Retinal OCT and OCT‐A will be completed on the Heidelberg SPECTRALIS II. Pupillometry and contrast sensitivity measures will be collected at each visit.ResultWe aim to use these data to develop a multivariate screening tool with sufficient sensitivity and specificity for identifying and tracking AD severity, including the preclinical stage of the disease.ConclusionLongitudinal study of structural, functional, metabolic, and angiographic retinal AD biomarkers in a large cohort could provide the foundation for the development of early stage screening biomarkers that can be applied by point‐of‐care clinicians. Our reference database will be open access, so that researchers worldwide can use these data to develop retinal AD biomarkers.