Detection of early Alzheimer’s disease at the eye clinic: The BeyeOMARKER study
Ilse Bader, Colin Groot, Stevie H. Tan, Wiesje M. van der Flier, Charlotte E. Teunissen, Yolande A.L. Pijnenburg, Femke H. Bouwman, Rik Ossenkoppele- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
Early detection of Alzheimer’s disease (AD) is essential for establishing a patient management plan, and for clinical trial selection and determining who will benefit most from future therapies. Effective screening for early AD will require large‐scale implementation of non‐invasive, scalable, and accessible biomarkers such as blood‐based biomarkers and retinal scans. With a high population throughput and a visually impaired population at increased risk for AD (HR = 1.47 (Kuźma et al., J Alzheimers Dis (2021)), eye clinics provide a prime proof‐of‐concept setting to explore the potential of implementing non‐invasive biomarkers in an alternative clinical setting. The BeyeOMARKER study aims to explore the feasibility of large‐scale screening using non‐invasive tools in eye clinics, with the ultimate goal of providing recommendations for AD screening in alternative clinical settings, and exploring factors underlying the association between eye disease and AD.
Method
The BeyeOMARKER study is a prospective, observational, longitudinal cohort study. At the eye clinic, ∼700 participants (aged ≥45) will be screened for early AD using plasma phospho‐tau181 (p‐tau181) and a short neuropsychological test battery (Montreal Cognitive assessment). After screening, 100 plasma p‐tau181 positive cases and 50 p‐tau181 negative controls (matched based on age, sex and eye disease) will be included into the longitudinal BeyeOMARKER cohort. This cohort will be invited to the memory clinic for a hyperspectral retinal scan, structural magnetic resonance imaging (MRI), and a comprehensive neuropsychological assessment including cortical vision tests (e.g., visuo‐perceptive and visuospatial abilities).
Result
Main outcomes of the BeyeOMARKER study are 1) a prevalence estimate of AD in a large, diverse population of visually impaired individuals, 2) the performance of hyperspectral retinal scans to detect AD pathology in this population and its complementary benefit over‐and‐above plasma p‐tau181, and 3) improved understanding on the eye‐brain connection in the context of AD through comparison of cognitive and cortical vision performance, and brain atrophy across visually impaired p‐tau181 positive and negative individuals.
Conclusion
The BeyeOMARKER consortium aspires to build a detailed roadmap for the implementation of non‐invasive screening for early AD within the eye clinic.