Retinal Functional and Structural Neural Indices: Potential Biomarkers for the Monitoring of Cerebral Neurodegeneration: The Maastricht Study

Abstract

Background: If retinal indices of neurodegeneration are to be biomarkers for the monitoring of cerebral neurodegeneration, it is important to establish whether potentially modifiable risk factors for dementia are associated with retinal neurodegenerative changes. Objective: To study associations of dementia risk factors with retinal sensitivity, an index of retinal neural function, and retinal nerve fiber layer (RNFL) thickness, an index of retinal neural structure. Methods: We used cross-sectional data from The Maastricht Study (up to 5,666 participants, 50.5% men, mean age 59.7), and investigated associations with regression analyses (adjusted for potential confounders). Results: Most risk factors under study (i.e., hyperglycemia, unhealthy diet, lower cardiorespiratory fitness, smoking, alcohol consumption, and hypertension) were significantly associated with lower retinal sensitivity and lower RNFL thickness. Conclusion: Findings of this population-based study support the concept that retinal neural indices may be biomarkers for the monitoring of therapeutic strategies that aim to prevent early-stage cerebral neurodegeneration and, ultimately, dementia.

Thinner inner retinal layers are associated with lower cognitive performance, lower brain volume, and altered white matter network structure—The Maastricht Study

“… 44 Also in support of this concept, we additionally found that retinal neurodegeneration and cerebral neurodegeneration have shared risk factors. 45 , 46 We recently showed in The Maastricht Study, using data from up to ∼5600 individuals, that most risk factors for dementia, including hyperglycemia and hypertension, were associated with retinal neurodegeneration, as quantified from lower RNFL thickness and worse retinal sensitivity. 45 , 46 Of note, however, as we found relatively weak associations of retinal neuronal variables with brain variables, retinal neuronal imaging biomarkers may by themselves (as singular biomarkers) not be sufficiently informative to use in a clinical care setting.…”

“… 45 , 46 We recently showed in The Maastricht Study, using data from up to ∼5600 individuals, that most risk factors for dementia, including hyperglycemia and hypertension, were associated with retinal neurodegeneration, as quantified from lower RNFL thickness and worse retinal sensitivity. 45 , 46 Of note, however, as we found relatively weak associations of retinal neuronal variables with brain variables, retinal neuronal imaging biomarkers may by themselves (as singular biomarkers) not be sufficiently informative to use in a clinical care setting. Future studies should aim to evaluate the added value of retinal imaging biomarkers on top of (a combination of) other non‐invasive and scalable biomarkers for dementia (such as blood‐based biomarkers for amyloid beta and tau in Alzheimer's disease).…”