Association of Retinal Nerve Fiber Layer Thickness With Brain Alterations in the Visual and Limbic Networks in Elderly Adults Without Dementia

Abstract

Importance: The eye is a sensory organ that is easily accessible for imaging techniques, allowing the measurement of the retinal nerve fiber layer (RNFL) thickness. The eye is part of the central nervous system, and its neurons may be susceptible to degeneration; therefore, changes in the RNFL thickness may reflect microstructural and volume alterations in the brain.

Objective: To explore the association between the peripapillary RNFL thickness and brain alterations in the visual and limbic networks in elderly people without dementia.

Design, setting, and participants: Cross-sectional analysis of the Three-City/Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires (Alienor) Study cohort (April 2009 to December 2010). The dates of analysis were July 2017 to August 2018. The setting was a population-based study in France. The brain volume analysis included 104 participants, and the diffusion tensor imaging analysis included 79 participants.

Main outcomes and measures: Global RNFL was assessed by spectral-domain optical coherence tomography. Brain volumes were assessed via T1-weighted magnetic resonance imaging by measurement of the global white and gray matter fractions and the hippocampal fraction. Brain microstructural alterations were assessed with diffusion tensor imaging at the level of the posterior thalamic radiations, the limbic system tracts (the fornix and cingulum bundles), and the posterior limb of the internal capsule (control region). Linear regression models adjusted for several confounders were performed.

Results: Among a total of 104 participants, the mean (SD) age was 80.8 (3.9) years, and the cohort was 56.7% women (n = 59). The mean (SD) global RNFL thickness was 89.3 (12.9) µm. A thicker RNFL was associated with a greater hippocampal fraction (quantity of increase β = 0.013; 95% CI, 0.001-0.025 per 10-μm increase in the RNFL thickness) and better diffusion tensor imaging variables in the global cingulum (mean diffusivity β = -0.007; 95% CI, -0.015 to -0.000) and the hippocampal part of the cingulum (mean diffusivity β = -0.009; 95% CI, -0.016 to -0.002 and radial diffusivity β = -0.010; 95% CI, -0.018 to -0.002) and the posterior thalamic radiations (fractional anisotropy β = 0.008; 95% CI, 0.000-0.017). No significant associations were found with other magnetic resonance imaging volumes or with other diffusion tensor imaging variables. In particular, there was no significant association with the control region of interest.

Conclusions and relevance: Results of this study suggest that in elderly individuals without dementia, a thicker RNFL was associated with better magnetic resonance imaging variables both in a region that included the visual pathways and in regions particularly involved in the neurodegenerative processes of Alzheimer disease.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Rougier reported being a consultant for Allergan and Bausch & Lomb; reported receiving funding for conferences from Bayer, Carl Zeiss Meditec, AbbVie, Laboratoires Théa, and Novartis; and reported receiving personal fees from Bayer, AbbVie, Allergan, Novartis, and Carl Zeiss Meditec. Dr Korobelnik reported being a consultant for Alcon, Allergan, Bayer, Carl Zeiss Meditec, Novartis, and Laboratoires Théa and reported receiving research grants from Roche and Alimera Sciences. Dr Schweitzer reported receiving personal fees from Laboratoires Théa, Alcon, Novartis, and Allergan. Dr Delyfer reported receiving advisory board or travel funding from Théa Laboratories, Bayer, and Novartis; reported receiving grants from Laboratoires Théa; and reported receiving personal fees from Allergan, Bayer, Novartis, and Bausch & Lomb. Dr Dartigues reported receiving research support and grants from Roche. Dr Delcourt reported receiving grants from Laboratoires Théa, Fondation Voir et Entendre, Association Retina France, and Conseil Regional d’Aquitaine; reported receiving personal fees from Allergan, Bausch & Lomb, Laboratoires Théa, Novartis, and Roche; and reported being a consultant for Allergan, Bausch & Lomb, Novartis, Roche, and Laboratoires Théa. Dr Helmer reported receiving grants from France Alzheimer (a charitable foundation) and reported receiving grants from Roche. All funding received by the authors was outside of the present work. No other disclosures were reported.

Figures

Figure.. Flowchart of the Selected Participants

Alienor indicates Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires; DTI, diffusion tensor imaging; MRI, magnetic resonance imaging; and RNFL, retinal nerve fiber layer. aValid MRI images without the presence of tumors or major cerebrovascular pathologies and showing good-quality processes.