Associations Between Thinner Retinal Neuronal Layers and Suboptimal Brain Structural Integrity in a Middle-Aged Cohort

Abstract

Purpose

The retina has potential as a biomarker of brain health and Alzheimer’s disease (AD) because it is the only part of the central nervous system which can be easily imaged and has advantages over brain imaging technologies. Few studies have compared retinal and brain measurements in a middle-aged sample. The objective of our study was to investigate whether retinal neuronal measurements were associated with structural brain measurements in a middle-aged population-based cohort.

Participants and Methods

Participants were members of the Dunedin Multidisciplinary Health and Development Study (n=1037; a longitudinal cohort followed from birth and at ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32, 38, and most recently at age 45, when 94% of the living Study members participated). Retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness were measured by optical coherence tomography (OCT). Brain age gap estimate (brainAGE), cortical surface area, cortical thickness, subcortical grey matter volumes, white matter hyperintensities, were measured by magnetic resonance imaging (MRI).

Results

Participants with both MRI and OCT data were included in the analysis (RNFL n=828, female n=413 [49.9%], male n=415 [50.1%]; GC-IPL n=825, female n=413 [50.1%], male n=412 [49.9%]). Thinner retinal neuronal layers were associated with older brain age, smaller cortical surface area, thinner average cortex, smaller subcortical grey matter volumes, and increased volume of white matter hyperintensities.

Conclusion

These findings provide evidence that the retinal neuronal layers reflect differences in midlife structural brain integrity consistent with increased risk for later AD, supporting the proposition that the retina may be an early biomarker of brain health.

Keywords:

• optical coherence tomography
• retina
• Alzheimer’s
• magnetic resonance imaging
• brain aging

Data Sharing Statement

Proposed data‐analysis projects from qualified scientists must have a concept paper describing the purpose of data access, IRB approval at the applicants’ university, and provision for secure data access. We offer secure access on the Duke and Otago campuses. These access requirements parallel those used by dbGap and the Health and Retirement Study.

Acknowledgments

We thank the Dunedin Study members and their families and friends for their long-term involvement. We also thank the members of the Advisory Board for the Dunedin Neuroimaging Study, all Unit research staff, and Dunedin Study founder Dr Phil A. Silva. The Dunedin Multidisciplinary Health and Development Research Unit is based at the University of Otago within the Ngāi Tahu tribal area whom we acknowledge as first peoples, tangata whenua (trans. people of this land).

The Dunedin Multidisciplinary Health and Development Research Unit is supported by the New Zealand Health Research Council (grant number 16-604), and also received funding from the New Zealand Ministry of Business, Innovation, and Employment. Funding support was also received from the US National Institute of Aging (grant numbers R01AG069939, R01AG032282, and R01AG049789) and the UK Medical Research Council (grant number MR/P005918/1). Dr Barrett-Young’s work is funded by the Rapanui Trust. The University of Otago Department of Psychology provided funding to Prof Poulton for the OCT machine.

Disclosure

Professor Tien Yin Wong reports personal fees from Bayer, Boehringer-Ingelheim, Eden Ophthalmic, Genentech, Iveric Bio, Novartis, Oxurion, Roche, Samsung, Shanghai Henlius, Zhaoke Pharmaceutical, Plano; he is an inventor, hold patents and co-founder of EyRIS and VisRE which have interests in, and develop digital solutions for eye diseases, including diabetic retinopathy, outside the submitted work. The authors report no other conflicts of interest in this work.