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Associations between Retinal Nerve Fiber Layer and Ganglion Cell Layer in Middle Age and Cognition from Childhood to Adulthood

Research output: Contribution to journalArticlepeer-review

Ashleigh Barrett-Young, Antony Ambler, Kirsten Cheyne, Hayley Guiney, Jesse Kokaua, Barbara Steptoe, Yih Chung Tham, Graham A. Wilson, Tien Yin Wong, Richie Poulton

Original languageEnglish
Pages (from-to)262-268
Number of pages7
JournalJAMA Ophthalmology
Issue number3
Accepted/In press2022
PublishedMar 2022

Bibliographical note

Funding Information: 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 R01AG069936, R01AG032282, and R01AG049789) and the UK Medical Research Council (grant number MR/ P005918/1). Dr Kokaua’s work is funded by the Sir Thomas Davis Te Patu Kite Rangi Ariki Health Research Fellowship (HRC20/115) and a Pacific Grant (HRC20/116) from the Health Research Council. The University of Otago Department of Psychology provided funding for the OCT machine. Publisher Copyright: © 2022 American Medical Association. All rights reserved.

King's Authors


Importance: The retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) have been proposed as potential biomarkers for Alzheimer disease (AD). Although a number of studies have shown that knowing the thickness of RNFL and GCL can help differentiate between patients with AD and healthy controls, it is unclear whether these associations are observable earlier in life. Objective: To examine whether RNFL and GCL thickness was associated with global cognitive performance in middle age and in childhood and with a decline in cognitive performance from childhood to adulthood and whether RNFL and GCL thickness was associated with decline in specific cognitive domains over the same period. Design, Setting, and Participants: This longitudinal cohort study involved members of the Dunedin Multidisciplinary Health and Development Study, a longitudinal representative birth cohort from New Zealand (n = 1037). Participants were born in 1972 to 1973 and followed up until age 45 years, with 94% of the living cohort still participating. Main Outcomes and Measures: Cognitive performance (Full Scale IQ, processing speed, perceptual reasoning, and verbal comprehension) measured at ages 7, 9, and 11 years (mean value) and age 45 years, and RNFL and GCL thickness measured via optical coherence tomography (OCT) at age 45 years. Results: Data were analyzed between August 2020 and April 2021. Data from 865 participants were included in the present study (50.2% male, 49.8% female; 92.2% of the 938 study members seen at age 45 years). Of the 73 participants who were excluded, 63 were excluded because of issues with OCT scans and 10 were excluded because of diseases affecting the retina. Thinner RNFL and GCL were associated with lower Full Scale IQ in childhood and at age 45 years. Thinner RNFL was also associated with a greater decline in processing speed from childhood to adulthood. Conclusions and Relevance: RNFL and GCL thickness in middle age was associated with cognitive performance in childhood and adulthood, and thinner RNFL with a decline in processing speed between childhood and adulthood. These data emphasize the potential utility of OCT measures as biomarkers of cognitive function; however, further longitudinal studies are needed to determine whether retinal thinning precedes cognitive decline and whether other confounding factors may account for this association.

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