Outer retinal thinning is associated with brain atrophy in early age-related macular degeneration

Yu Jiang; Thomas Swain; Nayoon Gim; Marian Blazes; Christine Mac Donald; Ariel Rokem; Julia P Owen; Niranjan Balu; Mark E Clark; Lukas Goerdt; Gerald McGwin; David Hunt; Christine A Curcio; Swati Rane Levendovszky; Emily H Trittschuh; Cynthia Owsley; Cecilia S Lee

doi:10.1016/j.ajo.2024.09.033

Outer retinal thinning is associated with brain atrophy in early age-related macular degeneration

Am J Ophthalmol. 2024 Oct 4:S0002-9394(24)00466-5. doi: 10.1016/j.ajo.2024.09.033. Online ahead of print.

Authors

Yu Jiang¹, Thomas Swain², Nayoon Gim³, Marian Blazes¹, Christine Mac Donald⁴, Ariel Rokem⁵, Julia P Owen¹, Niranjan Balu⁶, Mark E Clark⁷, Lukas Goerdt⁸, Gerald McGwin², David Hunt⁴, Christine A Curcio⁷, Swati Rane Levendovszky⁹, Emily H Trittschuh¹⁰, Cynthia Owsley⁷, Cecilia S Lee¹¹

Affiliations

¹ Department of Ophthalmology, University of Washington, Seattle, WA, USA.
² Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
³ Department of Ophthalmology, University of Washington, Seattle, WA, USA; Department of Bioengineering, University of Washington, Seattle, WA, USA.
⁴ Department of Neurological Surgery, University of Washington, Seattle, WA, USA.
⁵ Department of Psychology and eScience Institute, University of Washington, Seattle, WA, USA.
⁶ Department of Neuroradiology, University of Washington, Seattle, WA, USA.
⁷ Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL, USA.
⁸ Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Ophthalmology, University of Bonn, Bonn, Germany.
⁹ Department of Radiology, University of Washington, Seattle, WA, USA.
¹⁰ Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA; GRECC, VA Puget Sound Health Care System, Seattle, WA, USA.
¹¹ Department of Ophthalmology, University of Washington, Seattle, WA, USA; The Roger and Angie Karalis Johnson Retina Center, Seattle, WA, USA. Electronic address: leecs2@uw.edu.

PMID: 39369929
DOI: 10.1016/j.ajo.2024.09.033

Abstract

Purpose: Both retinal changes and age-related macular degeneration (AMD) have been shown to be associated with Alzheimer's disease and related dementias (ADRD). In AMD, the outer retina is impacted significantly and early, but little is known about its association with cognition or changes in brain morphometry. This study investigates the relationship between retinal and brain morphometry in older adults with early and intermediate age-related macular degeneration (AMD).

Design: Cross-sectional study.

Methods: Adults ≥ 70 years with normal, early, and intermediate AMD were recruited from Callahan Eye Hospital Clinics at the University of Alabama at Birmingham. Participants underwent cognitive testing, optical coherence tomography (OCT), and magnetic resonance imaging (MRI). Associations of retinal layer thickness with brain volume and thickness of specific brain regions were evaluated utilizing multivariable linear regression. The relevance of retinal thickness variables in brain volumetrics was quantified using least absolute shrinkage and selection operator (LASSO) regression models. Correlations between demographic variables, cognitive scores, and brain morphometry were evaluated.

Results: Participants with thinner outer retina had significantly smaller hippocampus (β = 0.019, p = 0.022), lower occipital cortex regions of interest (occipital ROIs) thickness (β = 5.68, p = 0.020), and lower cortical thickness in ADRD-related brain regions (β = 7.72, p = 0.006). People with thinner total retina had significantly lower occipital ROIs (β = 3.19, p = 0.009) and ADRD-related brain region (β = 3.94, p = 0.005) thickness. Outer retinal thickness in the outer Early Treatment of Diabetic Retinopathy Study (ETDRS) ring was the most frequently reported retinal variable associated with brain morphometry on LASSO regression. Total gray matter volume showed positive correlations with education (Pearson's r = 0.30, p = 0.022).

Conclusion: In older adults with normal retinal aging and early and intermediate AMD, thinner outer retina had specific associations with brain regions primarily involved in vision and cognition, such as lower hippocampal volume and lower thickness of the occipital ROIs and brain regions known to show early structural changes in dementia.

Keywords: Age-related macular degeneration; Alzheimer's disease; Alzheimer's disease and related dementia; aging; eye diseases; neuroimaging; retinal imaging.