Brain care score and retinal health: structural and metabolic insights from the UK Biobank

Abstract The retina is an extension of the central nervous system and a recognized indicator of systemic health, yet the link between the brain care score (BCS) and retinal health remains unclear. In this study, we aimed to assess the associations of BCS with retinal layer thickness and retinal biological age and to evaluate potential metabolic mediation for retinal thickness. A total of 28,657 UK Biobank participants with optical coherence tomography (OCT) imaging at baseline were included, of whom 14,656 had metabolomic data. We constructed a 19-point BCS incorporating physical, lifestyle, and social-emotional domains, with higher scores indicating better brain care. Eight retinal layers and overall macular thickness were assessed. Retinal aging was evaluated using the OCT age gap, defined as the difference between the retinal age predicted by a support vector machine model trained on OCT-derived structural metrics and chronological age. Using multivariable linear regression, higher BCS was associated with thicker neuroretinal layers, photoreceptor layers, and overall macular thickness. Exploratory indirect-effect analyses identified candidate metabolic patterns primarily involving lipid, unsaturated fatty acid, and branched-chain amino acid pathways. Furthermore, each 5-unit increase in BCS was associated with a reduced retinal age gap. Our study identified associations between higher BCS and thicker neuroretinal and photoreceptor layers, as well as a reduced OCT age gap. These findings link a higher BCS to more favorable retinal structural phenotypes and identify candidate metabolic patterns for further investigation.