Retinal microvascular dysfunction in mild cognitive impairment: Associations with cerebral small vessel disease, plasma biomarkers, and cognitive decline

INTRODUCTION: Mild cognitive impairment (MCI) is a transitional stage to dementia, with cerebral small vessel disease (SVD) as a key contributor. Since retinal microvascular changes may mirror cerebral pathology, we investigated the associations between retinal microvasculature, neuroimaging, and plasma biomarkers in individuals with MCI. METHODS: 61 MCI patients and 57 controls (CU) underwent retinal imaging, Neuroimaging (peak width of skeletonized diffusivity [PSMD], white matter hyperintensities [WMH]), plasma biomarker analysis, and cognitive assessment. Partial correlations and mediation analyses were adjusted for confounders. RESULTS: MCI exhibited greater retinal tortuosity (p < 0.05) and sparser vasculature (p < 0.001), correlating with higher PSMD, WMH volumes, and adverse plasma biomarkers (all p < 0.05). Mediation analysis revealed PSMD and WMH volumes partially mediated retinal-cognitive associations (p for all mediation < 0.05). DISCUSSION: Retinal microvascular dysfunction in MCI reflects concurrent cerebral SVD and neurodegeneration, supporting its potential as a non-invasive biomarker for early cognitive decline.