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.