Retinal structural and microvascular alterations as biomarkers of cerebral pathology and cognitive decline in Alzheimer's disease: An OCT/OCTA study

BackgroundRetinal structural and microvascular alterations detected by optical coherence tomography (OCT) and OCT angiography (OCTA) have emerged as promising biomarkers of Alzheimer's disease (AD). However, the extent to which retinal changes reflect cerebral neurodegenerative and vascular pathology and contribute to cognitive impairment remains incompletely characterized.ObjectiveTo investigate the relationships among retinal OCT/OCTA metrics, cerebral neuroimaging markers, and global cognitive performance in patients with AD.Methods115 AD and 101 cognitively unimpaired controls underwent OCT/OCTA imaging, 3.0T brain magnetic resonance imaging, and neuropsychological assessment. Retinal structural measures, including peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thicknesses, and retinal microvascular densities of the superficial vascular complex (SVC) and deep vascular complex were analyzed alongside white matter hyperintensity (WMH) volume, hippocampal volume, and cerebral small vessel disease (SVD) burden.ResultsCompared with controls, patients with AD exhibited significantly thinner pRNFL and GCIPL and lower SVC density (all p < 0.01). Retinal structural and microvascular alterations were associated with greater WMH burden, hippocampal atrophy, increased SVD burden, and lower Mini-Mental State Examination and Montreal Cognitive Assessment scores (all p < 0.05). Significant interactions were observed between GCIPL thickness and periventricular WMH volume in relation to cognitive performance. Mediation analyses demonstrated that WMH volume and SVD burden partially mediated the association between reduced SVC density and cognitive impairment.ConclusionsRetinal OCT/OCTA metrics are associated with cerebral neurodegenerative and vascular abnormalities and reflect cognitive dysfunction in AD, supporting their potential utility as accessible, noninvasive biomarkers for disease assessment and monitoring.