OCT-A Derived Retinal Biomarker in Mild Cognitive Impairment and Early Alzheimer’s Disease

To assess retinal structural and vascular changes using optical coherence tomography angiography (OCT-A) in subjects with mild Alzheimer’s disease (AD), mild cognitive impairment (MCI) due to AD, and healthy controls, and to evaluate their potential role as non-invasive biomarkers for early disease detection. Consecutive subjects referring to the Alzheimer’s Unit of IRCCS Neuromed between December 2020 and December 2024 were enrolled. Diagnosis of MCI due to AD and mild AD was based on NIA–AA criteria and supported by neuropsychological assessment, brain MRI and amyloid PET imaging. Healthy controls were cognitively evaluated and had no neurological or ophthalmological diseases. All participants underwent a complete ophthalmological examination and OCT/OCT-A imaging using a Canon OCT HS 100 4.8 system. Retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), foveal and parafoveal vascular density of the superficial and deep plexuses, and foveal avascular zone (FAZ) area, size and inner diameter were analyzed. Group comparisons were performed using ANOVA with Bonferroni correction and ANCOVA adjusted for age. Subjects with MCI and mild AD showed significant retinal vascular alterations compared with healthy controls. In particular, a significant enlargement of FAZ parameters, especially the inner diameter, and a reduction of deep capillary plexus vascular density were observed. These differences remained statistically significant after adjustment for age. No significant differences in RNFL or GCL–IPL thickness were detected between MCI subjects and healthy controls. OCT-A reveals early retinal vascular changes in biomarker-confirmed MCI and mild Alzheimer’s disease. Enlargement of the FAZ inner diameter may represent a promising, non-invasive retinal biomarker for early AD, warranting further validation in larger diagnostic cohorts.