Phd in SENSORINEURAL PLASTICITY

Thesis title: Alterazioni microvascolari retiniche e coriocapillari nei pazienti con early Alzheimer: potenzialità diagnostiche dell’OCTA

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of β-amyloid in the brain and widespread neurovascular dysfunction. Despite significant advances in neuroimaging and cerebrospinal fluid biomarkers, there is an urgent need for a reliable, non-invasive, and easily applicable biomarker, particularly for the preclinical and early stages of the disease. The retina shares the same embryologic origin and histological characteristics as the brain, making it an accessible and representative extension of the central nervous system. Microvascular alterations of the retina and choriocapillaris, similar to those described in cerebral tissue, have been reported in Alzheimer’s patients, suggesting that ocular imaging may serve as an early indicator of cerebral neurodegenerative processes. Objective: The aim of the present study was to analyze, through Optical Coherence Tomography Angiography (OCTA), the morphological and functional characteristics of the retinal and choriocapillaris microvasculature in patients with early Alzheimer’s disease, in order to identify possible vascular alterations compared with age-matched healthy controls. Methods: A total of 18 patients with early Alzheimer’s disease (study group) and 18 healthy age-matched subjects (control group) were enrolled. All participants underwent a comprehensive neurologic and neuropsychological assessment, including standardized cognitive tests, as well as a full ophthalmologic examination with high-resolution OCTA scans. Quantitative analyses focused on the vessel density of the superficial and deep retinal capillary plexuses and on the choriocapillaris flow area, calculated within an automatically generated fovea-centered circular region. Results: A significant reduction of the choriocapillaris flow area was observed in the Alzheimer’s group compared with healthy controls (p = 0.006), indicating impaired choriocapillaris perfusion in the early stages of the disease. Although differences in retinal capillary plexuses did not reach statistical significance, a trend toward decreased superficial capillary density was noted, consistent with an evolving microvascular impairment. Conclusions: These findings provide further evidence of retinal and choroidal microvascular involvement in Alzheimer’s disease. OCTA emerges as a promising, non-invasive diagnostic tool capable of detecting early vascular changes associated with neurodegeneration. Future research involving larger cohorts, longitudinal designs, and advanced OCTA software is warranted to further clarify the role of these vascular alterations as potential biomarkers of Alzheimer’s disease, and to explore their application in clinical screening and disease monitoring.