Retinal biomarkers in cognitive impairment and dementia: Structural, functional, and molecular insights

Cognitive impairment and dementia, including Alzheimer's disease (AD), pose a global health crisis, necessitating non-invasive biomarkers for early detection. This review highlights the retina, an accessible extension of the central nervous system (CNS), as a window to cerebral pathology through structural, functional, and molecular alterations. By synthesizing interdisciplinary evidence, we identify retinal biomarkers as promising tools for early diagnosis and risk stratification. Nevertheless, translating biomarkers into clinical practice faces significant translational hurdles, including methodological heterogeneity, confounding variables, lack of standardized protocols, and insufficient longitudinal validation in diverse populations. Overcoming these challenges through rigorous standardization and robust validation studies is essential to establish the clinical utility of retinal biomarkers. HIGHLIGHTS: Stage-specific diagnostic potential: Retinal biomarkers (e.g., OCT/OCTA changes, eye movements, molecular deposits) show alterations correlating with cognitive impairment stages (preclinical AD to dementia), assisting stage differentiation. Reflecting cerebral pathology: Multimodal retinal alterations (structural, functional, molecular) correlate with key brain pathologies (amyloid/tau burden, atrophy, small vessel disease), indicating shared pathways. Translation gaps and future: Clinical adoption faces barriers (method heterogeneity, confounders, limited validation). Future requires rigorous screening of candidate retinal biomarkers, extensive multicenter validation, and artificial intelligence (AI)-facilitated clinical translation.