Correlation Between Retinal Nerve Fiber Layer Thickness and Cognitive Decline in Elderly Patients Using Optical Coherence Tomography (OCT)

Background: Dementia and mild cognitive impairment are rising concerns in Pakistan’s aging population, yet access to conventional neuroimaging and cerebrospinal fluid biomarkers is limited. Retinal imaging via optical coherence tomography (OCT) offers a non-invasive window into central nervous system health, with thinning of the retinal nerve fiber layer (RNFL) proposed as an early indicator of neurodegeneration. Objective: To assess the relationship between peripapillary RNFL thickness as well as related retinal and systemic biomarkers and global cognitive function in elderly Pakistani patients. Methods: In this cross-sectional study, 120 participants aged 65 years or older were recruited from Syed Eye Care (Bahawalpur) and Allied Hospital II (Faisalabad) and stratified by Mini-Mental State Examination score into cognitively normal (n=40), mild cognitive impairment (n=40), and dementia (n=40) groups. Spectral-domain OCT measured average and quadrant-specific RNFL thickness, ganglion cell–inner plexiform layer thickness, and central macular thickness. Blood samples were analyzed for Alzheimer’s biomarkers (Aβ₄₂, total tau, phospho-tau), inflammatory marker (C-reactive protein), and vascular risk factors (homocysteine, cholesterol). Group comparisons utilized one-way ANOVA, and associations with cognitive scores were evaluated using Pearson correlation. Results: Average RNFL thickness decreased progressively from 89.1 ± 4.7 µm in controls to 81.7 ± 5.2 µm in mild cognitive impairment and 72.4 ± 4.5 µm in dementia (p < 0.001). Similar graded reductions were observed in ganglion cell–inner plexiform layer and central macular thickness (all p < 0.001). Blood Aβ₄₂ declined and tau species, C-reactive protein, homocysteine, and cholesterol increased significantly across cognitive groups (p < 0.01). Temporal RNFL thickness demonstrated the strongest correlation with cognitive performance (r = 0.66, p < 0.001). Conclusion: OCT-derived retinal measures, particularly temporal RNFL thickness, correlate strongly with cognitive impairment and systemic Alzheimer’s and vascular biomarkers in Pakistani elders. OCT screening may serve as a practical, non-invasive adjunct for early detection of neurodegenerative change in resource-limited settings.