Association of Retinal Nerve Fiber Layer Thickness, an Index of Neurodegeneration, With Depressive Symptoms Over Time

IMPORTANCE: Whether neurodegeneration contributes to the early pathobiology of late-life depression remains incompletely understood. OBJECTIVE: To investigate whether lower retinal nerve fiber layer (RNFL) thickness, a marker of neurodegeneration, is associated with the incidence of clinically relevant depressive symptoms and depressive symptoms over time. DESIGN, SETTING, AND PARTICIPANTS: This is a population-based cohort study from the Netherlands (The Maastricht Study) with baseline examination between 2010 and 2020 and median (IQR) follow-up of 5.0 (3.0-6.0) years. Participants were recruited from the general population. Individuals with type 2 diabetes were oversampled by design. Data analysis was performed from September 2020 to January 2021. EXPOSURES: RNFL, an index of neurodegeneration, assessed with optical coherence tomography. MAIN OUTCOMES AND MEASURES: Depressive symptoms were assessed with the Patient Health Questionnaire (PHQ)–9 (continuous score, 0-27) at baseline and over time via annual assessments. The presence of clinically relevant depressive symptoms was defined as a PHQ-9 score of 10 or higher. RESULTS: We used data from 4934 participants with depressive symptoms over time (mean [SD] age, 59.7 [8.4] years; 2159 women [50.8%]; 870 had type 2 diabetes [20.5%]). Lower RNFL thickness was associated with higher incidence of clinically relevant depressive symptoms (per 1 SD, hazard ratio 1.11; 95% CI, 1.01-1.23) and more depressive symptoms over time (per 1 SD, rate ratio, 1.04; 95% CI, 1.01-1.06), after adjustment for demographic, cardiovascular, and lifestyle factors. CONCLUSIONS AND RELEVANCE: The findings of this study suggest that lower RNFL thickness is associated with higher incidence of clinically relevant depressive symptoms and more depressive symptoms over time. Hence, neurodegeneration may be associated with the early pathobiology of late-life depression.