Aging
The Potential Role of Visual Acuity in the Effect of Age-Related Macular Degeneration on Dementia: A Discrete-Time Causal Mediation and Survival Analysis Mina Habib* Mina Habib Habib Habib Habib Habib Habib Habib Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, 650 Charles E Young Dr. S, Los Angeles, CA 90095
Alzheimer’s disease and related dementias remain a major public health challenge, with limited effective treatments. Prevention strategies are critical to addressing their increasing prevalence. We examined whether the association of age-related macular degeneration (AMD), a leading cause of vision loss, with incident dementia is mediated by visual acuity. We analyzed longitudinal study visit and electronic health record data (2003–2024) from 3,321 participants in the Adult Changes in Thought prospective cohort study. Parametric g-computation-based discrete-time causal mediation and survival analysis using pooled logistic regression estimated adjusted average, discrete-time (e.g. 5 years), and end-of-follow-up risk ratios (RRs) and differences (RDs, per 1,000) for the effect of AMD diagnosis on incident dementia (per DSM-IV criteria). We also estimated the proportions that are mediated and eliminated to quantify the role of visual acuity. Models were adjusted for sociodemographic and time-varying health-related variables. Inverse probability weights accounted for time-varying exposure, mediator, and attrition. Bootstrapping with 1000 resamples was used to obtain 95% CI. With an average baseline age of 75.9 and 8.4 years of follow-up, 23% (N = 766) developed dementia. On average over follow-up, AMD diagnosis was associated with increased dementia risk (RR: 1.13; 95% CI: 1.00,1.26; RD: 31.84; 95% CI: -1.30, 60.94). Five years post baseline, dementia risk was 1.33 times (95% CI: 1.09,1.59; RD: 33.57; 95% CI: 9.99, 56.97) among individuals diagnosed with AMD versus without. While mediation varied over time, -3% (pure indirect effect RR: 1.03, 95% CI: 1.01, 1.06) of the AMD–dementia relationship was mediated by visual acuity. If visual acuity were preserved in all with AMD, 3% of the total effect would be eliminated. Interventions to preserve visual acuity could offer a novel strategy to reduce dementia risk in individuals with AMD.
