Impact of the Improper Adjustment for Age in Research on Age-Related Macular Degeneration: An Example Using Data from...

Purpose: Confounding is an important problem in observational research. Improper modeling of the confounder will lead to residual confounding that may distort results and impact inferences. An example of this will be presented from research on age-related macular degeneration and depression. Methods: A 3-year prospective cohort study was performed using data from the Canadian Longitudinal Study on Aging consisting of 30,097 individuals aged 45-85 years. Incident depression was assessed using the Center for Epidemiologic Studies Depression scale. Participants were asked if they had ever had a physician diagnosis of age-related macular degeneration (AMD). Multivariable Poisson regression was used. Age was modeled in four ways including as a linear term, as a 4-category variable, as a spline, and as a polynomial. Models were compared using the Akaike's Information Criteria (AIC) with lower scores indicating better performance. Results: The point estimates and inferences differed depending on how age was modeled. Age had a J-shape relationship with the incidence of depression. The model with the lowest AIC was when age was entered as a categorical variable. When age was modeled in this way, AMD was not significantly associated with the incidence of depression (relative risk (RR) = 1.21, 95% Confidence Interval (CI) 0.97, 1.53). By contrast, when age was modeled as a linear term, AMD was significantly associated with the incidence of depression (RR = 1.28, 95% CI 1.02, 1.61). Conclusions: Researchers should clearly report their adjustment strategies and should be cautious when modeling the relationship between age and depression in order to minimize residual confounding.