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

Abstract

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.

Joint effects of meteorological factors and PM_2.5 on age-related macular degeneration: a national cross-sectional study in China

“…The association of PM 2.5 with AMD in the present investigation was consistent with other studies, such as the UK Biobank study [ 15 ], the Canadian Longitudinal Study [ 16 ], and a study in Taiwan [ 14 ]. The potential mechanisms underlying the effects of air pollution on AMD involve three aspects.…”

“…These results warrant attention in prospective cohort and mechanistic studies to further elucidate the relationship between meteorological factors, air pollution, and degenerative eye disease. The association of PM 2.5 with AMD in the present investigation was consistent with other studies, such as the UK Biobank study [15], the Canadian Longitudinal Study [16], and a study in Taiwan [14]. The potential mechanisms underlying the effects of air pollution on AMD involve three aspects.…”

“…According to the UK Biobank study, PM 2.5 is associated with self-reported AMD in participants ages 40–69 [ 15 ]. In the Canadian Longitudinal Study, increased PM 2.5 levels were associated with visual impairments from AMD in the single pollutant model [ 16 ]. In a study in Taiwan, AMD risk increased by 19% for every 10 µg/m 3 increase in PM 2.5 [ 14 ].…”

What did we learn in 35 years of research on nutrition and supplements for age‐related macular degeneration: a systematic review

“…In contrast to this, a high intake of alcohol was associated with a lower risk of progression of AMD (Agr ón et al 2021). This unexpected finding could be due to study design or confounding factors, such as age (Grant et al 2021). Higher age is strongly associated with AMD progression, while high alcohol consumption may be more prevalent in younger age groups.…”

“…This unexpected finding could be due to study design or confounding factors, such as age (Grant et al. 2021 ). Higher age is strongly associated with AMD progression, while high alcohol consumption may be more prevalent in younger age groups.…”