Does being physically active prevent future disability in older people? Attenuated effects when taking time-dependent confounders into account.

Background: Causal experimental evidence that physical activity prevents disability in older people is sparse. Being physically active has nonetheless been shown to be associated with disability-free survival in observational studies. Observational studies are, however, prone to bias introduced by time-dependent confounding. Time-dependent confounding occurs when an exposure (e.g. being physically active at some time-point) potentially affects the future status of a confounder (such as depression sometime later), and both variables have an effect on latter outcome (i.e. disability). "Conventional" analysis with e.g. Cox-regression is the mainstay when analyzing longitudinal observational studies. Unfortunately, it does not provide unbiased estimates in the presence of time-dependent confounding. Marginal structural models (MSM) - a relatively new class of causal models - have the potential to adequately account for time-dependent confounding. Here we analyze the effect of older people being physically active on disability, in a large long-term observational study. We address time-dependent confounding by using marginal structural models and provide a non-technical practical demonstration of how to implement this type of modeling.

Methods: Data is from 639 elderly individuals ascertained in the European multi-center Leukoaraiosis and Disability study (LADIS), followed-up yearly over a period of three years. We estimated the effect of self-reported physical activity on the probability to transit to instrumental disability in the presence of a large set of potential confounders. We compare the results of "conventional" modeling approaches to those estimated using marginal structural models, highlighting discrepancies.

Results: A "conventional" Cox-regression-like adjustment for salient baseline confounders signals a significant risk reduction under physical activity for later instrumental disability (OR 0.62, 95% CI 0.44-0.90). However, given MSM estimation, the effect is attenuated towards null (OR 1.00, 95% CI 0.57-1.76).

Conclusions: Contrary to most reports, we did not find that physical activity in older people prevents future instrumental disability, when taking time-dependent confounding into account. This result may be due to the characteristics our particular study population. It is, however, also conceivable that previous evidence neglected the effect of this type of bias. We suggest that analysts of longitudinal observational studies consider marginal structural models as a further modeling approach.