Causal Inference in Unrepresentative Databases: An Analysis of Vitamin E Supplementation in the National Alzheimer’s Coordinating Center Uniform Dataset

Self‐selection into research studies can lead to samples that are unrepresentative of the target population. For example, the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set is often used to identify risk factors of Alzheimer’s disease and overrepresents highly educated and non‐Hispanic White participants, relative to the US population. Sampling weights that are related to the self‐selection of enrolling in the NACC database can be used to estimate causal effects in the US population of older adults. We applied this strategy to estimate the effect of vitamin E supplementation on functional activities using NACC data and estimated sampling weights as proof of concept. A meta‐analysis found mixed evidence about the effect of vitamin E on functional outcomes in cognitively normal older adults (Browne et al. 2019).