Does the drug accelerate the decline, or the decline invite the drug? Reverse causation in studies of inappropriate medications and dementia progression.

In a recent retrospective cohort from Norwegian memory clinics, Kersten and colleagues reported that potentially inappropriate medications for people with cognitive disorders were associated with faster two-year progression of mild cognitive impairment and dementia. We note that this progression signal was confined to exposure measured at the end of follow-up, was absent at baseline, and did not survive multivariable adjustment, a pattern more consistent with reverse causation and confounding by indication than with a drug effect. We further suggest that a simple count of inappropriate medications be refined through burden-weighted and class-specific analyses. Anchoring exposure temporally, applying negative control outcomes or target-trial emulation, and pursuing pragmatic deprescribing trials would help separate genuine drug effects from the clinical trajectory that drives prescribing.