Objective: Observational data can be used to attempt to emulate a target trial of statin use and estimate analogues of intention-to-treat and per-protocol effects on dementia risk.

Methods: Using data from a prospective cohort study in the Netherlands, we conceptualized a sequence of “trials” in which eligible individuals ages 55-80 years were classified as statin initiators or non-initiators for every consecutive month between 1993 and 2007 and were followed until diagnosis of dementia, death, loss to follow-up, or the end of follow-up. We estimated two types of effects of statin use on dementia and a combined endpoint of dementia or death: the effect of initiation versus no initiation and the effect of sustained use versus no use. We estimated risk by statin treatment strategy over time via pooled logistic regression. We used inverse-probability weighting to account for treatment-confounder feedback in estimation of per-protocol effects.

Results: Of 233,526 eligible person-trials (6,373 individuals), there were 622 initiators and 232,904 non-initiators. Comparing statin initiation with no initiation, the 10-year risk differences (95% CI) were -0.1% (-2.3%, 1.8%) for dementia and 0.3% (-2.7%, 3.3%) for dementia or death. Comparing sustained statin use versus no use, the 10-year risk differences were -2.2% (-5.2%, 1.6%) for dementia and -5.1% (-10.5%, -1.1%) for dementia or death.

Conclusions: Individuals with sustained statin use, but not statin initiation alone, had reduced 10-year risks of dementia and dementia or death. Our results should be interpreted with caution due to the small number of initiators and events, and potential for residual confounding.