Do Statins Affect Cognitive Health? A Narrative Review and Critical Analysis of the Evidence

Statins are the first-line treatment for hypercholesterolemia and play a key role in the prevention of cardiovascular disease (CVD). Current studies report mixed effects of statins on cognitive health, including harmful, neutral, and protective outcomes. However, these ongoing controversies about the potential cognitive adverse effects of statins may compromise their use in CVD prevention. Several factors may influence how statins affect cognition, including the unique cholesterol homeostasis in the brain, the limited permeability of the blood-brain barrier to lipoproteins, and the varying lipophilicity of different statins. This review examines the evidence linking statins to cognitive function and considers the effect of different dosages and treatment durations.

Earlier studies suggested cognitive disturbances with statins, but recent evidence does not strongly support a link between statins and cognitive impairment. In fact, observational studies suggest potential neuroprotective benefits, though biases like selection bias, confounding and reverse causation limit definitive conclusions. Two large randomized controlled trials, STAREE and PREVENTABLE, are underway, and their results are expected to address some of these gaps in the literature. Due to insufficient evidence in the current literature, well-designed randomized controlled trials are needed for a better understanding of statins' effects on cognition. More data is needed regarding statin type, dose intensity, and treatment duration, which may affect cognitive outcomes. Future studies are also needed to examine how statins may affect cognition in specific high-risk groups, such as individuals with mild cognitive impairment, diabetes, cardiovascular disease, or chronic kidney disease.