Statin therapy may impact cognitive health, experts say to interpret results very carefully: JACC

USA: Statin use for lowering LDL-cholesterol levels may result in adverse neurocognitive effects related to HMGCR inhibition, which may be outweighed by its cardiovascular benefits but requires pharmacovigilance, states a genetic-based study published in the Journal of the American College of Cardiology. 

On the other hand, PCSK9 inhibitors, which also lower LDL-C levels but through a different mechanism may have a neutral cognitive profile. The experts who were not involved in the study, however, urged precaution in the interpretation of the findings. 

Lipid-lowering therapy with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition and statins are effective strategies for lowering the risk of cardiovascular disease, however, concerns there are concerns about potential long-term adverse neurocognitive effects. Considering this, Daniel B. Rosoff, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA, and colleagues aimed to evaluate the relationships of long-term PCSK9 inhibition and statin use on neurocognitive outcomes in a genetics-based study. 

For this purpose, the researchers extracted single-nucleotide polymorphisms in 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and PCSK9 from predominantly European ancestry-based genome-wide association studies summary-level statistics of LDL-cholesterol and performed drug-target Mendelian randomization. The potential neurocognitive impact of drug-based PCSK9 and HMGCR inhibition was proxied using a range of outcomes to capture the complex facets of cognition and dementia.