Supplementary file 1_The effects of cholesterol-lowering drugs on neurocognitive function: systematic review and meta analysis.docx

ObjectiveTo investigate if cholesterol-lowering drugs exert effects on neurocognitive function.
MethodsWe searched Pubmed, Embase and Cochrane Libarary from inception to March 23rd, 2023, and searched clinicaltrials.gov on January 23rd, 2024. Randomized controlled trials that evaluated neurocognitive events and neurocognitive function after using cholesterol-lowering drugs including statins, cholesterol absorption inhibitors, proprotein convertase subtilisin/kexin 9 inhibitors were collected. The literature screening, data extraction and quality evaluation were carried out independently by two researchers, and the random effect model was used to pool the data.
ResultsA total of 42 studies with 150,405 subjects were included. Cholesterol-lowering drugs did not increase the risk of neurocognitive events (RR: 0.99, 95% CI: 0.88–1.12). Subgroup analysis by the type of drugs did not suggest that statins (RR: 0.94, 95% CI: 0.72–1.25), ezetimibe (RR: 1.11, 95% CI: 0.71–1.74) or proprotein convertase subtilisin/kexin 9 inhibitors (RR: 1.00, 95% CI: 0.87–1.14) increased the risk of neurocognitive events. By pooling the outcomes of the neurocognitive test scale, we found that cholesterol-lowering drugs did not change neurocognitive function in the five domains of attention, psychomotor speed, executive function, working memory and memory, as well as global effect.
ConclusionCholesterol-lowering drugs including statins, cholesterol absorption inhibitors and PCSK9 inhibitors have no adverse effects on neurocognitive function. The decrease of low-density lipoprotein cholesterol will not lead to the decline of neurocognitive function.
Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42023404802, Identifier: CRD42023404802