NEJM Evid

LDL-cholesterol: How low can we go and still preserve cognitive health?

January 22, 2025

Exposure to long-term, very low levels of LDL cholesterol as a result of PCSK9 inhibition and statin therapy wasn't associated with cognitive decline over a median of 5 years of follow-up. However, further studies are needed to confirm these findings in adults at higher risk of dementia.

Study details: This prospective study enrolled adults with atherosclerotic cardiovascular disease (ASCVD) who had completed the EBBINGHAUS neurocognitive substudy of the FOURIER trial and were eligible for a long-term open-label extension. The study assessed the long-term cognitive effects of evolocumab, with cognitive function evaluated annually. Change from baseline in executive function, measured using the spatial working memory strategy index score, was the primary endpoint.

Results: Evolocumab treatment didn’t result in a significant change in executive function during follow-up, with similar scores between those who continued evolocumab and those who started it after the placebo phase. At the final study visit, executive function scores were similar between the randomly assigned groups.

Source:

Zimerman A, et al. (2025 January). NEJM Evid. Long-Term Cognitive Safety of Achieving Very Low LDL Cholesterol with Evolocumab. https://pubmed.ncbi.nlm.nih.gov/39718423/