Impact of Lowering Low-Density Lipoprotein Cholesterol with Contemporary Lipid-Lowering Medicines on Cognitive Function: A Systematic Review and Meta-Analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 32770521 · doi:10.1007/s10557-020-07045-2
What was done
A systematic review and meta-analysis of randomized controlled trials (RCTs) searched across PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov from inception to January 1, 2020. The authors evaluated the effect of contemporary lipid-lowering therapies (PCSK9 inhibitors [alirocumab, evolocumab], statins, and ezetimibe) on cognitive function in patients without baseline cognitive impairment. Thirty-three RCTs comprising 128,691 participants (66,330 intervention, 62,361 control) were analyzed using fixed- or random-effects models.
What was found
Contemporary lipid-lowering therapies significantly lowered LDL-C by -45.06% (WMD, 95% CI -50.12% to -40.00%, P < 0.001) and -64.01 mg/dL (95% CI -72.25 to -55.78, P < 0.001). There was no significant difference in the incidence of neurocognitive disorders between intervention and control groups (RR: 1.02, 95% CI 0.90 to 1.16, I2 = 0.0%, p = 0.696), with subgroup analyses by drug class and achieved LDL-C level showing consistent results. Global cognitive performance did not differ across pooled data (SMD: 0.02, 95% CI -0.01 to 0.04), while psychomotor speed showed a minor difference favoring the intervention (SMD: 0.09, 95% CI 0.02 to 0.16, P = 0.0024).
Why it matters
These findings provide strong evidence that aggressive LDL-C lowering and contemporary agents, including PCSK9 inhibitors, do not impair cognitive function or increase the risk of neurocognitive disorders.
Limits
The abstract does not report the follow-up duration of the included RCTs, limiting insight into potential long-term cognitive effects. Representation was uneven across medication classes (only two studies evaluated ezetimibe). Specific cognitive test batteries and domain evaluations were not detailed in the abstract.
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