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Impact of Lowering Low-Density Lipoprotein Cholesterol with Contemporary Lipid-Lowering Medicines on Cognitive Function: A Systematic Review and Meta-Analysis

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Abstract

Purpose

To evaluate the potential association between the lowering of low-density lipoprotein cholesterol (LDL-C) with contemporary lipid-lowering medicines and cognitive function.

Methods

Randomized controlled trials (RCTs) in databases including PubMed, Embase, and the Web of Science and all databases in the Cochrane Library and ClinicalTrials.gov were collected from inception to January 1, 2020. The cognitive function of patients receiving proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, statins and ezetimibe was evaluated using meta-analysis.

Results

A total of 2910 studies were obtained from databases and other sources. Thirty-three studies were selected by screening, including 11 studies on alirocumab, 9 studies on evolocumab, 11 studies on statins and 2 studies on ezetimibe. In our study, a total of 128,691 patients with no cognitive impairment were divided into an intervention group (66,330 patients) and a control group (62,361 patients). The data were subjected to a random-effects model or a fixed-effects model for meta-analysis. The contemporary lipid-lowering medicines significantly reduced LDL-C in terms of both percentage (WMD: −45.06%, 95% CI −50.12% to −40.00%, P < 0.001) and absolute value (WMD: −64.01 mg/dL, 95% CI −72.25 to −55.78, P < 0.001). Compared with the control group, patients receiving treatment with contemporary lipid-lowering medicines did not show a significant difference in the rate of neurocognitive disorder (RR: 1.02, 95% CI 0.90 to 1.16, I2 = 0.0%, p = 0.696). Subgroup analysis was performed according to the intervention and LDL-C stratification. The result of this subgroup analysis was consistent with the main findings. Regarding global cognitive performance, no difference in major cognition was found among the pooled data (SMD: 0.02, 95% CI −0.01 to 0.04, P = 0.002), except for psychomotor speed (SMD: 0.09, 95% CI 0.02 to 0.16, P = 0.0024).

Conclusions

Contemporary lipid-lowering medicines were not associated with cognitive impairment in RCTs. A low LDL-C level did not influence the incidence of cognitive disorder or global cognitive performance.

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Acknowledgments

All authors contributed to the analysis of the data and to the writing of the report. All authors approved the final version of the manuscript. This work was supported by the Natural Science Foundation of Zhejiang Province, Grant No. LY16H020008.

Funding

This work was supported by the Natural Science Foundation of Zhejiang Province, Grant No. LY16H020008.

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Authors and Affiliations

  1. Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China

    Hangying Ying, Jiacheng Wang, Zhida Shen, Meihui Wang & Binquan Zhou

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Correspondence to Binquan Zhou.

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Figure S1

Risk of bias graph (PNG 716 kb)

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Funnel plot for publication bias assessment (PNG 77 kb)

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Sensitivity analysis of random effects analysis (PNG 232 kb)

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Sensitivity analysis of subjects aged ≥60 years (PNG 112 kb)

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Sensitivity analysis of trials with total number of ≥ 500 and follow-up ≥1 year (PNG 99 kb)

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Sensitivity analysis by the “leave-one-out” method (PNG 65 kb)

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Sensitivity analysis of target trials except for ODYSSEY OUTCOMES (2018) (PNG 162 kb)

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Ying, H., Wang, J., Shen, Z. et al. Impact of Lowering Low-Density Lipoprotein Cholesterol with Contemporary Lipid-Lowering Medicines on Cognitive Function: A Systematic Review and Meta-Analysis. Cardiovasc Drugs Ther 35, 153–166 (2021). https://doi.org/10.1007/s10557-020-07045-2

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