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Updated: Jul 16, 2025

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Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke: A Scientific Statement

Larry B Goldstein, Peter P Toth, Jennifer L Dearborn-Tomazos

    Arteriosclerosis, Thrombosis, and Vascular Biology
    |September 14, 2023
    PubMed

    Insights

    Aggressive low-density lipoprotein cholesterol lowering does not appear to cause brain toxicity, cognitive decline, or dementia. While some studies suggest risks, the majority of evidence, including randomized trials, refutes these concerns.

    Area of Science:

    • Cardiovascular Medicine
    • Neurology
    • Pharmacology

    Background:

    • Concerns exist regarding potential neurotoxic effects of intensive lipid-lowering therapies.
    • Specifically, the impact of aggressive low-density lipoprotein cholesterol (LDL-C) reduction on cognitive function and stroke risk is debated.

    Purpose of the Study:

    • To critically evaluate current scientific evidence on whether intensive LDL-C lowering or lipid-lowering treatments cause brain toxicity.
    • To assess the association with cognitive impairment, dementia, and hemorrhagic stroke.

    Main Methods:

    • Comprehensive literature review of observational studies and randomized controlled trials.
    • Analysis of clinical and epidemiology studies, public health guidelines, and expert opinions.
    • Identification of knowledge gaps in existing research.

    Main Results:

    • The majority of observational studies and randomized trial data do not support a link between statin therapy and cognitive impairment or dementia.
    • Statin use is associated with a nonsignificant risk of hemorrhagic stroke in patients without prior cerebrovascular disease.
    • Achieving very low LDL-C levels does not elevate hemorrhagic stroke risk.

    Conclusions:

    • Current evidence largely refutes the hypothesis that aggressive LDL-C lowering causes brain toxicity, cognitive impairment, or dementia.
    • The risk of hemorrhagic stroke with statin therapy is minimal in the general population without cerebrovascular history.
    • Further research is needed to clarify hemorrhagic stroke risks in patients with a history of such events undergoing lipid-lowering treatment.

    Keywords:
    AHA Scientific StatementsPCSK9 inhibitorsblood-brain barriercholesterol, LDLcognitionezetimibehydroxymethylglutaryl-CoA reductase inhibitorsstroke

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