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The Effects of Statins on Cognitive Performance Are Mediated by Low-Density Lipoprotein, C-Reactive Protein, and Blood Glucose Concentrations.

ABSTRACT: Statins are widely used for cardiovascular disease prevention but their effects on cognition remain unclear. Statins reduce cholesterol concentration and have been suggested to provide both beneficial and detrimental effects. Our aim was to investigate the cross-sectional and longitudinal association between statin use and cognitive performance, and whether blood low-density lipoprotein, high-density lipoprotein, triglycerides, glucose, C-reactive protein, and vitamin D biomarkers mediated this association. We used participants from the UK biobank aged 40-69 without neurological and psychiatric disorders (n = 147 502 and n = 24 355, respectively). We performed linear regression to evaluate the association between statin use and cognitive performance and, mediation analysis to quantify the total, direct, indirect effects and the proportion meditated by blood biomarkers. Statin use was associated with lower cognitive performance at baseline (β = -0.40 [-0.53, -0.28], p = <.0001), and this association was mediated by low-density lipoprotein (proportion mediated = 51.4%, p = .002), C-reactive protein (proportion mediated = -11%, p = .006) and blood glucose (proportion mediated = 2.6%, p = .018) concentrations. However, statin use was not associated with cognitive performance, measured 8 years later (β = -0.003 [-0.11, 0.10], p = .96). Our findings suggest that statins are associated with lower short-term cognitive performance by lowering low-density lipoprotein and raising blood glucose concentrations, and better performance by lowering C-reactive protein concentrations. In contrast, statins have no effect on long-term cognition and remain beneficial in reducing cardiovascular risk factors.

SUBMITTER: Gentreau M

PROVIDER: S-EPMC10613010 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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The Effects of Statins on Cognitive Performance Are Mediated by Low-Density Lipoprotein, C-Reactive Protein, and Blood Glucose Concentrations.

Gentreau Mélissa M Rukh Gull G Miguet Maud M Clemensson Laura E LE Alsehli Ahmed M AM Titova Olga E OE Schiöth Helgi B HB

The journals of gerontology. Series A, Biological sciences and medical sciences 20231001 11

Statins are widely used for cardiovascular disease prevention but their effects on cognition remain unclear. Statins reduce cholesterol concentration and have been suggested to provide both beneficial and detrimental effects. Our aim was to investigate the cross-sectional and longitudinal association between statin use and cognitive performance, and whether blood low-density lipoprotein, high-density lipoprotein, triglycerides, glucose, C-reactive protein, and vitamin D biomarkers mediated this ...[more]

PMID: 37431946

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Project description:Low-density lipoprotein cholesterol (LDL-C) is an important modifiable risk factor for atherosclerotic cardiovascular disease. It is unclear whether the percentage LDL-C lowering with pharmacotherapies differs on the basis of baseline LDL-C levels. To evaluate the association between baseline LDL-C levels and the percentage LDL-C reduction with a statin, ezetimibe, and a PCSK9 inhibitor. This secondary exploratory study analyzed data from 3 randomized placebo-controlled clinical trials (Aggrastat to Zocor-Thrombolysis in Myocardial Infarction 21 [A to Z-TIMI 21], Improved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT], and Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk [FOURIER]) of lipid-lowering therapies (statin, ezetimibe, and a PCSK9 inhibitor) and included participants with atherosclerotic cardiovascular disease. Analyses took place form April to October 2020. In A to Z-TIMI 21, 1:1 randomization to simvastatin, 40 mg, daily for 30 days followed by 80 mg daily thereafter vs placebo for 4 months followed by simvastatin, 20 mg, daily thereafter. In IMPROVE-IT, 1:1 randomization to ezetimibe, 10 mg, daily plus simvastatin, 40 mg, daily vs placebo plus simvastatin, 40 mg, daily. In FOURIER, 1:1 randomization to evolocumab, 140 mg, every 2 weeks or 420 mg monthly vs matching placebo. The percentage LDL-C reduction at either 1 month (A to Z-TIMI 21, IMPROVE-IT) or 3 months (FOURIER) as a function of baseline LDL-C level. Data were modeled using a generalized linear regression model. A total of 3187 patients from A to Z-TIMI 21, 10 680 patients from IMPROVE-IT, and 25 847 patients from FOURIER were analyzed. There was a higher percentage reduction in LDL-C levels with evolocumab in patients with lower baseline LDL-C levels, ranging from 59.4% (95% CI, 59.1%-59.8%) in patients with a baseline LDL-C level of 130 mg/dL to 66.1% (95% CI, 65.6%-66.6%) in patients with a baseline LDL-C level of 70 mg/dL (P < .001). In contrast, across the same range of baseline LDL-C level, there was a more modest difference for simvastatin (44.6% [95% CI, 43.9%-45.2%] vs 47.8% [95% CI, 46.4%-49.2%]; P < .001) and minimal difference with ezetimibe (25.0% [95% CI, 23.3%-26.6%] vs 26.2% [95% CI, 24.2%-28.1%]; P = .007). The percentage LDL-C reduction with statins, ezetimibe, and PCSK9 inhibition is not attenuated in patients starting with lower baseline LDL-C levels and is 6.6% greater for PCSK9 inhibition. These data are encouraging for the use of intensive LDL-C-lowering therapy even for patients with lower LDL-C levels.

Dataset Information

The Effects of Statins on Cognitive Performance Are Mediated by Low-Density Lipoprotein, C-Reactive Protein, and Blood Glucose Concentrations.

Publications

The Effects of Statins on Cognitive Performance Are Mediated by Low-Density Lipoprotein, C-Reactive Protein, and Blood Glucose Concentrations.

Similar Datasets

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