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Review
. 2022 Aug 15:14:968039.
doi: 10.3389/fnagi.2022.968039. eCollection 2022.

Statins and cognition: Modifying factors and possible underlying mechanisms

Tahereh Jamshidnejad-Tosaramandani  1   2   3 , Soheila Kashanian  1   4 , Mohamed H Al-Sabri  3 , Daniela Kročianová  3 , Laura E Clemensson  3 , Mélissa Gentreau  3 , Helgi B Schiöth  3
Affiliations
Review

Statins and cognition: Modifying factors and possible underlying mechanisms

Tahereh Jamshidnejad-Tosaramandani et al. Front Aging Neurosci. .

Abstract

Statins are a class of widely prescribed drugs used to reduce low-density lipoprotein cholesterol (LDL-C) and important to prevent cardiovascular diseases (CVD). Most statin users are older adults with CVD, who are also at high risk of cognitive decline. It has been suggested that statins can alter cognitive performance, although their positive or negative effects are still debated. With more than 200 million people on statin therapy worldwide, it is crucial to understand the reasons behind discrepancies in the results of these studies. Here, we review the effects of statins on cognitive function and their association with different etiologies of dementia, and particularly, Alzheimer's disease (AD). First, we summarized the main individual and statin-related factors that could modify the cognitive effects of statins. Second, we proposed the underlying mechanisms for the protective and adverse effects of statins on cognitive performance. Finally, we discussed potential causes of discrepancies between studies and suggested approaches to improve future studies assessing the impact of statins on dementia risk and cognitive function.

Keywords: Alzheimer’s disease; cognitive function; factors; mechanisms; repurposing; statins.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Classification of recognized factors that can modify the statin effect on cognitive function. APOE4, apolipoprotein E isoform 4; CYP2C9, cytochrome P450 family 2 subfamily C member 9; CYP2P19, cytochrome P450 2 subfamily C member 19; CVD, cardio vascular disease; WMH, white matter hyperintensities; CKD, chronic kidney disease.
FIGURE 2
FIGURE 2
Statins-estrogen hormone interactions are probable because of the common metabolic pathways in the liver with the same cytochrome P450 enzymes. Also, statins could compete with estrogens for the same transporters.
FIGURE 3
FIGURE 3
Underlying mechanisms for statins’ detrimental and beneficial effects on cognitive function.
See this image and copyright information in PMC

References

    1. Abiodun O. A., Ola M. S. (2020). Role of brain renin angiotensin system in neurodegeneration: An update. Saudi J. Biol. Sci. 27 905–912. 10.1016/j.sjbs.2020.01.026 - DOI - PMC - PubMed
    1. Adhikari A., Tripathy S., Chuzi S., Peterson J., Stone N. J. (2021). Association between statin use and cognitive function: A systematic review of randomized clinical trials and observational studies. J. Clin. Lipidol. 15 22–32.e12. 10.1016/j.jacl.2020.10.007 - DOI - PubMed
    1. Adhyaru B. B., Jacobson T. A. (2018). Safety and efficacy of statin therapy. Nat. Rev. Cardiol. 15 757–769. 10.1038/s41569-018-0098-5 - DOI - PubMed
    1. Ahangari N., Doosti M., Ghayour Mobarhan M., Sahebkar A., Ferns G. A., Pasdar A. (2020). Personalised medicine in hypercholesterolaemia: The role of pharmacogenetics in statin therapy. Ann. Med. 52 462–470. 10.1080/07853890.2020.1800074 - DOI - PMC - PubMed
    1. Alisha K., Tripti S. (2021). Repurposing statins as a potential ligand for estrogen receptor alpha via molecular docking. Ile 5 7–89. 10.52711/0974-360X.2021.00650 - DOI

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