Abstract
Metformin is the safest and the most widely prescribed first-line therapy for managing hyperglycemia due to different underlying causes, primarily type 2 diabetes mellitus. In addition to its euglycemic properties, metformin has stimulated a wave of clinical trials to investigate benefits on aging-related diseases and longevity. Such an impact on the lifespan extension would undoubtedly expand the therapeutic utility of metformin regardless of glycemic status. However, there is a scarcity of studies evaluating whether metformin has differential cognitive effects across age, sex, glycemic status, metformin dose, and duration of metformin treatment and associated pathological conditions. By scrutinizing the available literature on animal and human studies for metformin and brain function, we expect to shed light on the potential impact of metformin on cognition across age, sex, and pathological conditions. This review aims to provide readers with a broader insight of (a) how metformin differentially affects cognition and (b) why there is a need for more translational and clinical studies examining multifactorial interactions. The outcomes of such comprehensive studies will streamline precision medicine practices, avoiding “fit for all” approach, and optimizing metformin use for longevity benefit irrespective of hyperglycemia.
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References
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Acknowledgements
We have to express our appreciation to Ali Winters, Lab Assistant, UNTHSC for sharing her pearls of artistic wisdom with us while creating the figures of this manuscript.
Funding
This work was financially supported by the National Institutes of Health grants 1R21NS087209-01A1 (SY), R01NS088596 (SY), and American Heart Association Grant 17POST33670981 (KC).
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Highlights
1. Metformin affects cognition.
2. Sex influences metformin pharmacokinetics and associated cognitive alterations.
3. Organic cation transporters and AMP-activated kinase might hold a key for metformin-associated cognitive alterations.
4. Age is a critical factor affecting metformin-associated cognitive alterations.
5. Metformin may inverse the pathological conditions induced cognitive variations.
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Chaudhari, K., Reynolds, C.D. & Yang, SH. Metformin and cognition from the perspectives of sex, age, and disease. GeroScience 42, 97–116 (2020). https://doi.org/10.1007/s11357-019-00146-3
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DOI: https://doi.org/10.1007/s11357-019-00146-3