Metformin Use Likely Reduces Alzheimer's Disease Risk
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Use of metformin likely reduces the risk for Alzheimer's disease (AD) in the general population. Expression of a mitochondrial complex I–related gene, NDUFA2, reduced AD risk and was associated with less cognitive decline in the brain. Mitochondrial function and the NDUFA2 gene are likely mechanisms of action in dementia protection.
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@bubun Genetically proxied metformin use equivalent to a 6.75 mmol/mol (1.09%) reduction of A1c was associated with 4% lower odds of AD (P = 1.06 × 10-4) in individuals who did not have diabetes. One metformin target, mitochondrial complex 1 (MCI), showed a robust effect on AD (P = 4.73 × 10-4) that was independent of AMP–activated protein kinase. Mendelian randomization of expression in brain cortex tissue showed that decreased expression of the MCI-related gene NDUFA2 was associated with reduced AD risk (P = 4.64 × 10-4) and less cognitive decline.