Real‐world relationship between blood biomarker‐based PhenoAge, metformin, and Alzheimer's disease

Abstract INTRODUCTION The biological aging process could be an important Alzheimer's disease (AD) pathogenesis. Metformin might be beneficial in anti‐aging and cognition and has mixed associations with AD and/or dementia. METHODS We used a US nationwide insurance claims dataset. We used Cox models to investigate the relationship between blood biomarker‐based PhenoAge and AD and PhenoAge‐stratified comparative AD risks between metformin and sulfonylureas. RESULTS We determined that a higher PhenoAge was associated with an increased risk of AD, and that metformin, compared with sulfonylureas, was associated with a reduced risk of AD only in individuals with a lower PhenoAge (hazard ratio: 0.42 to 0.50, p <0.01) but not with AD in individuals with a higher PhenoAge and in individuals with a lower age. DISCUSSION We found that a higher PhenoAge was associated with an increased risk of AD and that metformin was associated only with a reduced risk of AD in individuals with a lower PhenoAge.