High Dose metformin might eliminate Alzheimer Dementia Risk

Sun M, Chen WM, Wu SY, Zhang J. Metformin in elderly type 2 diabetes mellitus: dose-dependent dementia risk reduction. Brain. 2024 Apr 4;147(4):1474-1482

https://academic.oup.com/brain/article-abstract/147/4/1474/7329837?login=false

Abstract

This study aimed to investigate the controversial association between metformin use and diabetes-associated dementia in elderly patients with type 2 diabetes mellitus (T2DM) and evaluate the potential protective effects of metformin, as well as its intensity of use and dose-dependency, against dementia in this population. The study used a time-dependent Cox hazards model to evaluate the effect of metformin use on the incidence of dementia. The case group included elderly patients with T2DM (≥60 years old) who received metformin, while the control group consisted of elderly patients with T2DM who did not receive metformin during the follow-up period. Our analysis revealed a significant reduction in the risk of dementia among elderly individuals using metformin, with an adjusted hazard ratio of 0.34 (95% confidence interval: 0.33 to 0.36). Notably, metformin users with a daily intensity of 1 defined daily dose (DDD) or higher had a lower risk of dementia, with an adjusted hazard ratio (95% confidence interval) of 0.46 (0.22 to 0.6), compared to those with a daily intensity of <1 DDD. Additionally, the analysis of cumulative DDDs of metformin showed a dose-response relationship, with progressively lower adjusted hazard ratio across quartiles (0.15, 0.21, 0.28, and 0.53 for quartiles 4, 3, 2 and 1, respectively), compared to never metformin users (P for trend < 0.0001). Metformin use in elderly patients with T2DM is significantly associated with a substantial reduction in the risk of dementia. Notably, the protective effect of metformin demonstrates a dose-dependent relationship, with higher daily and cumulative dosages of metformin showing a greater risk reduction.

Metformin may reduce Alzheimer’s disease risk by increasing soluble amyloid-β42 levels

Daly, Timothy, and Bruno P. Imbimbo. “Metformin may reduce Alzheimer’s disease risk by increasing soluble amyloid-β42 levels.” Brain (2024): awae367

https://www.researchgate.net/profile/Timothy-Daly-2/publication/385652177_Metformin_may_reduce_Alzheimer’s_disease_risk_by_increasing_soluble_amyloid-b42_levels/links/672ddb1977f274616d636529/Metformin-may-reduce-Alzheimers-disease-risk-by-increasing-soluble-amyloid-b42-levels.pdf

  • Either the beta amyloid plaques are dissolving or do not get laid down as they are soluble.

Comment – I’m taking 2 gm/day in divided doses with some Vitamin B12 because it can make it go low after some years. It can cause GI problems and diarrhea among some but is less likely with the long-acting forms. I have noticed 50% reduction in my pains since I got to full dose which was brought forward earlier:

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