SIRT1 and dementia: Although these preclinical findings are promising and suggest metformin’s potential as a multi-target therapeutic for AD by modulating AMPK/mTOR/SIRT1 pathways [42], clinical evidence remains mixed, and observational studies suggest potential cognitive benefits but highlight conflicting data regarding its long-term impact on dementia prevention, emphasizing the need for large, long-term randomized trials like the TAME study to clarify metformin’s role in dementia prevention [43].