Low B-vitamin status—particularly B6, B12, folate, and riboflavin—correlates with cognitive dysfunction and dementia in older adults, while those with dementia show increased pro-inflammatory gut bacteria and elevated circulating cytokines. Preclinical evidence suggests B-vitamins may beneficially alter gut bacterial profiles and metabolic activity, potentially reducing neuroinflammation. The gut-brain-nutrition axis represents an emerging frontier in cognitive aging research. This triangulation of B-vitamin deficiency, gut dysbiosis, and brain inflammation offers a compelling mechanistic pathway that could revolutionize how we approach cognitive preservation. Unlike traditional approaches focusing solely on direct neural effects, this framework positions the microbiome as a critical mediator. The practical implications are significant—optimizing B-vitamin intake through diet or targeted supplementation could provide a cost-effective intervention for maintaining cognitive health. However, current human evidence remains limited to small clinical studies or single-vitamin approaches. The field needs large-scale, multi-vitamin intervention trials in healthy aging populations to validate these mechanistic insights and establish optimal dosing strategies for cognitive protection.