This paper is a commentary, not an original empirical study. It does not involve a defined sample or sample size; rather, it discusses existing evidence and trials regarding homocysteine, B vitamins, and dementia.

Commentary (debate/opinion piece) responding to the omission of raised plasma homocysteine as a risk factor in the Lancet Commission report.

JWM and AMcC are members of the American Society for Nutrition and the Alzheimer’s Prevention Expert Group of the Food for the Brain Foundation; BH has received speaker honoraria from the American Academy of Neurology and Warwar Pharma; HR and ADS are named inventors on a University of Oxford patent concerning use of B vitamins to prevent brain atrophy in mild cognitive impairment; ADS is also a member of the Scientific Advisory Boards of the Food for the Brain Foundation and Elysium Health, and a member of the Alzheimer’s Prevention Expert Group of the Food for the Brain Foundation ([pubmed.ncbi.nlm.nih.gov](https://pubmed.ncbi.nlm.nih.gov/40551597/?utm_source=openai)).

The commentary highlights that elevated plasma total homocysteine is a modifiable risk factor for cognitive decline, dementia, and Alzheimer’s disease, supported by prior consensus statements and intervention trials showing that B vitamin–mediated homocysteine lowering slows brain atrophy and cognitive decline ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12284325/?utm_source=openai)). It cites the VITACOG trial, where B vitamin treatment reduced homocysteine by ~30%, with cognitive and clinical benefits observed in participants with baseline homocysteine above the median; regional brain atrophy in Alzheimer’s-affected areas was reduced more than sevenfold ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12284325/?utm_source=openai)). It also notes observational evidence, including a UK Biobank study of 192,214 participants showing protective effects of dietary intake of methionine, folate, B6, and B12 against Alzheimer’s (hazard ratios 0.30–0.77 for top vs bottom quartile), and a Swedish cohort (n=2,570) where high blood methionine was associated with 46% lower dementia risk and high homocysteine with 60% greater risk; high methionine-to-homocysteine ratio correlated with slower brain atrophy ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12284325/?utm_source=openai)).