Intended for healthcare professionals

Rapid response to:

Feature Alzheimer’s Disease

Alzheimer’s disease: still a perplexing problem

BMJ 2014; 349 doi: (Published 08 July 2014) Cite this as: BMJ 2014;349:g4433

Rapid Response:

Alzheimer’s Disease, Dementia and Homocysteine

One of the most interesting aspects of the article about the “perplexing problem” of Alzheimer’s disease by Chinthapalli(1) is the fact that during a 13 year period, out of 101 drugs tested only 3 reached market, each with minimal therapeutic effects.

Many previous studies demonstrate a relationship between Alzheimer's dementia and the spectrum of cardiovascular diseases, including stroke, an accepted risk factor for Alzheimer's disease. Alzheimer's disease and cardiovascular diseases share a common risk factor, elevated blood levels of homocysteine, an amino acid which becomes elevated by inadequate dietary intakes of vitamins B2, B6, B9 (folate) and B12. Multivitamins reliably lower homocysteine in most if not all; they are the only “therapy”.

There is epidemiological evidence for both a declining dementia / Alzheimer’s disease epidemic and for improved stroke deaths since folate food fortification.(2,3) The authors of the Framingham Study concluded that homocysteine is “a strong, independent risk factor for the development of dementia and Alzheimer's disease”, a statement based on the finding of an almost doubled rate of dementia in the highest quartile of plasma homocysteine.(4)

Recent data show that B-vitamin supplementation virtually halts grey matter atrophy in areas of the brain related to Alzheimer’s disease while slowing some cognitive decline.(5) These observations support the concept that blood homocysteine and the B vitamins that influence the level of homocysteine are potentially causal and modifiable risk factors. Moreover, these parameters must be determined in future studies as confounding risk factors regarding Alzheimer’s disease.

Eddie Vos, M.Eng., Kilmer S. McCully, M.D.

1. Chinthapalli K. Alzheimer's disease: still a perplexing problem. BMJ. 2014 Jul 8;349:g4433. doi: 10.1136/bmj.g4433. PMID 25005430

2 Larson EB, Yaffe K, Langa KM. New Insights into the Dementia Epidemic.
N Engl J Med. 2013;369(24):2275-7. PMID 24283198

3. Yang Q, Botto LD, Erickson JD, et al. Improvement in stroke mortality in Canada and the United States, 1990 to 2002. Circulation. 2006;113(10):1335-43. PMID 16534029

4. Seshadri S, Beiser A, Selhub J, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med. 2002;346(7):476-83. PMID 11844848

5. Douaud G, Refsum H, de Jager CA, et al. Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci USA. 2013;110(23):9523-8. PIMD 23690582

Competing interests: No competing interests

23 July 2014
Eddie Vos
Forensic sciences
Kilmer S. McCully, M.D. Pathology and Laboratory Medicine Service VA Boston Healthcare System, 1400 Veterans of Foreign Wars Parkway, West Roxbury, MA 02132, USA
127 Courser Rd, Sutton QC Canada J0E 2K0