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American Journal of Clinical Nutrition, Vol. 73, No. 1, 127-128, January 2001
© 2001 American Society for Clinical Nutrition

Letters to the Editor

Homocysteine and B vitamins in dementia

Friedrich Leblhuber, Johannes Walli, Bernhard Widner, Erika Artner-Dworzak, Dietmar Fuchs and Karoline Vrecko

Department of Gerontology, Neurologic Clinic Wagner Jauregg, Linz, Austria, E-mail: Friedrich.Leblhuber{at}wj.lkh.ooe.gv.at
Institute of Medical Chemistry and Biochemistry, Leopold Franzens University, Innsbruck, Austria
Institute of Medical Chemistry, Karl Franzens University, Graz, Austria

Dear Sir:

Recently, Selhub et al (1) pointed out the importance of the B vitamins folic acid, vitamin B-6, and vitamin B-12 for the well-being and normal functioning of the brain. They also mentioned that the status of these vitamins is frequently inadequate in the elderly and that these inadequacies can result in hyperhomocysteinemia, a recently identified risk factor for atherosclerosis (2, 3) and Alzheimer disease (AD; 4). The authors further stated that these inadequacies can result in brain ischemia by way of occlusive vascular disease, stroke, or thrombosis.

Vascular disease risk factors such as hypertension are well recognized in AD (5). In our own series of 31 patients with cognitive decline (6), 7 of 19 AD patients had one or more vascular disease risk factors (hypertension, generalized atherosclerosis, atrial fibrillation, diabetes, and hypercholesterolemia). When we measured serum concentrations of vitamin B-12, folic acid, and homocysteine in these patients, both AD patients and those with vascular dementia had similarly elevated homocysteine compared with concentrations in healthy control subjects of similar age (Table 1Go), indicating that vascular disease risk factors may contribute to the pathophysiology of AD.


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  		TABLE 1.. Serum concentrations of homocysteine in patients with Alzheimer disease (AD) or vascular disease (VD) and in age-matched healthy control subjects1
 
We found an inverse correlation between the degree of cognitive impairment as determined by the Mini-Mental State Examination (MMSE) and homocysteine (r = -0.43; Spearman rank correlation), an inverse correlation between folic acid and homocysteine (r = -0.36), a correlation between MMSE and folic acid (r = 0.37), and a correlation between folic acid and vitamin B-12 (r = 0.60) (all P < 0.05). These results agree well with recent data reported by Nourhashemi et al (7), who also found a correlation between cognitive skills and B vitamins including folic acid and homocysteine.

In our study, 9 of 31 patients with dementia and hyperhomocysteinemia were treated with 50 mg vitamin B-1, 50 mg vitamin B-6, 5 mg folic acid, and 0.05 mg vitamin B-12 (Beneuran compositum TM; Nycomed Austria GmBH, Linz, Austria). After 4 wk of treatment, serum homocysteine concentrations had returned to normal in all 9 patients, dropping from 17.3 ± 1.9 to 10.7 ± 3.5 µmol/L (t = -7.72, P < 0.0001; paired t test).

These data suggest that homocysteine, identified as an independent risk factor for vascular diseases (3) may also be of relevance in AD (4) and in vascular dementia, and that folic acid would be an additional therapeutic option in patients with dementia. We agree with the conclusion of Nourhashemi et al (7) that further studies must be performed to elucidate the association between vitamin status and homocysteine concentrations and the possible role of immune activation, free radicals, and oxidative stress in dementia (8).

REFERENCES

  1. Selhub J, Bagley LC, Miller J, Rosenberg IH. B vitamins, homocysteine, and neurocognitive function in the elderly. Am J Clin Nutr 2000;71(suppl):614S–20S.
  2. Temple ME, Luzier AB, Kazierad DJ. Homocysteine as a risk factor for atherosclerosis. Ann Pharmacother 2000;34:57–65.[Abstract]
  3. Hankey GJ, Eikelboom JW. Homocysteine and vascular disease. Lancet 1999;354:407–13.[Medline]
  4. Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 1998;55:1449–55.[Abstract/Free Full Text]
  5. Skoog I, Lernfeldt B, Landahl S, et al. A 15 year longitudinal study on blood pressure and dementia. Lancet 1996;347:1141–5.[Medline]
  6. Leblhuber F, Walli J, Artner-Dworzak E, et al. Homocysteine and B vitamins in dementia. J Neural Transm 2000;107;1469–74.
  7. Nourhashemi F, Gillet-Guyonnet S, Andrieu S, et al. Alzheimer disease: protective factors. Am J Clin Nutr 2000;71(suppl):643S–9S.
  8. Sattler W, Leblhuber F, Walli J, Widner B, Fuchs D. Cerebrospinal fluid levels of {alpha}-tocopherol in patients with dementia. Pteridines 1999;10:220–4.



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