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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 1), indicating that vascular disease risk factors may contribute to the pathophysiology of AD.
View this table:
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).
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