Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter June 1, 2005

Homocysteine, vitamin B12 and folate in vascular dementia and in Alzheimer disease

Mariano Malaguarnera, Raffaele Ferri, Rita Bella, Giovanna Alagona, Anna Carnemolla and Giovanni Pennisi

Abstract

The association between elevated plasma levels of homocysteine (Hcy) and nutritional status has been shown in Alzheimer disease (AD) patients and also in vascular dementia (VaD). Moreover, a previous study provided evidence that the relation between a high Hcy level and low vitamin B12 and folate levels in AD patients is due to biochemical damage, rather than a nutritional deficit. The purpose of this study was to investigate the relationship between plasma Hcy levels and vitamins involved in its metabolism in AD and VaD. Twenty-two VaD patients, 22 AD patients and 24 healthy subjects were studied for Hcy, vitamin B12, vitamin B6 and folate. All patients and control subjects were comparable for age, educational level, nutritional and socioeconomic status. None of them showed macrocytic anemia or impaired renal function. Hcy was significantly increased in VaD patients (26.0±6.58 µmol/l) as compared to controls (10.7±3.0 µmol/l) and AD patients (22.3±4.51 µmol/l; p<0.001); however, AD patients also showed increased levels of Hcy. Folates were significantly reduced in both VaD (10.8±2.81 nmol/l) and AD (10.0±2.72 nmol/l; p<0.001) patients, while vitamin B12 showed significantly reduced levels only in AD patients (392.1±65.32 pmol/l; p=0.02). Vitamin B6 was not significantly different in the three groups.

Increased levels of Hcy associated with low vitamin B12 plasma levels were found only in AD patients. This observation led us to consider that vitamin B12 metabolism does not represent the direct consequence of the nutritional status and suggests that neuronal damage results in a functional vitamin B12 deficiency, as emphasized by recent reports. New therapeutic strategies are necessary, considering that available pharmaceutical forms of vitamin B12 are not utilized by neurons in oxidative stress conditions.


Corresponding author: Mariano Malaguarnera, Istituto di Medicina Interna e Geriatria-Università di Catania, Ospedale Cannizzaro, Via Messina, 829, 95126 Catania, Italy. Phone: 0039-095-7262008, Fax: 0039-095-7262011, E-mail:

References

1 Carson NAJ, Neill DW. Metabolic abnormalities detected in a survey of mentally backward individuals in Northern Ireland. Arch Dis Child 1962; 37:505–13.10.1136/adc.37.195.505Search in Google Scholar

2 Malaguarnera M, Pistone G, Motta M, Vinci E, Oreste G, Avellone G, et al. Elevated plasma total homocysteine in centenarians. Clin Chem Lab Med 2004; 42:307–10.10.1515/CCLM.2004.056Search in Google Scholar

3 Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B, Graham I. Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med 1991; 324:1149–55.10.1056/NEJM199104253241701Search in Google Scholar

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; 55:1449–55.10.1001/archneur.55.11.1449Search in Google Scholar

5 McCaddon A, Davies G, Hudson P. Nutritionally independent B12 deficiency and Alzheimer disease. Arch Neurol 2000; 57:607–08.10.1001/archneur.57.4.607Search in Google Scholar

6 Erkinjuntti T, Inzitari D, Pantoni L, Wallin A, Scheltens P, Rockwood K, et al. Research criteria for subcortical vascular dementia in clinical trials. J Neural Transm Suppl 2000; 59:23–30.10.1007/978-3-7091-6781-6_4Search in Google Scholar

7 McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984; 34:939–44.10.1212/WNL.34.7.939Search in Google Scholar

8 Dick JP, Guiloff RJ, Stewart A, Blackstock J, Bielawska C, Paul EA, et al. Mini-mental state examination in neurological patients. J Neurol Neurosurg Psychiatry 1984; 47:496–9.10.1136/jnnp.47.5.496Search in Google Scholar

9 Guidelines for the management of mild hypertension: memorandum from a World Health Organization – International Society of Hypertension meeting. J Hypertens 1993; 11:905–18.10.1097/00004872-199309000-00004Search in Google Scholar

10 Araki A, Sako Y. Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection. J Chromat 1987; 422:43–52.10.1016/0378-4347(87)80438-3Search in Google Scholar

11 Shin Buering Y, Rasshofer R, Endres WA. A new enzymatic method for pyridoxal 5′-phosphate determination. J Inherit Metab Dis 1981; 4:123–4.10.1007/BF02263621Search in Google Scholar

12 Matas C, Cabrè M, La Ville A, Prats E, Joven J, Turner PR, et al. Limitation of the Friedewald formula for estimating low density lipoprotein cholesterol in alcoholics with liver disease. Clin Chem 1994; 40:404–6.10.1093/clinchem/40.3.404Search in Google Scholar

13 Friedewald WT, Levy RI, Friedrickson DS. Evaluation of the concentration of low density lipoprotein cholesterol in plasma without use of the preparative ultracentrifuge. Clin Chem 1972; 18:499–502.10.1093/clinchem/18.6.499Search in Google Scholar

14 Snowdon DA, Tully CL, Smith CD, Riley KP, Markesbery WR. Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: findings from the Nun study. Am J Clin Nutr 2000; 71:993–8.10.1093/ajcn/71.4.993Search in Google Scholar

15 Wang HX, Wahlin A, Basun H, Fastbom J, Winblad B, Fratiglioni L. Vitamin B(12) and folate in relation to the development of Alzheimer’s disease. Neurology 2001; 56:1188–94.10.1212/WNL.56.9.1188Search in Google Scholar

16 Lehmann M, Gottfries CG, Regland B. Identification of cognitive impairment in the elderly: homocysteine is an early marker. Dement Geriatr Cogn Disord 1999; 10:12–20.10.1159/000017092Search in Google Scholar

17 Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 2002; 346:476–83.10.1056/NEJMoa011613Search in Google Scholar

18 Nilsson K, Gustafson L, Hultberg B. The plasma homocysteine concentration is better than that of serum methylmalonic acid as a marker for sociopsychological performance in a psychogeriatric population. Clin Chem 2000; 46:691–6.10.1093/clinchem/46.5.691Search in Google Scholar

19 McCaddon A, Davies G, Hudson P, Tandy S, Cattell H. Total serum Hcy in senile dementia of Alzheimer type. Int J Geriatr Psychiatry 1998; 13:235–39.10.1002/(SICI)1099-1166(199804)13:4<235::AID-GPS761>3.0.CO;2-8Search in Google Scholar

20 Hankey GJ, Eikelboom JW. Hcy and vascular disease. Lancet 1999; 354:407–13.10.1016/S0140-6736(98)11058-9Search in Google Scholar

21 White AR, Huang X, Jobling MF, Barrow CJ, Beyreuther K, Masters CL, et al. Hcy potentiates copper- and amyloid beta peptide-mediated toxicity in primary neuronal cultures: possible risk factors in the Alzheimer’s-type neurodegenerative pathways. J Neurochem 2001; 76:1509–20.10.1046/j.1471-4159.2001.00178.xSearch in Google Scholar PubMed

22 McCaddon A, Regland B, Hudson P, Davies G. Functional vitamin B(12) deficiency and Alzheimer disease. Neurology 2002; 58:1395–9.10.1212/WNL.58.9.1395Search in Google Scholar

Received: 2003-12-24
Accepted: 2004-6-3
Published Online: 2005-6-1
Published in Print: 2004-9-1

© Walter de Gruyter