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

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; p12 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.