Dementia hyperhomocysteinemia

In the early stages of vitamin B12 deficiency, classic signs and symptoms of megaloblastic anemia may not be evident and serum levels of vitamin B12 may be within normal limits. Therefore measurement of MMA and homocysteine is useful, as these parameters are often the first to change. Increased levels of serum MMA and homocysteine may be evident, as both of these are involved in enzymatic reactions dependent on vitamin Bn, and a deficiency in vitamin Bn allows for accumulation of these precursors. Elevations in MMA are more specific for vitamin Bn deficiency, while elevated homocysteine can be indicative of either vitamin Bn or folic acid deficiency, but offers greater specificity for folate plasma levels. Low levels of vitamin Bn result in hyperhomocysteinemia, which the majority of data suggest is an independent risk factor for cerebrovascular, peripheral vascular, coronary, and venous thromboembolic disease. Hyperhomocysteinemia may also be linked to dementia and Alzheimer s disease. ... 

Hyperhomocysteinemia has long been identified as a risk factor for dementia including Alzheimer s disease (AD) and vascular dementia (VaD) (Morris 2003). The relationship of homocysteine metabolism (methylation and transsulfuration pathways) to deficiencies of the vitamin B complex suggests that hypervitaminosis (Bg, B12 and folate) could contribute to hyperhomocysteinemia (Gonzalez-Gross et al. 2001). 

The apparent association of low vitamin B status and hyperhomocysteinemia and dementia raises the question which markers to select that are sensitive and specific enough to reflect the functional status of vitamin B12 and folate in the tissues so that they can be used to measure the risk of developing the disease (Table 46.2). 

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