Vitamin B12 and folate in relation to the development of Alzheimer’s disease
Carlos R MRieder, Neurology Service Hospital de Cliniicas de Porto Alegre Porto Alegre, Brazilsandi_moriarity@urmc.rochester.edu
Daniele Fricke
Submitted June 26, 2001
We read with interest the article by Wang et al. on the association
of low serum levels of vitamin B12 and folate with Alzheimer's disease
(AD) occurrence.[1] We think that it is difficult to establish a clinical
diagnosis of AD in patients with deficiency of vitamin B12 or folate. AD
in this situation could be hardly differentiated from other kinds of
dementia particularly from dementia associated with B12 deficiency and
vascular dementia.
Cobalamin (vitamin B12) is a co-factor in several metabolic pathways
and its deficiency may be associated with dementia. The authors have
controlled the hemoglobin levels. Nevertheless the dementia caused by
vitamin B12 deficiency may not be accompanied by anemia. Dementia may
be the sole manifestation of cobalamin deficiency.[2] The most important
pathway in the nervous system that is adversely affected by cbalamin
deficiency involves the conversion of homocysteine to methionine.
Demyelination clearly plays a major role in the neuropathogensis of
cobalamin deficiency and cognitive changes can occur as a result of
central demyelination. [3] Furthermore,it was recently showed that high
levels of homocystein are associated with poor word recall in the elderly.
[4] High homocysteinemia can be caused by deficiencies of folate or
vitamin B12.
Another issue to be considered refers to the ifferentiation of
vascular dementia. Elevated plasma levels of homocystein have been
implanted recently as a risk factor for atherosclerosis and stroke.
Homocysteine may be directly toxic to endothelium or thrombogenic.
Patients
with vascular dementia may be unremarkable. Hachinski Ischemic Scale has
been used in this study. However, no imaging study was performed. The
cognitive disorder of vascular dementia itself is heterogeneous and may
take several different forms. The pleomorphic nature of vascular
dementia contributes to diagnostic problems.
Although determination of the serum levels of vitamin B12 is the
principal diagnostic test for cobalamin deficiency, this test is neither
completely sensitive nor specific. We think that further testing for
evidence of deficiency should be done in patients with low levels of
vitamin
B12 in that situation, such as measured of homosysteine and methylmalonic
acid levels.
We think that the relation between vitamin B12 and folate and the
development of Alzheimer's disease is still not yet established.
References
1) Wang HX, Wahlin A, Basun H, Fastborn J, Winblad B, Fratiglioni L.
Vitamin B12 and folate in relation to the development of Alzheimer's
disease. Neurology 2001; 56:1188-1194.
2) Goebels N, Soyka M. Dementia associated with vitamin B12
deficiency: presentation of two cases and review of the literature. J
Neuropsychiatry Clin Neurosci. 2000; 12 (3): 389-394.
3) Chatterjee A, Yapundick R, Palmer CA et al: Leukoencephalopathy
associated with cobalamin deficiency. Neurology 1996; 46: 832-834.
4) Morris MS, Jacques PF, Rosenberg IH, Selhub J.
Hyperhomocysteinemia associated with poor recall in the third National
Health and Nutrition Examination Survey. Am J Clin Nutr 2001; 73: 927-
933.
We read with interest the article by Wang et al. on the association of low serum levels of vitamin B12 and folate with Alzheimer's disease (AD) occurrence.[1] We think that it is difficult to establish a clinical diagnosis of AD in patients with deficiency of vitamin B12 or folate. AD in this situation could be hardly differentiated from other kinds of dementia particularly from dementia associated with B12 deficiency and vascular dementia.
Cobalamin (vitamin B12) is a co-factor in several metabolic pathways and its deficiency may be associated with dementia. The authors have controlled the hemoglobin levels. Nevertheless the dementia caused by vitamin B12 deficiency may not be accompanied by anemia. Dementia may be the sole manifestation of cobalamin deficiency.[2] The most important pathway in the nervous system that is adversely affected by cbalamin deficiency involves the conversion of homocysteine to methionine. Demyelination clearly plays a major role in the neuropathogensis of cobalamin deficiency and cognitive changes can occur as a result of central demyelination. [3] Furthermore,it was recently showed that high levels of homocystein are associated with poor word recall in the elderly. [4] High homocysteinemia can be caused by deficiencies of folate or vitamin B12.
Another issue to be considered refers to the ifferentiation of vascular dementia. Elevated plasma levels of homocystein have been implanted recently as a risk factor for atherosclerosis and stroke. Homocysteine may be directly toxic to endothelium or thrombogenic. Patients with vascular dementia may be unremarkable. Hachinski Ischemic Scale has been used in this study. However, no imaging study was performed. The cognitive disorder of vascular dementia itself is heterogeneous and may take several different forms. The pleomorphic nature of vascular dementia contributes to diagnostic problems.
Although determination of the serum levels of vitamin B12 is the principal diagnostic test for cobalamin deficiency, this test is neither completely sensitive nor specific. We think that further testing for evidence of deficiency should be done in patients with low levels of vitamin B12 in that situation, such as measured of homosysteine and methylmalonic acid levels.
We think that the relation between vitamin B12 and folate and the development of Alzheimer's disease is still not yet established.
References
1) Wang HX, Wahlin A, Basun H, Fastborn J, Winblad B, Fratiglioni L. Vitamin B12 and folate in relation to the development of Alzheimer's disease. Neurology 2001; 56:1188-1194.
2) Goebels N, Soyka M. Dementia associated with vitamin B12 deficiency: presentation of two cases and review of the literature. J Neuropsychiatry Clin Neurosci. 2000; 12 (3): 389-394.
3) Chatterjee A, Yapundick R, Palmer CA et al: Leukoencephalopathy associated with cobalamin deficiency. Neurology 1996; 46: 832-834.
4) Morris MS, Jacques PF, Rosenberg IH, Selhub J. Hyperhomocysteinemia associated with poor recall in the third National Health and Nutrition Examination Survey. Am J Clin Nutr 2001; 73: 927- 933.