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 »  Abstract
 »  Introduction
 »  Material and methods
 »  Results
 »  Discussion
 »  References

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Year : 2001  |  Volume : 49  |  Issue : 3  |  Page : 284-6

Serum cobalamin levels in dementias.


Department of Neurology, C.N. Centre, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110 029, India.

Correspondence Address:
Department of Neurology, C.N. Centre, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110 029, India.
manjari@medinst.ernet.in

  »  Abstract

The present study attempts to find a correlation between low serum B-12 levels and dementias. A total of 178 patients of dementia were seen at the cognitive disorder clinic from 1996 to 1998. Serum B-12 levels were studied in 100 patients. 15 patients (39.5%) of Alzheimer's dementia had reduced B-12 levels, while only 5 patients (13.9%) with vascular dementias and 3 patients (11.5%) with other types of dementias had reduced levels. The incidence of low serum B-12 was statistically significant in the Alzheimer's group when compared with the other groups, individually as well as combined together (p<0.05). The aetiopathogenesis and significance of these findings is discussed and the literature is reviewed.

How to cite this article:
Tripathi M, Sheshadri S, Padma M V, Jain S, Meheshwari M C, Behari M. Serum cobalamin levels in dementias. Neurol India 2001;49:284


How to cite this URL:
Tripathi M, Sheshadri S, Padma M V, Jain S, Meheshwari M C, Behari M. Serum cobalamin levels in dementias. Neurol India [serial online] 2001 [cited 2019 Oct 15];49:284. Available from: http://www.neurologyindia.com/text.asp?2001/49/3/284/1239




   »   Introduction Top

Clues to the differential diagnosis of dementias emanate from the history and examination. Certain laboratory tests and neuroimaging studies are necessary in the work up of these patients to rule out reversible and potentially treatable causes of dementias. In the past decades low and low normal serum cobalamin values have been reported to occur more frequently in dementias, particularly of the Alzheimer's type and in normal ageing.[1],[2],[3],[4] The exact aetiological and pathophysiological significance of this finding has not been established. It is well known that vitamin-B12 deficiency can cause a wide variety of psychiatric and behavioural symptoms, without concomitant megaloblastic anaemia and classical neurological manifestations.[5],[6] Such atypical cobalamin deficiency states may precede the classic haematological and neurological features for several years.[6] B-12 deficiency is perhaps a continuum of various combinations, the classical features occurring only at the end of the spectrum.[7] In the present study, the cobalamin status was reviewed in cases of dementias.


   »   Material and methods Top

100 patients, seen in a two years period (1996-98) at cognitive disorders clinic had documented serum cobalamin levels (retrospectively analysed = 46, and prospectively analysed = 54). The patients were divided into three groups i.e. Alzheimer's type (group A), vascular dementia (group B) and others (group C). Dementia was diagnosed according to DSM IV criteria. Alzheimer's dementia was diagnosed by guidelines of the NINCDS-ADRDA group[8] and vascular dementia by NINCDS-ARIEN criteria.[9] Neurological examination included a detailed higher mental function examination, mini mental status examination (MMSE), and Blessed dementia rating scale. The nutritional intake was recorded as lacto vegetarian (LV) or mixed diet (m). Socio-economic stratification was done according to the monthly household income structure as : low (L) - < Rs 4000/month, middle (M) Rs 4000-15000/- per month and high (H) - > Rs 15000/month. Laboratory analysis documenting anaemia was noted. Serum cobalamin concentrations were determined with micropore enzyme immunoassay (MPEIA). The normal range was between 187-1057 pg/ml; indeterminate levels were between 157-187pg/ml, and low levels being < 157pg/ml. The data obtained was analysed by SPSS-6 version software. To test the relationship between these variables, correlation coefficient was found and p-values were obtained. An analysis of variance (ANOVA) was also performed.


   »   Results Top

Serum cobalamin levels were estimated in 100 cases of dementia. Clinical diagnosis of probable and possible Alzheimer's dementia (AD) was made in 38 patients (34 +4 respectively) (Group A). Probable and possible vascular dementia's was recorded in 36 patients (9+27 respectively) (Group B). Group C (n=26) comprised of other dementias (mixed, diffuse Lewy body disease, infections, nutritional, head injury, systemic, extra pyramidal etc). In group A, 15 patients (39.5%) had a decrease in serum B-12 levels whereas only five patients (13.9%) in the vascular group (group B) and 3 (11.5%) in the group C had decreased levels of B-12. The occurrence of decreased levels was significantly higher in the group A, when compared to both group B and to group D (group B and C put together, p<0.05). The decrease in the B12 levels in group A was statistically higher, the group A was even when the indeterminate values were ignored (p<0.05). The mean serum levels of cobalamin were also lower in the Alzheimer's group and this was statistically significant (p<0.05), [Table I]. The nutritional intake of a vegetarian diet was noted in 32% and a non-vegetarian diet in 68%. There was no significant difference in the incidence of low B12 levels between the two groups. Socio-economic stratification tended to show a higher incidence in patients with lower socio-economic class (L=32%, M=51%, H= 13% class) but this was not statistically significant. Analysis by ANOVA did not show any significant correlation between serum B-12 levels and the age and duration of dementias [Table I].


   »   Discussion Top

In this study, serum B-12 levels were recorded in 100 patients. None of these patients were noted to have any clinical features suggestive of classical cobalamin deficiency. A decrease in cobalamin levels was seen in varying proportions in all the three groups, but was however significant only in the suspected Alzheimer's disease group (both in the frequency as well as the mean levels being lower), which is in accordance with that observed in previous studies.[2],[3],[4],[10],[11] The frequency of this finding has varied from 25-30%, as compared to 5% in the healthy adult population. The higher incidence of 39.5%, in our series could indicate a poor nutritional intake (qualitative and quantitative) in the Indian population. There has been only one published report of serum B-12 levels in healthy adult population in Indians[12] where it was observed that lacto-vegetarians had a lower level of this vitamin. There is, however, no data on the incidence of decrease B12 levels in the normal adult population. One of the drawbacks of this study is that no normal adult control population has been analysed. However, the three groups in this study, serve as controls for each other and the number of Alzheimer's patients having low B-12 levels was significantly more than those in the other groups, (even only if marked levels of decrease were considered). The significantly lower mean concentrations in the Alzheimer's group compared to other dementias may indicate that Alzheimer's patients are particularly prone to cobalamin deficiency. The exact reason for this is not known and has led to cobalaminergic hypothesis for Alzheimer's dementia.[13] Age related atrophic gastritis[14] has also been documented. This could also be compounded by reduced intake in elderly patients. However, we did not observe any correlation between the age of the patients, the duration of dementia and decrease of serum cobalamin levels in our analysis.
Previous studies have also estimated the methylmalonic acid (MMA) levels in Alzheimer's patients versus other dementia's and normal controls. This finding has been interpreted to be of positive significance for lower serum cobalamin levels being of definite metabolic significance, reflecting an impaired tissue cobalamin function. MMA accumulates in cobalamin deficiency because adenosylcobalamin is an essential coenzyme in the conversion of methylmalonyl-COA to succinyl CoA, a normal step in the catabolism of proprionic acid. Increased levels of MMA in the serum and urine are an early and sensitive indicator of tissue cobalamin deficiency, reflecting reliably the body stores of the vitamin.[15] Cerebrospinal (CSF) B-12 levels have also found to be low and the CSF/serum B-12 ratios are also significantly lower in these patients probably indicating a transport function across the blood brain barrier.[16] Another interesting fact is that platelet monoamino-oxidase activity has been shown to be increased in patients with dementia particularly in Alzheimer's and has been inversely correlated with the B-12 levels. This finding reversed on treatment by supplementation, again indicating a significant correlation between B-12 levels and AD.[17] Gomes et al studied the effect of vitamin B12 activity on brain methionine adenosyltranferase (MAT) activity in postmortem brains of Alzheimer's dementia. In the samples of cortex gyrus frontalis, where the serum B12 was decreased, MAT activity was significantly increased. This finding was not found in patients undergoing treatment with the vitamin or in the normal brains. This study indicated that AD is associated with significant alterations of transmethylation mechanisms in specific regions of the brain.[18] In conclusion, our findings indicate that patients with Alzheimer's dementia are prone to cobalamin deficiency. This phenomenon may or may not be related to the aetiopathogenesis of the disease and may just be an association. A finding of low cobalamin levels warrants treatment but its implications may not be clinically significant. Further studies and analysis of other biochemical parameters are warranted in patients with decreased B-12 levels and dementia.
 

  »   References Top

1.Corey Bloom J, Thal LJ, Glasko D et al : Diagnosis and evaluation of dementia. Neurology1995; 45 : 211-218.   Back to cited text no. 1    
2.Kristensen MO, Gulmann NC, Christensen JEJ et al : Serum cobalamin and methylmalonic acid in Alzhemer's dementia. Acta Neurol Scand 1993; 87 : 475-481.   Back to cited text no. 2    
3.Cole MG, Prchal JF : Low serum cobalamin levels in Alzheimer's type dementia. Age Ageing 1984; 13 : 101-105.   Back to cited text no. 3    
4.Karnaze DS, Carmel R : Low serum cobalamin levels in primary degenerative dementia: do some patients harbour atypical cobalamin deficiency states? Arch Intern Med1987; 147 : 429-431.   Back to cited text no. 4    
5.Carmel R : Pernicious anemia: The expected findings of very low serum cobalamin levels, anemia and macrocytosis are often lacking. Arch Intern Med1988; 148 : 1712-1714.   Back to cited text no. 5    
6.Lindenbaum J, Healton EB, Savage DG et al : Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 1988; 148 : 1720-1728.   Back to cited text no. 6    
7.Herbert V : Don't ignore low serum cobalamin (Vitamin B-12) levels. Arch Intern Med 1988; 148 : 1705-1707.   Back to cited text no. 7    
8.McKhann G, Drachman D, Folstein M et al : Clinical diagnosis of Alzheimer's disease. Neurology 1984; 34 : 939-944.   Back to cited text no. 8    
9.Roman GC, Tatemichi TK, Erkinjunth T et al : Vascular dementia: diagnostic criteria for research studies. Report of NINDS-ARIEN. International workshop. Neurology 1993; 43 : 250-260.   Back to cited text no. 9    
10.Clarke R, Smith AD, Jobst KA et al : Folate, vitamin B-12, and serum total homocysteine levels in confirmed Alzheimers disease. Arch Neurol 1998; 55 : 1449-1455.   Back to cited text no. 10    
11.McCaddon A, Kelly CL : Familial Alzheimers disease and vitamin B-12 deficiency. Age Ageing 1994; 23 : 334-337.   Back to cited text no. 11    
12.Mehta BM, Rege DV, Satoskar RS : Serum vitamin B-12 and folic acid in lactovegetarians and non-vegetarian healthy adult Indians. Am J Clin Nutr 1964; 15 : 77-86.   Back to cited text no. 12    
13.McCaddon A, Kelly CL : Alzheimers disease : a 'cobalaminergic' hypothesis. Med Hypotheses 1992; 37 : 161-165.   Back to cited text no. 13    
14.Regland B, Gottfries CG, Lindstedt G : Dementia patients with low serum cobalamin concentration: relation to atrophic gastritis. Aging 1992; 4 : 35-41.   Back to cited text no. 14    
15.Lindenbaum J, Savage DG, Stabler SP et al : Diagnosis of cobalamin deficiency : relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations. Am J Hematol 1990; 34 : 99-107.   Back to cited text no. 15    
16.Regland B, Abrahamsson L, Blennow K et al : Vitamin B12 in CSF: reduced CSF/serum B12 ratio in demented men. Acta Neurol Scand1992; 85 : 276-281.   Back to cited text no. 16    
17.Regland B, Gottfries CG, Oreland L : Vitamin B12 induced reduction of platelet monoamino oxidase activity in patients with dementia and pernicios anaemia. Eur Arch Psychiatry Clin Neurosci 1991; 240 : 288-291.   Back to cited text no. 17    
18.Gomes-Trolin C,Gottfries CG, Regland B et al : Influence of vitamin B12 on brain methionine adenosyltranferace activity in senile dementia of Alzheimer's type. Journal of Neurol Transmission 1996; 103 : 861-872.   Back to cited text no. 18    

 

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