ORIGINAL ARTICLE
VOL 2(2):PAGE 47 - 49
SERUM VITAMIN B12 LEVELS IN MILD COGNITIVE IMPAIRMENT AND DEMENTIAS
AT A TERTIARY CARE CENTER IN INDIA - A THREE YEARS LONGITUDINAL STUDY
Vikas Dhikav, Mina Chandra*, Kuljeet Singh Anand, Lokesh Sharma**, Neera Sharma**
Memory Clinic, Departments of Neurology, Psychiatry* and Biochemistry**, Postgraduate Institute of Medical Education &
Research and Dr. Ram Manohar Lohia Hospital &, New Delhi, 110001
Corresponding Author: Vikas Dhikav
Corresponding email: [email protected]
ABSTRACT
Introduction
Vitamin B12 deficiency is a significant clinical entity which is often seen in clinical practice. Subjects with Mild Cognitive
Impairment and Dementias may develop Vitamin B12 deficiency due to nutritional issues or use of certain medications like
Metformin. The present study was conducted at Department of Neurology was done over a three year period (2012-2015) to study the
occurrence of Vitamin B12 deficiency in subjects with Dementia or MCI.
Material & Methods
Patients coming to the Department of Neurology, PGIMER and Dr Ram Manohar Lohia Hospital, New Delhi with complaints of
subjective memory loss were advised to seek detailed consultation at a specialized Memory clinic. All subjects underwent detailed
general physical examination, neurological evaluation and neuropsychological assessment. Diagnosis was made using Diagnostic &
Statistical Manual IV TR (DSM-IV TR) and Clinical Dementia Rating Scale with Mild Cognitive Impairment defined as CDR scores
0.5 and for Dementias as CDR scores > 1. All subjects had blood samples taken for assessment of Serum Vitamin B12 levels using
Chemiluminescence Assay. The data obtained was statistically analysed using SPSS Version 22.
Results
243 subjects (M: F=180: 54) of Mild Cognitive Impairment and Dementia were studied during the 3-year period. Serum B12
deficiency was found in 25/243 (10.5%) subjects. There was significant difference in B12 deficiency between MCI and Dementia
subjects ((p=<0.05).
Conclusions
B12 deficiency is common in MCI and Dementia and is observed in a significantly more number of subjects with Dementia as
compared to MCI.
Keywords
Serum B12, Vitamin, Deficiency, Cognitive Impairment, Dementia.
INTRODUCTION
METHODOLOGY
Mild Cognitive Impairment and Dementia are two common
causes of adult onset cognitive decline. Nutritional difficulties
are common in MCI and Dementia. Vitamin B12 deficiency may
occur as the sole etiological factor in MCI and Dementia or may
be comorbid with MCI and Dementia due to other etiologies.1-3.
Patients coming to the Department of Neurology, PGIMER and
Dr Ram Manohar Lohia Hospital, New Delhi with complaints of
subjective memory loss were advised to seek detailed
consultation at a specialized Memory clinic. All patients
underwent detailed general physical examination, neurological
evaluation and neuropsychological assessment. Diagnostic &
Statistical Manual IV TR (DSM-IV TR)9 and Clinical Dementia
Rating Scale10 with Mild Cognitive Impairment defined as CDR
Vitamin B12 or cobalamin is a water soluble vitamin. It is
commonly present in food of animal origin. It is absorbed in
ileum and combines with intrinsic factor in stomach for its
action. Unlike most other vitamins, it is stored in liver in
substantial amounts. After stopping consumption of B12, it will
take 3-5 years before the signs and symptoms of vitamin B12
deficiency can appear. B12 plays an important role in
hematological and nervous system. B12 deficiency is
associated with anemia, fatigue, peripheral neuropathy, Sub
acute Combined Degeneration of the Cord, ataxia, confusion
and dementia.4-8
scores= 0.5 and for Dementias as CDR scores ≥1. All patients
had blood samples taken for assessment of Serum Vitamin B12
levels using Chemiluminescence Assay. A reference range for
serum B12, 200-800pg/ml has been used in the current study.
The data obtained was statistically analyzed using SPSS Version
22.
AJCN 2014; 2 (2) : 47 www.ajcn.in
RESULTS
A total of 243 patients (M:F=180: 54) were evaluated during a
three year period from 2012 to 2015. 94 subjects were found to
have Mild Cognitive Impairment, 86 subjects had Alzheimer's
Disease, 30 subjects had Vascular Dementias, 6 subjects had
Dementia with Lewy Body, 12 subjects had Mixed Dementias, 8
subjects had, Fronto-Temporal Dementias, 4 subjects had
Normal Pressure Hydrocephalous, 3 subjects had
Pseudodementia, 5 subjects had Hypothyroid related Dementia,
5 subjects had Nutritional Dementia related to B12 deficiency, 2
subjects had Drug induced Dementias, Crutzfelt-Jacob's disease
each and 1 subject had Cortico-basal degeneration. Serum B12
deficiency was found in 25/243 (10.5%) subjects including 5
subjects with Nutritional Dementia related to B12 deficiency.
There was significant difference in B12 deficiency between MCI
and Dementia subjects (p=<0.05).
There are several limitations of the study. The sample size was
not adequate for dementia such that several subtypes of
dementia had subjects in single digits. Further, no measurement
of Homocysteine, Holotranscobalamin and Methyl Malonic
Acid levels were done which could have defined b12 deficiency
more accurately 22 and thus better established the causal role of
B12 deficiency in cognitive impairment.
CONCLUSION
Vitamin B12 deficiency is common and can be seen in up to one
tenth of subjects with Mild Cognitive Impairment and
Dementias. Hence Subjects with Mild Cognitive Impairment
and Dementias must be investigated for Vitamin B12 deficiency
and thereafter prescribed appropriate oral or parentral
supplementation.
CONFLICT OF INTEREST
DISCUSSION
Vitamin B12 deficiency is associated with damage to neural
tissues. The current study has investigated the frequency of B12
deficiency in various types of dementias and mild cognitive
impairment A total of 10.5% patients with MCI/Dementia had
the deficiency of Vitamin B12 in the present sample size. Our
results are in agreement with the published literature from India1-3
and the world 11-13. A wide range of Dementias have been reported
to have concomitant B12 deficiency like Alzheimer's Disease,
Vascular Dementia, Parkinson's Disease in a meta analysis of 43
studies.4 Further Vitamin B12 deficiency not only worsen
existing dementias but may precipitate onset of symptoms in
MCI. 14
Low levels of Serum B12 can be attributed to aging related
differences in Gastrointestinal absorption, predominantly
vegetarian diet and use of medications like Metformin 4, Proton
Pump Inhibitors and Histamine 2 Receptor Antagonists15.
Low levels of Vitamin B12 also results in raised
Hyperhomocysteinaemia which is in turn is vasculotoxic and
contributes to Vascular Dementia though atherosclerosis,
thrombo embolism, free radical injury and oxidative stress.16-18
However hyperhomocysteinaemia may be seen even in subjects
who have adequate serum B12 and folate levels 19 and hence
therapeutic supplementation may not reverse cognitive deficits
completely. Vitamin B12 supplementation may improve
executive functions and language impairments without actually
reversing dementia. 20 Therefore, while routine supplementation
with Vitamin B12 is not recommended for subjects with
Dementia, they may be encouraged to maintain adequate levels
of Vitamin B12 through dietary interventions. 21
The major strength of the study is the long duration of study of
three years. Further the study was done at a specialized Memory
Clinic at a premier tertiary care hospital in New Delhi which
receives subjects with subjective memory loss and different
types of Dementias. All diagnoses were established by trained
neurologist after detailed evaluation using standardized
diagnostic system (DSM-IV TR) and reliable scale based
assessment with CDR.
There is no conflict of interest to declare.
REFERENCES
1.
Agarwal R. Vitamin B₁₂ deficiency & cognitive impairment
in elderly population. Indian J Med Res. 2011; 134:410-2.
2.
Issac TG, Soundarya S, Christopher R, Chandra SR.
Vitamin B12 deficiency: an important reversible
comorbidity in neuropsychiatric manifestations. Indian J
Psychol Med. 2015;37(1):26-9.
3.
Tripathi M, Sheshadri S, Padma MV, Jain S, Meheshwari
MC, Behari M. Serum cobalamin levels in dementias.
Neurol India. 2001;49(3):284-6.
4.
Morris MS, Jacques PF, Rosenberg IH, Selhub J. Folate and
vitamin B-12 status in relation to anemia, macrocytosis,
and cognitive impairment in older Americans in the age of
folic acid fortification. –Am J Clin Nutr. 2007 Jan; 85(1):
193200. PMCID: PMC1828842, NIHMSID:
NIHMS16359
5.
Stabler SP.Vitamin B12 Deficiency. N Engl J Med 2013;
368:149-160January 10, 2013DOI:
10.1056/NEJMcp1113996
6.
N Sethi, E Robilotti, Y Sadan. Neurological Manifestations
Of Vitamin B-12 Deficiency. The Internet Journal of
Nutrition and Wellness. 2004; 2(1). Available at
https://ispub.com/IJNW/2/1/4476 last accessed 25 May
2015
7.
Lindenbaum J, Healton EB, Savage DG, Brust JC, Garrett
TJ, Podell ER, Marcell PD, Stabler SP, Allen RH.
Neuropsychiatric disorders caused by cobalamin
deficiency in the absence of anemia or macrocytosis. N
Engl J Med. 1988 Jun 30;318(26):1720-8.
8.
Licht DJ, Berry GT, Brooks DG, Younkin DP. Reversible
subacute combined degeneration of the spinal cord in a 14year-old due to a strict vegan diet. Clin Pediatr. 2001
Jul;40(7):413-5.
AJCN 2014; 2 (2) : 48 www.ajcn.in
9.
American Psychiatric Association. Diagnostic & Statistical
Manual of Mental Disorders. (4th ed. , text rev.) (DSM-IV
TR). Washington, DC.
10. Morris JC Clinical Dementia Rating: A Reliable and Valid
Diagnostic and Staging Measure for Dementia of the
Alzheimer Type. International Psychogeriatrics. 1997;
9(suppl.1): 173-176.
11. O'Leary F, Allman-Farinelli M, Samman S. Vitamin B12
status, cognitive decline and dementia: a systematic review
o f p r o s p e c t i v e c o h o r t s t u d i e s . B r J N u t r.
2 0 1 2 ; 1 0 8 ( 11 ) : 1 9 4 8 - 6 1 . d o i : 1 0 . 1 0 1 7 / S 0 0 0 7114512004175.
12. Moore E, Mander A, Ames D, Carne R, Sanders K, Watters
D. Cognitive impairment and vitamin B12: a review. Int
P s y c h o g e r i a t r. 2 0 1 2 ; 2 4 ( 4 ) : 5 4 1 - 5 6 . d o i :
10.1017/S1041610211002511.
13. Haan MN, Miller JW, Aiello AE, Whitmer RA, Jagust WJ,
Mungas DM, Allen LH, Green R. Homocysteine, B
vitamins, and the incidence of dementia and cognitive
impairment: results from the Sacramento Area Latino Study
on Aging. Am J Clin Nutr. 2007 Feb; 85(2): 511–517.
PMCID: PMC1892349, NIHMSID: NIHMS20304
14. Silva D, Albers U, Santana I, Vicente M, Martins IP,
Verdelho1 A, Guerreiro M, de-Mendonça A. Do MCI
patients with vitamin B12 deficiency have distinctive
cognitive deficits? BMC Research Notes 2013, 6:357
15. Lam JR, Schneider JL, Zhao W, Corley DA. Proton Pump
Inhibitor and Histamine 2 Receptor Antagonist Use and
Vitamin B12 Deficiency. JAMA. 2013;310(22):24352442. doi:10.1001/jama.2013.280490.
16. Beilby J, Rossi E. Homocysteine and disease. Pathology.
2000;32: 262–273.
17. We l c h G N , L o s c a l z o J . H o m o c y s t e i n e a n d
atherothrombosis. N Engl J Med.1998; 338: 1042–1050.
18. Selhub J, Bagley LC, Miller J, Rosenberg IH. B vitamins,
homocysteine, and neurocognitive function in the elderly.
Am J Clin Nutr. 2000; 71(suppl):.614S–20S.
19. Chandra M, Bajpai RC, Anand KS.“Homocysteine as a
marker of severity of Vascular Dementia” Paper presented
at Asia Pacific Regional Conference of Alzheimer's Disease
International at New Delhi, 7-9 November 2014.
20. Eastley R, Wilcock GK, Bucks RS. Vitamin B12 deficiency
in dementia and cognitive impairment: the effects of
treatment on neuropsychological function Int. J. Geriat.
Psychiatry, 2000; 15: 226-233.
21. Smith AD, Refsum H. Vitamin B-12 and cognition in the
elderly. Am J Clin Nutr, 2009; 89(2): 707S-711S.
22. Hunt A, Harrington D, Robinson S.Vitamin B12 deficiency.
BMJ 2014;349: g5226.
AJCN 2014; 2 (2) : 49 www.ajcn.in