Vitamin B₁₂ deficiency & cognitive impairment in elderly population.

Dementia, considered as disease of old age, is growing at an alarming rate and becoming a public health problem, increasing the financial and personal costs with an adverse impact on health care expenditure, and on families. It is well known that age is a risk factor for dementia1; and the prevalence increases with advancing age2. In Europe, prevalence of dementia among people older than 65 yr is about 10 per cent3. Preservation of cognitive ability well in old age is essential not only to promote an adequate health status but also to delay the onset of dementia and slow down its progress, thereby, reducing the societal costs each year for chronic care and lost productivity. As a curative treatment is currently not possible for dementia, a number of attempts have been made to find out the non genetic risk factors that may be modified to limit it4. Increased homocysteine levels in conjunction with low levels of folate, vitamin B12 and B6, which interact to control homocysteine, have been found to correlate with decreased cognitive performance5–7. The prevalence of high total serum homocysteine is age related and hyperhomocysteinemia is common in elderly population8 which negatively correlates with cognitive status. Deficiency of the B vitamins (folate, vitamin B6 and vitamin B12) may play a role in pathogenesis of cognitive impairment in the elderly through hyperhomocysteinemia. On the other hand, elevated plasma homocysteine concentrations are a sensitive marker for vitamin B12 and folate deficiency9. Homocysteine is produced from the methylation cycle, as it is totally absent from any dietary source. Both folate and vitamin B12 are required in the methylation of homocysteine to methionine and in the re-methylation and synthesis of S-adenosylmethionine, a major methyl donor in the central nervous system. Hence, research to date suggests that hyperhomocysteinemia due to disturbed monocarbon metabolism may contribute to cognitive impairment and Alzheimer's disease10 and can be considered a sensitive marker of cognitive impairment. On the other hand, raised plasma homocysteine concentrations are a sensitive marker for cobalamin and folate deficiency. Findings suggest that decreased vitamin B12 dependent transmethylation reactions might be involved in the pathogenesis of dementia11. Hence, increased homocysteine levels in association with low levels of folate, vitamin B6 and vitamin B12, shows significant correlation with decreased performance on cognitive tests5–7. For these reasons, B vitamin supplementation has been shown to prevent or reverse cognitive decline. However, effect of vitamin B12 oral supplementation shows heterogeneous results and is found related to the dose, route of administration and duration of treatment. A few trials have been conducted to assess the effect of vitamin B12 supplementation on cognitive function in humans1213, with duration of supplementation varying from 4 wk to 6 months. For most of the cognitive tests performed, no improvement was observed for vitamin B12. Only a few cognitive tests showed statistically significant improvement12. At least two studies are available in literature showing statistically significant worsening of cognitive functions after vitamin B12 supplementation1213. In case of folic acid supplementation, studies found cognitive improvement after folic acid intervention which correlated in linear fashion with the low levels of folate at baseline (< 6.8 nmol/l)14.

Several studies have found high incidence of vitamin B12 and folate deficiency in elderly in western population1516. However, no such data are available in elderly Indian population. With increasing ageing population, varied socio-economic strata and high prevalence of Helicobacter pylori infection along with vegetarian diet followed in majority of Indian households, the prevalence of vitamin B12 and folate deficiency may be much higher in Indian population. There are two studies so far in India showing prevalence of vitamin B12 and folate deficiency. One study conducted by Yagnik et al17, investigated the prevalence of low vitamin B12 concentration and hyperhomocysteinemia in rural and urban Indian men living in and around Pune, Maharastra. They reported vitamin B12 level of 150 pmol/l in 67 per cent of men and hyperhomocysteinemia (<15 umol/l) in 58 per cent subjects. They also reported 4.4 and 3.0 times higher risk of low vitamin B12 concentration and hyperhomocysteinemia respectively in vegetarians.

Shobha et al18 in the present study have highlighted the relationship of dietary habits of urban south Indian elderly subjects and plasma vitamin B12, folate and homocysteine levels with cognitive status and impact of vitamin supplementation on the normalization of the same. They found that daily vitamin B12 intake was 3.5 times higher than the FDA recommendation contrary to belief that dietary intake would be low in Indian population being majority population vegetarian (57%). Also, average daily dietary folate intake was almost equal to the FDA recommended daily intake of folate. There was low occurrence of vitamin B12 deficiency and vitamin supplementation had a significant impact on the normalization of the plasma B12, MMA, folate and homocysteine. However, no correlation was detected between plasma vitamin B12 and cognitive status in elderly population.

Cognitive impairment is multifactorial in origin sharing modifiable and non modifiable risk factors. As there are no curative treatments for it, the only possibility is that treatment may delay or slow down disease progression. It is highly appropriate to detect such modifiable risk factors like hyperhomocysteinemia, vitamin B12 and folate deficiency, etc. These nutrition related risk factors not only have been associated with lower cognitive function in old age, but incipient dementia may also change dietary habits, that is, malnutrition can be a consequence rather than a cause of cognitive impairment. In the absence of curative treatment for dementia, vitamin B12 and folate may be relevant to the clinical course of dementia and should be considered for therapeutic intervention. However, more therapeutic research is needed. Clinical trials must be initiated in high risk population to determine whether, lowering of blood homocysteine levels by vitamin B supplementation reduces the risk of cognitive impairment, the clinical onset of dementia. Longitudinal studies should also be undertaken to explore the association between nutrition status and cognitive impairment, and whether it is possible to inhibit or delay the onset of dementia by dietary modifications. Hence, at present, B vitamin supplementation should be reserved for the treatment of documented deficiency states.