Low B12 Linked to Brain Atrophy

By Michael Smith
OXFORD, England, 09 sept 2008-- Low levels of vitamin B12 are associated with increased rates of brain atrophy in older people, researchers here said.
In a small observational study, healthy volunteers who had low -- but still normal -- levels of the vitamin had greater brain atrophy five years later than those with higher levels, according to Anna Vogiatzoglou, M.Sc., of the University of Oxford, and colleagues.
Although the study was too small to investigate cognitive changes, the finding suggests that B12 level is "a potentially important modifiable risk factor for cognitive decline in the elderly," the researchers said in the Sept. 9 issue of Neurology.
"Many factors that affect brain health are thought to be out of our control," Vogiatzoglou said in a statement. "But this study suggests that simply adjusting our diets to consume more vitamin B12 through eating meat, fish, fortified cereals, or milk may be something we can easily adjust to prevent brain shrinkage and to perhaps save our memory."
The vitamin is necessary for the methylation of homocysteine, which leads to the formation of S-adenosylmethionine, an important methyl donor in the brain, the researchers noted.
In infants with B12 deficiency and people with errors of vitamin B12 metabolism, the deficiency of S-adenosylmethionine is associated with brain atrophy, reversible if treated, they said.
Deficiency of the vitamin has also been associated with cognitive deficits in some studies, although others have reported null results, but studies of brain atrophy in the elderly are limited, the researchers said.
To clarify the issue, they enrolled 107 people over 60 who were healthy, living in the community, and looking after themselves. They were given a detailed physical exam, their brain volume was measured by MRI, and several B12 markers were measured.
The volunteers were divided into thirds, based on their vitamin levels at baseline, with those above 386 picomoles per liter serving as a reference group for logistic regression analysis.
The other groups either had between 308 and 386 picomoles per liter or less than 308. None of the volunteers had a B12 deficiency -- defined as a serum level lower than 150 picomoles per liter.
The researchers also measured a range of other markers, but in an adjusted model only holotranscobalamin and transcobalamin saturation -- which reflect the biologically available fraction of total vitamin B12 -- remained significant.
When the process was repeated after five years, the average decline in percentage of brain volume per year was 0.69. Those in the lowest third of baseline vitamin B12 -- less than 308 picomoles per liter -- tended to lose more volume, compared with those with higher baseline levels.
Specifically, in an adjusted model:
Those in the bottom third of B12 had a six-fold increase in the risk of greater percentage brain volume loss, compared with the reference group. The odds ratio was 6.17, with a 95% confidence interval from 1.25 to 30.47, which was significant at P=0.026.
Those in the middle third were also more likely to have greater volume loss than those in the reference group. The odds ratio was 4.39, with a 95% confidence interval from 1.01 to 19.03, which was significant at P=0.048.
Those in the lower third of baseline holotranscobalamin levels -- less than 54 picomoles per liter -- were also six times more likely to have greater volume loss than the reference group, with an odds ratio of 5.99, which was significant at P=0.029.
Those in the lowest two-thirds of baseline transcobalamin saturation were six times more likely to have greater volume loss, with odds ratios of 6.64 and 6.63, which were significant at P=0.022 and P=0.029, respectively.
"Even though the sample consisted of subjects with relatively good vitamin B12 status, the study was able to find a strong association of vitamin B12 markers with brain volume loss," the researchers concluded.
The authors pointed out several limitations of the study including the small sample size and the fact that they did not investigate whether the loss in brain volume is focal or diffuse.
The also noted that "as with all cohort studies in contrast to randomized trials, we cannot exclude that residual confounding, due to unknown factors, might account for the findings."
They concluded that larger interventional studies will help to define whether optimization of vitamin B12 status will contribute to the maintenance of cognitive performance with successful aging.
The study was supported by the Alzheimer's Research Trust, the Medical Research Council, the Charles Wolfson Charitable Trust, the Norwegian Foundation for Health and Rehabilitation through the Norwegian Health Association, Axis-Shield plc, and the Johan Throne Holst Foundation for Nutrition Research.
The researchers said they had no disclosures.
Primary source: NeurologySource reference:Vogiatzoglou A, et al "Vitamin B12 status and rate of brain volume loss in community-dwelling elderly" Neurology 2008; 71: 826-832.