Low Vitamin B12 Tied to Brain Atrophy, Cognitive Impairment

Megan Brooks

September 27, 2011

September 27, 2011 — A new study provides more evidence that poor vitamin B12 status is a risk factor for brain atrophy and cognitive impairment, and highlights the importance of vitamin B12 metabolites that are not routinely assessed.

The study found that higher levels of several markers of vitamin B12 deficiency, most notably methylmalonic acid (MMA) and homocysteine, were associated with lower global cognitive function scores and lower total brain volume roughly 5 years later. However, the serum vitamin B12 concentration was not associated with either global cognitive function or total brain volume.

The results, from Christine C. Tangney, PhD, from Rush University Medical Center in Chicago and colleagues, were published September 27 in Neurology.

"Practice-Changing" Study

"What this study tells me is that I need to be taking B12 assessment in the elderly patient to a different level," Daniel C. Potts, MD, from Alabama Neurology and Sleep Medicine, PC, in Tuscaloosa, who was not involved in the study, noted in a telephone interview with Medscape Medical News. "I need to be routinely measuring the metabolites, and not just the serum B12," he said.

"With this study, I am probably going to change my practice a bit," added Dr. Potts, associate clinical professor, College of Community Health Sciences, University of Alabama School of Medicine, and member of the American Academy of Neurology.

Dr. Tangney's team studied 121 participants in the Chicago Health and Aging Project, an ongoing cohort study of adults aged 65 years and older living on the south side of Chicago.

They looked for interrelations between baseline levels of serum vitamin B12 and several vitamin B12-related markers, including MMA, homocysteine, 2-methylcitrate, and cystathionine, and brain magnetic resonance imaging and neuropsychological test results obtained an average of 4.6 years later.

According to the investigators, 17.5% of participants had elevated homocysteine levels, defined as higher than 14 μmol/L, and 15.2% had elevated MMA concentrations (>271 nmol/L). Serum homocysteine and MMA concentrations were highly correlated (P < .0001).

After adjusting for age, sex, education, race, and serum creatinine concentrations that can affect homocysteine levels, each of the vitamin B12-related markers, but not vitamin B12 itself, was associated with global cognitive scores.

For example, for each 1 μmol/L increase in homocysteine concentration, global cognitive score decreased by 0.03 standardized units (P = .04).

However, the relationship of the different vitamin B12 markers to the scores of the individual cognitive domains were not consistent.

Serum homocysteine concentration was not associated with any of the individual cognitive domains, although scores for perceptual organization and speed had marginal associations.

Serum concentrations of MMA, cystathionine, and 2-methylcitrate were each associated with lower episodic memory scores: the higher the concentrations, the lower the scores.

Higher MMA concentrations were also associated with lower perceptual speed, and higher cystathionine and 2-methylcitrate concentrations were each associated with poorer semantic memory.

"These associations remained in analyses that adjusted individually for [body mass index], smoking status, lifetime alcohol intake, hypertension, dementia, or APOE4," the authors say.

Similar to the cognitive function findings, serum vitamin B12 levels were not associated with any magnetic resonance imaging measures in adjusted models. Homocysteine concentration was the only vitamin B12 metabolite associated with the volume of white matter hyperintensity; the volume increased by 0.103 units/μmol/L increase in homocysteine level.

Elevated levels of serum homocysteine, MMA, cystathionine, and 2-methylcitrate were significantly associated with decreased total brain volume.

The investigators note that the effect of homocysteine on global cognition was "modified and no longer statistically significant with adjustment for white matter volume or cerebral infarcts." Likewise, the methylmalonate-global cognition effect was modified and no longer significant with adjustment for total brain volume.

Serum B12 Measurement "Not Enough"

Dr. Potts called this is "an important study that sheds some light for the first time on some individual components of cognition and what the B12 metabolites mean for those [components]."

"The global take-home for me," he added, "is that B12 may be playing a more important role than we once thought in terms of brain health in the elderly. I need to be more seriously considering the role of B12 in global cognitive health of an elderly person, and not just think that because they have a normal serum B12 level at their primary care physician that that's enough for me; it's not enough now, and I'm going to dig a little deeper," he said.

"At the very minimum, measure an MMA level, homocysteine plus a serum B12," he advised, as marginal vitamin B12 status in older adults is often missed by measuring serum vitamin B12 levels alone.

Dr. Tangney said it is too early to say whether increasing vitamin B12 levels in older people through diet or supplements could help prevent cognitive problems and brain atrophy, but it is "an interesting question to explore."

Results of the Vitamins in Cognitive Impairment (VITACOG) study, released 1 year ago and reported by Medscape Medical News at that time, provide some support for vitamin B supplementation.

In the study, treatment with a supplement containing vitamin B6, B12, and folate for 2 years reduced homocysteine levels and slowed brain atrophy in British adults with mild cognitive impairment, although concomitant changes in cognitive scores were not reported.

The current study was supported by the National Institute on Aging, part of the National Institutes of Health. Dr. Tangney has disclosed no relevant financial relationships. Some of the study authors have disclosed relationships with Pfizer, Bayer Schering Pharma, Avanir Pharmaceuticals, and Eli Lily and Company. Dr. Potts has disclosed no relevant financial relationships.

Neurology. 2011;77:1276-1282. Abstract


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