B12 shortage linked to cognitive problems

Studies in elderly show that even 'normal' levels of vitamin may not be enough

Not getting enough vitamin B12 may take a serious toll on the brain. Two new studies of the elderly link impairments of memory and reasoning with an indirect measure of vitamin B12 deficiency. Worse, brain scans reveal that those with signs of insufficient B12 are more likely to have shrinkage of brain tissue, vascular damage and patches of dead brain cells than are people with higher levels of the vitamin.

A third, ongoing study is recording neural changes — a slowing in the electrical signals conveying visual information — among people with B12 deficiency.

Conducted in seniors, mostly in their mid-70s to upper 80s (including a large group in Chicago), all three studies observed adverse changes even in people whose B12 levels in blood fall within the ostensibly normal, healthy range. While blood levels of B12 might have been normal, however, two biochemical markers of B12 deficiency often were not: Except in the visual study, brain problems largely correlated with rising blood concentrations of homocysteine and methylmalonic acid, or MMA, which accumulate in blood when cells of the body receive too little B12.

“The message of this Chicago study is watch your B12. It’s important for the brain,” says David Smith of the University of Oxford in England, whose team has begun investigating whether vitamin supplementation can slow cognitive decline in the elderly.

The new findings point to the apparent importance of brain changes in the absence of overt disease, says hematologist Ralph Carmel of New York Methodist Hospital, who was not involved in any of the new studies. The new data also argue against the common practice of relying exclusively on blood B12 levels to identify deficiency, he says.

In 2009, scientists at Rush University Medical Center in Chicago reported results from 516 randomly selected seniors showing that cognitive performance declined faster over a six-year period among those with elevated MMA. All had been taking part in an ongoing study of more than 6,100 men and women begun in 1993. One-third of the seniors, who were tested and surveyed about nutrition every three years, fell into this high MMA category, says Rush nutritionist Christine Tangney.

Now, in the September 27 Neurology, the same researchers report that high homocysteine values correlated with an accelerated shrinkage of brain tissue. Homocysteine blood levels also were linked to a higher number of what scientists call white matter hyperintensities — abnormal markings in magnetic-resonance imaging scans that are suspected of signaling patches of brain cells that died from blood starvation. High levels of hyperintensities mark people at risk of stroke, dementia and death.

The Rush team did the new work on a random subset of 121 of the original study participants, each about 80 years old, using a more sophisticated battery of 17 separate mental tests. While MMA levels again correlated with lower cognitive test scores, homocysteine levels did not.

MMA elevations marked people likely to score substantially worse than other seniors on how quickly they could assimilate information and ideas and on tests of “episodic memory” — a recall of recent events that can be colored by emotions. Two additional biomarkers of B12 deficiency were also linked to poorer episodic memory and with trouble recalling words.

Other researchers have shown how too little B12 might impact the brain at the cellular level. At the Experimental Biology meeting, April 10 in Washington, D.C., Joshua Miller of the UC Davis Medical Center in Sacramento reported data from 97 people linking subtle B12 deficiency with a slowing of certain visual signals to and their interpretation by the brain. Specifically, Miller looked at visual evoked potentials — the transmission of light signals from the eye to the nervous system. Signaling delays likely reflect a deterioration of the myelin sheath that insulates nerve fibers, he says.

Those in the lower half of B12 blood values had slower visual signaling speeds than did participants in the upper range, and the length of delays correlated with how low B12 measurements had been. The signal delay may indicate that tissues aren’t getting enough B12 even when blood levels are in the normal range.

“So we could think of this, perhaps, as a canary in the coal mine,” Miller says.

Miller adds that even though the evoked potentials his team measured in quick, noninvasive tests focused on the eyes, it’s likely that whatever B12 is doing to these neurons occurs elsewhere as well. So, subtle changes in visual evoked potential might identify early neural damage, he says, “and predict if you’re going to descend into dementia.” Identified early enough, there might still be time to intervene with vitamin therapy, he says, and halt further damage.

Previous studies support the idea that B12 shortfalls, even subclinical ones, might damage nerve signaling generally, says Carmel. What’s greatly needed now, he argues, are major B12-supplementation trials to establish whether vitamin therapy can substantially slow the development of dementia. To date, Carmel notes, Smith’s team at Oxford appears to be the only group investigating that.

B-vitamin therapy “stopped memory decline in people who began with high homocysteine levels,” Smith says. “It’s an amazing result — much better than we could have expected.”

His group gave B vitamins, including B6, B12 and folic acid, to 133 people over age 70 for two years. All participants had mild cognitive impairment. It’s a well-defined syndrome, Smith notes, and “50 percent of people with it go on to develop dementia within five years.”

The vitamin cocktail was chosen for its established efficacy in lowering homocysteine. Earlier work, Smith explains, “showed elevated homocysteine increases the risk of cognitive impairment, including Alzheimer’s disease and vascular dementia.” In the September 2010 PLoS One, the Oxford group had reported that, compared with seniors getting a placebo pill, the B-vitamin cocktail reduced brain shrinkage.

A new follow-up paper, posted online July 21 in the International Journal of Geriatric Psychiatry, shows “the biggest effect of supplementation was on memory,” Smith says.

But as impressive as the new studies are, Carmel says, niggling questions remain about how B12 deficiency damages the brain — and whether it acts alone or in consort with deficiencies of other vitamins.

The body tends to absorb B12 poorly after age 50, and several medicines further diminish the vitamin’s uptake. “So for many people, especially those with high homocysteine,” Smith says, “it seems to make sense to take these vitamins.”

Janet Raloff is the Editor, Digital of Science News Explores, a daily online magazine for middle school students. She started at Science News in 1977 as the environment and policy writer, specializing in toxicology. To her never-ending surprise, her daughter became a toxicologist.

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