Vitamins Slow Rate of Brain Shrinkage in Elderly

A cocktail of three common B vitamins slowed the rate of brain shrinkage over two years in elderly patients with mild cognitive impairment, according to researchers at the University of Oxford.

As a hospitalist, I see 10 or 20 brain scans every week. A healthy 40-year-old brain nicely fills out the allotted space in the skull. Most 70-year-old brains have an obvious degree of shrinkage. Those with the most shrinkage typically have worse mental functioning, often diagnosed clinically as dementia, or its precursor, mild cognitive impairment (MCI).

The medical term for brain shrinkage is brain atrophy. It reflects loss of brain cells or decrease in brain cell size. I see A LOT of atrophied brains and impaired mental functioning—aka cognition—in the elderly.

Not everybody with atrophy has mental impairment; healthy brains slowly atrophy with age. Alzheimer’s disease patients atrophy quickly; MCI patients atrophy at an intermediate rate. MCI patients converting over the years to Alzheimer’s show a faster rate of atrophy.

Mild cognitive impairment affects 14 to 18% of those over age 70 (five million in the U.S.). Half of these convert to Alzheimer’s disease or another dementia within five years. We desperately need a way to prevent or slow that conversion.

That’s why I was excited to see a research report in which brain atrophy was slowed with three simple daily vitamins: folic acid 0.8 mg, B12 0.5 mg, and B6 20 mg. The investigators will report later on whether the vitamins helped prevent mental decline.

These three vitamins are involved in homocysteine metabolism; they decrease blood levels of homocysteine. Read elsewhere if you want the boring details.

Methodology

Oxford area participants were at least 70 years of age and had mild cognitive impairment but not dementia. Blood homocysteine levels were drawn periodically. Participants were randomized to take either placebo (83 subjects) or the daily vitamins (85 subjects) for two years. MRI scans were done periodically to determine brain volume. Tests of mental functioning were done periodically. More subjects were in the study at the outset but some dropped out and others didn’t have technically adequate MRI scans.

Results

After adjustment for age, the annual rate of brain atrophy was 30% less in the vitamin group compared to placebo.

For the placebo group, the rate of brain atrophy was clearly related to baseline homocysteine levels: higher homocysteine, faster atrophy.

Although the study was not powered to detect an effect of treatment on cognition (findings to be reported separately), in a post hoc analysis, we noted that final cognitive test scores were correlated to the rate of atrophy.

Atrophy appears to be a major determinant of cognitive decline in this population.

There were no significant safety issues and no differences in adverse events between the groups.

The vitamin group lowered homocysteine levels by 32% compared to placebo.

Reduction in brain shrinkage rate was best in those with a higher baseline homocysteine level (over 13 micromol/L); those with the lowest baseline levels (<9.5 micromol/L) showed no effect of vitamin therapy. [In the U.S., 13% of those over 60 have concentrations over 13 micromol/L, whereas the median is 10 micromol/L.]

Comments

Although this is small study, I’m excited about the future clinical implications. The results need to be replicated. I can’t wait to hear from this group regarding the details of mental functioning tests. If preservation of brain function or other practical benefits don’t accompany a slower rate of atrophy , it’s no use taking the vitamins.

A 2008 study found no clinical benefit with a similar vitamin mix in Alzheimer’s patients with mild to moderate disease. In other words, the rate of mental decline was no different than the placebo group. Average homocysteine level was 9.16 micromole/L and fell by 30% during the 18-month-long study. Even those with the highest homocysteine levels showed no benefit. Perhaps B vitamins need to be started much earlier in the disease process to be effective.

The time may come where we screen all 60-year-olds for above-average homocysteine levels, starting them on the vitamin cocktail.

One caveat, however. Ten years ago doctors were quite excited about preventing heart disease events (e.g., heart attacks, cardiac deaths) and strokes in people with high homocysteine levels. We knew that high levels were associated with cardiac events and strokes, and we knew the B vitamins would lower the blood levels. We learned a couple years ago that B vitamin therapy actually didn’t help heart patients or those at high risk for heart disease. Nor do the vitamins prevent strokes. (If you’re a heart patient still taking Foltx, ask your cardiologist if it’s OK to stop it now.)

Steve Parker, M.D.

References:

Smith, A., Smith, S., de Jager, C., Whitbread, P., Johnston, C., Agacinski, G., Oulhaj, A., Bradley, K., Jacoby, R., & Refsum, H. (2010). Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial PLoS ONE, 5 (9) DOI: 10.1371/journal.pone.0012244

Aisen, P.S., et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: A randomized controlled trial. Journal of the American Medical Association, 300 (2008): 1,774-1,783.

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