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As More Alzheimer's Drugs Fail, Researchers Find Hope In Vitamins And Spice

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As more problems arise with pharmaceutical treatments for Alzheimer’s disease, two new studies suggest that compounds in cinnamon and vitamins B12, B6, and folate may offer some protection against the disease that presently affects some 5 million people in the U.S. Just today a new study in Science suggested that last year’s “breakthrough” pharmaceutical, bexarotene (Targretin) – a cancer drug that had initially received wide publicity for helping break up the plaques in Alzheimer’s – doesn’t seem to do this very well at all, and can have significant adverse side effects for the patient. "Something happened in that initial report – either something technically or otherwise, which we can't put our hands on at this point in time," study author Sangram Sisodia told US News & World Report. "Something is seriously wrong."

There may well exist Alzheimer’s medications that show promise, and this route shouldn’t be discounted. But two new studies also hint that other types of compounds may hold significant potential in delaying the onset of the disease, and perhaps even in slowing its progression in the brain.

One study out in the Journal of Alzheimer’s Disease yesterday found that two compounds in cinnamon, cinnamaldehyde and epicatechin, may prevent the aggregation of the protein tau. Tau is an important component of normal cell structure, but when it goes “rogue” and starts accumulating, it forms the clumps and knots that are the hallmarks of Alzheimer’s disease.

Previous work in vitro had suggested that the spice might prevent tau from aggregating, but the new study singled out cinnamaldehyde and epicatechin: It showed that cinnamaldehyde can bind to cysteine, an amino acid residue on tau, and protect it from oxidative damage that can lead to malfunction. Epicatechin, an antioxidant compound also found in plant foods like blueberries and, of course, red wine, also prevented against oxidative stress in the new study.

"Wouldn't it be interesting if a small molecule from a spice could help?" said Graves in a statement, "perhaps prevent it, or slow down the progression."

The other new study, in Proceedings of the National Academy of Sciences, suggests that the vitamins B6, B12, and folic acid may slow the progression of Alzheimer’s disease. A. David Smith and his team at Oxford have done quite a lot of compelling work in this area: The fact that B-family vitamins may play a significant role in dementia, or more specifically in warding it off has been consistently illustrated. What is news from the current study, however, is that high-dose B-vitamin treatment in people at risk for the disease “slowed shrinkage of whole brain volume,” and especially reduced shrinkage in areas known to be affected in Alzheimer’s disease.

Study participants were over 70 years old, and had mild cognitive impairment (MCI), a known risk factor for Alzheimer’s disease. At the end of the study period, certain areas of the brain implicated in Alzheimer’s disease, including the hippocampus and entorhinal cortex, showed much less volume loss in people receiving the high-dose B-vitamins compared to placebo – 0.5% and 3.7% volume loss, respectively. (Note that the 0.5% shrinkage rate is about what’s considered to occur with normal aging.) People with high homocysteine levels, which are associated with Alzheimer's risk and known to be reduced by B-vitamins, showed even greater benefit from the treatment.

“Our results show that B-vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD process and that are associated with cognitive decline,” the authors say.

More research will be needed to understand the how all of these compounds function in the brain, along with the others that have shown promise in preventing and/or slowing neurodegeneration. How these compounds might be used in the future to delay the onset or slow the progression of the most common form of dementia will take some work, particularly to determine optimal dosing and safety issues.

As Dr. Smith, founding director of the Oxford Project to Investigate Memory and Ageing, told Bloomberg News, the B-vitamin treatment is “the first and only disease-modifying treatment that’s worked. We have proved the concept that you can modify the disease.”

With the consistently disappointing news from the pharmaceutical side, this may be a route that’s well worth pursuing.

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