Alzheimers Disease

Fighting the Memory Thief

Few health problems are as feared as Alzheimer's disease. The fourth leading cause of death in adults (after heart disease, cancer and stroke), Alzheimer's affects approximately four million Americans. And this figure is expected to more than triple by the middle of the next century.

Alzheimer's is a disease that sneaks up slowly, ever so quietly stealing away an elderly person's memory and personality, eventually eroding his ability to take care of himself. Elderly people with Alzheimer's are then forced to rely on family or health care professionals for survival. Is there no hope?

Actually, yes, there is. A cure is probably decades away. But even in the high-tech world of brain research, some of the most promising treatments on the horizon actually include the use of a few simple vitamins.

Investigating an Elusive Enemy

A look at what's going on in the brain of someone with Alzheimer's disease makes the memory loss and other personality problems at least understandable. Once-healthy brain cells get tangled into knots and die off.

Far less clear is just what's killing those cells. For years, research focused on microscopic plaques, made of a substance called amyloid, that slowly build up in the area of the brain responsible for memory and mental functioning. Once the plaques start hardening, the havoc begins.

As it turns out, amyloid probably has quite a few partners in crime--and at least one could be hiding in your family tree. Some forms of a blood protein called ApoE that normally ferry cholesterol through the blood also appear to cause more amyloid to be deposited in the brain and may help it harden, says Leonard Berg, M.D., chairman of the medical and scientific advisory board for the Alzheimer's Association and director of the Alzheimer's Disease Research Center at Washington University in St. Louis. And the evidence implicating one form, ApoE-4, as a risk factor for this disease is convincing. Folks with two ApoE-4 genes are eight times as likely to develop Alzheimer's as those who inherit only ApoE-2 or ApoE-3. In one study of 46 adults with Alzheimer's, 21.4 percent had the requisite two ApoE-4 genes compared with 2.9 percent who had no ApoE-4 genes.

Other researchers think zinc can potentially increase the amount of toxic amyloid deposited in the brain. In laboratory experiments, investigators at Massachusetts General Hospital in Boston found that a slight increase in zinc caused amyloid "to curdle into gluelike clumps" within just two minutes. More information is needed on the role of dietary zinc in Alzheimer's, according to the study's lead researcher, Rudolph Tanzi, M.D., director of the genetics and aging unit at Massachusetts General Hospital and Harvard Medical School. But now there is enough evidence to warn against megadoses of elemental zinc. Because increased dietary zinc has been shown to markedly decrease mental functioning in people with Alzheimer's, Dr. Tanzi suggests that they get no more than the Daily Value of 15 milligrams.

During studies in the 1960s, animals injected with aluminum developed tangles similar to those found in people with Alzheimer's. Since then, studies using advanced measuring devices have found increased concentrations of aluminum in brain tissue obtained from people who had died from Alzheimer's, says Daniel Perl, M.D., director of the neuropathology division at Mount Sinai School of Medicine in New York City. "We still don't know where the aluminum is from or what it's doing there, but we're trying to determine whether it has an active role," he says.

Brain Rust Sets In

No matter what the cause of Alzheimer's may ultimately be, some researchers are convinced that the oxidative damage your brain suffers over a lifetime also plays a role in the development of this disease. When the body burns oxygen to produce energy, the process also spawns chemically unstable molecules that are known as free radicals. These molecules steal electrons from your body's healthy molecules to balance themselves, damaging all kinds of cells, including brain cells, in the process.

A number of things contribute to the production of free radicals: pollution, cigarette smoke, alcohol--in other words, living in the late twentieth century. "What makes me think oxidative damage is important is that one of the main risk factors for Alzheimer's is getting old," says Dr. Berg. "Oxidative damage accumulates during aging just from normal metabolism of brain cells."

In fact, 10 percent of people ages 65 and older have Alzheimer's, while 20 percent of those over age 75 have the disease. A whopping 40 percent of those over age 85 have it.

One theory suggests that the oxidation process might make amyloid even more damaging--and might kill some brain cells on its own.

Further complicating the search for an Alzheimer's cure: ApoE-4, zinc, aluminum, oxidation and even inflammation may each play some small role in causing the disease in all people who have it. "There probably won't be a single solution," says Dr. Berg. "The same symptoms and the same plaques and tangles come about from multiple different causes."

Vitamin E Might Provide Some Protection

While researchers explore different approaches for conquering Alzheimer's, at least one research team has turned to a vitamin breakthrough in stroke treatment for answers.

During a stroke, damaged brain cells release a neurotransmitter called glutamic acid. This chemical causes a chain reaction that destroys more brain cells, releasing even more dangerous glutamic acid.

Exposing brain cells to vitamin E in the laboratory seems to shield them from the effects of a stroke, says David Schubert, Ph.D., professor of neurobiology at the Salk Institute for Biological Studies in San Diego. "Vitamin E actually has a protective effect on brain cells, limiting the number killed by the glutamic acid," he explains.

In another study, Dr. Schubert's laboratory showed that bathing brain cells in vitamin E protects them from a toxic protein found in amyloid plaques.

How? Just as soaking a peeled apple in lemon juice prevents oxidation from turning it brown, antioxidants such as vitamin E protect brain cells by neutralizing free radicals.

There's a hitch, however, in using vitamin E to prevent and treat Alzheimer's. Vitamin E doesn't cross what's called the blood-brain barrier very well. A natural protective mechanism, this barrier literally shields the brain from most substances. "It's a problem. Vitamin E is not the ideal compound to use in any type of therapy in this respect," says Dr. Schubert.

In the quest for a cure, however, researchers are attempting to fuse vitamin E with something like a steroid so that it can cross your blood-brain barrier more effectively, says Dr. Schubert.

It's too early to tell whether vitamin E supplements alone can help ward off Alzheimer's disease. But Dr. Schubert says there's enough potential to warrant taking supplements. "Vitamin E is pretty hard to get in your diet, because it's primarily in vegetable oils," he says. "And if you don't eat enough, the vitamin E in your blood and brain actually decreases as you get older. That can be elevated somewhat by vitamin E supplements."

Although you should see your doctor first, about 400 international units of vitamin E a day should be enough for most people, he says. The Daily Value for vitamin E is 30 international units.

The Thiamin Connection

While vitamin E researchers try to protect the brain against the ravages of amyloid plaques, those studying thiamin have taken a different approach: improving the memory of people with Alzheimer's.

In one study, 11 people with Alzheimer's symptoms were directed to take either 1,000 milligrams of thiamin or placebos (look-alike dummy pills) three times a day for three months. (This is a lot of thiamin, as the Daily Value is just 1.5 milligrams!) Tests before and after the study showed that memory improved slightly for those taking thiamin.

That might not seem like a particularly impressive finding. But people in the later stages of Alzheimer's disease generally experience a significant drop in mental functioning every six months. "We found some not very noticeable but clinically measurable positive results," says John Blass, M.D., director of the dementia research service at the Burke Medical Research Institute in White Plains, New York.

In another study inspired by Dr. Blass's work, researchers at the Medical College of Georgia in Augusta treated 18 Alzheimer's patients for five months with megadoses of thiamin ranging from 3,000 to 8,000 milligrams a day, with the dose changing from month to month.

At the end of each month, the participants were given a brief bedside exam that included questions about the date, the name of the hospital and the city, county and state, says Kimford Meador, M.D., head of the Section of Behavioral Neurology at the college. When the results were analyzed, Dr. Meador says, the research team discovered that some participants improved slightly the month they took 5,000 milligrams of thiamin a day.

"Overall, even in those whose scores dropped, they didn't drop as fast as they 'should have,' " says Dr. Meador. In other words, he would have expected people in the later stages of the disease to perform poorly, but while taking the vitamin, they were doing better than expected.

"In particular, on the bedside exam you can expect a three-point drop almost every four to six months. We didn't see that in these people," he explains. "Our people either maintained where they were or dropped a point or two--not as far as they should have. At this stage of the research, this is pretty much the best you can hope for."

Why might something like thiamin help protect memory? It's possible that thiamin helps make an important neurotransmitter called acetylcholine, which helps the nerve impulses that carry thought leap across the gaps between brain cells, more available in the brain, explains Dr. Meador. And acetylcholine is lower in people with Alzheimer's. Interestingly, research shows that thiamin deficiency in older folks may run as high as 37 percent, he says.

Does this mean that people with Alzheimer's could benefit from taking large doses of thiamin? Much more research needs to be done before answering that question for sure, says Dr. Meador. "The effect of the treatment is not tremendous in and of itself, but it looks like it's an innocuous treatment and of mild benefit," he says. "I'd like to stress that it's not a final answer and that we studied small numbers. But until something better comes along, why not?" Taking 5,000 milligrams of thiamin a day caused only mild nausea in some people, says Dr. Meador. If you or a family member would like to try this therapy, make sure you discuss it with your doctor.