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Alzheimer's Disease -- Where Are We Today?
May 26, 2009
By Michael Craig Miller, M.D.
Harvard Medical School
Alzheimer's disease is a frightening illness. It threatens to rob people of their memories of themselves and how to do normal daily activities.
We don't yet know how to prevent or cure Alzheimer's disease. We do know some of the risk factors age, family history, and inheriting some unlucky genes. But it's still unclear what sets off the disease process.
Here's an update on recent research to help understand and treat this illness.
Scrubbing Away Amyloid
People with Alzheimer's develop sticky deposits in the brain called amyloid protein. Experts believe that these proteins disrupt communication along brain circuits.
Researchers have been trying to develop medicines that can either clear amyloid deposits from the brain or prevent them from forming in the first place. Their hope is that these drugs, if given early enough, might halt or even reverse the Alzheimer's disease process.
But so far, the results have been disappointing:
- Pharmaceutical companies had to stop working on two promising compounds because clinical trials showed that they were no better than placebo pills at improving patients' memory or thinking.
- Researchers thought a new vaccine would trigger the immune system to clear the brain of the amyloid deposits. But the vaccine caused brain inflammation in 6% of patients.
The vaccine research led to an interesting discovery, however. The vaccine did clear deposits from the brains of some of the patients. But those patients still developed severe dementia. This finding suggests that the amyloid deposits may not be the right target.
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Other Possible Targets
Researchers are now looking for new approaches to treatment.
Nature Medicine published a study last year from Brigham and Women's Hospital and Harvard Medical School showing that toxic fragments released by amyloid deposits may kick the Alzheimer's disease process into gear.
Researchers also are focusing on the brain's blood supply. The same factors that damage blood vessels and increase the risk of stroke may also contribute to thinking problems in Alzheimer's. So they are looking at whether statins might also reduce the risk of dementia. Statins are drugs that lower cholesterol levels.
Two studies of statin use had conflicting results. They were published within months of each other in Neurology last year:
The Religious Orders Study has been following 929 Catholic nuns and priests who were 75 years old, on average, when they entered the study between 1994 and 2006. Each year researchers test the participants' thinking and memory skills. Taking statins has not protected against Alzheimer's. Taking statins also has not slowed the disease once it started.
The Sacramento Area Latino Study on Aging began in 1998. It followed 1,674 people who were 60 or older. After five years, people who took statins were about half as likely to develop dementia or thinking problems, compared with those who did not take statins. Some critics pointed out that the result seemed too good to be true. One reason was that 42% of people in the study took statins for less than 2 years.
No doubt we need a lot more study to find reliable new treatments.
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We're Not There Yet
The research on other Alzheimer's treatments has also been disheartening.
B vitamin supplements Folate and other B vitamins reduce the levels of homocysteine. This is an amino acid. At high levels, it may increase the risk of heart disease and stroke. In 2007, a review of 14 small studies concluded that vitamin B supplements did not protect thinking ability in healthy people, or in people who already had some thinking problems. A larger, 18-month study of 340 people was also done. It showed that vitamin B supplements did lower homocysteine levels. This didn't protect people against Alzheimer's, however.
Ginkgo biloba This dietary supplement is often promoted as a memory booster. But it came up short in a study of 3,069 people 75 years or older. All of the poeple in the study were healthy or had only mild thinking problems when the study started. They were randomly assigned to take ginkgo biloba or a placebo pill. After six years of treatment, both groups were equally likely to have developed Alzheimer's. Ginkgo biloba also did not stop mild thinking problems from getting worse.
Combining Alzheimer drugs The five drugs available now for treating Alzheimer's reduce symptoms only slightly when used alone. Researchers from Massachusetts General Hospital looked at the effect of combining drugs that have different actions.
They treated 382 patients over several years. Some patients received no Alzheimer's drugs. Some received a single drug and others got a combination of drugs. As the study went on, all patients had worsening thinking problems and were less able to function independently. The only difference was that patients who got combination therapy declined more gradually.
Exercising the brain A study published in November 2008 provided additional evidence that "cognitive reserve" the degree of intellectual strength, the extent of learning and the durability of memory may help delay symptoms of Alzheimer's. Cognitive reserve appears to be related to years of education. People with more cognitive reserve may be able to make up for thinking problems by using other parts of their brain that are not yet damaged by the illness.
In this study, subjects took a series of tests of thinking ability. They also had brain scans to see how much amyloid plaque there was. Among people with the same amount of amyloid plaque, those with more education did better on the tests. Thus, education may create a cognitive reserve that can delay the worst symptoms of Alzheimer's disease. Long-term studies are needed to prove this theory.
Keeping physically active Two studies published in 2008 add to the evidence that overall cardiovascular fitness and physical activity may help delay cognitive decline. It's possible that exercising keeps blood vessels healthy or increases blood flow to the brain.
The Rush Memory and Aging Project enrolled 521 people with an average age of 82. They did not have dementia. The researchers administered cognitive tests and recorded the people's physical activity. The more active people were on a daily basis, the better they performed on tests of cognitive function.
In the Fitness for the Aging Brain Study, 138 subjects, ages 50 and older, reported memory problems but did not yet meet the criteria for dementia. Researchers divided the subjects into an exercise group and a non-exercise group. Afer 18 months, the exercise group scored better on tests of cognitive function and memory. The gains were modest, but similar to those produced with drug treatment.
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What Can I Do Now?
It is easy to become discouraged about the state of research on Alzheimer's disease and its treatment. Combining Alzheimer's medications appears to be the best hope for treatment for now.
But you don't need a doctor's prescription to stay mentally and physically active, which gives you the best chance of keeping your brain in top shape.
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Michael Craig Miller, M.D. is editor-in-chief of the Harvard Mental Health Letter and an assistant professor of psychiatry at Harvard Medical School. Dr. Miller has an active clinical practice and has been on staff at Beth Israel Deaconess Medical Center for more than 25 years.