From Dr C. E. Koop - Doctors Corner

ATLANTA -- Researchers may have identified a new approach to treating Alzheimer's disease, which has been linked to high cholesterol levels in its victims.

An estimated 4 million people in the United States suffer from Alzheimer's which causes an ongoing decline of memory and reasoning ability and can result in personality changes; it is the most common cause of dementia in older people. Some studies have shown a relationship between high cholesterol levels and increased susceptibility to Alzheimer's disease. While scientists are unclear on the cause of the disease, they do know that brain cells affected by Alzheimer's often show an increase in levels of a protein called amyloid beta-peptide (a-beta).

When a-beta levels are increased in cells, they join together to form a chain. These chains then form the plaques and tangles in the brain that are the hallmark of advanced Alzheimer's disease. Writing in the October issue of Nature Cell Biology, researchers led by Dr. Dora M. Kovacs of Harvard Medical School in Charleston, Massachusetts, showed that cholesterol levels are directly linked to the amount of a-beta produced. They also report that an enzyme called ACAT, which participates in the body's normal production of cholesterol, might regulate the production of a-beta, and therefore may be a target for therapies directed towards Alzheimer's. Using cells specially engineered to overproduce cholesterol, Kovacs' team also showed that drugs that block the actions of ACAT strongly reduce the production of a-beta, and therefore may be useful in treating the disease.

"Our results point to a novel target for the treatment of Alzheimer's disease," Kovacs told Reuters Health. Kovacs also noted that studies in patients taking cholesterol-lowering statin drugs, which lower cholesterol in a different way than ACAT inhibitors, reduced the patients' risk of developing not only Alzheimer's, but other types of dementia as well. "A lot more work has to be done before ACAT inhibitors can really be considered for the treatment of Alzheimer's disease," Kovacs said. But she pointed out that ACAT inhibitors--unlike many other medications--are expected to be able to cross the blood-brain barrier, which can hinder the delivery of drugs to brain cells. Since the current study used only individual cells, the next "major obstacle," Kovacs explained, will be to test ACAT inhibitors in mice specially bred to have Alzheimer's disease. "A potential use for ACAT inhibitors for the treatment of Alzheimer's disease is timely," Kovacs said, "since a potentially safe class of ACAT inhibitors have just recently been developed for the treatment of atherosclerosis," disease that also can result from high cholesterol levels.



Drug Keeps Alzheimer's Patients Sharper Longer

Study: Mental Decline Slowed With Donepezil
Adam Marcus - HealthScoutNews

Some Alzheimer's patients who take a drug that preserves a brain chemical linked to memory and learning can still cook, clean and otherwise care for themselves months longer than those who don't use the drug, say researchers. Two studies in this month's issue of the journal Neurology say donepezil prevents mental decline in patients with mild-to-moderate forms of Alzheimer's by blocking the destruction of acetylcholine, a molecule that helps the mind stay focused and attentive. Ordinarily the disease depletes this chemical. While other studies have shown the drug preserves the ability to function over several months, the latest work is the first to show it helps for longer periods. Dr. David Geldmacher, an Alzheimer's expert at Case Western Reserve University in Cleveland who has studied donepezil, calls the finding "very meaningful" for families touched by the disease. "Many families are less interested in cognitive test scores than in function," he says. The studies also will be useful for neurologists who want to know how long they should prescribe donepezil, Geldmacher says. The American Academ of Neurology issued guidelines earlier this year that make the drug the standard of care for patients with mild or moderate forms of Alzheimer's.

The Food and Drug Administration hasn't approved donepezil for people with severe dementia, the extreme mental decline that eventually comes with Alzheimer's, Geldmacher says. But mounting evidence suggests the drug might delay the progression of the disease for these patients, too. Ultimately however, neither donepezil nor other Alzheimer's drugs now on the market can prevent dementia from setting in for good. And the drug may not be for everyone. It can cause nausea, diarrhea, sleep loss, vomiting, muscle cramps, fatigue and loss of appetite, though previous studies show these side effects are usually mild and temporary. In the first trial, Richard Mohs and his colleagues at Mount Sinai School of Medicine in New York City followed 415 Alzheimer's patients for slightly more than a year. Those who took donepezil kept up their daily activities, from maintaining hobbies to doing the laundry, about five months longer than untreated patients. And people in the donepezil group were about 45 percent more likely than those taking placebos to show no clinical loss of function after 48 weeks.

"For Alzheimer's patients and their families, five months can mean another birthday celebration or another holiday, and five months more that they can stay in their own homes," says a statement by Mohr In the second year-long study, a group led by Dr. Bengt Winblad of Sweden's Karolinska Institute showed that donepezil cut by about half losses of mental ability and daily function compared with placebo treatment. That trial included 286 Swedish and Dutch patients with mild or moderate Alzheimer's dementia. The trial "confirms the results of [other work], which have suggested that donepezil is an effective treatment in the long term and stresses the importance of continued donepezil treatment for optimal benefits in patients with mild-to-moderate" Alzheimer's disease, the researchers write.

Both studies found donepezil safe at the top dose of 10 milligrams per day. Eisai Inc. of Teaneck, N.J., which makes and markets the drug as Aricept funded the New York trial. New York City-based Pfizer Inc., which distributes and markets the drug, supported both studies.