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Hunting for a cure for Alzheimer's disease

Dr. Marc Gordon of the Litwin-Zucker Research Center.

Dr. Marc Gordon of the Litwin-Zucker Research Center. (Dec. 7, 2010) Photo Credit: Uli Seit

More than 5 million Americans are living with Alzheimer's disease, the most common cause of dementia in older people, and researchers estimate the number could triple by 2050, as the population ages.

A degenerative brain disease with an unforgiving prognosis, Alzheimer's gradually robs people of the ability to perform simple tasks. People with Alzheimer's often become confused or agitated. They often don't recognize friends and family.

Existing medicines may help slow the decline in the ability to think and remember, but there's nothing that can halt, reverse or prevent the condition. Thus, the hunt for a cure, or at least better treatments, continues in labs around the globe.

"There's been an enormous explosion of research, and everybody, I think, is getting it that this is a major public health issue, putting aside how devastating the disease can be on an individual level," said Dr. Marc L. Gordon, chief of neurology at Zucker Hillside Hospital in Glen Oaks, a member of the North Shore-Long Island Jewish Health System.

 

CURRENT THINKING

Scientists, frankly, don't know what triggers the disease process known as Alzheimer's, but the resulting brain damage offers some clues.

In Alzheimer's, communication between nerve cells in the brain becomes disrupted, and those cells, called neurons, begin to die off. As cell death progresses, the affected areas of the brain begin to shrink, according to the U.S. National Institute for Neurological Disorders and Stroke.

What causes those cells to die isn't exactly clear, although it's believed that certain abnormalities - called plaques and tangles - found in the brains of people with Alzheimer's play a critical role.

 

TREATMENTS

Two types of medications have been approved by the U.S. Food and Drug Administration for treating the symptoms of Alzheimer's:

Cholinesterase inhibitors: This group of drugs, recommended for mild to moderate Alzheimer's, works by slowing the breakdown of acetylcholine, a brain chemical that helps with communication between neurons. Approved drugs include Razadyne (galantamine), Exelon (rivastigmine) and Aricept (donepezil).

Namenda (memantine): This drug, approved for moderate to severe Alzheimer's, belongs to a class of drugs called N-methyl-D-aspartate (NMDA) receptor agonists. It regulates the production of glutamate, a chemical messenger in the brain that, in excessive amounts, can lead to cell death.

Gordon, a clinical staff member of the Litwin-Zucker Research Center for the Study of Alzheimer's disease and Memory Disorders at North Shore-LIJ, said the available drugs don't reverse the disease but have been shown in studies to be superior to placebos.

 

RESEARCH

The path of discovery is riddled with aborted efforts. In recent years, a number of experimental drugs that looked promising in earlier studies failed to pan out, Gordon noted.

In August, for example, Eli Lilly and Co. announced that it was halting development of a drug that researchers had hoped would reduce beta-amyloid plaques. But the company reported that people taking the drug in trials had shown worse cognitive functioning and were not as able to do daily tasks as were those taking a placebo.

Meanwhile, scientists are trying to understand how the disease unfolds. William Van Nostrand, a professor in the neurosurgery and medicine departments at Stony Brook University, is studying the accumulation of beta-amyloid in the blood vessels of the brain. His lab has shown that, in mice, the aggregation of this protein leads to brain changes that result in impaired performance on learning and memory tasks.

"We feel it's certainly a component of the disease, not the whole story," he said.

Other studies are focused on identifying so-called biomarkers, or changes in the brain of someone with Alzheimer's. With this information, clinicians hope to identify and treat people earlier in the course of the disease and develop more effective treatment regimens.

Gordon and his colleagues are currently conducting a study involving people with mild Alzheimer's who take one of the cholinesterase inhibitors. The team is using a brain imaging technique called MRI spectroscopy to observe chemical changes that occur in study participants' brains after 24 weeks on their current medication and after another 24 weeks on their current drug plus Namenda.

Lorna Role, professor and chairwoman of the Department of Neurobiology and Behavior at Stony Brook, is taking a radically different approach. Her technique, which is being tested in mice, uses fiber-optic light probes to activate neurons that make acetylcholine, a chemical messenger related to attention and memory.

 

THE LONG ISLAND SCENE

Programs and services are available to help Long Island residents with Alzheimer's and their families.

The Long Island Alzheimer's Foundation in Port Washington (liaf.org) offers adult day care, in-home respite care, family support groups and educational conferences. The Long Island chapter of the Alzheimer's Association (alz.org/longisland) runs support groups across Nassau and Suffolk counties and offers care consultation, educational programs and other resources.

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