Researchers see hope for Alzheimer’s treatment, prevention

PITTSBURGH—Alzheimer’s disease is one of the conditions that Americans are most afraid they will get, second only to cancer. Yet at least a generation of focused research has gone by without an effective treatment or sure advice on how to prevent it.

University of Pittsburgh Alzheimer’s researchers are among those leading studies and while huge challenges still exist in making progress, they see hope in recent reports.

The new research is examining both treatment and prevention, using the latest technology of imaging a person’s brain. In addition to the changes in the way a person thinks, Alzheimer’s is associated with physical changes, including beta amyloid plaque and tau protein “tangles” in the brain.

Oscar Lopez, a professor of neurology at Pitt and director of the University of Pittsburgh Alzheimer’s Disease Research Center, said he is concerned that, despite improved technology, it will still take another 10 years to get useful results.

There are a handful of studies, including the multisite A4 Study at Pitt, that are examining people without any sign of Alzheimer’s and following them for 10 years with brain scans. They hope this will explain why one person develops the disease and another doesn’t. Dr. Lopez is the principal investigator in Pittsburgh.

“We’ll follow them as they are normal, for about four to five years; then symptoms begin to appear and dementia is diagnosed. Then we can understand these early scans and know how fast the disease progresses.”

Dr. Lopez also oversees the Pittsburgh arm of the ongoing global, multisite study known as ADNI. It is assessing information collected from cognitive tests, imaging,

genetics and amyloid and tau biomarkers as patients are followed over several years through normal aging to diagnoses of mild cognitive impairment or dementia, including Alzheimer’s. This study will provide information about the individuals who are more vulnerable to develop Alzheimer’s disease.

“Some people have amyloid processes but have no symptoms. Others have no amyloid,” Dr. Lopez said about questions researchers have. “What makes a person vulnerable? It is a chemical connection; does stiffness in the arteries correspond to amyloid in the brain? We now know that hypertension is connected to Alzheimer’s.”

“Watching people go through aging takes time,” Dr. Lopez said—and money.

“Even with all the technology (to aid research), there is still the human factor ... you need to follow people through the aging process. The whole process will take two generations.”

In the meantime, National Institutes of Health funding for Alzheimer’s research is not keeping up with the need, he said, and that is discouraging young scientists. “We lost one generation of researchers. That’s significant damage.”

Technology, in particular, is costly, Dr. Lopez said. Armed with new technology, recent studies point to malfunctioning tau as the main cause of the decline in thinking and memory in Alzheimer’s, not the buildup of beta amyloid fragments in the brain, which has been the focus of research for more than 20 years.

The good news is that achievements are being made in therapies and technology— and the public mindset is in the right place, said William “Bill” Klunk, Pitt professor of psychiatry and neurology, and co-director of the research center.

“We have reached the point where it’s worth the effort,” said Dr. Klunk, also chair of the Alzheimer’s Association Medical and Scientific Advisory Council, which guides the direction of the group’s research program.

“The Alzheimer’s Association has worked hard with its collaborators, to draw attention to the need for more funding, and that has shown some success,” he said, adding that although more than $500 million for research was in this year’s federal budget, an additional $300 million is requested for next year.

The association predicts that without a medical breakthrough, by 2050 there will be 13.8 million Americans over age 65 with the disease. The likelihood of developing Alzheimer’s doubles every five years after age 65. After age 85, the risk is almost 50 percent.

It’s not just amyloid or tau proteins, Dr. Klunk said. “In older people, there is more incidence of the disease, there are more pathologies in the brain, more protein deposits. There are subtle blood flow changes. All of these things change. It’s more likely that their Alzheimer’s disease is a combination of more than one thing going on in the brain.”

There are several trials at Pitt testing drugs to treat or prevent Alzheimer’s. Trials now recruiting include the A4 Study, which is testing a drug, given by IV infusion, that might prevent or delay the onset of Alzheimer’s in people who may be at risk, as seen in a brain imaging test known as a PET scan. More information is available at a4study.org.

Four medications now are most frequently prescribed to treat the symptoms of Alzheimer’s disease: Aricept, Razadyne, Exelon and Namenda.

“Medications can slow down the progression of the disease,” Dr. Lopez said. “The risk of going to a nursing home is diminished, but they’re not magic.”

In addition, plasma exchange is being tested at Pitt as a treatment of symptoms in patients with mild to moderate Alzheimer’s. The unwanted amyloid proteins are removed from the blood and the plasma is returned to the body. It is only excess amyloid that gets to the brain that is a concern.

Also underway and not seeking more patients is a “passive immunization” study that tests doses of an antibody to clear beta amyloid from the brains of patients with mild to moderate Alzheimer’s.

Pitt is also part of a multisite international study of people who have a genetic risk for Alzheimer’s.

Known as the DIAN Trial, it is still recruiting and will assess safety of two drugs in people who have a genetic mutation for inherited early-onset Alzheimer’s disease, which makes up fewer than 1 percent of total Alzheimer’s cases.

“The game change is the anti-amyloid therapies themselves,” Dr. Klunk said. “Without those antibodies or therapies or imaging technologies, none of these trials could exist.”

He said it’s a critical time now to see results: There are fewer companies, such as Eli Lilly and GE Healthcare, to pursue development of imaging tools and drug therapies.

Dr. Klunk said he was highly encouraged by recent news from drug company Biogen Idec, saying an experimental drug was found to slow down the decline of mental function in Alzheimer’s patients in a small clinical trial. The drug, aducanumab, was being tested for safety and not for dosage, but higher doses of the drug brought better results. It is designed to clear amyloid plaque from the brain.

“Results might come in two or three years,” Dr. Klunk said. “We’ll see.” Dr.

Klunk said.