Rush Medical Center Docs Seek to Solve Alzheimer’s Mystery

THINKING ABOUT THE BRAIN: Doctors and scientists at Rush University Medical Center are looking for better ways to identify and treat the disease.

Outside the laboratories of the Alzheimer’s Disease Center at Rush University Medical Center, dozens of freezers line the halls. Their ghoulish contents—1,400 human brains—may one day lead to a cure for Alzheimer’s, the irreversible, progressive disease that slowly destroys memory and cognitive skills. An estimated 2.4 million to 5.1 million people in the United States already suffer from it, and the disease is becoming more prevalent as the elderly population increases. “It’s hard to get old and not have some Alzheimer’s changes in your brain,” says Dr. David A. Bennett, the center’s director.

No simple test exists to check for the disease in a living person—although the Food and Drug Administration (FDA) may soon approve a brain scan that can do just that. Until then, Rush researchers are trying to develop ways to identify early signs of Alzheimer’s by studying data gathered from more than 8,600 volunteers over 17 years. Some of those volunteers—including priests, nuns, and brothers participating in Rush’s Religious Orders Study—agreed to donate their brains to Rush after they died, providing doctors with an opportunity to look for postmortem correlations between lifestyle and Alzheimer’s. (Rush shares tissue samples from those brains, as well as data, with other medical institutions around the country.) “We don’t have a way of curing the disease right now,” says Dr. Raj C. Shah, medical director of the Rush Memory Clinic. “Everything is focusing on ‘Can we intervene earlier?’”

Early intervention is of course dependent on early diagnosis. Rush researchers are looking for specific biomarkers—in urine, blood, and spinal fluid—that might predict increased inflammation in the brain that could affect memory. They are also studying genetic factors. People with a gene called APOE4, for example, have the highest risk of developing Alzheimer’s, just as women with the gene BRCA1 or BRCA2 are at highest risk for developing breast cancer. And as part of the multicenter Alzheimer’s Disease Neuroimaging Initiative sponsored by the National Institutes of Health (NIH), Rush researchers are using a positron emission tomography (PET) scan—the one awaiting FDA approval—to look for excessive amounts of a protein called amyloid, one of the hallmarks of the disease.

But these kinds of tests raise problems of their own. Given that there is no cure for the disease, “do you want to have the option to know if you’re going to get it or not?” asks Elliott J. Mufson, a Rush neuroscientist leading an NIH project that is trying to decipher the biology that drives the development of Alzheimer’s. What’s more, the amyloid PET scan and other tests “bring up a lot of ethical issues about who you scan,” says Dr. Julie Schneider, an associate professor of neurology and neuropathology. “Does it have any value to know you have this pathology in your brain if you’re not going to get this disease for 10, 20 years?” Eventually the FDA would need to decide who could get the test—and insurers must determine who would get coverage.

There is an exciting upside to early diagnosis: People with Alzheimer indicators could be targeted for clinical trials of new drugs, says Schneider. “If you find something that works, you could use it prior to the person getting symptoms rather than waiting until the person gets memory loss and trying to reverse it.”

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On other fronts, Rush researchers are looking for ways to slow, halt, or cure the disease. For instance, they are participating in a controlled double-blind trial called ASPREE—ASPirin in Reducing Events in the Elderly—designed to see if low-dose aspirin given over a five-year period helps prevent functional decline in healthy adults over age 70. The study, which is still enrolling participants, will involve 19,000 individuals from across the United States and Australia.

Additionally, Rush researchers are trying to determine the cascade of events that cause changes in the brain, which might lead them to methods of preventing cell death and reversing cell atrophy. Elsewhere, scientists in Rush’s neurogenetic diseases lab have injected cells programmed to make nerve growth factor into the brains of Alzheimer’s patients, who have less of it naturally as their disease worsens.

For the past two decades, Rush researchers have also been investigating how to best help caregivers, whose health tends to suffer while they look after loved ones with Alzheimer’s. “We’ve spent far more money in trying to find the cure,” says Carol J. Farran, a professor in Rush’s College of Nursing who is principal investigator of the Telephone Resources and Assistance for Caregivers (TRAC) study. “That’s important, but in the meantime, families are dealing with the day-to-day issues.”

With that in mind, researchers studied Alzheimer’s support groups and education before starting to teach caregivers the skills they need to handle behavior—such as the tendency of an Alzheimer’s patient to wander. Now, after a University of Pennsylvania study found a significant increase in mortality rates among stressed-out caregivers, Rush is following about 200 of them as part of an NIH-funded study on how exercise might improve the helpers’ own health.

Maria Matariyeh is one of the participants in that study. Her mother and father, both in their early 80s, suffer from Alzheimer’s, and both of them live with her, her husband, and her 20-year-old son in Downers Grove. Her mother suffers from severe dementia and can’t brush her own teeth, but she is passive. Her father, by contrast, suffers from violent mood swings. “Caregivers need to be able to understand that Alzheimer’s comes with all this baggage,” says Matariyeh. “It remains this horrible mystery. This is just like life being taken from [Alzheimer’s patients] one day at a time. They’re essentially gone, but their bodies are here.” With a little help from Matariyeh’s friends at Rush, that may not be the case for future generations.

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Illustration: Pietari Posti

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