Washington University physicians at Barnes-Jewish Hospital are applying the principles of preventive medicine to their research into Alzheimer’s disease.
The goal of preventive medicine is to stop an illness before it starts or to discover and treat a disease before it becomes serious. Screenings for high blood pressure and diabetes, drugs to lower cholesterol, and lifestyle changes such as exercise and a balanced diet are a few examples of how preventive medicine has helped thousands of people remain healthy.
Now Washington University physicians at Barnes-Jewish Hospital are applying the principles of preventive medicine to their research into Alzheimer’s disease. As collaborators within Washington University’s Alzheimer’s Disease Research Center (ADRC), the researchers are developing ways of identifying patients at risk for the disease years before dementia symptoms begin.
The researchers believe that beginning preventive treatment before brain damage occurs is essential to halting the progression of this devastating disorder.
Unraveling the puzzle of Alzheimer’s
Alois Alzheimer, a German physician, first described Alzheimer’s disease in 1906. For many years it was thought to be a rare disease. Patients who lost their ability to think, remember and reason usually were diagnosed as having senile dementia—thought an inevitable result of aging—or hardening of the arteries (arteriosclerosis). It wasn’t until the 1970s that a group of pioneering researchers began examining dementia and its causes.
At Washington University, Leonard Berg, MD, and his colleagues established a dementia research team that in 1979 obtained funding from the National Institutes of Health(NIH) to inaugurate the Memory and Aging Project. From that initial effort has grown the ADRC, which continues to receive grant funding from the National Institute on Aging of the NIH.
It is one of only 32 federally designated centers dedicated to fostering innovative Alzheimer’s research, and the only such center in Missouri.
"As recently as the 1980s, we were unable to tell whether patients truly had Alzheimer’s disease until they died and the brain was examined at autopsy," says John C. Morris, MD, director of the ADRC. "Although definitive diagnosis still requires an autopsy, there has been an explosion of knowledge about the disease over the past 30 years."
Researchers now know that Alzheimer’s disease is caused by a build-up of particular proteins in the brain, which results in plaques and tangles.
As more and more of these plaques and tangles develop in certain areas of the brain, healthy nerve cells work less efficiently, gradually lose their ability to communicate with each other and eventually die. This leads to the cognitive impairments associated with the disease.
Diagnosing Alzheimer’s in the living brain
Perhaps the most startling, and at the same time promising, discovery made to date about Alzheimer’s is that brain plaques likely begin to develop years before symptoms arise and may have a genetic component. Much of the evidence supporting this conclusion has been uncovered at Washington University.
"We represent the leading group in the world using cutting-edge technologies that allow us to identify during life the changes in the brain associated with Alzheimer’s disease," says David M. Holtzman, MD, Barnes-Jewish neurologist-in-chief and chairman of neurology at Washington University.
One new method of gauging changes in the brain involves collecting spinal fluid through a lumbar puncture.
"The spinal fluid is made up of material coming directly from the cells in the brain," says Holtzman. "By looking at the particular proteins we know are involved in Alzheimer’s disease, we think we can identify the changes that occur in these biological markers while people’s cognitive abilities are still normal."
He adds, "Over the next five to 10 years, this test has the potential for being integrated into a regular doctor’s office visit. At a certain age, patients would get a spinal tap, these proteins would be assessed, and their relative risk for the disease revealed."
Another promising screening for the disease involves the use of a new imaging agent, Pittsburgh Compound B (PiB), during positron emission tomography (PET) scans.
"The unique aspect of the PiB agent is that when it is injected into the vein, it travels to the brain, recognizes the abnormal proteins associated with Alzheimer’s, binds to them and gives off a signal that is readily visible through the PET scanner," explains Morris. "This was never before possible except through examining brain tissue under a microscope. Based on the positive results we’ve seen so far in our studies, we believe that this imaging capability is going to revolutionize our treatment approach to Alzheimer’s disease. It likely will allow us to first diagnose the disease 10 to 20 years before symptoms appear and then to intervene with preventive medications to slow or stop the disease’s progression."
Currently, medications do exist for lessening the symptoms of Alzheimer’s disease, although Morris admits they are limited in their effectiveness.
"We now know that by the time the symptoms of Alzheimer’s begin, the brain already has been badly damaged; in some vulnerable areas, 30 percent to 60 percent of nerve cells are gone," says Morris.
"Our hope is that if we begin prescribing these drugs well before this damage begins, they will be
more effective in stopping the disease’s progress."
The Adult Children Study: Learning from the next generation
Integral to the research being conducted by ADRC researchers is the Adult Children Study, which was begun in 2005 and is funded through a second major grant from the National Institute on Aging.
Two groups of volunteers between the ages of 45 and 74—one group whose members had a parent with Alzheimer’s, the other group whose parents did not have the disease—are undergoing diagnostic tests over many years’ time. The testing ranges from cognitive evaluations to examining spinal fluid and PET scans for biomarkers of the disease.
"A unique aspect of the Adult Children Study is that all the measurements we are taking will be done over time every two to three years," says Mark A. Mintun, MD, Washington University radiologist at Barnes-Jewish Hospital. "If you look at someone just once, you don’t know whether over their lifetime they’ve always had memory problems, don’t do well on tests or can’t remember numbers. But if you see them over time, they become their own baseline. You are sensitive to any decreases in their function and can compare them over time."
A subgroup within the Adult Children Study is made up of children with a parent whose Alzheimer’s disease was caused by a rare genetic mutation that always results in early-onset Alzheimer’s—which means the child has a 50-50 chance of inheriting the gene. Washington University is the coordinating center for another National Institute on Aging grant involving 10 sites around the world that will collect and compare data on these volunteers.
"The participants in the Adult Children Study are the most dedicated and highly motivated research volunteers you could want. And it’s because they have seen Alzheimer’s disease in their parent," says Morris.
"They know what it is. Honestly, I don’t know whether we will have preventive therapies for them in their lifetimes. Hopefully we will. But most of them participate because they want to help, if not themselves, certainly others such as their children."
The hope for the future
Morris emphasizes that Alzheimer’s disease is not an inevitable result of aging. Although age is a major risk factor for the disorder, many older adults in their 80s and 90s remain alert and active throughout their lives.
"We are at an exciting time in the history of Alzheimer’s research," he says. "We are developing the means of identifying people at risk for the disease before substantial brain damage occurs, and there are many promising drugs in development with the potential for effectively stopping the progression of the disease. In addition, we are working to discover how diet, exercise and ongoing mental stimulation play a role in maintaining cognitive health."
For patients with Alzheimer’s disease seeking treatment at Barnes-Jewish Hospital, this multifaceted approach to research means they have
access to pioneering diagnostic and treatment options.
"The leading clinical and research experts in the world see patients here at Barnes-Jewish Hospital," says Holtzman. "Our commitment is to provide the best care possible to our current patients while finding the means to ensure a brighter future for the generations to come."
A Volunteer’s Perspective
Dianne Kerley, 55, watched both her grandmother and mother slowly slip away as they succumbed to the symptoms of Alzheimer’s disease.
"My mom was diagnosed with possible Alzheimer’s disease when she was 64 in 1993. She passed away in 2008. Throughout those 15 years we watched as she drew into herself and lost her memories of her older adult life," says Kerley. "Eventually she didn’t remember my dad and didn’t recall that she had a younger brother."
As do many adult children of Alzheimer’s patients, Kerley also experienced the reversal of roles required as a caregiver. "I ended up taking on a parenting role with her, especially after my dad died," she says. "It was difficult dealing with all the practical matters in addition to the sadness of basically losing the parent you love even though she is still with you."
Kerley’s greatest wish is that her son will not have to experience the same sense of loss and responsibility with her. For that reason, she was one of the first volunteers in the Adult Children Study being conducted by the ADRC.
"We want to be a part of making this world better for our children and grandchildren by helping to discover ways of stopping the progression of—or better still, eliminating—this disease," Kerley says.