By Mike King, Photography by Jack Kearse
Just as the parents of the Baby Boom generation were terrified years ago by what they assumed was a death-for-certain diagnosis of cancer, their middle-aged children worry today about something they believe is even worse—living long enough to develop Alzheimer's disease (AD). Only now, the worry is as much for themselves as their parents.
Reaching out to African Americans
Emory's Monica Parker wanted to reach beyond traditional sources of churches and hospitals to expand the number of African Americans participating in Alzheimer's disease (AD) research. The primary care physician was looking for those "who are educated and less likely to suffer from chronic diseases, one that is consistent with the overall population of Atlanta."
Her first stops were to the sisters of Delta Sigma Theta and Alpha Kappa Alpha, Atlanta chapters of the nation's largest sororities of college-educated African American women. Both chapters signed on to raise money and awareness. Their advocacy has led to an expanding pool of African Americans deeply invoved in AD research at Emory.
One result has been the creation of a Registry for Remembrance, a community/academic partnership that cultivates a cohort of African Americans in Atlanta for participation in neurologic research. The group, now numbering more than 125, has been meeting and providing data to researchers for about four years.
Among the suggestions for improving public screenings are to structure them in the context of an educational event. The participants also expressed a preference and more trust for researchers who share similar ethnicity. Several of the registry participants have enrolled in clinical trials for new drugs and treatments at Emory.
Louise Turner and her mother, Anne Eighmie, were among the first to join. Turner remembers that when she volunteered to undergo a spinal tap for research into biomarkers to identify AD, she was only the eighth minority person out of more than 800 people studied so far.
But perhaps the greatest service the registry provides is the ability for participants to share concerns about how the disease progresses and how to cope with the daily aspects of caregiving, Turner says. "This is exactly the kind of outreach to minority communities that researchers must make if everyone is to share the benefits."
The disease—and its assault on the circuitry of the brain that controls memory—has supplanted cancer as the most feared medical condition among those 60 years of age and older.
With good reason: In the past decade, the death rate from stroke, heart disease, and HIV/AIDS in the United States decreased in each category by double digits, while that from AD rose by more than 33%. Then there's this: Among the top 10 causes of death, AD (now number six) is the only one that cannot be cured, prevented, or even significantly slowed.
No wonder we're terrified.
Still, this often-repeated narrative masks what's happening on the frontlines of the battle at places like Emory, one of about 30 research and clinical care centers for AD designated by the NIH. Here, knowledge about the disease is increasing exponentially, and new approaches to diagnosis and treatment reveal themselves routinely. Renewed experiments have begun with gene therapy and a vaccine, both of which might slow the process and even reverse it. Moreover, caregivers and patients are being trained to stimulate the brain's plasticity—with good nutrition, exercise, playing music, working on computer puzzles, keeping a daily memory diary—that could alter the disease's course. With advancements in these areas, there is even talk about prevention.
And finally, advocates say, there is hope that the government-funded research establishment may be getting the message: AD and related dementias need significantly more investment to deal with the anticipated threefold increase in patients as the population ages over the next 40 years.
All this leads to a more hopeful observation: There is now a very real prospect that AD—like cancer before it—is not quite the unyielding foe we all fear, especially when confronted by advancements in neuroscience and the indomitable spirit of patients and the ones who care for them.
Two patients and two caregivers
Anne Eighmie reached the century mark last year, her sixth year since being diagnosed with AD. Her daughter, Louise Turner, 70, takes care of her mom in her Decatur home.
Turner vows never to put "mommy" in a nursing home. "I'm luckier than most caregivers," she says, explaining that her mom remains mobile. They walk about a mile a day and often go out for lunch. Her daily routine includes giving her mother a foot massage just before bed. "I sleep in a room next to her, like a new mother. When she gets up, I get up," Turner says. "Every day, I'm exhausted."
Three years ago Cecile Bazaz, an accountant and executive with SunTrust, started noticing forgetfulness on the job—missed deadlines, trouble remembering passwords—which she attributed to menopause. But when the problems worsened, her husband, Alister, thought something else might be the cause.
Tests determined that Bazaz, then 51, had early-onset AD. She quit her job and went on long-term disability. Her husband found ways to work from home to be close to her. Now she is unable to read, drive a car, or perform other daily functions.
"We're in this for the long haul," Alister Bazaz says. "We don't accept that there is nothing to be done. We will do whatever is necessary."
Eighmie and Bazaz illustrate the scope of the AD challenge. Eighmie's longevity represents the highest risk for the disease—almost a 50/50 chance you will get it if you live long enough. Bazaz is among the 5% to 10% of patients who are diagnosed with AD before they turn 65.
In the space between are 5.4 million Americans who now live with AD or related dementias and the 15.2 million friends and family members who provide unpaid care for them valued at more than $210 billion a year.
Both patients and their caregivers are actively involved in programs at the Emory Alzheimer's Disease Research Center (ADRC)—one of only 28 such centers in the country funded by the National Institute on Aging that combine clinical care and research.
At Emory, clinicians who see patients are deeply involved in research, and scientists working to develop new methods of testing and drugs for AD often know patients by name. These patients are surrounded by a team of physicians and advanced practice nurses who work closely with families, as well social workers, neuropsychologists, and primary care physicians attempting to expand the pool of participants in ongoing research.
The prevailing narrative that the relentless course of AD can't be stopped is woefully outdated. Yet it is deeply rooted in public consciousness, according to Allan Levey, director of Emory's ADRC. It developed because the ability to test for the disease was limited until recently. In fact, for many years, the only conclusive diagnosis was to examine the brains of patients thought to have died of AD.
That's far from the case today. At Emory and elsewhere, more sophisticated imaging techniques and relatively simple tests, such as examining spinal fluid, are able to reveal changes in the brain that can be precursors of AD. Scientists now understand that the course of the disease is not as compressed as once thought—that instead of a few years, there may be two or three decades of changes to the brain before the worst symptoms of full-blown AD begin to show.
Similar discoveries in the 1960s and 1970s about coronary artery disease—showing that cholesterol buildup on the interior walls of blood vessels commences years before symptoms—led to development of drugs to slow the process. Combined with better diet and exercise, these interventions have significantly reduced both morbidity and mortality for heart disease.
The prospect for doing the same for AD is very real, Levey says. More sophisticated testing and earlier intervention with drugs and behavior therapy could alter its trajectory. More than 500 research volunteers enrolled at Emory believe the same thing
The on-again, off-again efforts to find a vaccine for AD were dealt a major blow 12 years ago when a small number of patients developed encephalitis during experiments with a promising vaccine. Animal studies showed that the vaccine blocked the production of beta-amyloid, a protein that is supercharged in the brains of patients with AD, causing plaque buildup in the neuropathways. The threat to patients was considered too risky so experiments were halted in 2001.
But vaccine proponents were encouraged because in the patients who didn't develop encephalitis, the vaccine—as it did in animal trials—slowed down, and in some cases, even reversed the buildup of plaque that causes cell death within the brain.
In the latest round of trials, Emory neurologist James Lah and others are using preformed antibodies rather than a live version of the virus that was thought to carry the risk. "It's called passive immunity because you're not triggering the immune reaction in your own body," says Lah. "Instead you are delivering antibodies that are made elsewhere and using that as a tool to clear out something you don't want to be there."
Cecile Bazaz comes to the clinic every six weeks for lab work and scans of her brain to detect any signs of inflammation. Every three months she returns for an infusion of the vaccine.
Although he doesn't know whether his wife's treatment is working, Alister Bazaz says that the knowledge gained makes it worth it. "If you don't participate in something like this, you feel detached," he says. "And that's not the way to fight this disease."
Emory also is one of a dozen centers nationwide experimenting with gene therapy with a nerve growth factor protein called CERE-110 that is injected directly into areas of the brain damaged by AD. The goal is for the growth factor to nourish brain cells that produce acetylcholine, an essential player in memory and cognitive function. If CERE-110 can keep these brain cells healthy, then acetylcholine levels may not drop so rapidly and the deterioration associated with AD will be slowed—perhaps even halted.
At Emory, clinician-scientists are testing a drug originally developed to treat attention deficit and hyperactivity disorder (ADHD) as a potential treatment for mild cognitive impairment (a precursor to AD). The medication, Strattera, is one of the few used to treat ADHD that is not a controlled substance, and it has been under study for a host of neurologic conditions, including autism. The theory—based on Emory scientist David Weinshenker's studies in animals—is that it may reduce inflammation and other brain pathology that are involved in progressive degeneration, slowing the disease progression.
Getting an earlier start
These trials are focused on a therapeutic response to changes in the brain—important, Lah says, but "they are getting to the party too late." That's why the Emory ADRC concentrates on early detection and intervention.
New developments in proteomics—identifying the molecular signature of proteins that trigger reactions within cells—offers real hope of identifying novel elements besides amyloids that play a role in cognitive impairment, Lah says. Identifying these biomarkers would allow physicians to use a simple blood test to detect their presence in the same way that prostate specific antigen tests can signal the potential for prostate cancer.
Emory researcher William Hu has developed a tool to detect biomarkers using spinal fluid. The simple, 15-minute test should "very soon" become a standard screening method for AD, the way colonoscopies are now routinely used in patients over 50 to detect the possibility of colon cancer, Lah says.
"The great promise of biomarkers is that they allow us a way to identify the disease in its pre-symptomatic stage," he says. "No one who works on this disease likes the idea of waiting around until someone shows advanced disease before starting treatment."
Among other advancements, Lah and his colleagues have developed a screening test that primary care physicians and neurologists can use to identify mild cognitive impairment that is simpler and less time-consuming than the hour-long series of memory and cognition tests traditionally used. The test, dubbed the MC-FAQ, takes less than five minutes with the patient and includes a functional-activities questionnaire that is filled out by a family member or someone close to the patient. It is much more effective at picking up mild cognitive impairment and undiagnosed dementia than previous screening methods.
Treat the caregivers too
Louise Turner knew some of the signs of AD to look for in her mother. More than 10 years ago, she and her brother had noticed that their mom often repeated stories she had just told. Turner remembered that several cousins had been diagnosed with AD.
Then in 2004 while her husband was being treated at Emory for a diabetic ulcer on his foot, Turner met Monica Parker, a primary care physician who is a member of the AD team. Turner introduced Parker to her mom, and the doctor helped both mother and daughter come to grips with what was ahead.
Research shows that the risk of developing AD doubles every five years beyond the age of 65. About a third to 40% of Americans living beyond the age of 85 will develop it. For these elderly Americans, whose sons and daughters are dealing with their own health issues, a big question is, who will take care of them?
According to the Alzheimer's Association, an estimated 800,000 Americans with dementia live alone—most of them women over 80—and up to half have no identifiable caregiver. They are the most vulnerable of patients—financially, physically, and psychologically. When family members step up to care for them, Parker says, clinicians must be ready to support the caregivers.
Among other things, Parker asked if Turner and her mom would be interested in enrolling in an outpatient services program for patients with AD at Emory. Since then, Eighmie has been involved in several ADRC projects, making her daughter something of a lay expert on AD. Turner has become a valuable resource in helping train the caregivers of patients seen by ADRC physicians.
While caring for her mother has been difficult at times, it has been worth it, Turner says. Eighmie has lived long and well enough that her grandchildren and great-grandchildren know her as someone unafraid to face the future. That wouldn't have happened, Turner says, "without a strong commitment within the AD team at Emory to work with the families of patients."
Alister Bazaz feels the same way. He agrees with Levey's approach that once a loved one is diagnosed with AD, no matter the age, the treatment plan must be comprehensive. Rather than shy away from their circle of friends after Cecile's diagnosis, the Bazazes talked openly about her condition and helped demystify AD.
Recently, they attended a new museum moments program for patients with dementia and families at Emory's Michael C. Carlos Museum. Developed by Emily Lu, a freshly minted Emory doctor, the program uses specially trained tour guides who help cognitively impaired visitors connect to art. "Living in the moment," Bazaz describes it.
"It was a wonderful experience to be among patients and families, to see their minds through their eyes light up," he says.