Illustrations by Emiliano Ponzi
(Editor's note: The names of some patients and their families have been changed to protect their privacy.)
Retiring from her practice as a psychotherapist and closing her office on the North Side of Chicago was a big move for Helen, a patient at Northwestern University's Alzheimer's center. But she expresses few regrets today. "I had been in business a long time and developed a lot of close relationships over the years," she says. "But I had to move on."
Helen's retirement came earlier than she might have predicted, but it came none too soon for her loved ones. They knew that memory loss had affected her practice, clients had been leaving and her workload was significantly down. Helen initially said nothing was wrong. But after some strong coaxing, she agreed to a full neurological exam. The result was a diagnosis of early-stage Alzheimer's disease, an undeniable sign that her life was going to change in many ways.
Helen and her partner, Roger, tell this story in a series of interviews conducted after weekly sessions of their Alzheimer's support group — for early-stage patients and caregivers — at the University's Cognitive Neurology and Alzheimer's Disease Center on the Chicago campus. Support groups such as these enable people to talk about their experiences and fears connected with Alzheimer's disease or a related dementia, for which there are no known cures. These support groups also help medical professionals and therapists understand a disease that is occurring with more frequency — at a rate that will continue to accelerate — in America's aging population.
Every Alzheimer's story is different. In Helen's case, Roger countered her initial denial of any problem with an intervention-like meeting at her daughter's house. Quite naturally, Helen reacted with anger as loved ones listed mental lapses that she herself did not notice. But her family was insistent, and she gradually came to terms with her new reality.
Now Helen seems serene. She has obvious memory loss, but she gets around by herself on foot and by public transportation near her high-rise home without too much trouble. People who know her note that she suffers periods of depression, but in interviews she says she feels a "sense of freedom" now that she's no longer working. As she describes her journey so far, she doesn't dwell on the negative. "I don't feel it's ruined my life," Helen says of her memory loss. "It's just made me write things down and plan more carefully."
Helen's response to her diagnosis of Alzheimer's-type dementia is hardly typical. Many families dealing with the disease encounter strong denial and sharper anger. Helen's story diverges from the conventional image of patients who display vacant stares, have angry outbursts and need restraints on chairs and beds to keep them from wandering off. Those nightmarish things happen all too often. But Helen represents one of an endless number of profiles among patients who come to the Alzheimer's center for treatment and to participate in research.
"From cells to social work," is how the clinical and research professionals explain their work at the Cognitive Neurology and Alzheimer's Disease Center, which is based at the Feinberg School of Medicine. (Additional research is being conducted in laboratories on the Evanston and Chicago campuses.) The center's mission is "to explore how the brain generates complex functions — memory, language, emotions — in health as well as in disease," says Marsel Mesulam, the Ruth and Evelyn Dunbar Distinguished Professor of Psychiatry and Behavioral Sciences at Feinberg and director of the center. More specifically, the researchers study the causes and effects of dementia and seek to make patients and families the beneficiaries of that research.
The daunting breadth of the center's mission reflects nothing if not an arduous road ahead. At the moment, each case of Alzheimer's disease still marches inevitably and sadly toward full cognitive breakdown. Its prevalence, moreover, is certain to increase as other diseases are conquered and the population gets older. (Age is the disease's greatest risk factor.) In 2009 5.3 million people in the United States are known to be living with Alzheimer's or a variant; in 2010 a half-million new cases will be diagnosed, and by 2050 there will be a million new cases annually, according to the Alzheimer's Association, based in Chicago.
The term dementia actually refers to a number of diseases, including what might be called classic Alzheimer's, first discovered in 1906 when German neuropathologist and psychiatrist Alois Alzheimer studied a patient with profound senility. Alzheimer found during an autopsy that the patient's brain was riddled with amyloid plaques and neurofibrillary tangles. Because diagnosis of this and like diseases remains provisional (certainty depends upon autopsy results), dementia of the "Alzheimer's type" refers to the most common disease along these lines, which first attacks short-term memory.
Variants are commonly known as "non-Alzheimer's dementias," which present different symptoms and evidently affect different regions of the brain. Science has made strides in individualizing many such diseases. Mesulam, for example, is credited with discovering "primary progressive aphasia," which begins its progression by destroying speech. Yet distinctions within the general category of Alzheimer's disease rarely lead to specific medical treatments. Those treatments are limited to a few drugs that can delay the death of brain cells but with only moderate success and no effect on the substances that are killing them.
Despite the long-term nature of his work, Mesulam is pleased with progress in this field, though he admits that we are only at the beginning of understanding the brain. "We are dealing with the most complicated device in the known universe," he says.
If Helen, the former psychotherapist, represents the gentle side of a terrible disease, its harsher and crueler effects are illustrated in plenty of other cases. Steve, a Medill School of Journalism alumnus and patient at the center, is one of the statistical few stricken by Alzheimer's before the age of 50 (the average age for the onset of symptoms is 75). His problems began while working as a magazine editor, a job he had performed with distinction for 16 years. He noticed that he was having trouble, initially with his eyes, and thinking about it, he complained that maybe he wasn't getting enough sleep.
In fact, Steve's colleagues at work were noticing other things that looked more serious. He was making persistent mistakes on his computer, for example, and he was constantly troubled by other parts of his job that he had previously mastered but now could not do without error.
Steve's wife admits that she saw symptoms without understanding them at first. "He was always a little absent-minded, and it seemed like just a more intense version of his normal self," she says. A major complication, however, was that their adolescent son was having behavior problems typical of a teenager, and she was dealing with those issues, as well as her husband's behavioral changes, almost every day.
As Steve's problems at work continued, his supervisors started to track his lapses. Then after six months, they asked him to take a leave of absence and undergo a neurological examination. The diagnosis, backed up by psychological and chemical tests and also by second and third opinions, was an early–onset Alzheimer's condition, including the classic symptoms of short-term memory loss and confusion.
Steve's present life takes place largely at home. He has found some television shows that he likes, and he says he enjoys eating, this being a common sensory pleasure for Alzheimer's patients. "I take walks a lot, but I have to take the same way every time because I don't want to get lost," he says. "I have to find ways of enjoying myself without getting lost."
Whether the disease appears mild or harsh, Alzheimer's remains ineluctably progressive and justifiably feared. Its ferociousness, along with epidemiological projections, has driven urgent research into its causes in this country and throughout the world.
The Alzheimer's center at Northwestern was founded in 1994 when Feinberg's neurology department recruited Mesulam and his wife, Sandra Weintraub, a neuropsychologist, from Harvard University to organize an integrated program here.
Fifteen years ago Mesulam and Weintraub found "significant human resources already working in the area" at Northwestern in fields from molecular research to clinical medicine, Mesulam explains. Within two years Northwestern became a national Alzheimer's center, funded by the National Institute on Aging. As in many areas of modern research, interdisciplinarity is intense; collaboration among chemists, neurobiologists, gerontologists, psychologists and others is the center's strength.
Still, a cure seems a long way off, as one learned at the 15th annual Alzheimer's Day, conducted by the center at Northwestern Memorial Hospital's Feinberg Pavilion last spring. About 400 individuals attended the daylong series of talks and films; attendees included medical professionals as well as lay people, many senior citizens, motivated by their stake in an Alzheimer's breakthrough.
This turnout was encouraging in terms of interest, but in other ways the news was not promising.
"I'm not going to mislead you that there are any quick fixes or that an answer is around the corner," Mesulam said in his welcoming remarks. Yet he did point out that dozens of researchers were on hand to discuss their studies in topics ranging from pharmacology to clinical psychology and social work techniques. The volume of this work is impressive and reflects its urgency despite funding that appears small compared with funding for research on other diseases.
The keynote speaker for Alzheimer's Day, Jeffrey L. Cummings, a neurologist and professor of neurology and psychiatry at the University of California, Los Angeles, came with largely the same message. He explained that two proteins, amyloid beta and tau, seem to go haywire in the brains of Alzheimer's patients and may be keys to understanding the cause of the disease. Both have been intensely studied in laboratories and patient trials, but Cummings reported that efforts to identify either substance as the key cause of Alzheimer's have been inconclusive. His conclusion was that a clear road to successful therapy has simply not emerged.
But as Cummings answered questions from the floor, he also made it plain that the elements of a brain-healthy lifestyle and strategies to prevent Alzheimer's may be less difficult to outline and prove. He mentioned rigorous mental activity (through bridge, crossword puzzles and other games) as typical of the lucid elderly — though cause and effect are hardly definitive. He mentioned antioxidants in red wine as quite possibly a good thing (when consumed, naturally, in moderation). Exercise, adequate sleep and social engagement are also regarded as major elements of a brain-healthy lifestyle.
While these observations are not empirical, Cummings suggested that we are closer to an understanding of what prevents Alzheimer's disease than what cures it. "We need to study the entire course of Alzheimer's disease, not just the dementia," he says.
As the complexity of Alzheimer's disease manifests itself in many ways, it is also reflected in the great variety of research being done at Northwestern and many other institutions into causes and cures. Both amyloid beta and tau are being investigated for their roles, the latter by Lester I. Binder, professor of cell and molecular biology at Feinberg, as part of his research into the larger central nervous system.
Amyloid beta may provide clues into the causes of Alzheimer's disease, partly because it has been studied longer than tau. Certainly the nature and behavior of amyloid beta is the focus of Alzheimer's work being done in Northwestern laboratories in Evanston and Chicago. The approaches of two such laboratories, those of professors Robert Vassar and William Klein, also are uncovering the layers of mystery now shrouding a disease that will someday almost certainly be cured at the molecular level.
Klein's lab in the Department of Neurobiology and Physiology in the Weinberg College of Arts and Sciences focuses on a substance that he discovered in 1996 (along with longtime colleagues) called an ADDL, or amyloid beta-derived diffusible ligand. ADDLs are proteins that turn out to be toxic when they attach themselves to synapses, the brain connections that enable memory. Based on knowledge that amyloid plaques are present in the brains of Alzheimer's patients, Klein hypothesized and proved the key pathogenic role of ADDLs in this process. ADDL proteins, which show up in patient's brains before plaques do, have become regarded by researchers and drug companies as triggering the synapse deterioration and brain cell death that mark Alzheimer's disease and dementia in patients.
In very recent laboratory tests Klein discovered that ADDLs attack the insulin receptors in neurons, or brain cells, largely in the hippocampus, one of the main memory centers of the brain. This finding substantiates earlier evidence that ADDLs are the culprit in memory loss and present in the early stages of Alzheimer's progression; now Klein's objective is to find ways to neutralize or eliminate the ADDLs as a possible cure for Alzheimer's.
One of Klein's approaches has been to regard the toxicity of ADDLs as an insulin deficiency in the brain, perhaps related to aging, which has led him and others to call Alzheimer's a kind of "brain diabetes." In fact, tests show that introducing insulin and some existing diabetes drugs to cells in the laboratory can protect those cells from the damaging effects of ADDLs, potentially a new strategy for treatment. At the same time, Klein's lab, along with a biotech startup he co-founded with colleagues Grant Krafft, adjunct professor of molecular pharmacology and biological chemistry at Feinberg, and Caleb Finch, a gerontologist from the University of Southern California, continue to seek a compound that can directly neutralize the ADDLs. Klein believes that this will be the basis for a future groundbreaking Alzheimer's drug.
Related to Klein's research is the amyloid-based work of Vassar, professor of cell and molecular biology at Feinberg. Vassar was honored with the 2009 Potamkin Prize, given by the American Academy of Neurology for contributions in the field of neurodegenerative diseases. This was for work that followed his discovery, some 10 years ago, of the beta secretase enzyme, BACE1, which is key in creating the amyloid beta protein, the problematic substance from which Klein's ADDLs are made.
Vassar's lab has determined that one possible cause of amyloid beta trouble occurs when the body produces too much BACE1. Knowing that BACE1 is produced in response to physical stress in the brain, Vassar went on to discover that a glucose deficiency in the brain, a possible stress factor due to aging, also causes excessive BACE1 production, which in turn leads to an increase in amyloid beta production. Vassar's current hypothesis is that Alzheimer's disease may begin as a vascular or circulatory problem, especially in the elderly, and by addressing those problems Alzheimer's might be treated or prevented.
Vassar explains that his amyloid-based work addresses the same larger phenomenon — the disease pathway — that Klein and others are trying to understand. "The challenge of Alzheimer's disease is to figure out at what point in the pathway do we intervene therapeutically," he says. In fact, Vassar talks about a "cocktail" of drugs that could address the disease at many points along this pathway. Like most researchers in this field, Vassar hesitates to predict when any true breakthrough may occur, although he is cautiously optimistic about future progress.
While a decade may be the blink of an eye in some respects, it is an eternity for people suffering from a disease. This means that the front line of Alzheimer's treatment does not involve medicines to cure it, but rather interventions that help people live with it.
The social and psychological part of treatment is key for patients and their families, as anyone with firsthand experience can attest. The story Stacey Silverman Singer (C83) tells about her father illustrates the point with harsh clarity.
Before he exhibited signs of Alzheimer's disease, Singer's father had enjoyed a long career as a merchant in Grand Forks, N.D. He retired before becoming ill and left his successful clothing store to his son. An early sign that something was wrong came a few years later when her father announced, at age 88, that he was opening a competing store, would put his son out of business and then induce his son to come back and work for him.
Things deteriorated quickly after a local banker made opening the new store possible. The father hired employees who stole from him. He made bizarre merchandising decisions that nearly bankrupted his entire family. He frequently went to his son's place of business and berated him in public for no apparent reason.
Singer's father died after three years of what can only be described as a mix of Alzheimer's-steamed fury and financial disaster. In the end, Singer blamed the disease less than her father's small community: the banker who was compliant; the police who would not arrest the father for erratic driving; and even friendly doctors who sugarcoated what should have been a clear diagnosis. Eventually, it was Singer's aggressive legal intervention with banks and police that prevented her father's antics from getting worse.
It was a bitter chapter that left Singer and her family with little more than the tragic memory of her father's last years. "My husband and I have sworn up and down that we will never do this to our kids," she says. They have even signed legal paperwork — living wills with provisions to prevent the kind of turmoil that they experienced — to be as sure of that as they possibly can.
These secondary effects are common and diffuse, so the social work treatments for Alzheimer's patients and their families take many forms, explains Darby Morhardt, a clinical social worker and the Alzheimer's center's education director. Many of these approaches involve social networks for Alzheimer's patients — new networks and old ones — that need to be strengthened and not neglected.
The first pressure point, of course, is the family. "It's a family crisis when you get a diagnosis of Alzheimer's," Morhardt says. "You have the potential of going one way or the other. Families can either come together, or they can fall apart." The objective of many social work interventions, such as support groups, is to encourage communication, which Alzheimer's renders so fragile.
"It's nice to have a place to go to be with people who are struggling with the same thing," says Helen, the recently retired psychotherapist, about her early-stage support group sessions. She calls the group "a safe place," a sanctuary from a world that asks too many questions and makes too many demands that she is increasingly unable to meet.
Sarah, another member of her group, agrees that it helps just to talk, "to do what you've always been doing," she says. "I just hope that it doesn't change."
As Sarah describes her situation it becomes clear that even well-meaning families can have a less than positive effect. "Well, my younger sister was a drama major, and she acts it," Sarah says. "Every time she comes to my house, she just gets so intense. She comes in and checks me out, and I get so that I feel I ought to burn all of my clothes and start over."
Sarah still lives independently in her condominium, though she has a paid companion who comes in every day and drives her to appointments. She takes particular pleasure, she says, in another program of the Alzheimer's center, the Buddy Program, which matches patients with first-year Northwestern medical students.
"This is fun," Sarah says of her travels around Chicago with her buddy, Amar Oza (WCAS08), a first-year Feinberg student, "especially if they're from out of town, because I like to share what's going on in the city. My challenge is to stay as normal — whatever that means — as possible and as independent as possible, because that's what life right now is all about."
The effect of life enrichment strategies on Alzheimer's remains largely anecdotal, not empirical. But the "use it or lose it" theory of brain function remains an undisputed element of Alzheimer's therapy in the early stages. "I have seen profound impact," says Morhardt. "If nothing more it can significantly delay nursing home placement."
Ultimately, of course, the object of many social interventions is not the patient but the caregivers, whose role is arduous. For this reason, support groups for family and loved ones have been an important initiative at the Alzheimer's center. Some insights gleaned in these sessions are utilitarian, such as when and how to tell friends that a patient has Alzheimer's. But others verge on the existential, not too surprising in the context of a disease that slowly robs the patient of cognition.
Care of a parent or spouse with Alzheimer's represents "a chance to heal old wounds," Morhardt says. "That includes mother-daughter relationships, which are often very difficult. And we've seen siblings come together when their parent has Alzheimer's."
Another alumna caring for a family member, Shelly Colman (C81), tells about her relationship with her 92-year-old mother, who has dementia brought on or exacerbated by a stroke. "A lot of her personality is distorted, some aspects are exaggerated. But then sometimes she seems normal," she explains. Her mother still refuses to admit that she makes mistakes, now more emphatically and often more irrationally than ever. "Clinically it's very interesting, but personally it's just very hard."
Colman adds that one thing has definitely changed for the better: Her mother is now more willing to be touched. "We weren't a physically affectionate family," she says. "When she's agitated I can stroke her, basically, and that helps. And when I put my hand out, she'll take it."
The lesson for those in support groups — and those who otherwise pay attention to something that may seem easier to deny — is that relationships don't end with Alzheimer's. Rather they change.
This came across with particular poignancy in an interview at the center one morning after a support group. The bitterness of Roger, Helen's partner, darts out when this reporter asks if certain mistakes that patients made were sometimes funny. In fact, caregivers often release stress by laughing at a patient's miscues.
Roger doesn't see it like that. "This is not a laughing matter," he says firmly, "not a laughing matter for me, not a laughing matter for her children. And I get very upset with this line of questioning."
There is a pause, then Helen asks to speak. "Well, I don't take it that way," she says. "I laugh easily. I feel like I have a lot of work to do, and I'm enjoying it. Understanding myself is the big thing right now. I want to know why I did things, even as a little kid, while I still can."
Jay Pridmore is a freelance writer in Lake Forest, Ill.
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