Alzheimer's Disease: A 100-Year Journey

MADISON - One hundred years ago at a medical conference in Germany, psychiatrist Alois Alzheimer presented the first documented case of the disease that would bear his name.
On November 10, 2006 - almost exactly a century later - health care professionals gathered at a conference in Madison to reflect on how far Alzheimer's disease treatment and research has come.
Dr. Alzheimer presented his trailblazing case of a 51-year-old woman named Auguste Deter on November 4, 1906. Deemed to be delusional and psychotic, the woman was admitted to an asylum in Frankfurt, Germany in 1901.
Deter had begun losing her ability to find her way around her home, and she would hide objects that she later couldn't find, according to Dr. Alzheimer's account. And as her functional abilities declined, Deter's husband was left to venture out and do most of the household shopping - leading her to believe her husband was engaging in infidelity.
"She would fly into a fit of jealous rage, thinking he was having affairs," explained John Morris, MD, a Washington University School of Medicine neurologist who spoke about Alzheimer's research advances at "Alzheimer's Disease: Annual Update" at the Madison Concourse Hotel.
The conference was sponsored by the University of Wisconsin School of Medicine and Public Health, the Department of Medicine, the Wisconsin Alzheimer's Institute and the Office of Continuing Professional Development in Medicine and Public Health. The conference was organized by Mark Sager, MD, director of the Wisconsin Alzheimer's Institute.
A Trailblazing Discovery
Four years after entering the asylum, Deter died at age 55 - bedridden and withered down to 74 pounds. When Dr. Alzheimer studied the woman's brain after her death, he found it had atrophied and that numerous nerve cells had disappeared. He noted "millet-seed lesions," characterized by the deposits of a peculiar substance spread over the entire cerebral cortex.
"We clearly have a distinct disease process," Dr. Alzheimer declared to his fellow psychiatrists at the Germany conference.
One hundred years later, in a history lesson of sorts at the Madison conference, Morris said Alzheimer was disappointed when his findings failed to immediately make waves. In fact, Morris explained, Alzheimer's report barely caused a ripple, since the field of psychiatry was in the throes of Freudian psychoanalysis at the time.
"That's why no one appreciated what Alzheimer was trying to say," Morris said. "Well, a lot has happened in 100 years."
Though it took decades for Alzheimer's disease to finally make it to the forefront, there have been significant research and treatment advances since a shift began in the 1980s: 
  • In 1983, the National Institutes of Health (NIH) spent $22 million on Alzheimer's disease research. Now, that number has ballooned to $640 million annually.
  • There was no Alzheimer's disease research structure in the early 1980s; now, there are 29 National Institute on Aging-funded Alzheimer's Disease Centers.
  • In the 1980s, diagnosis was uncertain, and there were no prescription medications available to treat the disease. Now, says Morris, Alzheimer's disease has a diagnostic accuracy of 90% and there are currently five FDA-approved drugs on the market - and many more treatments are being researched. 
"Things have really accelerated, but it's only been in the last two decades," Morris said. "We're really, in a way, in the infancy of research."
"But I think all of us are very daunted by the task and by the fact that the population is aging so rapidly," Morris added. "As we all know, we still have a ways to go."
Alzheimer's and Mild Cognitive Impairment
As Alzheimer's disease has become better understood and potential risk factors have been identified, physicians are now able to more accurately diagnose the disorder and initiate appropriate therapy.
But Morris contends that truly effective therapies may need to be initiated before the onset of symptoms. That's because cerebral changes associated with Alzheimer's likely begin many years before dementia is even diagnosed.
This is where a memory condition called mild cognitive impairment (MCI) comes into play, Morris says. MCI is a general term used to describe people who have some problems with their memory but do not show other symptoms of dementia, such as impaired judgment or reasoning.
Scientists are still working to understand MCI and its relationship to Alzheimer's disease. But some - including presenters at the UW School of Medicine and Public Health conference - believe MCI is an identifiable risk state that has important predictive value for Alzheimer's.
"Not everybody in this MCI group is destined to get Alzheimer's disease. Not everybody with MCI is going to go on to dementia at all," Morris notes.
But he believes that doctors should soon be able to accurately diagnose the subset of people with mild cognitive impairment who will go on to get Alzheimer's disease.
Early, accurate diagnosis is particularly important to patients and families so they can plan for the future while the patient is still able to contribute to decision-making, Morris says. Early diagnosis also allows for therapy to be initiated when the person's overall functioning is relatively good.
Key research questions
In addition to the research that's under way to more clearly determine the relationship between MCI and Alzheimer's, other research is focusing on answering three key questions: 
  • What happens in the brain to cause the transformation from healthy aging to Alzheimer's?
  • Can certain factors protect against the disease or increase risk? 
  • What can be done to slow the progression of Alzheimer's or lessen its effects? 
One newer type of treatment designed to lessen the effects of Alzheimer's is based on the different types of memory we have. One type, called declarative memory, involves explicit information about facts - for example, being able to recall what you had for breakfast or remembering a person's name.
In people with Alzheimer's, declarative memory slips, but they're often able to retain a type of memory based on habits, called procedural memory. Examples include using your turn signal when you drive or knowing how to brush your teeth.
"This distinction is something we think we might be able to capitalize on," says Glenn Smith, PhD, a Mayo Clinic neuropsychologist who spoke at the UW School of Medicine and Public Health conference.
New Memory Approaches
One Mayo study was based on a memory notebook system, in which patients would use a notebook to record goals for the day, as well as events and other notes.
But the study didn't stop there. As Smith explained, if you simply tell people to write themselves notes to remember things, you're basically asking them to use their declarative memory to replace the declarative memory that they've lost.
So, in 12 sessions over the course of six weeks, the approach was "drill, drill, drill," Smith explained, until the participants were using the notebook automatically - shifting from using their reduced declarative memory to their largely intact procedural memory.
Eight weeks after the study, nearly 80% of study participants had continued using their notebooks to remember things. Now, Smith says researchers are examining functional outcomes of the study - Are caregivers sensing less burden? Are patients feeling more self-sufficient?
Another conference speaker discussed behavioral interventions for people with dementia, explaining that previous approaches have been largely environmental - for example, training caregivers and helping with routines.
But innovative new approaches have recently taken root, says Lyn Turkstra, PhD, an associate professor in the University of Wisconsin-Madison's Department of Communicative Disorders.
"People used to try and train people to remember better by practice," explained Turkstra. "Well, it doesn't work."
So newer approaches focus on behavioral interventions that help improve patients' daily functioning, including computer-assisted simulations and an approach called Spaced Retrieval Training. SRT is a memory approach that gives people practice at successfully recalling information over progressively longer intervals of time.
"The Breakfast Club"
Turkstra also discussed a "Breakfast Club" approach used in long-term care settings to improve communication among Alzheimer's patients.
The club is essentially a social group centered around a meal. Through the processes of preparing, serving, eating and cleaning up after the meal, a behavioral intervention like the Breakfast Club focuses on the preserved skills that Alzheimer's patients maintain even after their memories decline.
Through "forced choices" (e.g., regular or decaf coffee?) and mealtime conversation structured by a facilitator, the Breakfast Club participants' social communication skills begin to improve. And as the group becomes accustomed to the ritual of making a meal together, the participants' functional independence also improves.
"With a little bit of knowledge, we can make big changes in how we manage people… in community care settings," Turkstra says.

Date Published: 06/15/2007

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