Commenting on Recent Research News

• Predicting Alzheimer's Disease Before Symptoms Show
  Les Shaw, PhD, professor of Pathology and Laboratory Medicine, is interviewed in an Ivanhoe syndicated TV segment, aired by stations in Denver and Wilmington, North Carolina, discussing a spinal fluid test that can detect the presence of Alzheimer's disease markers. "When we're dealing with a slowly evolving disease, the changes that occur in the brain, CSF and imaging tests, are small over time." The goal with the test is to identify people who are getting the disease early and enrolling them in treatment trials. A Penn patient, diagnosed with Alzheimer's at the age of 54, is also interviewed.
• Money Woes Can Be Early Clue to Alzheimer’s
  In an interview with the New York Times about money troubles in patients with Alzheimer's disease, Jason Karlawish, MD, an associate professor of Medicine and Medical Ethics as well as Associate Director of and a practicing clinician in the Penn Memory Center, says it is generally agreed that decisions by a competent adult should be respected. But, he said, “What do we mean when we say someone has enough decision-making capacity to be ‘competent’? The law, psychology and finance are all waking up to issue of decision-making capacity.”
• New Developments in the Battle Against Alzheimer's
  Five million Americans suffer from Alzheimer’s disease and that number is expected to grow considerably with the aging population. But there is some good news. Recently there have been some promising new developments that could lead to advances in the diagnosis and the treatment of the disease. WHYY's Radio Times sits down with two Alzheimer’s researchers to talk about the latest developments in the field: John Trojanowski, MD, PhD, Professor of Geriatric Medicine and Gerontology at University of Pennsylvania, Director of the Institute on Aging and Director of the NIA Alzheimer's Disease Core Center and Jason Karlawish, MD, an Associate Professor of Medicine and Medical Ethics at the University of Pennsylvania and Associate Director of the Penn Memory Center.
• Alzheimer's brain tangles offer clue to worsening The Associated Press reports that the sticky gunk coating Alzheimer's patients' brains gets all the notoriety, but another culprit is gaining renewed attention: Protein tangles that clog brain cells and just might determine how fast patients go downhill. "We've been saying for years, 'Hedge your bets guys, you don't know what's going to pay off,'" says John Q. Trojanowski, MD, PhD, co-director of the Center for Neurodegenerative Disease Research, which this spring began collaborating with drugmaker AstraZeneca to hunt anti-tau compounds.
• Alzheimer’s: More Bad News for a $172B Disease
  John Trojanowski, MD, PhD, director of Penn's Institute on Aging, comments in The Fiscal Times about new targets for stopping Alzheimer's in light of the latest failed drug trial for the disease. “Is a-beta the right target? Are the drugs being tested too late in the disease process?” he asks. “That’s why we have to push forward with [other] biomarkers. Most drugs in development are a-beta focused. We need to not put all our eggs in one basket.”

• Spinal Taps May Be Useful in Predicting Brain Disorders
  A brief needle-in-the-back test could someday tell you, if you were inclined to know, whether you're likely to suffer from neurological diseases such as Alzheimer's or Parkinson's, and how bad the condition might be. Although nobody likes the idea of a needle in the spine, a lumbar puncture is fairly safe. For diseases like Alzheimer's, by the time a person has trouble with memory or dementia, many brain cells are already dead or dying. By late stages, "it's hard to do much to arrest the disease or rescue the brain from the horrors of this awful disease," comments Leslie Shaw, PhD, professor of Pathology and Laboratory Medicine, in the Los Angeles Times. There is an ongoing "quest," Shaw says, to find ways to catch Alzheimer's early. In 2004, several researchers banded together to start the $70-million ADNI project, hunting for predictive biomarkers in spinal fluid as well as telltale signs of early Alzheimer's in brain scans.

• What to Tell Alzheimer’s Patients After a Trial Goes Awry
  Last week Eli Lilly announced that its promising Alzheimer’s drug was making patients worse and that it was halting two large clinical trials. The New York Times interviewed Jason Karlawish, MD, Associate Professor of Medicine and Medical Ethics, about whether or not patients and their families should be told about complications with other Alzheimer's trials. Karlawish said, “you’d have a case about whether this information should be told” in regards to another trial using a similar medication to the Eli Lilly trial.
• Blows to Head Linked to Disease
  Repeated blows to the head from playing sports are linked to signs of a brain condition similar to Lou Gehrig's disease, according to a small study published Tuesday that bolsters concerns about the long-term damage of traumatic head injuries. More research is needed to establish if head trauma causes the condition or coincides with it. But the Boston University study provides "good circumstantial evidence ... that there's a linkage" between repetitive head trauma and ALS-like disease, said John Trojanowski, MD, PhD, director of the Institute of Aging, in the Wall Street Journal.
• Rare Sharing of Data Leads to Progress on Alzheimer's
  The New York Times describes how a group of scientists and executives from the National Institutes of Health, the Food and Drug Administration, the drug and medical-imaging industries, universities and nonprofit groups joined in a project that experts say had no precedent: a collaborative effort to find the biological markers that show the progression of Alzheimer’s disease in the human brain. “It was unbelievable,” said Dr. John Q. Trojanowski, MD, PhD, director of Penn's Alzheimer's Disease Core Center. “It’s not science the way most of us have practiced it in our careers. But we all realized that we would never get biomarkers unless all of us parked our egos and intellectual-property noses outside the door and agreed that all of our data would be public immediately.” “Companies were caught in a prisoner’s dilemma,” said Jason Karlawish, MD, of the Penn Memory Center. “They all wanted to move the field forward, but no one wanted to take the risks of doing it.”
• Alzheimer's Spinal Test CBS 3 reports that a screening test developed largely at the University of Pennsylvania has proved surprisingly good at predicting who will go from relatively mild memory decline to full-blown Alzheimer's disease. Leslie Shaw, PhD, professor of Pathology and Lab Medicine, notes that "Alzheimer's is a slowly developing disease, and it starts out when we're perfectly normal, and gradually develops over years and years of time."
• Spinal Fluid Test a New Tool for Diagnosing Alzheimer's Disease
  PBS Newshour reports that doctors may be able to reliably predict a person's chance of developing Alzheimer's disease from a simple analysis of their cerebral spinal fluid. There is no cure for Alzheimer's, but John Trojanowski, MD, PhD, director of Penn's Alzheimer's Disease Core Center and senior author of the study, hopes this test will be a useful tool to scientists working to develop treatments that slow the progress of the disease. "We currently have a symptomatic treatment for Alzheimer's Disease, which is like taking an aspirin for pneumonia instead of an antibiotic," he said. "That will make you feel better, but it doesn't cure the progress. We're studying therapies to slow the disease, and our hope is these biomarkers will accelerate the pace of those clinical trials."
• Alzheimer test developed largely at Penn proves effective
  The Philadelphia Inquirer reports that a screening test developed largely at the University of Pennsylvania has proved surprisingly good at predicting who will go from relatively mild memory decline to full-blown Alzheimer's disease. And that's raising hopes that new drugs might fight the disease early, before the brain becomes irreparably damaged, said John Trojanowski, MD, PhD, director of Penn's Alzheimer's Disease Core Center who helped develop the test - a measure of three proteins in patients' cerebrospinal fluid. Another Penn researcher, Leslie Shaw, PhD, professor of Pathology and Lab Medicine, also played a lead role in developing the test. The test is unlikely to be widely used until there's something people can do to stave off the disease, said Jason Karlawish, MD, an associate professor in Geriatric Medicine and Medical Ethics.
• Potential New Alzheimer's Test
  Leslie Shaw, PhD, professor of Pathology and Lab Medicine, appears in a CBS Evening News story about a biomarker test for Alzheimer's disease. "Alzheimer's is a slowly developing disease, and it starts out when we're perfectly normal, and gradually develops over years and years of time." This spinal fluid test accurately predicted 100 percent of patients with significant memory loss who were on their way to developing Alzheimer’s disease.
• Spinal-Fluid Test Is Found to Predict Alzheimer’s John Q. Trojanowski, MD, PhD, is interviewed in a New York Times article about a spinal fluid test that can detect signature biomarkers in early stages of Alzheimer's disease. Researchers report that a spinal fluid test can be 100 percent accurate in identifying patients with significant memory loss who are on their way to developing Alzheimer’s disease. The article notes that, although there has been increasing evidence of the value of this and other tests in finding signs of Alzheimer’s, the study, which will appear Tuesday in the Archives of Neurology, shows how accurate they can be. The new result is one of a number of remarkable recent findings about Alzheimer’s. But, said Dr. John Trojanowski, a University of Pennsylvania researcher and senior author of the paper, given that people can get the test now, “How early do you want to label people?” The article also appeared in the International Herald Tribune.
• In Push to Detect Early Alzheimer’s Markers, Hopes for Prevention
  The New York Times asks whether Alzheimer’s disease, a terrible degenerative brain disease with no treatments and no clear guidelines for diagnosis before its end stages, will become like heart disease? That is the hope behind new diagnostic guidelines being proposed by the National Institute on Aging and the Alzheimer’s Association. But, said Dr. Jason Karlawish, MD, associate director of the Penn Memory Center and associate professor of Geriatric Medicine and Medical Ethics, it is not unreasonable to worry about the role of drug companies. “They are driven by profits over progress and by trying to move a drug as fast as they can into the clinic without getting all the good evidence they need,” Dr. Karlawish said. The challenge, he said, is to avoid a rush to approve drugs that are not truly effective and to find a way to keep prices reasonable.
• Alzheimer's Assn. Graduation Club Copes Together
  Steven Arnold, MD, director of the Penn Memory Center and professor of Psychiatry and Neurology, is interviewed in a Los Angeles Times article looking at a group known as the Graduation Club, an Alzheimer's Association support group that encourages members to discuss their hopes, fears and frustrations, many of which come from knowing the road that lies ahead. "One of the tendencies that people with Alzheimer's have is to become more withdrawn," says Dr. Arnold. "They can't really keep up with conversations, so they tend to avoid those circumstances." Interacting with people who are sensitive to what they're going through, he says, can comfort people with the disease and help alleviate that isolation, as well as the depression that the Alzheimer's Association estimates affects 20%-40% of patients. "Many people with early Alzheimer's disease have remarkable insight that something is happening with them, and it can be very distressing," Arnold says.
• Taking an Alternative Path in Fighting Alzheimer's Disease
  Ideas about how to treat Alzheimer’s fall into two main categories. The main one pins its hopes on blocking amyloid beta peptides that form areas of plaque on the brain. But there is also another protein, tau, that is part of the disease. The third article in a New York Times occasional series called "The Vanishing Mind," which covers the Alzheimer's disease epidemic, features Penn's Center for Neurodegenerative Disease Research (CNDR) drug-discovery program and the tau research of John Q. Trojanowski, MD, PhD, director of the Penn Institute on Aging and CNDR co-director and Virginia M.-Y. Lee, PhD, MBA, CNDR director. Trojanowski states there is a danger in the intense focus on amyloid beta. "That lulls everyone into thinking that if we treat a beta we will solve the problem,” he said. “That would be wonderful if it’s true. But we need to have other targets, too.”
• Depression and Dementia are Linked
  A WHYY Radio story notes that two new studies published in the journal Neurology support the theory that depression and dementia are linked. Steven Arnold, MD, director of the Penn Memory Center, says several factors could explain the link. "Certainly one of the leading hypotheses is that depression and psychological distress can have a chronic wear and tear effect on the brain, making the brain more vulnerable to some of the deterioration, or degeneration. Depression could also cause reduced social interactions and a withdrawal from other activities that keep the brain healthy. Some experts suggest depression could be an early sign of dementia."
• The Aging Drinker
  Risky alcohol use affects older people as well as the young, but for somewhat different reasons. “There are people who clearly are addicted, the classic alcoholic, but that decreases with age,” David Oslin, MD, associate professor of Psychiatry, said in an interview with the New York Times. Only 1 percent to 1.5 percent of those in their 70s and 80s (including that 85-year-old) are alcohol-dependent, he said, compared with 2.4 percent of those ages 50 to 70 and 4 percent of younger people.
• Hopes for Alzheimer’s Drug Are Dashed
  John Trojanowski, MD, PhD, co-director of the Center for Neurodegenerative Disease Research, is quoted in the New York Times about a Pfizer drug trial, called Dimebon, which showed virtually no effect after six months in treating the cognitive decline or behavioral problems associated with Alzheimer’s when compared with a placebo. “It just seemed too good to believe,” said Trojanowski, director of the Alzheimer’s Center and Penn Institute on Aging.
• Dr. John Trojanowski was recently interviewed for SAGE Crossroads on the biomarkers of aging, the key to advancing longevity science. More information...

• Rapid Response to Alzheimer’s Disease News for the Penn Memory Center Community - January 2008

By Steven E. Arnold, MD

"Perispinal Etanercept Treatments for Alzheimer’s Disease"

We’ve been receiving many calls inquiring about a newly published case report in the Journal of Neuroinflammation describing a novel treatment for Alzheimer’s disease. The authors described their experience injecting a powerful anti-inflammatory medicine around the spinal cord in the neck and then turning the patient upside down briefly to promote diffusion of the drug towards the brain. The medicine is called etanercept (Enbrel) and is currently approved for use in rheumatoid arthritis, psoriasis, and other autoimmune disorders. The authors of the case report describe immediate and sustained symptomatic improvement with weekly treatments. The patient was more alert, more attentive, calmer, his language improved, and his thinking was clearer. Memory impairment, the cardinal feature of Alzheimer’s disease, did not notably improve using a standard test of remembering a brief list of words.

Scientifically, this anecdote is of interest to us because it represents an initial test of a novel anti-inflammatory drug and a novel way to administer a drug that otherwise is not able to get into the brain. Clinically however, it is just an anecdote. The authors say they have used this treatment in other patients with success, but compelling evidence has not been provided, let alone a placebo-controlled clinical trial that is the gold-standard method to demonstrate the benefit of a new medicine. Furthermore, the potential complications and side effects of such invasive treatments are not well described.

We are aggressive in evaluating and using any beneficial treatment for cognitive impairments, but are rigorous in our evaluations. At this point, we do not feel perispinal etanercept treatment has enough evidence to widely recommend it.

--Steven E. Arnold, M.D.

Steven E. Arnold, MD
Professor of Psychiatry and Neurology
Director, Penn Memory Center
Director, Geriatric Psychiatry Section
Associate Director, Institute on Aging
Ralston House
3615 Chestnut Street
Philadelphia, PA 19104-2676

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