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Medical historians may be familiar with the story of Dr. William Beaumont, but Jason Karlawish, MD, casts it in a new light in his novel, Open Wound: The Tragic Obsession of Dr. William Beaumont. The story is fascinating on many levels, but it is Karlawish’s portrayal of Beaumont’s unstoppable, desperate, and almost dangerous ambition that takes center stage in this engaging historical account.
Efforts to develop a blood test for Alzheimer's disease are progressing, as a new study co-authored by experts from the Perelman School of Medicine at the University of Pennsylvania found a group of biomarkers that hold up in statistical analyses in three independent groups of patients. The study, a unique collaborative effort between researchers at Penn, Emory School of Medicine in Atlanta and Washington University in St. Louis as well as the Alzheimer's Disease Neuroimaging Initiative (ADNI), was just published online in Neurology.
Previous efforts to develop better and more clinically useful Alzheimer's diagnostic tests, including research from Penn, have focused on spinal fluid biomarkers and radiologic tests like MRIs and PET scans. These newer tests can detect various levels of proteins implicated in the Alzheimer's disease process, such as amyloid-beta and tau proteins. In this study, researchers found that the levels or amounts of four different biomarkers detected in blood plasma were different in people with mild cognitive impairment or Alzheimer's, when compared to healthy controls.
The research team from Penn included Steven E. Arnold, MD, Jason Karlawish, MD, Virginia M.-Y. Lee, PhD, MBA, and John Q. Trojanowski, MD, PhD.
As the Alzheimer’s disease (AD) field moves closer to using genetic and biomarker data to identify people at risk, researchers are urgently trying to tackle whether and how to disclose that information to people in both routine clinical care and research settings. This past February, the Alzheimer Research Forum, an online scientific knowledge base for Alzheimer's disease, published a detailed account of the issues involved and ongoing studies aimed at these goals. At the 2012 Alzheimer’s Association International Conference in Vancouver, three of the featured researchers updated attendees on their projects at a plenary session dedicated to the topic.
One topic of discussion at the AAIC session was the questions of whether it is psychologically harmful to divulge ApoE4 carrier status, which is associated with a higher risk of Alzheimer's disease, to cognitively normal people. Jason Karlawish, MD, explored perhaps an even more contentious issue of whether doctors or researchers should reveal plaque status to cognitively normal people, as research on whether cognitively normal people with plaque progress to Alzheimer's disease is at an earlier stage. "We have great concern that it may cause despair," said Dr. Karlawish.
In an interview with Research Media Europe Dr. Virginia Lee, director of the Center for Neurodegenerative Disease Research (CNDR) within the Perelman School of Medicine at the University of Pennsylvania, outlines the center's efforts to implement its mission to discover effective drugs and efficient treatments for Alzheimer's Disease, Parkinson’s disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis (ALS).
On July 23, 2012, Pfizer announced that the primary clinical endpoints—change in cognitive abilities and change in daily functioning—compared to placebo, were not met in the Janssen Alzheimer Immunotherapy Phase 3 trial of intravenous (IV) bapineuzumab in patients with mild-to-moderate Alzheimer’s disease who carry the ApoE4 (apolipoprotein E epsilon 4) genotype (the ELN 302 study).
Because bapineuzumab was not effective in this study of patients with Alzheimer’s disease who have an ApoE4 gene, the Janssen AI and Pfizer Joint Steering Committee has decided that participants in this study who enrolled in a follow-on extension study will no longer receive doses of bapineuzumab. However, these patients will have a follow-up evaluation.
Based on a comprehensive review of the data by the independent safety monitoring committee, all other bapineuzumab studies (for non ApoE4 carriers) are continuing as planned and without modifications. The subjects in the Pfizer bapineuzumab study (for ApoE4 carriers) will have the option to continue in the study.
It is important to note that the extension study is not ending because of safety concerns, but rather because the data were showing that the study drug was not helping people improve compared to placebo.
If you or a loved one are enrolled in a bapineuzumab study at the Penn Memory Center, you can expect a phone call from your research coordinator shortly. If would like to speak with them sooner, please contact the coordinator for the study in which you are enrolled (Janssen – Patricia Martinez: 215-746-2557 or Pfizer – Jessica Nunez: 215-662-4379.)
About Alzheimer’s disease
Alzheimer’s disease, the most common form of dementia, is a degenerative brain disease that is not a normal part of aging. Currently there is neither a cure nor a treatment that delays the course of Alzheimer’s disease, which gradually destroys a person’s cognitive and functional abilities, including memory and the ability to perform activities of daily living, such as bathing and eating. Alzheimer’s disease is the sixth leading cause of death in the United States, estimated to affect more than five million people. It is estimated that there were 35.6 million people with dementia, including Alzheimer’s disease, worldwide in 2010. This number is projected to nearly double every 20 years, increasing to 65.7 million in 2030 and 115.4 million in 2050 worldwide. Furthermore, the total worldwide costs of dementia, including Alzheimer's disease, were estimated around one percent of global gross domestic product (GDP) in 2010, at more than US $600 billion. This includes costs attributed to informal unpaid care, community or residential-based care and treatment.
VANCOUVER — While clinical trial results are being released regarding drugs intended to decrease amyloid production - thought to contribute to decline in Alzheimer's disease - clinical trials of drugs targeting other disease proteins, such as tau, are in their initial phases.
Penn Medicine research presented today at the 2012 Alzheimer's Association International Conference (AAIC) shows that an anti-tau treatment called epithilone D (EpoD) was effective in preventing and intervening the progress of Alzheimer's disease in animal models, improving neuron function and cognition, as well as decreasing tau pathology.
By targeting tau, the drug aims to stabilize microtubules, which help support and transport of essential nutrients and information between cells. When tau malfunctions, microtubules break and tau accumulates into tangles.
"This drug effectively hits a tau target by correcting tau loss of function, thereby stabilizing microtubules and offsetting the loss of tau due to its formation into neurofibrillary tangles in animal models, which suggests that this could be an important option to mediate tau function in Alzheimer's and other tau-based neurodegenerative diseases," said John Trojanowski, MD, PhD, professor of Pathology and Laboratory Medicine in the Perelman School of Medicine at the University of Pennsylvania.
The Penn Memory Center will be enrolling subjects into the BMS-Tau study shortly. Please contact Michelle Hampton at 215-615-3133 with any questions.
By Jason Karlawish, M.D.
The earliest maps of a new land, when viewed beside contemporary maps, often have the look of a child's drawing. The borders are rough, whole regions are missing, others misrepresented. If people followed such a map, they might get terribly lost. And yet, some map is better than none at all.
This week, at the Alzheimer's Association International Conference in Vancouver, researchers from the Mayo Clinic reported results of their study of potential biomarkers for preclinical Alzheimer's disease. "Biomarker," a relatively new term in medicine, is a kind of shorthand for any of the various hints that clue us in to the complex ways in which a disease develops. In Alzheimer's disease research, the most studied biomarkers include MRI and PET scan images of the brain.
Their results suggest that among cognitively normal older adults there is a potentially large population who occupy an uncharted territory. Their biomarker results are neither normal, nor clearly abnormal. Dr. David Knopman, the investigator who presented the results, admitted that he and his colleagues "hadn't expected to encounter this result."
VANCOUVER — Diagnostic tests are increasingly capable of identifying plaques and tangles present in Alzheimer's disease, yet the disease remains untreatable. Questions remain about how these tests can be used in research studies examining potential interventions to treat and prevent Alzheimer's disease. Experts from the Perelman School of Medicine at the University of Pennsylvania will today participate in a panel at the Alzheimer's Association International Conference 2012 (AAIC 2012) discussing ways to ethically disclose and provide information about test results to asymptomatic older adults.
In contrast to diseases like cancer — where tumor progression and genetic markers can be measured to determine appropriate preventative steps or targeted treatments — Alzheimer's disease tests has improved diagnosis and assessment of risk, but no treatments or preventative measures are available to alter the disease progression.
Scientists at 26 institutions across the nation are investigating the effects of Resveratrol, a compound found in red grapes, on healthy brain aging. In the "Red Wine Study" at Georgetown University Medical Center, doctors are investigating whether the compound can help to slow or stop the progression of Alzheimer's disease. Raymond Turner, MD, is leading the study at Georgetown, and he says that while researchers don't yet know exactly how Resveratrol works they believe it can activate a gene associated with brain aging. Georgetown is one of 26 institutions in the country participating in this study, and the Penn Memory Center at the University of Pennsylvania is one such institution. According to Patricia Martinez, study coordinator for the Resveratrol study at the Penn Memory Center, “Resveratrol, a compound found in the skin of red grapes and in dark chocolate, is being tested to determine if it can delay the progression of Alzheimer’s disease. Here at the Penn Memory Center we are conducting this study in order to evaluate the safety, tolerability and effectiveness of Resveratrol in people with mild to moderate Alzheimer’s disease."
Roy Hamilton, MD, Associate Professor of Neurology and a researcher and clinician at the Penn Memory Center, has been named to the newly created faculty Council on Diversity and Inclusion at the Perelman School of Medicine.
Starting July 1 the Council will work closely with the Office of Admissions and Financial Aid and the Office of Student Affairs to promote and strengthen diversity and inclusion efforts at the Perelman School of Medicine. The restructuring of the diversity and inclusion activities will allow for expanded community-based training sites for students, additional opportunities for student outreach to underserved populations, and further support for diversity recruitment.
Dr. Hamilton will join Dr. Horace Delisser, Dr. Iris Reyes, and Dr. Benoit Dube on the Council to provide new resources in order to strengthen current successful programs while designing and implementing new initiatives for diversity and inclusion at the Perelman School of Medicine.
Jason Karlawish, Professor of Medicine, Medical Ethics, and Health Policy at the University of Pennsylvania and Associate Director of the Penn Memory Center, has been named to the American Bar Association (ABA) Commission on Law and Aging.
The ABA Commission on Law and Aging is a 15-member interdisciplinary group of experts in aging and law. The mission of the Commission is to strengthen and protect the autonomy, quality of life, dignity, and legal rights of elders.
As a clinician at the Penn Memory Center Dr. Karlawish has investigated the development of Alzheimer’s disease treatments and diagnostics, decisional capacity for older adults, informed consent, and voting rights for persons with cognitive impairment and residents of long term care facilities. Dr. Karlawish brings his background in advocacy for older adults and his longtime support of mobile polling to assist the Commission in pursuing their mission through policy development, advocacy, education, and research at the national level.
"It is an honor to be named to the American Bar Association Commission on Law and Aging. I look forward to working with the Commission to develop policies and promote research necessary to protect the legal rights of older adults,” Dr. Karlawish said.
Steven Arnold, MD, professor of Neurology and Psychiatry and director of the Penn Memory Center, tells the Philadelphia Inquirer that diabetics are 50 to 100 percent more likely to get the fatal, memory-destroying Alzheimer’s disease. Arnold is the senior author of a new study in the Journal of Clinical Investigation that looked at the brains of people with Alzheimer's disease and mild cognitive impairment, often a precursor to dementia. He found insulin resistance in their brains, even though the people did not have diabetes. Arnold said the chemical differences between those who did and did not have memory problems were striking. "I've never seen a difference this large," he said. Arnold said it's likely that people with diabetes have brain insulin resistance, but others could have it, too. Arnold is now seeking funding to test whether a diabetes drug that lowers blood sugar and increases sensitivity to insulin, metformin, can help people with dementia or mild cognitive impairment.
Insulin resistance in the brain precedes and contributes to cognitive decline above and beyond other known causes of Alzheimer's disease, according to a new study by researchers from the Perelman School of Medicine at the University of Pennsylvania. The team identified extensive abnormalities in the activity of two major signaling pathways for insulin and insulin-like growth factor in non-diabetic people with Alzheimer's disease. This is the first study to directly demonstrate that insulin resistance occurs in the brains of people with Alzheimer's disease. The study is now online in the Journal of Clinical Investigation. "If we can prevent brain insulin resistance from occurring, or re-sensitize brain cells to insulin with any of the currently available insulin-sensitizing diabetes medicines, we may be able to slow down, prevent, or perhaps even improve cognitive decline,” said senior author, Steven E. Arnold, MD, professor of Psychiatry and Neurology. Arnold is also the director of the Penn Memory Center, a National Institute on Aging-designated Alzheimer's Disease Core Center.
Scientists have for the first time improved memory by applying direct electrical stimulation to a key area in the brain as it learns its way around a new environment, the New York Times reports. Experts said that the new study, appearing Thursday in the New England Journal of Medicine, was tantalizing but not yet conclusive, because the number of patients tested — six — was small, and the biological effects of electrical stimulation are still poorly understood. “People should run to replicate this study, because the implications are incredibly exciting, both for understanding the mechanism for encoding new memories, and ultimately for the treatment of neurological diseases” like dementias, said Michael J. Kahana, PhD, a Penn neuroscientist, who was not involved in the research.
USA Today - The government announced plans Tuesday to find new ways to combat Alzheimer's disease, increasing research funding more than 25% over the next two years and beefing up caregiver support and public awareness campaigns. The action, a total of $156 million, sets into motion the National Alzheimer's Project Act (NAPA), signed into law by President Obama last year. Alzheimer's, which is a form of dementia that causes progressive loss of intellectual and social skills, is the only disease among the top killers for which there is no prevention, cure or treatment that will slow its progression. The plan calls for $130 million for research and $26 million for caregiver support and education.
Jason Karlawish, MD, professor of Medicine and Medical Ethics, with the Penn Memory Center, speaks with NPR's Talk of the Nation about patient requests for skin cancer drugs to be prescribed off label for Alzheimer's disease. A medical study in Science finds that an FDA-approved skin cancer drug, marketed as Targretin, can reduce Alzheimer's-like symptoms in mice, but it is unclear if the drug will have the same effect on humans. Some researchers want to begin testing the drug for its efficacy in treating patients with AD. "I don't even know what dose you would take to see if it gets into the brain, where you could then begin to measure if it positively affects the brain or not," Karlawish said. "The first studies that need to be done in humans are studies that would involve a few volunteers to learn how the drug penetrates the brain and affects amyloid levels, and then more studies to learn if it is a safe and effective treatment for Alzheimer's disease."
In an uplifting story in the New York Times, Robert Leleux recounts his grandmother's diagnosis with Alzheimer's disease and the lessons she taught by forgetting. "So often, I hear people say they’d rather die than get Alzheimer’s. This is, in part, because they believe the disease will force them to abandon themselves to oblivion. But my grandmother showed me that we are more than the sum of our memories. She taught me the vital importance of forgetting; and that sometimes it’s only our commitment to remembering that prevents us from accepting the love and peace that surrounds us," writes Leleux.
Washington Post - “Aging is not a mild form of dementia,” says cellular neurobiologist John Morrison, who specializes in aging. Until recently, many scientists thought brain cells died as we aged, shrinking our brains and shedding bits of information that were gone forever. Newer findings indicate that cells in disease-free brains stay put; it’s the connections between them that break. With this new perspective has come an explosion of research into how we can keep those connections, and our brain function, intact for longer.
ScienceWatch.com, a science metrics and analysis group, interviewed Virginia Lee, PhD, director of the Center for Neurodegenerative Disease Research, and John Trojanowski, MD, PhD, director of the Institute on Aging, for their Special Topics analysis of Alzheimer's Disease research over the past decade. The work of Lee ranks at #2 by total cites and #8 by total papers, based on 217 papers cited a total of 13,693 times, and the work of Trojanowski ranks at #3 by total cites and #6 by total papers, based on 239 papers cited a total of 13,237 times.
University of Pennsylvania researchers have used a new brain-imaging technique in a way that could improve the diagnosis and monitoring of Alzheimer's disease. Penn scientists used an MRI innovation, called "arterial spin labeling," to image blood flow in the brain and match patterns of flow with cognitive decline. In a study published last week in Neurology, experts read the new type of MRI and PET scans of Alzheimer's patients and healthy people. Both technologies enabled them to reliably identify the patients. MRI is preferable to PET for several reasons, said John A. Detre, MD, a professor of Neurology and Radiology who was senior author of the study. For one thing, MRI is more widely available. For another, PET requires a radioactive tracer. This makes PET about twice as expensive as MRI, and the radiation exposure, while low, means patients can't have repeated PET scans to track brain changes.