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.

Philadelphia Inquirer

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.

Penn Medicine News Release

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.
Washington Post

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.
Science Watch.com

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.
Philadelphia Inquirer

The New York Times writes that "the relationship between doctor and patient is hard enough to parse when both are in the same room. When one opts out, it becomes even harder. And of the gallons of ink spilled over the centuries in attempts at clarification, few efforts in recent memory lay out the frustrations and confusions and crystalline moments of grace better than Jason Karlawish, MD’s marvelous new book 'Open Wound,' a historical novel tracing the peculiar career of a 19th-century American doctor. Dr. Karlawish, a professor of Geriatrics and Medical Ethics and associate director of the Penn Memory Center, is well attuned to the overtones of his compelling story, from the graphic examples of the principles of autonomy and beneficence to the clear parallels between the rough American frontier and the primitive state of medical research." The New York Times' Science Times also speaks with Dr. Karlawish on their weekly podcast.
New York Times
New York Times podcast

Neurology Today reports from a unique ALS meeting where speakers were asked to be provocative, to shake things up, and to try to find new angles on the pathogenesis of this difficult disease. John Trojanowski, MD, PhD, co-director of the Center for Neurodegenerative Disease Research, proposed a possible convergence point in the spread of protein aggregates from cell to cell. “There is a precedent for transmission” in Parkinson disease and Alzheimer disease, which have patterns of spread through the nervous system that are highly suggestive of cell-to-cell transmission of pathology, he said. His collaborator, Virginia Lee, PhD, has recently demonstrated that purified alpha-synuclein can be taken up by neurons and trigger formation of protein aggregates reminiscent of Lewy bodies. "This could be how ALS progresses once it develops. We think this cell-to-cell spread of neurodegeneration is a whole new, radical concept of the mechanism of these diseases.”
Neurology Today

Researchers from the Perelman School of Medicine at the University of Pennsylvania found a new way of diagnosing and tracking Alzheimer's disease, using an innovative magnetic resonance imaging (MRI) technique called Arterial spin labeling (ASL) to measure changes in brain function.  The team determined that the ASL-MRI test is a promising alternative to the current standard, a specific PET scan that requires exposure to small amounts of a radioactive glucose analog and costs approximately four-times more than an ASL-MRI. Two studies now appear in Alzheimer's and Dementia: The Journal of the Alzheimer’s Association and Neurology. “In brain tissue, regional blood flow is tightly coupled to regional glucose consumption, which is the fuel the brain uses to function. Increases or decreases in brain function are accompanied by changes in both blood flow and glucose metabolism,” explained John A. Detre, MD, professor of Neurology and Radiology at Penn, senior author on the papers, who has worked on ASL-MRI for the past 20 years. “We designed ASL-MRI to allow cerebral blood flow to be imaged noninvasively and quantitatively using a routine MRI scanner.”
Penn Medicine News Release

USA Today - The over-the-river-and-through-the-woods trip to grandmother's house is prime time to also assess Mom and Dad's health before a crisis occurs, aging experts say. Counseling experts are already witnessing a 66% growth in calls this year from adult children seeking advice on complex medical, legal and financial issues involving aging parents, according to a report being released Wednesday by the ComPsych Corporation, an international provider of 13,000 employee-assistance programs. Add to that high volume the 18% increase during November and December, when families gather after long absences.
USA Today

The story out of Penn State is so epic, so tragic, the Philadelphia Inquirer wanted to know what scholars of Greek tragedy and Shakespeare had to say about it. Jason Karlawish, MD, professor of Medicine and Medical Ethics, and author of Open Wound, a novel based on the case of a 19th century American doctor, William Beaumont, who both treated and used one of his patients as an experimental subject: "The events seem lifted from the pages of a Greek tragedy. A great and wildly successful man falls as a result of his own blindness to the truth set before him and his willful denial of the power he holds. Now, the Furies are released into his city. The people demand retribution and radical atonement. That Paterno's life story is one of rising up from humble origins to achieve greatness not only for himself but a devoted community only adds to that community's insatiable grief and rage."
Philadelphia Inquirer

The Penn Current covered a newly published JAMA commentary by Zachary Meisel, MD, MPH, MS, an assistant professor of Emergency Medicine, and Jason Karlawish, MD, a professor of Medicine, calling for physicians to incorporate storytelling into the way in which they report research results to the public. “If individuals can link something about the science to a personal experience, it’s more likely to be ‘stickier’ for them,” says Meisel. “They’ll retain the information and put it into a context that allows them act on it. It helps them move from simply getting information to getting it and changing their behavior.” And in cases where negative stories are used to undermine public health initiatives -- such as in public discussion about vaccine safety -- Meisel said narratives can help to set the facts straight. “When stories are used to undermine science, we have to fight fire with fire,” he said.
Penn Current

In the scientific realm, anecdotal evidence—the individual patient, the single result—tends to be shunned in favor of large, dense data sets and impersonal statistical analyses. Although that foundation must remain the core of solid research, examples and narratives should be invoked to round out the explanation of what the hard science says, Zachary Meisel, MD, MS, an assistant professor of Emergency Medicine and Jason Karlawish, MD, a professor of Medicine and Medical Ethics, contended in an essay published last week in JAMA.  “Stories are an essential part of how individuals understand and use evidence,” they wrote. And they can have a powerful effect on public opinion and policy, say the authors, both of whom are senior fellows in the Leonard Davis Institute of Health Economics. The Scientific American “Observations” blog covered their piece, along with The Daily Beast, MedCity News, and Science 2.0.
Scientific American blog post
The Daily Beast blog post
MedCity News article
Science 20 article

American Medical News reports that one-third of physician visits include at least one family member in the exam room. Even as the push toward the patient-centered medical home stresses the invaluable role that families can play in improving compliance and health outcomes, the presence of a relative raises a host of complicated issues for physicians to navigate. "Now you've got potentially two patients in the room," says Jason Karlawish, MD, professor of Medicine and Medical Ethics. "You even have a kind of third patient, which is the relationship between the family member and the patient. If you ignore that, you ignore it at your own peril." One step to making the interaction with patients' relatives a positive one is to assess why they came along, says Dr. Karlawish, a geriatrician. "Ask questions," he says. "Just as you ask the patient for their chief complaint, you can turn to the family member and say, 'And you, is there anything in particular that you wanted to bring up?'
American Medical News article

Doctors should consider the use of narrative -- in the form of patient stories and testimonials -- as a powerful tool for translating and communicating evidence-based policies to the public to buoy buy-in on important health issues such as cancer screenings and vaccination mandates, according to two physicians from the Perelman School of Medicine at the University of Pennsylvania writing this week in JAMA. They suggest two strategies: The use of so-called "counternarratives," which can play a role in neutralizing personal stories – often promoted by celebrities via the news media -- that support disproven theories, and narratives about the process of scientific study and discovery, to unmask the often hidden work of researchers and guidelines committees. The commentary is authored by Zachary Meisel, MD, MPH, MS, an assistant professor of Emergency Medicine and a senior fellow in the Leonard Davis Institute of Economics and Jason Karlawish, MD, a professor of Medicine and Medical Ethics and a senior fellow in the Leonard Davis Institute of Health Economics.
Penn Medicine News Release

A story on PennLive.com notes that Lancaster area news anchor Kim Lemon thought her husband had suffered a stroke and took him to the emergency room, where the doctor suggested he had Parkinson’s disease. The couple’s daughters, Meg, 25, and Morgan, 22, began researching their dad’s symptoms online and came across the Neurological Department at University of Pennsylvania. There, at last, John was diagnosed with Lewy body dementia, the second-most common form of progressive dementia after Alzheimer’s disease. Intent on helping others with LBD, John has committed to donating his brain to a research bank at the University of Pennsylvania. “I’m so proud of John. He’s been so brave,” Kim said. “He’s involved in all kinds of research studies and everything he’s taking part in will not benefit him. I have a great deal of respect and empathy for him because he sees and feels his decline and I know he feels a sense of powerlessness.”
PennLive.com article

Aging Well looks at challenges primary care physicians face when coordinating elders’ care with other physicians who also treat the patient. John Bruza, MD, an associate professor of Geriatric Medicine in the Perelman School of Medicine, says that at Penn all of the health network’s subspecialties use the same EHR system. This has made the management of some highly complex patients much easier. “It facilitates almost instantaneous communication with providers,” says Bruza. In fact, that kind of coordination works so well among complex patients—those seeing multiple doctors on a regular basis—that Bruza says he may encourage certain patients to reconsider an outside specialist they’re seeing in order to try to keep everything within the same health system or network. “That’s not something I’d recommend for the majority of my patients but for those that are quite complex, I might suggest they consider it,” he says.

Aging Well article