Dr. Trojanowski Discusses New Paths for Alzheimer’s Research in Recent P&T Article

According to Susan Worley’s recent article ‘After Disappointments, Alzheimer’s Researchers Seek Out New Paths’ for Pharmacy & Therapeutics journal, right now, the only Alzheimer’s treatments that are available are those that simply address the symptoms, but cannot modify the disease. However, researchers are revisiting earlier studies of disease-modifying treatments in hopes of proving that unsuccessful clinical trials from the past were not entirely unproductive.

John Q. Trojanowski, MD, PhD, Director of the IOA and Penn Alzheimer’s Disease Core Center (ADCC), discussed the three most important lessons that we have learned from failed clinical trials.

Lesson #1. Researchers must find a way to intervene at an earlier stage of Alzheimer’s disease, increasing the vitality of designing prevention or clinical trials that address prodromal Alzheimer’s disease.

Lesson #2. “We must use biomarkers in all patient populations to increase confidence in diagnosis and also to monitor target engagement, as well as response to therapy.”

Lesson #3. New drugs must be developed “that address other AD targets, such as tau tangles.”

Also featured in the article, Dr. Reisa Sperling, MD, Director of the Center for Alzheimer’s Research and Treatment at Brigham and Women’s Hospital and Massachusetts General Hospital and Professor of Neurology at Harvard Medical School, reiterates the significance of these lessons and emphasizes “the need to treat the right target at the right stage of disease.”

Both Trojanowski and Sperling seem to agree that pursuing these new targets through combination therapy is the way to go. Dr. Trojanowski “tend[s] to agree with colleagues who say that we are now witnessing the last of the era of monotherapy clinical trials.” He explains that in the past, researchers in other therapeutic areas have been a bit resistant to the idea of combination therapy, however, “particularly for AIDS, it has turned out to be the winning strategy.”

There is also increasing hope for the development of new technologies for diagnosing Alzheimer’s disease. Patients,families, and clinicians alike are yearning for new strategies based on imaging to replace the current and much more invasive methods such as lumbar punctures used to collect cerebrospinal fluid (CFS).brianscan

According to the article, the International Society to Advance Alzheimer’s Research and Treatment (ISTAART) is working on developing new standards for AD biomarkers, mirroring the way that blood tests can determine cholesterol, “so that eventually simple predictive and diagnostic tests can be effectively implemented” when screening for Alzheimer’s.

As for recent clinical trials studying AD, there are currently five underway which are discussed in the article.

#1. The A4 Study (The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease)

#2. The DIAN-TU Study (The Dominantly Inherited Alzheimer’s Network Trials Unit)

#3. The API ADAD Study (Alzheimer’s Prevention Initiative Autosomal Dominant Alzheimer’s Disease)

#4. The TOMMORROW Trial

#5. The SNIFF Study (The Study of Nasal Insulin in the Fight Against Forgetfulness)

Overall, this “new era” of Alzheimer’s disease prevention trials which combines methods of modulating beta-amyloid levels with the use of biomarkers provides the information needed to develop drugs that address non-amyloid targets and to continue moving research in the direction of combination therapy.

To read the full P&T article, including further descriptions of the current clinical trials, click here.

Image Source: www.medicinenet.com via Medical Body Scans/Photo Researchers Inc.

IOA and CNDR Directors Named 2014 J. Allyn Taylor International Prize in Medicine Recipients!

John&VirginiaCongratulations to our very own Virginia M.-Y. Lee, PhD, MBA, Director of the Center for Neurodegenerative Disease Research, and John Q. Trojanowski, MD, PhD, Director of the Institute on Aging, on being named the 2014 J. Allyn Taylor International Prize in Medicine co-recipients!

They have been chosen for this award in honor of their lifelong dedication and work towards finding ways to understand and treat the life altering neurodegenerative diseases such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), frontotemporal degeneration (FTD), progressive supranuclear palsy (PSP), and related disorders.

The J. Allyn Taylor International Prize in Medicine is awarded annually by the Robarts Research Institute at Western University in London, Ontario to acknowledge individuals who have made significant contributions in a particular field of research. Candidates are nominated by their peers in the scientific community and a jury decides the winners. 48 different researchers have been awarded since it s debut in 1985.

Recipients receive a $25,000 cash reward, an engraved medal, and a framed certificate. The award is supported by the C.H. Stiller Foundation and will be presented to Drs. Lee and Trojanowski at the 2014 J. Allyn Taylor International Prize in Medicine Symposium on November 20, 2014 in London Ontario.

For more information on the J. Allyn Taylor International Prize in Medicine award and symposium, click here.

To read the full Penn Medicine News Release on this award, click here.

MVP: Gift of William Bates, Jr., Supports Young Scientists, Advances Alzheimer’s Research, and Connects to Family Heritage

By giving to the Center for Neurodegenerative Disease Research (CNDR), William Bates, Jr., has become one of Penn Medicine’s Most Versatile Players. Among his gift’s many roles: A tribute to his wife of 61 years, Elizabeth, who died from Alzheimer’s disease. A contribution to a cure. A strike against the escalating crisis in research funding for young scientists. And, more unexpectedly, a renewal of his lifelong connection to Penn.

In 2008, Mr. Bates established the Bates Family Travel Fellowship, an endowed fund supporting postdoctoral fellows at the CNDR. Conference attendance is a professional necessity for these young scholars, but often they cannot afford the associated expenses. This award enables recipients to travel and attend meetings with top scientists from around the world, fostering the intellectual collaboration needed to advance a cure.

Given decreased federal dollars for science, gifts like this are more crucial than ever. Currently, the National Institutes of Health (NIH) can fund just half of viable proposals, leaving many promising ideas – and careers – unrealized.

“We have a serious risk of losing the most important resource that we have, which is this brain trust, the talent and the creative energies of this generation of scientists,” said NIH director Francis Collins.

As home to the largest Biomedical Graduate Studies program in the nation, Penn educates the researchers who will meet the biggest scientific challenges of the coming decades, including the urgent search for an Alzheimer’s cure. Today, five million Americans suffer from the disease; by 2050, that number is projected to grow to 14 million.

Federal cutbacks mean that further progress depends increasingly on the philanthropy of friends like Mr. Bates, who takes the mission of Penn’s young scientists seriously – and very personally. “I don’t think anything would please me more than to see a breakthrough in my lifetime,” he said.

William Bates, Sr., chief surgeon at both Graduate Hospital and Penn Presbyterian

For Mr. Bates, a personal connection to Penn Medicine is nearly a birthright. His father, William, earned both his undergraduate and medical degrees from Penn; his mother, her nursing degree. During World War I, his parents were part of a Penn initiative to establish wartime medical facilities in France.

After the war, Dr. Bates set up his medical practice in Philadelphia, eventually becoming chief surgeon at both Graduate Hospital and Penn Presbyterian. Mr. Bates vividly recalls the telephone – “always ringing” – next to his father’s seat at the dinner table.

Mr. Bates’s 45-year career in banking was highlighted by his becoming vice chairman of the Philadelphia National Bank (now Wells Fargo) and at the same time serving a term as chairman of the board of VISA, the credit card organization. He “retired” at 65, only to launch Consumer Loan Services, a first-of-its-kind consulting firm serving small lenders. Within five years, the company grew from a single room furnished with a folding table and chairs to a 200-employee operation.

But his well-earned retirement was overshadowed by his wife’s Alzheimer’s diagnosis. After her death in 2006, the memory of her suffering “became an overwhelming desire to try to do some good.” This desire is shared by Mr. Bates’s two sons, William and Jeffrey, who have pledged to continue support for the CNDR past his lifetime.

For Mr. Bates, philanthropy has yielded new connections to Penn. Over the years he has met with CNDR directors Drs. Virginia Lee and John Trojanowski and the recipients of the travel award. “I get so much pleasure from seeing these young people at the beginning of their careers, with all of it ahead of them,” he said.

Supporting Penn’s next generation of scientists also led Mr. Bates to recover a little piece of his own history. With the help of Penn Medicine’s development staff, he located a portrait of his father that once hung in the lobby of Graduate Hospital. Today, the portrait resides in his home.
At 92, Mr. Bates has an extraordinary connection to Penn’s past. But the CNDR’s search for an Alzheimer’s cure keeps him looking to the future. “I hope I’m still here when this puzzle is solved,” he said. “It would be the most wonderful gift I could have.”

To learn more about how to support the Institute on Aging contact Michael Sofolarides, director of development at Penn Medicine, at 215.573.0187 or msof@upenn.edu.

“Detection of Cognitive Impairment in Multicultural Communities” and the AD8 Dementia Screening

Last week, the Institute on Aging welcomed James E. Galvin, MD, MPHProfessor of Neurology, Psychiatry, and Nursing, New York University, to participate in the IOA Visiting Scholars Series. His presentation, titled “Detection of Cognitive Impairment in Multicultural Communities,” discussed different methods of diagnostic testing as well as the process and factors of these methods.

The risk of Alzheimer’s disease in African Americans and Hispanics is 1.5 – 2 times greater than in Caucasians, and the risk in women is 1.5 times greater than men. While most of Alzheimer’s and dementia cases are not caught until later in the disease, he explained that early detection of these conditions through clinical diagnoses is increasingly important, especially in order to enroll in research as soon as possible.

Patients or their family members are often the first to report any early signs or symptoms of cognitive impairment, most commonly after noticing a decline in memory. However, the process of a diagnosis does not end there. Clinical screenings such as the Mini Mental State Exam (MMSE), Mini-Cog, or Clinical Dementia Rating (CDR) can be administered, but some of these methods can be very time consuming and impractical for routine use. More formal neuropsychological testing can also be a very helpful tool, but depending on geographic location and the prevalence of specialists in your area, this option is not always readily available. For example, in New York, it is as if there is a psychologist on every corner, explained Dr. Galvin, however, in more Midwestern states such as Missouri, specialists are exceptionally more difficult to come by.

Dr. Galvin stressed the idea that regardless of what screening or evaluative method is used, one of the main factors to focus on during the detection of cognitive impairment is the onset of obvious change in a person’s mood or behavior. If an elderly person is experiencing symptoms related to dementia, it should only raise concern if these symptoms are recently developed, new occurrences.

Another common theme that seems to surround the issue of early diagnoses is the relatively low level of understanding, awareness, and familiarity with the detection of these conditions, both in the patient and the physician. Patients often recognize their symptoms, but not the severity of the problem, therefore they are not identifying with the condition. According to research, they are also typically very willing to undergo screening and evaluation, however, they are simply unaware that Primary Care Physicians are able to do so.

Dr. Galvin also revealed that generally speaking, physicians tend to “lack knowledge about dementia” and are much more likely to recognize a well developed disease compared to a new onset. More experienced physicians are also more likely to simply “screen” by asking a patient general questions such as “How is your memory?” whereas younger, less experienced physicians are more likely to provide a much more in-depth screening.

As previously mentioned, more formal screenings for dementia can be time consuming and very hard to come by, which can be quite an inconvenience toward the goal of early detection. In an effort to address this issue, Dr. Galvin and his colleagues developed the AD8 test (see image below), a “brief, valid, and reliable informant-based measure that is sensitive and predictive in discriminating nondemented older adults from those with even mild forms of dementia from all causes in an efficient, inexpensive, culturally sensitive and socially acceptable manner that is generalizable and translatable to the community-at-large.”

Screen Shot 2014-06-24 at 10.32.42 AM

Taking only a few minutes to administer, this “yes/no” format questionnaire provides a significantly more convenient way to detect change in a patient compared to their previous levels of function and ultimately detect even mild levels of cognitive impairment. It is often paired with performance measurement tests such as Mini-PPT (Mini Physical Performance Test) and the use of measurement tools such as Dynamometer to test grip strength, Body Composition Scales to measure impedance, and tape measures to determine girth. Such tests are very helpful in detecting sarcopenia, the loss of muscle mass and strength as you age, which has been linked to a higher risk of cognitive impairment.

View Dr. Galvin’s full description of AD8 here:


The 2014 Sylvan M. Cohen Annual Retreat

“The Gender Gap in Aging & the 21st Century Longevity Revolution”

This year the Institute on Aging’s Sylvan M. Cohen Annual Retreat was held on Wednesday, May 14 in the Smilow Center for Translational Research at the University of Pennsylvania. Its focus was on the cognitive differences between aging men and women and our growing efforts toward sustaining longevity.

To tackle these topics, the IOA partnered with the Penn Center for the Study of Sex and Gender in Behavioral Health and Medicine. The IOA was delighted to welcome Co-Directors, C. Neill Epperson, MD, and Tracy L. Bale, PhD, as well as visiting scholar Susan M. Resnick, PhD, Chief of the Laboratory of Neuroscience at the National Institute on Aging, NIH as presenters.

Lectures covered different cognitive aspects of the aging process, contributing stress factors, and how these factors differ between men and women. The Retreat concluded with the IOA’s annual Poster Session, ranging in a variety of topics in basic science, clinical research, and education & community.

Over 45 posters, submitted by Penn affiliates as well as from other area colleagues, universities, and community groups were displayed throughout the lobby of the Smilow Center. After thorough review and deliberation from our judges, first and second prizes were awarded to the best poster submissions in two separate categories; basic science and clinical research/education & community.

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A Telephone-based Intervention for Chronic Pain in Older Adults Enrolled in a Behavioral Health  Care Management Program

By: J. Zimmerman, J. Haratz, S. Leong, A. Helstrom, A. Benson, S. DiFilippo, J.E. Streim, D.W. Oslin

“Penetrating Torso Injuries in an Elderly Population: An Urban Trauma Center’s Experience”

By: D. Scantling, K. Delgado, D. Holena, J. Pascual, P. Reilly, S. Allen


Defining Kapβ2 as a Protein Disaggregase for ALS Disease Protein: FUS”

By: L. Guo, H. Wang, N. Singh, J. Shorter



MMP-9 in Subsets of Spinal Motor Neurons Drives Loss of Fat Muscle Innervation in ALS

By: K. Spiller, A. Kaplan, C. Towne, K.C. Kanning, P. Aebisher, C.E. Henderson





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