Genetics of Aging-Related Neurodegeneration: The Sylvan M. Cohen Annual Retreat & Poster Session 2017

On Tuesday, May 23, 2017, the Institute on Aging (IOA) hosted their annual Sylvan M. Cohen Retreat and Poster Session in collaboration with co-sponsors, the Penn Neurodegeneration Genomics Center (PNGC).

The 2017 retreat focused on the ‘Genetics of Aging-related Neurodegeneration’ and for the second year in a row, it began with opening remarks from the Dean of the Perelman School of Medicine, J. Larry Jameson, MD, PhD. “I’m mainly here to thank you for your scientific collaboration,” said Dean Jameson. He used this time to express the importance and impact of these contributions in the field of genetics and aging, especially in trying to solve the puzzle of very complex conditions such as neurodegeneration.

Lectures were presented by Penn’s Gerard (Jerry) D. Schellenberg, PhD, Director of the PNGC, Adam Naj, PhD, Assistant professor of Epidemiology in Biostatistics and Epidemiology, and Nancy Zhang, PhD, Assistant professor of Statistics, as well as this year’s keynote speaker, Philip De Jager, MD, PhD, Associate Neurologist at Brigham and Women’s Hospital and Associate Professor of Neurology at Harvard Medical School.

Lectures:

• “Alzheimer’s Disease Genetics; Progress in Gene Therapy” – Jerry Schellenberg, PhD
• “Genetic Risk Factors Associated with Coincident Alzheimer’s and Parkinson Disease in Neuropathologically Confirmed Cases” – Adam Naj, PhD
• “Structural Variant Profiling in Alzheimer’s Disease Genetics” – Nancy Zhang, PhD
• “The molecular network map of the aging cortex: v1.0: an integrative approach targets the epigenomic and inflammatory components of Tau pathology” – Philip De Jager, MD, PhD

As usual, the event concluded with the annual poster session on aging. Prizes were awarded to the top posters in each of the following categories: Basic Science and Clinical Research/Education & Community.

Poster Winners:

BASIC SCIENCE:

1^st Place:

Title: “Integrative analysis identifies immune-related enhancers and IncRNAs perturbed by genetic variants associated with Alzheimer’s disease”
Presenter: Alexandre Amlie-Wolf
Authors: Alexandre Amlie-Wolf, Mitchell Tang, Jessica King, Beth Dombroski, Elizabeth Mlynarski,Yi-Fan Chou, Gerard D. Schellenberg, Li-San Wang
Affiliation(s): University of Pennsylvania, Genomics and Computational Biology Graduate Group

2^nd Place:

Title: “Differential Vulnerability to a-synuclein Pathology Among Neuronal Subpopulations”
Presenter: Luna Esteban
Authors: Luna Esteban, Dawn M. Riddle, Virginia M.Y. Lee, Kelvin C. Luk
Affiliation(s): Center for Neurodegenerative Disease Research

 

Clinical Research/Education & Community

1^st Place:

Title: “Correlates of Sleep Indices Among Community Dwelling Older Adults Enrolled in a Collaborative Care Management Program”
Presenter: Ashik Ansar
Authors: Ashik Ansar, MD, PhD, Shahrzad Mavandadi, PhD, Kristin Foust, Suzanne DiFilippo, RN, Joel E.. Streim, MD, David W. Oslin, MD
Affiliation(s): Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania

2^nd Place:

Title: “The Impact of Cognitive Reserve and Brain Atrophy on Survival in Neurodegenerative Diseases”
Presenter: Carrie Caswell
Authors: Carrie Caswell, MS (1), Sharon X. Xie, PhD (1), Murray Grossman, MD, EdD (1), Corey T. McMillan, PhD (1), Lauren M. Massimo, PhD, CRNP (1,2)
Affiliation(s): (1) University of Pennsylvania, (2) Penn State University

To view the full lectures from the 2017 Sylvan M. Cohen Annual Retreat, click here.

To view more photos from the 2017 Sylvan M. Cohen Annual Retreat, click here.

 

“Through the Eyes of the Caregiver: Frontotemporal Degeneration (FTD) and the Penn FTD Center” premieres at the Penn FTD Center Caregiver Conference 2017

On Friday, May 12, 2017, the Penn Frontotemporal Degeneration (FTD) Center hosted its 9^th annual Penn FTD Caregivers Conference at the University of Pennsylvania. The day-long conference held at the Smilow Center for Translational Research welcomed 150 attendees and consisted of a series of lectures that covered information around the latest scientific advances in research on FTD and its related disorders, such as Amyotrophic lateral sclerosis (ALS) also known as Lou Gehrig’s Disease and Corticobasal degeneration (CBD), as well as practical caregiving issues such as strategies for symptom management, understanding the genetics of FTD and genetic testing options, respite and supportive resources for caregivers, and legal and long-term care planning.

One of the highlights of this year’s conference was the premiere of “Through the Eyes of the Caregiver: Frontotemporal Degeneration (FTD) and the Penn FTD Center,” a short film sharing the stories of three caregivers whose loved ones are patients at the Penn FTD Center.

“The brunt of this disease falls solely on those closest to the individual with the disease unfortunately and it is very difficult to navigate the healthcare system and obtain the types of resources that give structure to a patient’s day-to-day life and to help a caregiver keep a patient safe and cognitively stimulated,” said David Irwin, MD, assistant professor and Cognitive Neurologist in the Penn FTD Center. The goal of this video is to show caregivers and family members of those with FTD that they are not alone in this life-altering process and that there are many support groups and community and medical resources available to them – including many at the Penn FTD Center – to help them every step of the way.

Watch “Through the Eyes of the Caregiver: Frontotemporal Degeneration (FTD) and the Penn FTD Center”*:

Two Penn FTD Caregivers Conference sponsors, the Alzheimer’s Association Delaware Valley Chapter and the Association for Frontotemporal Degeneration (AFTD), were also in attendance to answer questions and present information on the many advocacy and community resources that they offer for patients with FTD or related disorders and their families and caregivers.

Learn more about the Penn FTD Center at: https://ftd.med.upenn.edu

* Learn more about each individual caregiver by watching their full story! Click the “i” icon bubble in the top right hand corner of the video for a drop down menu with links to each caregivers story! If you are watching on a mobile phone, click the title of the video which will open a drop down menu containing the links to each caregiver’s story as well as a link to the Virtual Tour of Penn’s FTD PPG and Penn FTD Center to learn more about the FTD research and care taking place at Penn.

Eliezer Masliah, MD, Director of NIA’s Division of Neuroscience visits Penn

On Tuesday, May 2, 2017, Eliezer Masliah, MD*, Director of the National Institute on Aging’s (NIA) Division of Neuroscience, paid a visit to the University of Pennsylvania’s Institute on Aging (IOA), Center for Neurodegenerative Disease Research (CNDR), and Penn Neurodegeneration Genomics Center (PNGC).

The reason for Dr. Masliah’s visit was not just to learn about the neurodegenerative disease and aging-related research that is taking place in these centers here at Penn, but also to see how they all collaborate and work toward mutual goals. This gave him the opportunity to see firsthand how NIA and National Institutes of Health (NIH) funding is being used and made worthwhile to support the groundbreaking work of these centers.

Several topics were covered during the visit including the inception and mission of the new Penn Neurodegeneration Genomics Center (PNGC), directed by Gerard D. Schellenberg, PhD, and its five NIH-funded projects, the Alzheimer’s Disease Genetics Consortium (ADGC), Alzheimer’s Disease Sequencing Project (ADSP), Consortium for Alzheimer’s Sequence Analysis (CASA), Center for Genetics and Genomics of Alzheimer’s Disease (CGAD), and the NIA Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS). Dr. Schellenberg and other PNGC members, including co-director Li-San Wang, PhD, associate professor of Pathology and Laboratory Medicine and principal investigator of NIAGADS, presented some of the current work and future plans for PNGC to achieve their overarching goal to “completely resolve the genetics of Alzheimer’s disease.”

After the morning session, Dr. Masliah joined John Q. Trojanowski, MD, PhD, Director of the IOA, and Virginia M.-Y. Lee, PhD, Director of CNDR, with several of their lab members as well as several Penn faculty working in neurodegeneration, for an open discussion on the multidisciplinary approach of the IOA and CNDR. A key feature of these centers is their ability to collaborate across many different disciplines within the University of Pennsylvania’s Perelman School of Medicine. This includes faculty members from several different departments such as Pathology and Laboratory Medicine, Neurology, Psychiatry, Geriatric Medicine, and Epidemiology to name a few.

Among the many topics discussed, one that was of particular interest to Dr. Masliah was the large number of young investigators and finding out what it was that attracted them to Penn. Many of the lab members were eager to participate and to share their outlook on why Penn was the right place to start their research career. Overall, they agreed that the collaborative, multidisciplinary nature of these centers is what appealed to them most. They also praised Penn for its training and the encouraging environment that it provides for applying for research grants and other funding opportunities. Additionally, Penn is well known for its state of the art databases and data sharing, providing top-notch integration and access to resources for its investigators. Dr. Masliah was especially impressed with CNDR’s Integrative Neurodegenerative Disease Database (INDD) which tracks nearly 17,000 patients and/or research subjects at Penn’s several neurodegenerative disease related centers.

The visit concluded with a lecture by Dr. Masliah, titled “Advancing the National Plan to Address AD through National and International Collaborations.” During his talk, Dr. Masliah discussed the recent $2 billion NIH budget increase which includes $400 million new Alzheimer’s disease funds, new NINDS funding opportunities in partnership with NIA on Lewy body dementia (LDB), and the 17 new Alzheimer’s disease FOA’s.

In terms of what to expect for the future, Dr. Masliah says to stay tuned for changes in pay-lines for FY17, more funding for fellowship and K awards, and more funded FOA’s and 27 new FOA’s.

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* In his position as the Director of the NIA’s Division of Neuroscience, Dr. Masliah oversees the world’s largest research program on Alzheimer’s disease-related dementias and cognitive aging. He is an internationally renowned neuroscientist and neuropathologist and has approximately 800 original research articles and 70 book chapters. 

Unlocking the Mysteries of Delirium

What is delirium and how should we handle it?

Last month, Edward Marcantonio, MD, MS, the IOA’s most recent visiting scholar and professor of Medicine at Harvard Medical School*, offered some answers to these questions during his lecture at the University of Pennsylvania.

In the 1980’s, as he was just beginning his career in the medical field, Dr. Marcantonio was taught that it was essentially “normal” for older people to go a little crazy – or “bonkers” as he calls it – during their hospital stay. The belief was that there really was not much that could be done about it, but if the symptoms became overly bothersome, prescription medications such as haloperidol or diazepam — drugs commonly used for mental or psychiatric disorders — would “take care of it.”

Today, while we are much better at recognizing what delirium actually is – and understanding that it is not “normal” – there is still some confusion across disciplines in the terminology used to identify this condition. Delirium is often referred to as acute confusional state, altered mental status, subacute befuddlement, or postoperative psychosis.

Regardless of what term is used, the diagnosis of delirium, or any of the other aforementioned names, is characterized by confusion, restlessness, and a disturbance in attention and awareness that develops acutely and tends to fluctuate. Delirium is typically referred to as one of two types—prevalent delirium or incident delirium. Prevalent delirium is when the condition is present and observed at the time of hospital admission and incident delirium develops during the hospital stay.

Delirium is even more common than most people realize. According to Dr. Marcantonio, it is experienced in 30-40% of medical inpatients over 70 years old, 15-50% of surgery patients over 70 years old, and at least 75-80% of intensive care unit patients over 18 years old.

In his line of research, Dr. Marcantonio focuses on two main aims: 1) improving delirium identification at the bedside and 2) understanding the pathophysiology of delirium and its association with dementia.

Improving delirium identification at the bedside

Because symptoms of delirium can come and go and vary in severity, identifying it can be quite a challenge. “When I got started in the field there were a number of studies that sent research teams out doing gold standard delirium assessments and then compared that to what was diagnosed in clinical care and it turned out that less than 50% of cases were recognized,” said Dr. Marcantonio.

In the 1990’s, the Confusion Assessment Method (CAM) was developed to help detect delirium in patients. The CAM looks at four key features: 1) acute change/fluctuating course, 2) inattention, 3) disorganized thinking, and 4) altered level of consciousness. In order to officially diagnose delirium according to the CAM diagnostic algorithm, the patient must be experiencing both features 1 and 2, in addition to either 3 or 4. While recognizing these features as signs of delirium can produce a successful diagnosis, there still needed to be a standardized way to identify these features in the patients. With this in mind, Dr. Marcantonio developed a series of methods and assessments for detecting delirium – some taking as little as 30 seconds to administer.

Learn more about these assessments in Dr. Marcantonio’s full lecture starting at 0:20:28:
Full lecture

Understanding the pathophysiology of delirium and its association with dementia

Although a variety of situations, such as dehydration, visual or hearing impairment, immobility, and sleep deprivation, can increase the chances of developing delirium, current research suggests that one of the strongest risk factors – aside from aging – is dementia.

One emerging hypothesis is that delirium may represent a state of neuroinflammation. It is believed that this neuroinflammation could be the link between delirium and dementia and if this theory is confirmed, it could have some very important therapeutic effects for both conditions.

Learn more about the link between dementia and delirium in Dr. Marcantonio’s full lecture starting at 0:40:05:
Full lecture

Although we have come a long way over the years to better understand delirium, there is still much work left to do. The ultimate goals are to establish effective and efficient assessments of delirium as a part of daily hospital vital sign checks and to develop pathophysiologically-based treatments to improve the short and long-term outcomes of this condition.

To view the full lecture, click here.

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* Dr. Marcantonio is also the Section Chief for Research in the Division of General Medicine and Primary Care at Beth Israel Deaconess Medical Center (BIDMC).

 

Can postponing ill-health via comprehensive damage repair extend human lifespan indefinitely?

On Tuesday, December 6, 2016, the Institute on Aging (IOA) welcomed Aubrey de Grey, PhD, Chief Science Officer at the SENS Research Foundation, for a Visiting Scholars Series lecture on “Rejuvenation biotechnology: Postponing ill-health via comprehensive damage repair.”

The SENS Research Foundation is a public charity doing biomedical research with a focus on developing new medicines that may be more effective than current methods in postponing the ill health of old age.

“I do think that the general concept of eliminating damage that the body does to itself is something in which the sky is the limit,” said Dr. de Grey.

He compared this idea to the example of restoring vintage cars. He explained that since we are able to keep cars going essentially forever just by periodic and comprehensive preventative maintenance, we should be able to do the same thing for the human body, ultimately maintaining people in “truly youthful health indefinitely.”

While he does recognize that the human body is much more complex, Dr. de Grey believes that “the further we get in the process of developing methods for eliminating the various types of damage that the body does to itself, the more slowly we will accumulate damage because we will only be left with the residual damage that we haven’t yet worked out how to fix.”

Watch Dr. de Grey’s full lecture here!

The Longevity Dividend

On Tuesday, November 29, 2016, the Institute on Aging hosted its annual Vincent J. Cristofalo Lectureship and reception featuring this year’s keynote speaker, S. Jay Olshansky, PhD, professor of public health at the University of Illinois at Chicago.

S. Jay Olshansky, PhD, with IOA Director, John Trojanowski, MD, PhD and the family of Vincent J. Cristofalo.

The Vincent J. Cristofalo Lectureship Reception.

Dr. Olshansky’s research focuses primarily on human longevity, exploring the health and public policy implications associated with individual and population aging, global implications of the re-emergence of infectious and parasitic diseases, and most recently, the topic of his Cristofalo Lecture; the pursuit of the scientific means to slow aging in people, or as he calls it “The Longevity Dividend.”

“The Longevity Dividend,” a term borrowed from the era of the “peace dividend,” is basically the idea that if we can find a way to slow the basic biological aging process, both society and individuals will reap huge economic and health benefits.

Over the years, human life expectancy has become longer but the success of extended lifespans come with a price. With the ridding of many infectious diseases came the rise of other conditions such as cardiovascular disease, cancer, and Alzheimer’s disease; three different diseases with one thing in common—the process of aging being their most powerful risk factor.

“The rise of these diseases are nota consequence of failure… they are a consequence of success. You’ve lived long enough to experience them. But, the consequences of success might be very dangerous.” – S. Jay Olshansky, PhD

Dr. Olshanksy shared more on the “longevity dividend” during our video interview here:

In addition to his current research on “The Longevity Dividend,” Dr. Olshansky and his colleagues have also conducted research on “facial analytics” combined with biodemography. The study of facial analytics uses components of the face to measure disease risk, longevity risk, and survival prospects. Through this research, Dr. Olshansky and his team are trying to find new ways of allowing organizations and industries to use what we know about ourselves to improve the ways that they do assessments of health and survival.

Recently, Dr. Olshansky and his colleagues published an article in Computer that lays out the framework for building a “health data economy.”

“I think a new form of “currency” will be developed and this “currency” will be your own health data,” explained Dr. Olshansky. The idea is to take data from Fit Bits and other wearable monitoring devices monetize this information, for instance, selling your recorded health data to companies and organizations in exchange for things like money, lower premiums on health insurance policies, coupons, and more. He believes that this resource could be the new form of collecting health data and could inspire a whole new generation of citizen scientists.

To watch Dr. Olshansky’s full lecture on “The Longevity Dividend,” click here.

To learn more about the Vincent J. Cristofalo lectureship, click here.

Delirium and Aging

Delirium, a medical condition characterized by acute confusion, disorientation, or other mental health disruptions that affect thinking and behavior, affects nearly 7 million hospitalized Americans annually. While this condition can occur at any age, it mainly affects individuals 65 years or older and is often misdiagnosed as dementia.

As stated in an article originally published by Kaiser Health News and shared by Next Avenue, “while delirium and dementia can coexist, they are distinctly different illnesses. Dementia develops gradually and worsens progressively, while delirium occurs suddenly and typically fluctuates during the course of a day.” Particularly susceptible patients are those on ventilators or being heavily sedated in intensive care units, as well as those recovering from surgery.

“After an older adult undergoes anesthesia, they can often experience postoperative delirium,” explained Lee A. Fleisher, MD, chair of Anesthesiology and Critical Care at Penn, in a recent Penn Medicine News Blog on postoperative delirium and the uncertainties of anesthesia. “Patients in this state may hallucinate, they may forget why they are in the hospital, or have difficulty communicating or understanding what is going on around them.”

However, delirium can also result from something as simple and easily treated as a urinary tract infection.

According to research published in 2009 and referenced by Next Avenue, an estimated 40% of delirium cases are actually preventable; yet, the underlying cause is still unknown.

With all of this in mind, health care professionals, government agencies, and related nonprofit organizations gathered at the American Society of Anesthesiologists’ Brain Health Summit to discuss, among other topics, the postoperative risks of delirium and delayed cognitive recovery and whether or not they are significant enough to include in consent and patient education materials. They also considered ways to reduce the risks and to increase research funding.

The Penn Medicine News Blog says that “while the Summit provided some direction and tactics for industry leaders to act upon, there are still other options that can be explored and implemented to advance learning, protect patients, and uncover the uncertainties around anesthesia and postoperative delirium.”

“Encouraging patients to follow a balanced diet and exercise regularly in the lead up to surgery, allowing patients to bring mementos and family photos to their hospital room after surgery, even asking families and caregivers to keep a close eye on small declines in patients’ cognitive function preoperatively – simple things like the patient not being as sharp as he or she once were – may help clinicians properly prepare for patient care, and may help patients readjust after surgery and avoid postoperative delirium,” Fleisher said. “While these have not been scientifically proven to help, we think that even the smallest measures may make a difference for patients who are coming out of anesthesia.”

To learn more about delirium and aging, join the Institute on Aging on Tuesday, April 18, 2017 for our Visiting Scholars Series lecture by Edward Marcantonio, MD, SM.

Dr. Marcantonio is the Section Chief for Research in the Division of General Medicine and Primary Care at Beth Israel Deaconess Medical Center and Professor of Medicine at Harvard Medical School. His research concentrations focus on delirium and cognitive function.

For more information, visit: www.med.upenn.edu/aging/events

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Photo credit: news.pennmedicine.org/blog