Cerebrovascular Disease and Alzheimer’s: A lecture by IOA Visiting Scholar, Richard Mayeux, MD, MSc

Screen Shot 2017-12-13 at 1.55.13 PMOn Thursday, November 30, 2017, the University of Pennsylvania’s Institute on Aging (IOA) hosted their last Visiting Scholars Series lecture for the 2017 season featuring Richard Mayeux, MD, MSc. Dr. Mayeux is currently the Gertrude H. Sergievsky Professor of Neurology, Psychiatry and Epidemiology in the Gertrude H. Sergievsky Center and Taub Institute for Research on Alzheimer’s Disease and the Aging Brain. In addition, he is also the Chair of the Department of Neurology at Columbia University, New York.

Dr. Mayeux’s talk highlighted his research on cerebrovascular disease and its link to late-onset Alzheimer’s disease (LOAD). As described in a 2016 JAMA Neurology publication, Dr. Mayeux and his colleagues conducted a study of 6,553 participants — 4,044 women and 2,509 men with a mean age of 77 years. Upon using generalized mixed logistic regression models to test the association of cardiovascular disease (CV) risk factors with late-onset Alzheimer’s, they found that “in familial and sporadic LOAD, a history of stroke was significantly associated with increased disease risk and mediated the association between selected CV risk factors and LOAD, which appears to be independent of the LOAD-related genetic background.”

Essentially, the findings support the idea that 1) cerebrovascular disease is prevalent in the aged, and 2) cerebrovascular disease may trigger Alzheimer’s disease in a genetically susceptible person. Currently, Dr. Mayeux is working on a new grant to further investigate his idea and to look into how to handle the fact that cerebrovascular disease contributes to the phenotype of Alzheimer’s disease.

To read Dr. Mayeux’s full 2016 publication, “Contributions of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Center,” click here.

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The 2017 Joseph A. Pignolo Award in Aging Research: Nathan Basisty, PhD

On Wednesday, November 29, 2017, the Institute on Aging hosted their annual Joseph A. Pignolo Award in Aging Research. This year’s speaker, Nathan Basisty, PhD, a postdoctoral research fellow at The Buck Institute for Research on Aging, received the award for his 2016 paper titled “Mitochondrial-targeted catalase is good for the old mouse proteome, but not for the young: ‘reverse’ antagonistic pleiotropy?” published in Aging Cell.

Dr. Basisty’s research focuses heavily on the role of protein homeostasis in aging. Protein homeostasis is the process by which a cell retains an equilibrium of proteins to maintain its proper functions. According to a 2013 publication in Nature, it is believed that “a cell’s failure to maintain proper protein homeostasis has a major role in ageing and age-related diseases” (Nature Reviews Molecular Cell Biology 14, 55-61 (2013) BH Toyama and MW Hetzer). Dr. Basisty and his team are also looking at the role of this process in longevity with several interventions intended to extend lifespan in mammals.

In terms of future research, Dr. Basisty plans on expanding his studies to focus on method development to improve how well proteins can be characterized in the cell as well as how we can characterize the way proteins are regulated — or “turnover” — in the cell.

Learn more in Dr. Basisty’s short video interview below:

Learn more about the Jospeh A. Pignolo Award in Aging Research here.

“Modeling Neurodegenerative Diseases,” CNDR’s 2017 Marian S. Ware Research Retreat

Screen Shot 2017-11-09 at 1.27.43 PMOn Thursday, October 19, 2017, Penn’s Center for Neurodegenerative Disease Research (CNDR) hosted its annual Marian S. Ware Research Retreat. This year’s topic was “Modeling Neurodegenerative Diseases” and featured a variety of expert speakers within the field.

“As is the tradition with CNDR retreats, every year we focus on a different aspect of neurodegenerative disease. This year, our theme was how to model the complexity of these conditions, for example at the molecular, cellular, and systems levels. The internal and external speakers provided a rich sampling of cutting-edge work being done on each of these areas,” said Kelvin Luk, PhD, Research Assistant Professor of Pathology and Laboratory Medicine and organizer of this year’s CNDR Retreat.

“Among the highlights were the trainee presentations, while we were treated to some spectacular methods for visualizing intact tissues and modeling how disease might be spreading across the central nervous system. Our keynote speaker also finished off by giving a glimpse of the disease process as it advances in living AD patients.

Overall, I think/hope it was enjoyed by all that were present. The feedback was very positive and we were able to bring together many members of the local (Penn and extramural) community from very diverse backgrounds.” – Kelvin Luk, PhD

In addition to the lectures, the day-long event also includes an annual poster session where scientists in all stages of their career, from Penn and beyond, can present their current and recent neurodegenerative-disease related research. The top three posters are selected by experienced judges and are awarded prizes. See this year’s poster winners below!

2017 Marian S. Ware Research Retreat Poster Winners

1st Prize:

Poster Title: “Genome-wide Co-translational Decay of Canonical mRNAs”
Authors: Fadia Ibrahim, Manolis Maragkakis, Panagiotis Alexiou, and Zissimos Mourelatos
Affiliation: University of Pennsylvania Perelman School of Medicine, Department of Pathology and Laboratory Medicine, Division of Neuropathology

2nd Prize:

Poster Title: “Amnestic and Non-Amnestic Phenotypes of Alzheimer’s Disease: An MRI-Based Phasing Analysis”
Authors: Fulvio Da Re1,2,3, Jeffery S Phillips1,4, Laynie Dratch1, Carlo Ferrarese3, David J. Irwin1,4, Corey T. McMillan1,4, Eddie Lee5, Leslie M Shaw5, John Q Trojanowski5, David A Wolk4,6, and Murray Grossman1,4
Affiliation: 1) Penn FTD Center, University of Pennsylvania, 2) PhD Program in Neuroscience, University of MilanoBicocca, Milan, Italy, 3) School of Medicine and Surgery, Milan Center for Neuroscience (NeuroMI), University of MilanoBicocca, Milan, Italy, 4) Perelman School of Medicine, University of Pennsylvania, 5) Center for Neurodegenerative Disease Research, University of Pennsylvania, 6) Penn Memory Center, University of Pennsylvania

3rd Prize:

Poster Title: “Tau and Synuclein: a Tojan horse in the making?”
Authors: Hannah J. Brown, Fares Bassil, Shankar Pattabhiraman, Bin Zhang, Dawn Riddle, John Q. Trojanowski, Virginia M.-Y. Lee
Affiliations: Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine

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Full list of 2017 CNDR Retreat Speakers:Screen Shot 2017-11-09 at 1.26.02 PM.

Learn more about CNDR here.

Penn Medicine’s 6th Annual 5K for the IOA & Memory Mile Walk

It was a warm Fall morning on Sunday, September 24, 2017 as 371 runners and walkers and 70 volunteers gathered for Penn Medicine’s 6th Annual 5K for the IOA and Memory Mile Walk.

The fundraiser, which takes place throughout Penn Park and the University of Pennsylvania campus, raised a total of $49,260 this year for Alzheimer’s and aging-related disease research efforts at Penn’s Institute on Aging.

In addition to its usual run and walk, the event also included pre and post-race yoga sessions, entertainment provided by DeeJay007, and photobooth fun for the whole family. This year’s overall male winner, Alexis Tingan (pictured below, left), finished the race in 17 minutes and 35 seconds, with the overall female winner, Sara McCuaig (pictured below, right), not far behind him with a time of 19 minutes and 24 seconds.

To view the full list of race results, click here.

Last week, CBS Philly interviewed PJ Brennan, MD, Chief Medical Officer at Penn Medicine who created the event in memory of his father who lost his battle with Alzheimer’s disease. “I thought it would be a fun way to get my community here together and bring some attention to the work that the Institute on Aging does and raise some money for this novel research,” said Brennan during the interview.

To view more photos of the event, click here.

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

077On 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:

1st Place:

172Title: “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

2nd Place:

173Title: “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

1st Place:

175Title: “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

2nd Place:

176Title: “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.

 

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

EliezerMasliah_Flyer5217On 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.


* 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?

EdwardMarcantonio_FlyerLast 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).