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The Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center and 1Florida ADRC present
  • 18th Annual Mild Cognitive Impairment Symposium
  • Special Topic Workshop
  • Alzheimer's Public Educational Forum

January 18-19, 2020 | Miami, Florida, USA

2015 SPEAKER BIOS, ABSTRACTS, AND POWERPOINT PRESENTATIONS

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Ranjan Duara, MD

Program Director

duara_headshotDr. Ranjan Duara is the Medical Director of the Wien Center for Alzheimer’s Disease and Memory Disorders at Mount Sinai Medical Center in Miami Beach. He is a Professor of Neurology at the Herbert Wertheim College of Medicine (Department of Neurology) at Florida International University and is affiliated with the University of Miami, Miller School of Medicine, Miami, Florida (Depts. of Medicine, Neurology and Psychiatry). He completed internal medicine and neurology residencies in India, the United Kingdom and at Thomas Jefferson University Hospital in Philadelphia, and did a fellowship in neuroscience and neuroimaging at NIH.

Dr. Duara’s research has focused primarily on early diagnosis of Alzheimer’s disease and other dementias, neuroimaging, genetic epidemiology and the methodology for staging the transition from normal cognitive aging to dementia. He has contributed to over 200 articles in peer-review scientific journals as well many book chapters.

He is the Principal Investigator for the State of Florida Alzheimer’s Disease Initiative Brain Bank. He has also been an investigator in numerous clinical trials of novel agents for the treatment of Alzheimer’s Disease.

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Dr. Duara’s Introductory Speech at the 13th Annual MCI Symposium

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Sandra Black, MD, FRCP(C)

Speaker – Forum

Sandra Black PhotoDr. Sandra Black, MD, FRCP(C) is an internationally renowned cognitive and stroke neurologist who holds the inaugural Brill Chair in Neurology, Department of Medicine, University of Toronto and Sunnybrook Health Sciences Centre. A leading clinical trialist in dementia, she is the current Executive Director of the Toronto Dementia Research Alliance, a multi institutional University of Toronto collaborative network. She is also the Sunnybrook Site Director of the Heart & Stroke Foundation Canadian Partnership for Stroke Recovery and the Hurvitz Brain Sciences Research Program Director at Sunnybrook Research Institute.

In 2011 she was named to the Order of Ontario, “for being an assiduous physician leader and influential architect of the Ontario Stroke System, a specialized continuum from prevention to reintegration.” She has authored/ co-authored over 430 papers in a 25-year research career that has bridged dementia and stroke, with a recent focus on interactions of Small Vessel Disease and Alzheimer’s disease.

Dr. Black has earned numerous mentorship and research awards, including election to the Royal Society of Canada in 2012, the highest honour accorded to Canadian scholars, cited for “combining enormous dedication to patients with cutting-edge science”. 

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Dr. Black’s Public Educational Forum Lecture

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Vascular Factors which Modify Risk for Dementia

Sandra Black Sunnybrook Research Institute, Toronto, ON, Canada

 

With population aging, direct healthcare expenses for dementia are now exceeding the costs of heart disease or cancer. Aging is a very important risk factor for dementia and in community-based autopsy studies, mixed pathologies, particularly Alzheimer’s pathology with coexisting small or large strokes, is the commonest finding in people with dementia.

In fact, while Alzheimer’s Disease (AD) is thought to be the commonest and Vascular Dementia (VaD) the second commonest cause of dementia, these pathologies alone or together account for 80% of all dementias. Hence, preventing heart disease and stroke is not only important in itself, but it is also a key strategy for preventing or delaying dementia.

Small vessel disease of the brain is more common than large vessel disease and causes silent strokes and age-related white matter changes. Population studies suggest that a quarter of elderly population have tiny holes in the brain’s white matter, called silent strokes, and over 95% of that population show white matter hyperintensities, which appear on MRI scans as white spots or patches. In about 20% of the population, these patches can be quite extensive and are associated with poor balance and walking, slowed mental processes, impaired thinking and decision making, and often depression.

In addition to aging, vascular risk factors for cognitive impairment are similar for AD and VaD, with hypertension being at the top of the list. Cardiac disease, including atrial fibrillation, hypercholesterolemia, diabetes and smoking, which are potentially modifiable, are all implicated. Previous stroke and genetic profile (such as apolipoprotein E e4) also can play a role, and life-style choices – healthy diet and regular physical exercise – are very important for brain protection. For example, aerobic physical activity increases brain blood flow, and releases brain growth factors that favour neuroplasticity and brain repair.

It is also important to note that AD itself causes small vessel disease since amyloid, a key toxic protein in AD, often deposits in and weakens small vessel walls allowing red blood cells to leak into the brain as so-called microbleeds. The weakened vessel wall can also result in significant bleeding into the brain. In fact, amyloid is second only to hypertension as the cause of hemorrhagic stroke. Hence, AD should be counted as a major risk factor in stroke!

This lecture will review how modern neuroimaging is helping us to understand vascular factors that contribute to dementia, including the potential role of small vessel disease. Key take-home messages will be that hypertension at any age is bad for the brain and a major driver not only of heart disease and stroke, but also of small vessel brain disease. Modern brain imaging techniques reveal that the brain and its blood vessels are very sensitive to vascular risk factors that also injure other target organs such as the heart, the lungs and the eyes. Hence, hypertension control, a heart-healthy diet, not smoking and life-long regular daily exercise should be key societal and personal health-care goals.

Richard J. Caselli, MD

Speaker – Workshop

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Dr. Richard Caselli is a behavioral neurologist whose clinical specialty is Alzheimer’s disease and related cognitive disorders.  He obtained his AB and MD degrees from Columbia University in New York City, completed his medical internship and Neurology residency at the Mayo Clinic in Rochester, Minnesota, and a Behavioral Neurology and Cognitive Science fellowship with Dr. Antonio Damasio at the University of Iowa.  He initially joined the staff of the Mayo Clinic in Rochester in 1988 and in 1990 moved to Mayo’s Arizona campus where he has remained since then.  He has received both the Mayo Clinic Arizona Distinguished Clinician and Distinguished Investigator Awards, as well as the Lifetime Educator Award. He is Professor of Neurology in the Mayo Clinic College of Medicine, served as Chair of the Department of Neurology from 2000 to 2010, and was a member of the Mayo Clinic in Arizona Board of Governors from 2002-2010.  He is currently Associate Director of the Arizona Alzheimer’s Disease Center,  Director of the Clinical Core coordinating the clinical participation of its six member institutions, and Associate Director of the Mayo Clinic Center for Individualized Medicine.

Dr. Caselli’s research program focuses on cognitive aspects of aging, Alzheimer’s disease, and other forms of dementia, particularly the way in which genetic risk factors for dementia influence how our mind changes with age before the onset of memory loss and dementia.  Some of his findings have included the identification and characterization of the potentially reversible autoimmune encephalopathies that can mimic degenerative dementias; an early categorization of the asymmetric cortical degeneration syndromes (that now include frontotemporal lobar degeneration syndromes and related disorders, and variant forms of Alzheimer’s disease that may mimic these conditions); and the preclinical effects of APOE e4 (the most prevalent genetic risk factor for Alzheimer’s disease) on cognitive aging patterns and how they differ between healthy aging and preclinical Alzheimer’s disease.  He is also now serving on the Alzheimer’s Prevention Initiative committee on genetic disclosure for the upcoming APOE e4 homozygote disease prevention trial.

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 Dr. Caselli’s Workshop Lecture

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Correlating Cognition and Biomarkers in Preclinical APOE e4 and PS1 Mutation Carriers

Richard J. Caselli Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA

 

Background: Therapeutic trials of agents that clear or in other ways disrupt the aggregation of fibrillar amyloid have failed to mitigate cognitive decline in patients with Alzheimer’s dementia leading to the hypothesis that intervention during the dementia stage of disease may be “too little, too late”, and in turn has led to the development of earlier disease stage therapeutic strategies targeting presymptomatic individuals who are at genetic or biomarker defined imminent risk for symptomatic cognitive decline. Trial design for presymptomatic cohorts requires an understanding of the time course of change in measurable biomarker and cognitive outcomes during this preclinical period.

Methods: Two genetically defined cohorts of cognitively normal individuals, APOE e4 and PS1, were administered a battery of neuropsychological tests and a subset also had amyloid-PET (and in some cases other forms of biomarker testing).  APOE cohort members were identified through local media ads in Maricopa County and PS1 carriers were members of a previously described large Colombian kindred.

Results: Memory decline begins soon after cerebral amyloid detection in both APOE e4 and PS1 carriers. In APOE e4 carriers accelerated memory decline is the predominant neuropsychological characteristic of early stage preclinical AD.  Executive decline is a prominent feature of cognitive aging in general and is more pronounced in clinical (vs incident) MCI patients. Among APOE e4 cohort members, subjective cognitive impairment (SCI) groups (self and informant) were at increased risk for clinical conversion despite higher levels of psychological distress but the predictive value for individual patients was poor so that SCI does not appear to be a reliable proxy for preclinical AD.

Conclusions: APOE e4 and PS1 carriers share similar preclinical profiles regarding the chronology of biomarker and cognitive change, and both are cognitively characterized at onset by declining memory skills followed later by executive skills and other domains. Genetic, biomarker, and objective neuropsychological testing are more reliable indicators of preclinical AD than SCI.

Steven T. DeKosky, MD

Discussant – Forum

Steven DeKoskyDr. Steven DeKosky is currently Visiting Professor in the Department of Radiology, and Adjunct Professor of Neurology at the University of Pittsburgh School of Medicine. From September 2013 to April 2014 he was Visiting Professor in the Department of Medical Ethics and Health Policy at the University of Pennsylvania Perelman School of Medicine. From 2008 to 2013 he was Vice President and Dean of the University of Virginia School of Medicine and held the James Carroll Flippin Professor of Medical Science; he also served as Physician-in-Chief of the University of Virginia Health System, Professor of Neurology and Psychiatry and Neurobehavioral Sciences, and Director of the Alzheimer’s Disease Center.

He received a bachelor’s degree in psychology from Bucknell University and did graduate work in neuroscience and psychology at the University of Florida, graduating from the University of Florida College of Medicine in 1974. He completed an internship in internal medicine at The Johns Hopkins Hospital and a three-year residency in neurology at the University of Florida, and then was a Postdoctoral Fellow in Neurochemistry at the Clinical Neuroscience Research Center at the University of Virginia. He joined the faculty of the University of Kentucky College of Medicine from 1979 to 1990, where he co-founded the Alzheimer’s Disease Research Center and was interim chair of the department of neurology from 1985 to 1987.

In 1990 he moved to the University of Pittsburgh as Professor of Psychiatry (primary) and Neurology, and from 1992-2000 was Director of the Division of Geriatrics and Neuropsychiatry in the Department of Psychiatry/Western Psychiatric Institute and Clinic, also at the University of Pittsburgh. In 2000 he became Professor and Chair of the Department of Neurology at the University of Pittsburgh, a position which he held until he moved to the University of Virginia in 2008. Dr. DeKosky was Director of the Pitt’s NIH-funded Alzheimer’s Disease Research Center (ADRC) from 1994-2008.

Dr. DeKosky has served on and led numerous NIH review and advisory committees, and taught and mentored in clinical research training programs sponsored by the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS). He was a member of the Food and Drug Administration’s Peripheral and Central Nervous System Drugs Advisory Committee from 2004-2007.  From 2010-2013 he served on the National Advisory Council of the National Center for Complementary and Alternative Medicine (NCCAM) of the NIH. Following that term, he was appointed to and currently serves on the NIH’s Council of Councils in 2013; the Council of Councils oversees the Common Fund of the NIH.

Dr. DeKosky was a member of the national Board of Directors of the Alzheimer’s Association from 1994 to 2002 (Board Vice Chair in 2001-2002), and again from 2003 to 2010. He was Chair of the Association’s Medical and Scientific Advisory Council from 1997 to 2002, chaired the Association’s Strategic Planning Committee from 1997 to 2000, and served on the Ethics Advisory Board and the Public Policy, Finance, and Development Committees. He is a former member of the Board of Directors for Alzheimer’s Disease International (ADI), the international organization of national Alzheimer’s Associations, and is now a member of the ADI Medical and Scientific Advisory Panel, a group he chaired from 2003-2006. He also serves on the National Advisory Board for the Center for Humanities, Compassionate Care, and Bioethics at SUNY-Stony Brook.

He was the founding Chair of the Advisory Council of ISTAART, the International Society to Advance Alzheimer’s Disease Research and Treatment; in 2011 he was elected to a second 3-year term as Chair. As Chair of ISTAART he served (ad hoc) on the Medical and Scientific Advisory Council for the Alzheimer’s Association. He is now Immediate Past Chair of ISTAART. He lectures nationally and internationally on multiple dimensions of Alzheimer’s Disease, including the cognitive, neurobehavioral, genetic, imaging, and basic research underpinnings of the disease.

Dr. DeKosky has served as Chair of the Section on Geriatrics of the American Academy of Neurology (AAN), and chaired the AAN Practice Parameters Committee for Early Detection, Diagnosis and Management of Dementia. In 2003 he was elected to the Neurology Council of the American Board of Psychiatry and Neurology (ABPN); in 2010 he was elected President of the Neurology Council and Vice President of the ABPN. He continues to chair the ABPN’s Part B (Behavioral Neurology, Cognition, and Psychiatry) Examination Committee.

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Dr. DeKosky’s Moderated Discussion

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Bradford C. Dickerson, MD

Chair and Speaker – MiniSymposium 2

Brad Dickerson, Neurology, portrait, portrait for bookDr. Brad Dickerson is a behavioral neurologist and neuroscientist at Harvard Medical School and Massachusetts General Hospital in Boston, MA. He is the Director of the Massachusetts General Hospital Frontotemporal Disorders Unit and Neuroimaging Lab in Boston, and the Tommy Rickles Endowed Chair in Primary Progressive Aphasia Research at MGH. He is also a staff behavioral neurologist in the MGH Memory Disorders Unit and a co-investigator in the Alzheimer’s Disease Research Center. He is an Associate Professor of Neurology at Harvard Medical School. He completed undergraduate studies in biomedical engineering at Southern Methodist University in Dallas, medical school at University of Illinois at Chicago College of Medicine, and neurology residency at MGH and Brigham and Women’s Hospitals in Boston; he did fellowships in neuroimaging at the Martinos Center for Biomedical Imaging and in behavioral neurology at Brigham and Women’s Hospital in Boston.

Dr. Dickerson runs a busy weekly clinic caring for patients with various forms of cognitive impairment and dementia, as well as providing training for clinical and research fellows. His research has focused primarily on the use of quantitative structural and functional neuroimaging techniques to understand the neurobiology of Alzheimer’s disease, Primary Progressive Aphasia, Frontotemporal Dementia, and other dementias, and on the relationships between imaging measures and behavior. He also investigates the neural substrates of changes in memory, affect, and other abilities in healthy young adults and in normal aging. He has published more than 85 articles in peer-reviewed scientific journals as well as many book chapters. He is the Principal Investigator on multiple NIH and foundation grants studying aging and dementia, and serves on the medical advisory boards for the Association for Frontotemporal Degeneration and the Massachusetts chapter of the Alzheimer’s Association. He has won a number of awards, including the prestigious American Academy of Neurology Norman Geschwind Award in Behavioral Neurology and Honorable Mention for the Schwartz Center Award for Compassionate Care.

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Dr. Dickerson’s Mini-Symposium Lecture

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MCI of the FTLD type: Clinical Features and Imaging and Molecular Biomarkers

Bradford C. Dickerson Harvard Medical School and Massachusetts General Hospital, Cambridge, MA, USA

 

Surprisingly, despite substantial research on MCI in the past decade, there is a striking paucity of literature on the MCI/prodromal phase of FTLD. If we ultimately aim to intervene in the neurodegenerative processes of FTLD as early as possible, it is critical to identify the condition in its MCI phase, as the field has been doing for AD. Here I will review our research on the clinical and neuroimaging features of MCI of the FTLD type, and provide a framework for thinking about the use of biomarkers to assist in the development of clinical therapeutic trials targeting this population.

Dennis W. Dickson, MD

Speaker – MiniSymposium 1

dennis-dicksonDr. Dennis Dickson has devoted his career to the neuropathology of degenerative brain disease, particularly disorders that produce dementia and parkinsonism, and has published over 400 peer-reviewed papers and 50 book chapters. He is the neuropathologist for the Mayo Clinic and the Florida Alzheimer Disease Research Centers and the Mayo Clinic Parkinson’s Disease Center. He is also the neuropathologist for brain banks of the State of Florida Alzheimer Disease Initiative and the Society for Progressive Supranuclear Palsy. He has personally evaluated over 3000 brains of individuals with degenerative brain disease.

He started his professional career in the laboratory of Dr. Robert D. Terry at Albert Einstein College of Medicine in New York and is still the neuropathologist for the Einstein Aging Study, one of the first prospective, longitudinal studies of aging and dementia. His studies at Einstein lead to the recognition that some clinically normal individuals have as much amyloid deposition in their brains as patients with Alzheimer’s disease (AD).

With a strong clinicopathologic foundation, Dr. Dickson was one of the first to emphasize that tau, not amyloid, was the most important cause of dementia in AD. He was also one of the first to realize that Lewy body disease (LBD) was a common cause of dementia in the elderly, and that LBD could be differentiated from AD clinically and pathologically. He and his coworkers described cholinergic deficiencies in LBD, and he discovered novel hippocampal pathology in LBD. He has participated in formulation of neuropathologic criteria for LBD and performed studies that validated these criteria. His long-standing interest in tau and its role in dementia lead to research into other disorders where tau pathology is a prominent feature, including Pick’s disease, progressive supranuclear palsy (PSP), frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17) and corticobasal degeneration (CBD). He has played a part in developing neuropathologic criteria for PSP, FTDP-17 and CBD. The discovery of mutations in the tau gene confirmed the importance of tau beyond doubt and seeded research on transgenic mice carrying mutant tau.  Dr. Dickson demonstrated that these mice develop neurofibrillary degeneration and neuronal loss.

Dr. Dickson received BS (Biochemistry) and MD degrees from the University of Iowa College of Medicine, where he was a member of the Alpha Omega Alpha Honor Medical Society. In recognition of his contributions to medical research he was awarded the Metropolitan Life Award in 2001, the Saul R. Korey Award from the American Association of Neuropathologists in 2007, the Fred Springer Award from the American Parkinson’s Disease Association in 2008, and the Alfred Meyer Award from the British Neuropathological Society in 2009. He is past president of the American Association of Neuropathologists. He is the editor of a monograph sponsored by the International Society of Neuropathology, “Neurodegeneration: The Molecular Pathology of Dementia and Movement Disorders.”

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Dr. Dickson’s Mini-Symposium Lecture

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Neurodegenerative Tauopathies – Clinicopathologic Correlations

Dennis W. Dickson Mayo Clinic, Jacksonville, FL, USA

 

While Alzheimer’s disease is the most common of the neurodegenerative tauopathies, genetic evidence suggests that tau is not the driving force in this disorder.  In contrast, neurodegenerative tauopathies are disorders in which tau pathology plays a primary role.  Neurodegenerative tauopathies can be classified by clinical presentations – behavioral variant frontotemporal dementia, progressive nonfluent aphasia, progressive asymmetrical rigidity and apraxia (i.e. corticobasal syndrome), progressive amnestic dementia, akinetic-rigid parkinsonism with vertical gaze palsy (i.e. progressive supranuclear palsy (PSP) syndrome), pure akinesia with gait failure, parkinsonism with cerebellar ataxia, and progressive motor deficit with spasticity (i.e. primary lateral sclerosis syndrome).  They can also be classified by the nature of the tau protein that accumulates within neurons and glia, with two major isotypes of tau defined by alternative splicing of exon 10 in the microtubule binding domain to generate 3 repeat tau (3R tau) and 4 repeat tau (4R tau). Alzheimer type tau is 3R+4R and other disorders of this class include Guam Parkinson dementia complex, tangle predominant dementia (recently termed primary age related tauopathy (PART)) and chronic traumatic encephalopathy.  The tauopathies with predominance of 4R tau include PSP, corticobasal degeneration, argyrophilic grain disease and globular glial tauopathy.  The major tauopathy with predominance of 3R tau is Pick’s disease.  Mutations in the tau gene (MAPT) have been shown to produce the entire pathologic and biochemical range of degenerative tauopathies depending upon the specific mutation and its effect on tau gene splining, tau protein aggregation, or both.  The availability of animal and cellular models based upon specific MAPT mutations permits development of diagnostic biomarkers and eventual therapies for this group on neurodegenerative disorders.

Kimiko Domoto-Reilly, MD

Discussant – MiniSymposium 2

Domoto-Reilly headshotDr. Kimiko Domoto-Reilly is Assistant Professor of Neurology at the University of Washington in Seattle. She completed her neurology residency training at the combined Harvard Medical School/Massachusetts General Hospital/Brigham & Women’s Hospital program, followed by clinical fellowships in behavioral neurology at BWH and in neuropsychiatry at MGH, before being appointed an Instructor of Neurology at MGH.

She was a member of Dr. Brad Dickerson’s Frontotemporal Dementia Unit and Neuroimaging Laboratory at MGH, and as part of her research fellowship obtained a Masters in Medical Science from Harvard Medical School. Dr. Domoto-Reilly has recently moved to the University of Washington to establish a clinical research unit focused on Frontotemporal Dementia and related neurodegenerative diseases. Current research interests include using multimodal imaging (molecular PET, structural MRI) and post-mortem analysis to elucidate clinicopathologic relationships. She sees patients in the Memory and Brain Wellness Center, and conducts research at the Alzheimer’s Disease Research Center and the Integrated Brain Imaging Center.

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Dr. Domoto-Reilly’s Moderated Discussion

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Mary Ganguli, MD, MPH

Chair – Forum

ganguliDr. Mary Ganguli is Professor of Psychiatry, Neurology, and Epidemiology at the School of Medicine and Graduate School of Public Health, University of Pittsburgh.

Dr. Ganguli is a geriatric psychiatrist and psychiatric/neuroepidemiology at the University of Pittsburgh, where she teaches residents, fellows, and graduate students. She provides geriatric psychiatry outpatient services at the University of Pittsburgh Medical Center.

She has been conducting population-based studies of cognitive impairment and dementia since 1987. She served on the Neurocognitive Disorders Work Group of DSM-5, and is a member of the AAN Practice Parameter Work Group on MCI. She previously served on the National Advisory Council on Aging. She is Associate Editor of the Journal of the American Geriatrics Society and of International Psychogeriatrics, and an Editorial Advisory Board member of Alzheimer Disease and Associated Disorders.

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Dr. Ganguli’s & Dr. Duara’s Introductory Public Educational Forum Speech

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Todd E. Golde, MD, PhD

Keynote Lecturer; Chair – MiniSymposium 1

Golde, Todd

Dr. Todd Golde is a Professor of Neuroscience at the University of Florida, where he directs the Center for Translational Research in Neurodegenerative Disease.  Dr. Golde received his MD, PhD from Case Western Reserve University. He completed a residency in Laboratory Medicine at University of Pennsylvania. After beginning his independent career at University of Pennsylvania, he moved to Mayo Clinic Florida where he rose from Assistant Professor of Pharmacology to both Professor of Neuroscience and chair of Mayo Clinic’s internationally recognized Department of Neuroscience. Dr. Golde has published over 180 peer-reviewed manuscripts which have been cited over 15000 times. Dr. Golde is well known for his translational research in Alzheimer’s disease and his work on γ-secretase modulators and immunotherapy for neurodegenerative diseases. His scientific honors include the Paul Beeson Faculty, an Alzheimer’s Association Zenith, and MetLife Foundation Awards.

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Dr. Golde’s Mini-Symposium Lecture

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Assessing the Current Roadmap for Developing Novel Disease Modifying Therapies for Neurodegenerative Diseases

Todd E. Golde University of Florida, Gainesville, FL, USA

 

Despite tremendous advances in our understanding of the pathogenesis of Alzheimer’s disease and the myriad of other Neurodegenerative disease that we now recognize as proteinopathies, we have not yet developed therapeutic agents or strategies that have proven to modulate disease course.

Given:

i) this lack of success,

ii) the huge unmet medical need, and the

iii)  enormous cost of developing and evaluating therapies for these disorders, it is essential that we collectivity examine and critically evaluate our current and past strategies for developing novel therapies for AD and other neurodegenerative proteinopathies. Indeed, if we were to conduct a Strength, Weakness Opportunities and Threat (SWOT) analysis of our current strategies what would this analysis reveal? Are we on the right track, or do we need to retool and refine efforts?  What are the major obstacles that might arise over the next few years?

During this seminar I will provide my own assessment of the state of therapeutic development for Neurodegenerative disease, by exploring key questions that I believe must be answered in order to insure that we successfully develop therapies that have significant impact on disease course.  I will also evaluate our likelihood of successfully answering these questions given the current resources available.

Michael Greicius, MD, MPH

Speaker – MiniSymposium 2

Michael GreiciusDr. Michael Greicius is an Associate Professor in the Department of Neurology and Neurological Sciences at the Stanford University School of Medicine. He is the medical director of the Stanford Center for Memory Disorders and the principal investigator of the Functional Imaging in Neuropsychiatric Disorders (FIND) Lab.

His research involves the use of imaging to identify and characterize the large array of brain networks whose actions and interactions support normal human behavior.  His lab also uses network-based imaging approaches and genetics to gain insights into Alzheimer’s disease and other brain disorders.

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Dr. Grecius’ Mini-Symposium Lecture 

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Brain Networks in Neurodegenerative Disease

Michael D. Greicius Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA

 

The advent of resting-state fMRI, with its ability to image large-scale distributed brain networks, has provided novel insights into our understanding of neurodegenerative disease. This talk will provide a brief introduction to the basic principles and clinical advantages of resting-state fMRI as well as some of its limitations and pitfalls. While resting-state fMRI can characterize roughly 15-20 distinct networks, the focus here will be mainly on one network, known as the default-mode network (DMN), and its relationship to Alzheimer’s disease (AD). Over the past decade, findings from multiple labs have converged to make a strong case that the DMN is integral to episodic memory function, targeted early in the course of AD, and deteriorates as AD progresses.

As the evidence linking the DMN to AD strengthened, it slowly became clear that this was not the only example of a canonical brain network being targeted by a canonical neurodegenerative disease. In recent work, a parallel link between the brain’s salience network and behavioral variant frontotemporal dementia has been established. In fact, the case has been made that each clinically distinct neurodegenerative disease marches along a functionally (and spatially) distinct brain network.

This systems-level understanding of neurodegenerative disease lends support to basic neuroscience work suggesting that the pathogenic proteins of several neurodegenerative diseases have the capacity to spread, trans-synaptically, along a network.

Keith A. Johnson, MD

Speaker – Workshop

johnson1

Dr. Keith Johnson is a PET researcher and Neurologist who studies brain aging and dementia. His multi-modality neuroimaging research is focused on the detecting the molecular pathology of Alzheimer’s disease and other neurodegenerative disorders in vivo. His work relates PET markers of misfolded brain proteins — beta-amyloid and tau — to functional and structural imaging markers and cognition.

The major goal of his research is to enable development of preventive therapy on the basis of early detection of brain pathology in disorders such as Alzheimer’s disease dementia, frontotemporal dementia, and traumatic encephalopathy. Dr. Johnson’s research is propelled by his experience as a Neurologist caring for patients with these illnesses, interpreting and disclosing clinical brain PET data, and integrating image data with clinical decision-making. In 2007, he organized the first international gathering of scientists studying human brain amyloid-beta imaging, known as Human Amyloid Imaging. HAI is held annually and jointly funded by the NIH and industry contributors.

In 2013, Dr. Johnson co-led an international team, assembled by the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging, that developed appropriate use criteria for amyloid-beta PET used in clinical practice. More recently, Dr. Johnson has launched a multi-disciplinary neuroimaging research program, with key collaborators in Neuropathology, Neurology, and Psychology at the Massachusetts General Hospital and Harvard University to investigate brain tau pathology in living humans.

Dr. Johnson is Professor of Radiology at Harvard Medical School. He is Director of Molecular Neuroimaging in the Division of Nuclear Medicine and Molecular Imaging at the MGH, Attending Neurologist in the Memory Disorders Unit at the Brigham and Women’s Hospital, and Clinical Associate in Neurology at the MGH. He co-directs both the Harvard Aging Brain Study and the Neuroimaging Program of the Massachusetts Alzheimer’s Disease Research Center.

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Dr. Johnson’s Workshop Lecture

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T807 Tau PET in Aging and Dementia

Keith A. Johnson Massachusetts General Hospital, Boston, MA, USA

 

Autopsy studies of aging and dementia led to the hypothesis that Tau deposition is accelerated at the time when an older person begins to have impaired cognition, particularly in the setting of amyloid deposition. [F18] T807 is a PET tracer that selectively binds tau aggregates, as demonstrated with autoradiography and immunohistochemistry. T807 PET has enabled imaging of tangle pathology in vivo and has been applied to a variety of dementia phenotypes and to older and younger normal controls.

T807 PET methods for acquisition and processing will be discussed and findings will be presented for Alzheimer disease dementia, mild cognitive impairment, and clinically normal subjects. Also presented will be preliminary exploration of the associations of T807 signal with PET measures of amyloid-beta, FDG metabolism, brain structure and clinical phenotype. Our preliminary findings suggest that T807 PET is a promising new biomarker that relates to both clinical and cognitive status.

Keith A. Josephs, MD

Speaker – Workshop

keith-josephsDr. Keith Josephs completed a Bachelor’s Degree in Mathematics in 1992 and a Master’s Degree in Mathematics in 1993 both from the University of Florida. He obtained his Medical degree in 1997 from the Medical College of Pennsylvania. He completed a 1-year internship in Medicine at the Mayo Clinic in 1998 followed by a three year residence program in Neurology at Mayo Clinic which was completed in 2001. Between 2001 and 2002 he studied as a Movement Disorders Fellow, at Mayo Clinic. In 2002 he was awarded a Mayo Foundation Scholarship to the United Kingdom where he studied Degenerative Neuropathology and Dementia for 1-year. After returning to the Mayo Clinic, he began working on his second Master’s Degree in Clinical and Translational Research in 2004 which was awarded in 2006. He was appointed Professor and Consultant of Neurology in 2011.

Dr. Josephs has dedicated his research career to the investigation of neurodegenerative diseases where he has made seminal discoveries. He has identified and characterized five previously unrecognized neurodegenerative diseases, such as neurofilament inclusion body disease, frontotemporal lobar degeneration with primary lateral sclerosis, progressive supranuclear palsy with corticospinal tract degeneration, primary progressive apraxia of speech and semantic dementia with corticospinal tract degeneration. His work combining clinical neurology, neuropathology and quantitative neuroimaging has revolutionized the classification of neurodegenerative diseases by identifying biomarkers of degenerative pathology. These works have resulted in international recognition as a world leader in the neurodegenerative field and over 260 scientific publications.

He is recipient of several prestigious awards, including the Judson Darland Prize for Outstanding Achievement in Clinical Investigation by the American Philosophical Society, the Harold Brenner Pepinsky Early Career Award in Neurobehavioral Science by Ohio State University, the Norman Geschwind Prize in Behavioral Neurology from the American Academy of Neurology, the Geriatric Research Award from the American Academy of Neurology and the Basic Science Research award from the Mayo Clinic. Dr. Josephs is an elected member of the ANA and serves on the editorial board of Acta Neuropathologica, Neuropathology and Applied Neurobiology, and Neuroscience Discoveries. He was recently invited to be on the editorial board of Parkinsonism and Related Disorders beginning January 2015. 

He is a current member of the Postdoctoral Programs Committee for the Mayo Clinic Center for Translational Science Activities, the Research Awards Committee for the Department of Neurology and the Academic Promotions Committee for the Department of Neurology, Mayo Clinic. He is also a member of the Clinical Research Training Curriculum Subcommittee of the Mayo Clinic Center for Translational Science Activities. He is currently principal investigator of two NIH funded R01s, as well as co-investigator of an NIH funded RO1 and an Alzheimer’s Association grant.

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Dr. Dickson Lecturing on Behalf of Dr. Josephs at the Alzheimer’s Diagnostic and Treatment Workshop

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Role of TDP-43 in Non-Alzheimer’s and Alzheimer’s Neurodegenerative Diseases

Keith A. Josephs Department of Neurology, Mayo Clinic, Rochester, MN, USA

 

TDP-43 is a nuclear DNA binding protein that is involved with the regulation of DNA transcription. In normal neurons, TDP-43 can be identified in the nucleus. In neurodegenerative diseases, TDP-43 is predominantly deposited outside the nucleus as neuronal cytoplasmic inclusions and dystrophic neurites, where it has undergone a series of post-translational modifications and proteolytic cleavage to produce abnormal C-terminal fragments. Such fragments have been shown to be cytotoxic.

Abnormal TDP-43 immunoreactive lesions at postmortem have been shown to be associated with frontotemporal lobar degeneration and amyotrophic lateral sclerosis. The former is clinically characterized by behavioral and personality changes and aphasia, while the latter is characterized by signs and symptoms of upper and lower motor neuron dysfunction.

Recently, it has been found that almost 60% of Alzheimer’s disease brains also have abnormal TDP-43 deposition which first targets the amygdala before spreading to hippocampus and then neocortex. Interestingly, TDP-43 deposition in Alzheimer’s disease is not associated with clinical features of frontotemporal lobar degeneration or amyotrophic lateral sclerosis. Instead, TDP-43 in Alzheimer’s disease is associated with memory loss and hippocampal atrophy, the cardinal features that have been previously ascribed to two other Alzheimer’ associated proteins; beta-amyloid and tau. In fact, patients who die with TDP-43, beta-amyloid and tau are 10x more likely to be cognitively impaired at death compared to those that die with only beta-amyloid and tau. It remains unknown, however, whether TDP-43 represents a second or secondary pathological process in Alzheimer’s disease, or whether TDP-43 is the primary driving factor behind the characteristic features of Alzheimer’s disease.

This lecture will focus on the role of TDP-43 in these neurodegenerative diseases.

Claudia H. Kawas, MD

Speaker – Forum

Claudia KawasDr. Claudia Kawas, the Al and Trish Nichols Chair in Clinical Neuroscience and Professor of Neurobiology & Behavior and Neurology, at the University of California, Irvine, is a geriatric neurologist and researcher in the areas of aging and dementia. Her work is concentrated on the epidemiology of aging and Alzheimer’s disease, in the determinants of successful aging, longitudinal and clinical pathological investigations, clinical trials, and most recently, studies in cognitive and functional abilities of the Oldest Old (over 90 years of age).

Dr. Kawas is a graduate of Swarthmore College (Pennsylvania), and completed her medical studies at the University of Louisville (Kentucky) and neurology residency training and a fellowship in dementia and aging at Albert Einstein College of Medicine, Bronx, New York. After 15 years on the faculty at Johns Hopkins School of Medicine, Dr. Kawas moved to the University of California, Irvine in 2000, where she is Principle Investigator of The 90+ Study and Associate Director of the UCI Institute for Memory Impairments and Neurological Disorders.

Dr. Kawas serves on committees for the National Institutes of Health and the Scientific Advisory Board of several organizations, including the Medical and Scientific Advisory Council of the National Alzheimer’s Association, The Dana Foundation, and the United States Food & Drug Administration. Over the past 25 years, Dr. Kawas has published more than 150 peer-reviewed manuscripts, and has worked on numerous longitudinal studies of aging and dementia, including the Bronx Aging Study, the Baltimore Longitudinal Study of Aging (NIA), and most recently, The 90+ Study, a population based sample of more than 1,600 people aged 90 years and older.

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Risk Factors for Dementia in the Oldest Old

Claudia H. Kawas, University of California, Irvine, CA, USA

In most of the world, the oldest old comprise the fastest growing segment of the population. As the leading consumers of healthcare and the individuals most affected by dementia, these pioneers of aging present research opportunities to better understand successful aging and dementia.

The 90+ Study, a population-based sample of more than 1600 people aged 90 years and older (Laguna Woods, California), comprises one of the largest studies of oldest old in the world.  Participants (76% women; mean age 97 years) are followed longitudinally every 6 months with neuropsychological and neurological examinations, medical record review, informant questionnaires and interviews.  DNA and brain donation are also requested.

Initial results in this population-based sample show a very high prevalence and incidence of dementia, mild cognitive impairment and functional disability in the oldest old.  However, typical neuropathological lesions associated with dementia, including Alzheimer disease, cerebrovascular, and other lesions, are not necessarily present. Moreover, risk factors associated with dementia and AD in younger old individuals (such as ApoE4) do not appear to be operant in the oldest old. Our preliminary studies suggest that physical performance measures (e.g. gait speed, balance and handgrip) and systemic factors (e.g. arterial oxygen saturation) are associated with dementia in the oldest old and require further investigation.  Epidemiological, clinical, and pathological studies of the 90+ Study will be presented, and implications for the study of dementia in younger individuals will be discussed.

Neva Kirk-Sanchez, PhD, PT

Speaker – Forum

Neva Kirk SanchezDr. Neva Kirk-Sanchez is Associate Professor of Clinical Physical Therapy, and Interim Chair of the Department of Physical Therapy at the University of Miami Miller School of Medicine.

Dr. Kirk-Sanchez specializes in chronic disease management including the effects of exercise and physical activity on neurodegenerative diseases such as dementia and mild cognitive impairment.  She has been involved in clinical trials examining the effect of exercise in people with severe dementia in the nursing home setting and people with mild cognitive impairment living in the community.  She has conducted studies examining the relationship between physical performance, physical activity, and cognition and memory.  Most recently she is working to better understand the relationships between balance, fall risk, and cognitive function.

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How Does Exercise Benefit People at Risk for Dementia?

Neva Kirk Sanchez University of Miami, Miami, FL, USA

 

Aging is associated with declines in both cognitive and physical abilities.  Maintaining high levels of exercise, physical activity, and physical fitness are key strategies to prevent declines in memory and cognition associated with aging.  Exercise to increase physical fitness can lead to positive changes in brain structure and function through many pathways.

For people with cognitive impairment, exercise can reduce the risk for falls and prevent problems with walking and other daily activities.  Being more physically active throughout the life-span can improve brain health, memory, and thinking.

Physical activity programs should include aerobic, strengthening, and balance exercises, and should be structured, individualized, high intensity, and long duration.  Exercise is an important factor in preventing declines in physical and cognitive function for all older adults, including those with mild cognitive impairment or dementia.

Susan M. Landau, PhD

Speaker – Workshop

landauDr. Susan Landau is Research Neuroscientist at the Helen Wills Neuroscience Institute at the University of California, Berkeley and the Lawrence Berkeley National Laboratory. Her research focuses on the longitudinal evaluation of multiple biomarkers in aging, mild cognitive impairment, and Alzheimer’s disease. Recent work with the Alzheimer’s Disease Neuroimaging Initiative (ADNI) has examined the predictive role of amyloid PET imaging, and other genetic, cerebrospinal fluid, and imaging biomarkers in cognitive decline at different phases of disease. Other recent work has examined the role of cognitive activity and lifestyle factors in aging and amyloid deposition, and the impact of chemotherapy on neural and cognitive function.

Dr. Landau studied cognitive psychology and neuroscience at Wesleyan University and completed a PhD at UC Berkeley, where she also received a National Science Foundation Graduate Research Fellowship award. She has carried out research on learning, working memory, and dopamine in healthy aging and dementia using PET and functional MRI. She has received additional training in cognitive neuroscience and neuroimaging at Dartmouth University, in neuropsychological evaluation at the Memory and Aging Center at the University of California San Francisco, and in electrophysiology at the Center for the Neural Basis of Behavior at the University of Pittsburgh.

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Understanding Biomarker Relationships in Alzheimer’s Disease: The ADNI Experience

Susan M. Landau Helen Wills Neuroscience Institute, University of California, Lawrence Berkeley National Laboratory, Berkeley, California, USA

 

As amyloid PET imaging becomes more frequently used in research and in clinical trials, a key question that has emerged is how amyloid measurements relate to other biomarkers (such as FDG-PET and structural MRI) across different phases of disease.  Recently acquired longitudinal data from The Alzheimer’s Disease Neuroimaging Initiative (ADNI) has made it possible to examine longitudinal amyloid PET measurements in relation to these other biomarkers.

Amyloid and other biomarkers appear to change at different rates according to the phase of disease and other factors such as APOE4 genotype. Finally, we examine the prevalence of non-amyloid pathology in subjects who have undergone rigorous clinical screening for AD and MCI. Approximately 12% of the ADNI AD patients and 25% of MCI patients have no biomarker evidence of amyloid deposition, and these individuals differ from their amyloid-positive counterparts on other biomarkers and on their longitudinal trajectories. Together, this data demonstrates that integrating information across multiple biomarkers longitudinally provides insight into individual AD trajectories.

At the conclusion of this presentation, the attendees should be able to 1) Explain the relative importance of different biomarkers for characterizing pathology in AD 2) Describe differences between MCI and AD patients with respect to amyloid deposition and hypometabolism 3) Discuss current models of how amyloid changes over the course of AD.

Eckhard Mandelkow, PhD

Discussant – MiniSymposium 1

MandelkowEkDr. Eckhard Mandelkow studied physics in Braunschweig, New Orleans, and Hamburg, and received his PhD at the Max-Planck-Institute for Medical Research in Heidelberg (for work on the structure of tobacco mosaic virus). This was followed by postdoctoral training at Brandeis University, Waltham MA (structure of cytoskeletal proteins). Later he moved to the Deutsches Elektronensynchrotron (DESY) in Hamburg, Germany, as director at the Max-Planck-Unit for Structural Molecular Biology and professor at Hamburg University.

His research focuses on structural molecular biology by X-rays using synchrotron radiation, image reconstruction in electron microscopy, cytoskeleton (microtubules, motor proteins), the structure, function, and aggregation of tau protein and protein kinases in Alzheimer disease, and the development of tau aggregation inhibitors. He is recipient of a 2010 Metlife Award and a 2011 Potamkin Award. In 2011 he joined the German Center for Neurodegenerative Diseases in Bonn (DZNE) as a Principal Investigator.

Eva-Maria Mandelkow, MD, PhD

Keynote Speaker

MandelkowEvaDr. Eva-Maria Mandelkow studied medicine in Heidelberg and Hamburg, followed by a three-year internship at university hospitals in Hamburg and Heidelberg. She then carried out a PhD thesis at the Max Planck Institute for Medical Research, Heidelberg, with research on enzyme kinetics of the motor protein myosin. This was followed by postdoctoral research at Brandeis University, Waltham, MA and at the Scripps Research Institute in La Jolla, CA. Dr. Mandelkow joined the Max Planck Institute in Heidelberg as research scientist where she studied the self-assembly of microtubules by cryo-electron microscopy. In 1986, she became Principal Investigator at the Max Planck Unit for Structural Molecular Biology at Deutsches Elektronen-Synchrotron (DESY), Hamburg.

The current research interests of her group include the cell biology of tau protein and its role in Alzheimer disease, with emphasis on cell models, transgenic mouse models, and development of therapeutic approaches. She is recipient of a 2007 Breuer Award, a 2010 Metlife Award and a 2011 Potamkin Award. In 2011 Dr. Mandelkow moved to the German Center for Neurodegenerative Diseases in Bonn (DZNE) as a Principal Investigator.

Animal Models of Tauopathy and Treatment Strategies

Eva-Maria Mandelkow DZNE, German Center for Neurodegenerative Diseases, Bonn, Germany MPI for Metabolism Research, Hamburg Outstation, c/o DESY, Hamburg, Germany CAESAR Research Center, Bonn, Germany

 

Tau is a neuronal microtubule-associated protein. In Alzheimer Disease, Tau is altered by hyperphosphorylation, mislocalization, aggregation etc. We are interested in the physiological functions of Tau protein and its role in neurodegeneration in Alzheimer Disease, frontotemporal dementia, progressive supranuclear palsy, and other tauopathies. We are developing cell and animal models to observe the spreading of Tau pathology, the interaction with A-beta, and the effects of aggregation inhibitor compounds. This includes transgenic mice in which Tau is expressed either in a “pro-aggregant” form, or in a non-aggregating form, which can be compared with Tau knockout mice or mice expressing wildtype forms of Tau. The aberrant mislocalization and aggregation of Tau, combined with loss of synapses and microtubules are among the hallmarks of AD. Microtubules play essential roles in the maintenance of axons and dendrites because they provide the tracks for intracellular transport by motor proteins and the distribution of cell components. However, the causes and mechanisms of microtubule breakdown in AD are poorly understood.

To elucidate the cascade of events leading to microtubule breakdown we exposed mature wildtype and Tau knockout neurons to A-beta oligomers and analyzed changes in the Tau/microtubule system. Microtubule breakdown occurs in dendrites invaded by Tau and is mediated by spastin, a microtubule-severing enzyme. Spastin is recruited to microtubules modified by polyglutamylation, mediated by translocation of the enzyme Tubulin-Tyrosine-Ligase-Like-6. Photoconversion of Tau labeled with Dendra2 reveals that missorted Tau in dendrites is newly synthesized and not derived from the axon. Long-term observations show that the toxic effects induced by A-beta are reversible and involve the activitation of the kinase MARK. In absence of Tau (TauKO neurons), microtubules and synapses are resistant to A-beta induced toxicity because without Tau the mislocalization of TTLL6 and the polyglutamylation of microtubules are prevented, so that there is no recruitment of spastin and no microtubule breakdown. Reintroduction of Tau re-establishes A-beta induced toxicity in TauKO neurons, which requires phosphorylation of the KXGS-motifs in the repeat domain of Tau. The results provide a rationale for microtubule stabilization as a therapeutic approach.

Research supported by DZNE (German Center for Neurodegenerative Diseases), Max-Planck-Society, Tau Consortium.

Ann McKee, MD

Speaker – MiniSymposium 1

McKeeDr. Ann McKee is the Director of the Neuropathology Laboratories for the New England VA Medical Centers, Director of the CTE Center, Associate Director of the Boston University Alzheimer’s Disease Center and Professor of Neurology and Pathology at Boston University School of Medicine. She is a board certified neurologist and neuropathologist with a primary research focus on neurodegeneration and mild traumatic brain injury. Over the last decade, her work has focused on chronic traumatic encephalopathy (CTE) and CTE with Motor Neuron Disease, as well as other neurodegenerative conditions, including Alzheimer’s disease (AD), Lewy Body disease, and Frontotemporal dementia. Dr. McKee’s work has been critical to understanding the clinical and pathological features of Chronic Traumatic Encephalopathy. She has published widely on the largest series of CTE ever established, pioneered the worlds largest brain bank devoted to mild TBI and CTE, determined critical features of the disease course and pathogenesis and developed the neuropathological criteria for CTE diagnosis and progression.  Dr. McKee directs the brain banks at VA Boston and Boston University School of Medicine, including the CTE Center and Alzheimer’s disease Center and the VA TBI Brain Bank for the Chronic Effects of Neurotrauma DOD-VA National Consortium.  She is the Principal Investigator on a NINDS-NIBIB funded UO1 on the Neuropathology and Neuroimaging of CTE and Posttraumatic Neurodegeneration. She is also a neuropathologist for the VA ALS and PTSD brain banks. She serves on the Medical Advisory Board for the Sports Legacy Institute, the Mackey White Traumatic Brain Injury Committee for the National Football League Players’ Association and the Dana Alliance for Brain Initiatives. She has been the keynote speaker for multiple conferences and international organizations, including the Adams Lecture, the Deborah Warden Lecture and the Deans Distinguished Lecture at Case Western Reserve University School of Medicine.  She recently received the Ethos award from Santa Clara University. 

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Emerging Concepts in Chronic Traumatic Encephalopathy

Ann C. McKee Boston University School of Medicine, Boston, MA, USA

 

Chronic Traumatic Encephalopathy (CTE) is a progressive degenerative disease of the brain found in athletes and military personnel with a history of repetitive brain trauma, including symptomatic concussions as well as asymptomatic subconcussive hits to the head. CTE has been known to affect boxers since the 1920s. However, recent reports have been published of neuropathologically confirmed CTE in retired professional football players and other athletes who have a history of repetitive brain trauma.

Dr. McKee will describe the neuropathological changes associated with CTE. She will also highlight the neuropathological differences between CTE and other neurodegenerative diseases such as Alzheimer’s disease, Lewy Body disease, and Parkinson’s disease. In addition, she will describe the clinical changes associated with CTE and discuss current research happening at the CTE Center at the Boston University School of Medicine.

Ian McKeith, MD, FRCP, FMedSci

Speaker – MiniSymposium 1

Ian McKeithDr. Ian McKeith is Professor of Old Age Psychiatry at Newcastle University. He is an NIHR Senior Investigator, Director of the UK National Dementias and Neurodegenerative Diseases Research Network (DeNDRoN) and CRN National Theme Director for DeNDRoN and Neurological Disorders.

His dementia research now based in the Newcastle BRU in Lewy Body dementias, includes clinico-pathological brain banking studies, population based epidemiology and clinical trials. He established the Consortium on Dementia with Lewy Bodies which developed consensus guidelines for diagnosis and treatment which are now used globally. He has published over 400 peer reviewed articles and in 2008 he received a lifetime achievement award from the UK Royal College of Psychiatrists.

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How to Diagnose Early (Prodromal) Lewy Body Dementia

Ian McKeith Newcastle University Institute for Aging, Newcastle upon Tyne, UK

 

Prodromal Lewy body dementia could be defined by a relevant clinical deficit which is combined with a biomarker suggestive of an underlying alpha-synucleinopathy.  Cases presenting with prodromal cognitive symptoms are most likely to be characterized as non-amnestic MCI with prominent attentional, executive and visuo-perceptual dysfunction. Conversion to DLB is reported to occur in two-thirds of such cases within a seven year follow up with baseline presence of REM sleep behavior disorder, fluctuations, daytime sleepiness and mild Parkinsonism increasing risk. Non-cognitive prodromal presentations include psychiatric (unexplained delirium, stupor, mood disorders and psychosis), hyposmia and autonomic dysfunction (constipation, orthostatic dizziness and urinary incontinence). Since most of these symptoms lack disease specificity, it is the order of their appearance and the total number of symptoms experienced that may be most important in identifying early stage Lewy body disease.

Biomarkers available for current use include structural MRI for medial temporal lobe preservation, perfusion and metabolic SPECT/PET for occipital hypofunction, dopamine transporter SPECT for nigro-striatal dysfunction and cardiac scintigraphy. Although these techniques may in combination be useful for confirmation of moderate or advanced LB disease cases, it is as yet unclear how they can contribute to prodromal diagnosis. Histological confirmation by autonomic ganglia or cutaneous nerve biopsy may ultimately provide the best evidence of an underlying alpha-synucleinopathy in early stage cases and might be considered necessary before starting long-term, disease-specific preventative treatment.

Zachary A. Miller, MD

Speaker – MiniSymposium 1

miller, zacDr. Zachary Miller grew up in the Washington DC metro area. He obtained an undergraduate degree double majoring in Molecular Biology and Fine Arts from Haverford College. Following this he spent two years as a research assistant at MIT’s Whitehead Institute for Biomedical Research in Dr. Harvey Lodish’s lab. He received his medical degree from the University of Pittsburgh and pursued medical internship as well as neurology residency training at the University of Washington.

Dr. Miller came to the UCSF Memory and Aging Center as a behavioral and cognitive neurology fellow with particular interests in enhanced creativity and visual function that can occur in the setting select neurodegenerative diseases of the language network. He completed his fellowship and is now an Assistant Professor of Neurology at the UCSF Memory and Aging Center who specializes in the care of patients suffering from cognitive decline or dementia such as Alzheimer’s disease and frontotemporal dementia. His current research interests have grown to encompass the study of novel factors including neurodevelopment and chronic inflammation, which are associated with the development of selective neurodegenerative disorders.

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New Approaches towards Interventions in Frontotemporal Dementia

Zachary A. Miller Memory and Aging Center, University of California, San Francisco, CA, USA

 

Frontotemporal lobar degenerative syndromes provide extremely compelling models to study the effects of select therapeutic interventions. The common genetic forms of disease, GRN, C9ORF72, and MAPT produce specific underlying pathologies with relatively predictable clinical phenotypes, facilitating the development of robust biomarkers and clinical endpoints to test out novel interventions on. Similarly, the high clinicopathological correlation between disorders like progressive supranuclear palsy (with underlying tau pathology) and semantic variant as well as frontotemporal dementia with motor neuron disease (with underlying TDP-43 pathology) provide unique abilities to target homogenous and exquisitely characterized clinical populations for pharmacological and non-pharmacological interventions.

Given the advantageous properties of these genetic and clinical populations, the NIH’s Rare Diseases Clinical Research Network has funded a network center grant to study all of these above disorders. This grant will allow for unprecedented infrastructure in fast tracking clinical biomarker and therapeutic developments.  Currently, there are ongoing efforts in tauopathies to investigate the effects of microtubule stabilizers for the treatment of PSP, CBD, and AD as well as increasing interest in developing anti-tau antibodies to target transynaptic transmission of select conformational species.  Within GRN carriers several candidate compounds have been developed and tested with the goal of raising serum (and ultimately CSF) PGRN levels. Within the primary progressive aphasias, increasing efforts have been placed on rehabilitative strategies. Lastly, many novel targets may be on the horizons as we better understand the relationships between disorders of the immune system and FTD.

John C. Morris, MD

Keynote Speaker and Chair – Workshop

morris bDr. John C. Morris is a leading researcher in the fight against Alzheimer’s disease. Dr. Morris is the Harvey A. and Dorismae Hacker Friedman Distinguished Professor of Neurology, Professor of Pathology and Immunology, Professor of Physical Therapy, and Professor of Occupational Therapy at Washington University. He also is the Director and Principal Investigator of the Charles F. and Joanne Knight Alzheimer’s Disease Research Center at Washington University School of Medicine. Dr. Morris is a member of the Alzheimer’s Association’s Medical & Scientific Advisory Committee. He chairs the Clinical Task Force for the NIA’s Alzheimer Disease Centers program. He is author or co-author of over 400 peer-reviewed journal articles and 50 chapters and reviews. He edited the first and second editions of the Handbook of Dementing Illnesses.

He has received many honors, including the Distinguished Achievement Citation from his alma mater, Ohio Wesleyan University (2000), the Lifetime Achievement Award from the Alzheimer’s Association (2004), the 2004 MetLife Foundation Award for Medical Research, the 2005 Potamkin Prize for Research in Pick’s, Alzheimer’s, and Related Disease from the American Academy of Neurology and the Physician-Scientist Lifetime Achievement Award (2005) and the 2006 Dr. Neville Grant Award for Clinical Excellence from the Barnes-Jewish Hospital Foundation (St. Louis, MO). In 2008, he received the Washington University Academic Women’s Network Mentor Award. In 2010, he received the Carl and Gerti Cori Faculty Achievement Award from Washington University.

Dr. Morris  is ranked in the top 1% of investigators in the field of Neuroscience and Behavior by Essential Science Indicators database.

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Longitudinal Changes in Autosomal Dominant AD: Implications for Treatment

John C. Morris Washington University, St. Louis, MO, USA

The failure of Phase 3 clinical trials of putative disease-modifying drugs to demonstrate clear benefit for individuals with symptomatic Alzheimer disease (AD) has accelerated consideration of treatment trials in asymptomatic persons with preclinical AD. Using elevated cerebral levels of florbetapir retention with PET imaging as an indicator of preclinical AD, the Anti-Amyloid Treatment in Asymptomatic AD (A4) study will evaluate the monoclonal antibody, solanezumab, for its ability to prevent or lessen cognitive decline in healthy individual’s age 65-85y. However, this trial requires a large sample size (500 randomized to drug, 500 to placebo) because it is not possible to provide individual-level prediction as to whether florbetapir-positive persons inevitably progresses to symptomatic AD or if they do, when symptom onset will occur.

Autosomal dominant AD, albeit quite rare in comparison with late-onset AD (LOAD), overcomes these limitations as virtually all asymptomatic mutation carriers are destined to develop symptomatic AD with an age of onset (AAO) that generally matches the AAO of the affected parent. Moreover, the now-established characterization of the temporal ordering of AD biomarker abnormalities in asymptomatic MCs may extrapolate to LOAD, permitting better timing of anti-amyloid interventions in preclinical AD. Two ADAD-based clinical trials have begun:  the Dominantly Inherited Alzheimer Network-Trial Unit (DIAN-TU), and the Alzheimer Prevention Initiative.  Progress in the parent DIAN study of biomarkers in asymptomatic MCs as well as in the adaptive DIAN-TU clinical trial will be provided.

Ronald C. Petersen, MD, PhD

Speaker – Forum

headshot_petersenDr. Ronald Petersen is the Cora Kanow Professorship in Alzheimer’s Disease Research, and a Mayo Clinic Distinguished Investigator at the Mayo Clinic.

He is on the National Advisory Council on Aging, and is the chair of the Advisory Council on Research, Care and Services for the National Alzheimer’s Project Act by the Secretary of the Department of Health and Human Services.

Dr. Petersen is a recipient of the 2004 MetLife Award for Medical Research in Alzheimer’s Disease, and the 2005 Potamkin Prize for Research in Pick’s, Alzheimer’s and Related Disorders of the American Academy of Neurology.

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Factors which Modify Longevity in MCI and Dementia: The Mayo Clinic Experience

Maria Vassilaki, Ronald C. Petersen, Rosebud O. Roberts Mayo Clinic, Rochester, MN, USA

 

Mild cognitive impairment (MCI) is an important clinical entity in aging and dementia, and previous studies have demonstrated increased mortality in MCI cases compared to cognitively normal (CN) individuals.  We assessed the likelihood of death in individuals with MCI enrolled in the population-based prospective Mayo Clinic Study of Aging (MCSA).

The MCSA was established in 2004 and, at that time, was enrolling individuals 70-89 years of age.  The subjects were evaluated by a study coordinator and a physician and underwent neuropsychological testing at baseline and at 15-month intervals to assess their cognitive status.  The subjects were all free of dementia at enrollment, and progression to MCI or dementia was assessed.  Mortality rates for MCI versus cognitively normal individuals were estimated using Cox proportional hazards models.  Over a median follow-up period of 5.8 years, 331 of the 862 MCI cases, and 224 of 1,292 CN participants died.  Compared to the CN individuals, the mortality rate was elevated in persons with MCI.  In addition, the effect was modified by sex, history of heart disease and levels of physical activity suggesting that our lifestyle activities such our dietary habits and exercise routine might play a role in influencing one’s likelihood of early death.

Rosa Rademakers, PhD

Moderator – MiniSymposium 1

rosa-rademakersDr. Rosa Rademakers is currently a Professor of Neuroscience in the College of Medicine at Mayo Clinic and the Mildred A. and Henry Uihlein II Professor of Medical Research. She completed a Bachelor’s degree in Biology in 1997, a Master’s degree in Biochemistry in 1999 and a PhD degree in Science in 2004, all at the University of Antwerp in Belgium. She also completed a postdoctoral fellowship at the University of Antwerp before moving to the Mayo Clinic Florida in 2005, where she started her independent career in 2007.

As a research scientist, Dr. Rademakers is focused on studying the molecular genetics of neurodegenerative diseases, with a special interest in the group of disorders referred to as frontotemporal lobar degenerations (FTLD) and amyotrophic lateral sclerosis (ALS). Her work aims to identify the novel causal genes for FTLD and ALS using family-based studies and to identify susceptibility genes that increase the risk to develop these neurodegenerative diseases in the general patient population. In 2011, Dr. Rademakers’ laboratory identified an expanded section of DNA known as a repeat expansion as the most common cause of FTLD and ALS identified to date. This mutation explained the disease in more than 10% of FTLD patients and approximately 25% of ALS patients with other family members with dementia or ALS. Her research is funded by the National Institute on Aging, National Institute of Neurological Disorders and Stroke, ALS Association, ALS Therapy Alliance and the Consortium for Frontotemporal Dementia Research. Dr. Rademakers holds three patents for detecting and treating dementia and diagnostics based on dementia-causing genes and has received the Paolo Gontijo Medicine Award and the acclaimed Sheila Essey Award for ALS Research from the ALS Association in partnership with the American Academy of Neurology. Dr. Rademakers’ has published more than 200 articles in peer-reviewed journals such as Nature, Nature Genetics, Neuron, Lancet Neurology, Brain, Neurology and Proceedings of the National Academy of Sciences U S A.

Katya Rascovsky, PhD

Speaker – MiniSymposium 2

KatyaRascovsky smallDr. Katya Rascovsky is a Research Assistant Professor at the Penn Frontotemporal Degeneration Center, Department of Neurology, University of Pennsylvania Perelman School of Medicine. She received her BA in Biological Basis of Behavior and Psychology from the University of Pennsylvania and a MA in Psychology from New York University. From 1995-1999 she worked in a memory disorder’s clinic and taught neuropsychology in her native country of Colombia.  In 2005, she was awarded her PhD in Clinical Psychology from the University of California, San Diego. Dr. Rascovsky completed a two-year postdoctoral fellowship in Neuropsychology at the Memory and Aging Center, University of California San Francisco, where she also worked as an Instructor and Assistant Professor.  

Dr. Rascovsky’s research has focused on identifying the cognitive and behavioral markers of behavioral variant frontotemporal dementia (bvFTD). Her research also includes studies of survival and clinical progression of patients with frontotemporal degeneration. Current research interests include social norm violation, politeness and compulsivity in bvFTD, as well as studies of impulsivity using neuroeconomic methods.  She also conducts cross-cultural studies of young-onset dementia in Latin America.

Clinical and Imaging Characteristics of Early bvFTD

Katya Rascovsky Penn Frontotemporal Degeneration Center, University of Pennsylvania, Philadelphia PA, USA

 

The behavioral variant of frontotemporal dementia (bvFTD) is characterized by progressive frontotemporal atrophy leading to alterations in complex thinking, personality and behavior. Given the gradual behavioral changes typical of bvFTD, diagnosis of the syndrome can be challenging.

In this talk, we will discuss the very early behavioral and cognitive symptoms of bvFTD, clinical features that may aid in differential diagnosis, and imaging changes characteristic of the syndrome.

Emily J. Rogalski, PhD

Speaker – MiniSymposium 1

rogalskiDr. Emily Rogalski is an Associate Professor and the Director of Neuroimaging for the Cognitive Neurology and Alzheimer’s Disease Center (CNADC) at Northwestern University’s Feinberg School of Medicine.

Her research falls under the broad umbrella of aging and dementia and uses a multimodal approach to investigate two aging perspectives: primary progressive aphasia (PPA) in which neurodegenerative disease invades the language network and SuperAging in which individuals are seemingly resistant to the deleterious changes in memory associated with “normal” or more typical cognitive aging. Her investigations assist in defining the clinical and anatomical features of different dementia syndromes as well genetic and other risk factors. She also develops educational programs, support groups and therapies to improve quality of life for patients with dementia. She has received research support from the National Institutes of Health, the Association for Frontotemporal Degeneration (AFTD), Alzheimer’s Association and other philanthropic sources. 

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Clinical and Imaging Features of Prodromal PPA

Emily J. Rogalski Northwestern University Feinberg School of Medicine, Chicago, IL, USA

 

Primary Progressive Aphasia (PPA) is a neurodegenerative syndrome characterized by a gradual dissolution of language, but relative sparing of other cognitive domains during the initial stages of the disease. Research has led to substantial progress in understanding the clinical characteristics, genetics, and neuropathology of this syndrome, which has resulted improved education and recognition of the disease. Because of these advancements, patients are finding the clinic at an earlier stage allowing for characterization at milder stages of disease, when therapeutic interventions are most likely to succeed.

This presentation will describe initial observations related to the diagnosis, classification and clinicoanatomical features of the early and mild impairment stages of PPA from a cohort of patients followed longitudinally at Northwestern University.

Supported by DC008552 from the National Institute on Deafness and Other Communication Disorders; AG13854 (Alzheimer Disease Core Center) from the National Institute on Aging; and NS075075 from the National Institute of Neurological Disorders and Stroke. This is not an industry-sponsored study.

Jonathan Rohrer, MD, PhD

Speaker – MiniSymposium 2

Jonathan RohrerDr. Jonathan Rohrer is a neurologist and dementia researcher at the UCL Institute of Neurology in Queen Square, London, UK. His research has focused on the neuroimaging and neuropsychology of frontotemporal dementia (FTD), particularly in relation to their underlying genetic causes. Research in the field of FTD has led to the publication of over 90 Pubmed-referenced papers and he has spoken at a number of international conferences about the work.

Since 2011 he has co-ordinated the Genetic FTD Initiative, GENFI, a multicentre cohort study of presymptomatic genetic FTD (www.genfi.org.uk), and has been the clinical lead for the International FTD GWAS Consortium. He has also set up FTD UK (www.ftduk.org), an annual scientific meeting of UK researchers who work in the FTD field (running since 2011), and runs a website dedicated to providing research updates to the general public about FTD: FTD talk (www.ftdtalk.org).

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Imaging Characteristics of Prodromal Familial FTLD

Jonathan Rohrer University College London Institute of Neurology, London, UK

 

The Genetic Frontotemporal dementia Initiative (GENFI) comprises thirteen sites across Europe (UK, Italy, Netherlands, Sweden, Portugal) and Canada. Participants were recruited who were either known carriers of a pathogenic mutation in progranulin, tau or C9orf72, or who were at risk of carrying a mutation because a first-degree relative was a known symptomatic carrier. Participants underwent a standardized clinical and neuropsychological assessment. MRI was performed and grey matter volumes for the frontal, temporal, parietal, occipital, cingulate and insular cortices generated using a cortical parcellation of the volumetric T1-weighted scan. A subcortical parcellation of the thalamus, hippocampus, amygdala and striatum was also performed. Linear mixed effects models were used to examine whether the association between values of markers and time to expected onset of symptoms differed between mutation carriers and noncarriers.

Data were analysed from 220 participants consisting of 118 mutation carriers (40 symptomatic, 78 asymptomatic) and 102 noncarriers. MMSE, CBI-R and most neuropsychology markers showed mean differences between mutation carriers and noncarriers around 5 years before onset. For the imaging markers, differences in group means between mutation carriers and noncarriers were seen at the earliest time point for the insula and temporal lobe (around 10 years before onset). For the individual genetic subtypes, different gene-specific patterns of neuroanatomical involvement were seen. In summary, imaging and cognitive changes can be identified up to ten years before the expected onset of symptoms in familial FTD.

Christopher C. Rowe, MD, FRACP

Speaker – Workshop

Chris RoweProfessor Rowe is the Director of the Department of Nuclear Medicine and Centre for PET and a consultant neurologist to the Memory Disorders Clinic at the Austin Hospital, Melbourne. He has published extensively on SPECT in epilepsy and beta-amyloid imaging in Alzheimer’s disease. Chris applies state-of-the-art neuroimaging technology to develop and confirm new diagnostic tests and biomarkers.

Dr. Rowe is a Professorial Fellow, University of Melbourne and Florey Institute of Neuroscience and Mental Health. He is the Neuroimaging Stream Leader of the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL) and the CRC for Mental Health and the Chair, Neuroimaging Professional Interest Area, US Alzheimer’s Association. In 2011 he received the Kuhl-Lassen Award, US Society of Nuclear Medicine, for his work in developing a test for the treatment of epilepsy and the diagnosis of Alzheimer’s disease. He is the first Australian researcher to receive a major international award from this Society.

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Cross-sectional and Longitudinal Studies in LOAD: AIBL Experience

Christopher C. Rowe on behalf of the AIBL research group Department of Nuclear Medicine and Centre for PET, Memory Disorders Clinic, Austin Health, Melbourne, Australia

 

Background: The Australian Imaging, Biomarkers and Lifestyle study of aging (AIBL) commenced in 2006 with the aim to further the understanding of the development of Alzheimer’s disease and develop better diagnostic methods.

Methods: 1200 participants (including 800 healthy persons aged over 60) (HC) were enrolled and evaluated at 18 month intervals with 54% retention at 6 years. 288 had PiB PET and MRI at baseline and subsequent evaluations. Later, more participants had at least one amyloid scan and MRI creating a pool of 333 HC subjects (mean age 70 at entry) with known amyloid status and 4.5 years of longitudinal cognitive data. Amyloid burden was measured as the ratio of cortical to cerebellar grey PiB binding and termed SUVR. Rates of change for Aβ deposition and cognitive decline were derived from the slope of the regression plots over at least 3 years of imaging.

Results: Aβ deposition (0.05 vs 0.01 SUVR/yr, p<0.0001) and memory decline (-0.17 vs -0.02 SD/yr, p=0.02) were significantly faster in PiB+ vs PiB- HC. Rates were similar in MCI. Aβ deposition was slightly slower in AD (0.03 SUVR/yr). Cognitive decline was inversely associated with baseline SUVR in all groups: HC (R2=0.12, p=0.044), MCI (R2=0.23, p=0.023), and AD (R2=0.71, p=0.033).

Thirteen percent of HC showed clinical progression (15 to MCI, 8 to dementia) and 59% of the MCI cohort progressed to probable AD over 3 years. Multivariate analysis showed beta-amyloid imaging as the single variable most strongly associated with progression. Of combinations, subtle memory impairment (Z-score -0.5 to -1.5) with a positive amyloid scan most strongly associated with progression in healthy individuals (Odds Ratio 16 [95%CI 3.7-68], PPV 50% [95%CI 19-81], NPV 94% [95%CI 88-98]). Almost all amnestic MCI (Z-score ≤ -1.5) with a positive amyloid scan developed AD (Odds Ratio ∞, PPV 86% [95%CI 72-95], NPV 100% [95%CI 80-100]). Hippocampal atrophy and e4 status did not add further predictive value.

Interpolating the longitudinal imaging data in those showing increase over 4.5 years revealed that it takes 12 years of accumulation to reach detectable levels (i.e. SUVR 1.5) and then another 19 years (95% CI 16–22) to reach the levels observed in mild AD. As AD progressed, the rate of Aβ deposition slowed towards a plateau. In contrast the time before mild AD (CDR 1.0) to cross the threshold for abnormality was 4-5 years for hippocampal volume and 3-4 years for memory impairment.

In the amyloid positive HC, APOE-e4 was associated with faster cognitive decline while low education and evidence of cerebrovascular disease on MRI were associated with lower baseline performance but did not alter the rate of cognitive decline. Conclusion: Aβ deposition extends for more than two decades and can be detected with PET, providing a wide window for intervention to prevent progression to dementia. In persons with objective memory impairment, positive amyloid imaging reliably predicts progression to dementia and therefore can be used to define prodromal or early AD.

Reisa A. Sperling, MD

Discussant – Workshop

Sperling-Headshot[1]Dr. Reisa Sperling is a neurologist, specializing in Alzheimer’s disease and imaging research. She is a Professor in Neurology at Harvard Medical School. She is the Director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital, and the Director of Neuroimaging for the Massachusetts ADRC at Massachusetts General Hospital.

Dr. Sperling’s research is focused on the early diagnosis and treatment of early Alzheimer’s disease (AD). She is the Principal Investigator of the Harvard Aging Brain Study, funded by a NIA Program Project grant. Dr. Sperling led the NIA-Alzheimer’s Association workgroup to develop guidelines for “Preclinical Alzheimer’s disease,” and currently serves on the NIA Council. She is the Project Leader for the ADCS Anti-Amyloid Treatment in Asymptomatic AD (A4) study – a three-year secondary prevention trial in 1000 clinically normal older individuals with PET amyloid imaging evidence of early Alzheimer’s disease pathology.

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Prashanti Vemuri, PhD

Speaker – Workshop

prashanthi_vemuri_smDr. Prashanthi Vemuri is an Assistant Professor at the Aging and Dementia Imaging Laboratory, Department of Radiology, Mayo Clinic Rochester.  In 2009 she completed a fellowship with Dr. Clifford Jack at the Mayo Clinic in imaging of neurodegenerative diseases. She is a recipient of the NIH K99/R00 Pathway to Independence grant from the NIA, Alzheimer’s Association New Investigator grant award and was awarded the AFAR-GE healthcare junior investigator award for excellence in aging and imaging research.Dr. Vemuri’s areas of research are developing and validating biomarkers to improve the understanding and management of neurodegenerative disorders and utilize biomarkers to improve our understanding of cognitive reserve i.e. the disconnect between brain pathology and cognitive performance in individuals. As an imaging researcher with an engineering background, her career goal is to improve our understanding of key mechanistic questions related to neurodegenerative diseases using mathematics, imaging and engineering technology.

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Cross-sectional and Longitudinal Imaging studies in Non-demented Subjects: Mayo Clinic Study of Aging

Prashanthi Vemuri Mayo Clinic, Rochester, MN, USA

 

Universally observed cognitive decline in the elderly will have a significant impact on public health. The cognitive function in an individual is influenced by two primary components in addition to age, sex and APOE: the degree of brain pathology and cognitive reserve. Mayo Clinic Study of Aging (MCSA) is a population-based sample that has been systematically collecting imaging and cognitive reserve data on non-demented elderly between 70-90 years since 2004. Cross-sectional and longitudinal imaging data from MCSA has allowed us to investigate the relationships between biomarkers, cognition and cognitive reserve.

The first part of the presentation will focus on the recent studies from MCSA that have investigated the relationships between biomarkers of pathology and cognition (specifically those published in preclinical AD stages and vascular disease). The second part of the presentation will focus on the impact of cognitive reserve on cognition, and on the relationship between biomarker and cognition. New data will be presented on demographic and cognitive reserve predictors of the rate on biomarker decline.

Robert S. Wilson, PhD

Speaker – Forum

RS WilsonDr. Robert S. Wilson is a Professor in the Departments of Neurological Sciences and behavioral Sciences of Rush University Medical Center in Chicago, IL.

He received his PhD in Clinical Psychology from Wayne State University in 1976 and completed a fellowship in neuropsychology at Rush University Medical Center in 1978. His research involves assessing change in cognitive function (and other behaviors) and incident cognitive impairment and dementia in older persons in population-based studies, clinical-pathologic studies, and behavioral neuroscience studies. His primary focus is on identifying potentially modifiable behaviors that influence late life cognitive health.

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Personality Factors that Modify Risk for MCI/Dementia

Robert S. Wilson Rush University Medical Center, Chicago, IL, USA

 

The presentation will provide new data from longitudinal clinical-pathologic cohort studies.  The initial focus will be characterizing how common dementia related pathologies deflect trajectories of cognitive aging.  Then, after statistically controlling for pathologic effects, the focus will shift to personality (e.g., conscientiousness) and lifestyle (e.g., cognitive activity) factors that are associated with residual variability in cognitive decline not attributable to dementia related pathology and mechanisms underlying these associations.

David A. Wolk, MD

Speaker – MiniSymposium 2

headshot_wolkDr. David Wolk is an Associate Professor of Neurology in the Cognitive Neurology Division of the University of Pennsylvania Perelman School of Medicine. He is also Assistant Director of the Penn Memory Center. His primary clinical interest has been in the diagnosis and care of individuals with a variety of neurodegenerative conditions.

Dr. Wolk’s research has focused on the cognitive neuroscience of memory decline associated with aging and Mild Cognitive Impairment/Alzheimer’s Disease using techniques including behavioral testing, Event-Related Potentials, structural and functional MRI, and amyloid PET imaging. A highly related additional line of his work has been the development and examination of biomarkers for detection of early disease changes that differentiate normal aging from evidence of neurodegenerative pathophysiology. This work has also included use of morphometric structural imaging methods, MRI measures of cerebral blood flow, and molecular imaging techniques. In addition to early disease detection, Dr. Wolk has explored the relationship of these measures to phenotypic variation for trying to better understand heterogeneity in these populations.

Dr. Wolk completed his medical training at Johns Hopkins University, a Neurology residency at the University of Pennsylvania, and clinical Fellowship training in Cognitive and Behavioral Neurology at Brigham and Women’s Hospital/Harvard Medical School; where he also completed a post-doctoral research fellowship studying memory in Alzheimer’s Disease. Amongst a number of honors, he is the recipient of the American Academy of Neurology’s Norman Geschwind Prize in Behavioral Neurology.

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What is the Etiology of Amyloid Negative Mild Cognitive Impairment?

David A. Wolk University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

 

A significant proportion, up to ~50% in some studies, of patients with amnestic Mild Cognitive Impairment (MCI) do not display evidence of cerebral amyloidosis based on cerebrospinal measures of ABeta or amyloid PET. While it is clear that those with evidence of brain amyloid are, overall, at an increased risk of progressing to clinical Alzheimer’s Disease (AD), the etiology of cognitive impairment of those without amyloid remains unclear.   Of particular interest are those patients who display evidence of AD-like neurodegenerative change despite the absence of evidence for cerebral amyloid, a group that has been recently designated as SNAP, or suspected non-AD (or ABeta) pathology. Whether this group represents individuals with other neurodegenerative or non-neurodegenerative conditions, AD with sub-threshold amyloid, or the recently formalized pathologic designation of primary age-related tauopathy (PART) remains uncertain.

This talk will discuss evidence for these various possibilities based on analysis of clinical cohorts, as well as data about the longitudinal outcomes of these groups. Further, a significant minority of clinical AD patients are also amyloid-negative and they will be discussed in this context.  Given their prevalence, these groups represent important populations to gain an enhanced understanding with potential implications for their clinical management and as potential targets in therapeutic trials.

Robert Woods, PhD

Speaker – Forum

Bob WoodsDr. Robert Woods has been a practicing clinical psychologist working with older people for 40 years, training and working initially in Newcastle-upon-Tyne. Subsequently he combined extensive clinical work with older people with academic appointments at the Institute of Psychiatry, London and University College London.

Since 1996, he has been Professor of Clinical Psychology of Older People at Bangor University. He is Director of NEURODEM Cymru, the dementias and neurodegenerative diseases research network for Wales and co-Director of the Dementia Services Development Centre Wales. He has published 11 books and over 160 journal articles and book chapters.

His research has involved the systematic development of evidence-based psychosocial interventions for people with dementia and their care-givers, including cognitive stimulation and reminiscence approaches.

He also leads a major epidemiological study of cognitive impairment in Wales, the CFAS Wales study, involving 3500 older people. He is an Alzheimer’s Society Ambassador, and a member of the Medical & Scientific Advisory Committees for Alzheimer Europe and Alzheimer’s Disease International.

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Cognitive Engagement and Risk for MCI and Dementia

Robert Woods Bangor University, Bangor, UK

 

There is considerable interest world-wide as to whether the risk of cognitive impairment in later life can be reduced by engaging in cognitive activities. This is evidenced in the popularity of ‘train the brain’ games, for example. The theory of cognitive reserve is relevant to this issue.

Cognitive reserve is an active process, where brain networks are used more effectively and alternative brain networks and compensatory strategies are used to maintain function and performance, despite physical changes to the brain that may be occurring alongside ageing. The association between higher educational levels and reduced risk of dementia is seen as an example of the effects of cognitive reserve, and studies have shown that engagement in a wide range of cognitive activities (from reading to playing a musical instrument) may also be associated with reduced risk.

These studies are typically retrospective and reflect the lifestyle choices made by individuals at the time; there may of course be an underlying factor related to both these choices and risk of cognitive impairment, There are few intervention studies where the effects of cognitive engagement or cognitive training have been evaluated prospectively – in general cognitive training has specific rather than general effects on cognitive function and performance. Participants generally perform better on the tasks they practice, but do not show improvement on other tasks.

Cognitive engagement at present probably needs to be seen in the context of other factors, such as mood, social networks and physical exercise, and can be recommended insofar as it is enjoyable and adding to well-being in the present.