
Targeting the Vasculature in Alzheimer's Disease and Vascular Cognitive Impairment
Friday, May 4, 2012
Presented By
Vascular pathology has been long established, but is under-appreciated, as a contributing factor in Alzheimer's disease (AD). It is likely that vascular alterations are both a cause and a consequence of neuronal loss. This conference will present the current clinical knowledge of the vascular connection to AD pathogenesis and will highlight novel vascular approaches to intervention that can be applied to Alzheimer's disease therapeutic development.
Networking reception to follow.
Registration Pricing
Member | $25 |
Student / Postdoc / Fellow Member | $10 |
Student / Postdoc / Fellow Nonmember | $40 |
Nonmember Academic | $60 |
Nonmember Not for Profit | $60 |
Nonmember Corporate | $80 |
Presented by
Agenda
* Presentation times are subject to change.
Friday, May 4, 2012 | |
8:30 AM | Registration and Continental Breakfast |
8:55 AM | Welcome |
9:00 AM | Opening Remarks |
Session I. Overview and Pathogenic Mechanisms | |
9:15 AM | Vascular Contributions to Cognitive Impairment and Dementia |
9:35 AM | Q&A session |
9:45 AM | The Overlap between Neurodegenerative and Vascular Factors in Dementia |
10:05 AM | Q&A session |
10:15 AM | Gain-of-Function Somatic Mutations Initiate the Vascular Damage that Leads to Alzheimer's Dementia: A Hypothesis |
10:35 AM | Q&A session |
10:45 AM | Understanding Cerebral Amyloid Angiopathy |
11:05 AM | Q&A session |
11:15 AM | Coffee Break |
Session II. Vascular Outcomes in Clinical Trials | |
11:45 AM | MRI Markers of Vascular Cognitive Impairment |
12:05 PM | Q&A session |
12:15 PM | The effects of Abeta Immunotherapy on the Vasculature |
12:35 PM | Q&A session |
12:45 PM | Hypertension, Cognitive Decline and Dementia: The Hidden Role of Obstructive Sleep Apnea |
1:15 PM | Lunch Break |
Session III. Vascular Targets for Alzheimer’s Disease Drug Discovery | |
2:15 PM | TBI and AD: Vascular Coag-Inflammatory Pathways and Therapeutic Targets |
2:35 PM | Q&A session |
2:45 PM | Leukocyte Plugging of Capillaries Reduces Brain Blood Flow in Mouse Models of Alzheimer's Disease |
3:05 PM | Q&A session |
3:15 PM | Fibrinogen and β-amyloid Association Alters Thrombosis and Fibrinolysis: A Possible Contributing Factor to Alzheimer's Disease |
3:45 PM | Coffee Break |
4:15 PM | Guarding Vascular Health with High Density Lipoproteins |
4:35 PM | Q&A session |
4:45 PM | Closing Remarks |
5:00 PM | Networking Reception |
6:00 PM | Close |
Speakers
Organizers
Howard Fillit, MD
Alzheimer's Drug Discovery Foundation
Howard Fillit, MD, a geriatrician, neuroscientist and a leading expert in Alzheimer's disease, is the founding Executive Director of the Alzheimer's Drug Discovery Foundation (ADDF). The ADDF's mission is to accelerate the discovery and development of drugs to prevent, treat and cure Alzheimer's disease, related dementias and cognitive aging.
Dr. Fillit has had a distinguished academic medicine career at The Rockefeller University and The Mount Sinai School of Medicine where he is a clinical professor of geriatrics and medicine and professor of neurobiology. He is a Co-author of more than 250 scientific and clinical publications, and is the senior editor of the leading international Textbook of Geriatric Medicine and Gerontology. Previously, Dr. Fillit was the Corporate Medical Director for Medicare at New York Life, responsible for over 125,000 Medicare managed care members in five regional markets. Dr. Fillit has received several awards and honors including the Rita Hayworth Award for Lifetime Achievement. He also serves as a consultant to pharmaceutical and biotechnology companies, health care organizations and philanthropies.
Jennifer Henry, PhD
The New York Academy of Sciences
Speakers
Barry W. Festoff, MD
University of Kansas Medical Center and pHLOGISTIX LLC
Barry W. Festoff, MD, is Professor of Neurology, Integrative Physiology and Pharmacology at the University of Kansas Medical Center (KUMC), where he has been since 1976, when he joined KUMC and the VA Medical Center in Kansas City (KCVAMC). He founded the Neurology Service at the VAMC, was its first Chief and Director of the Neurobiology Research Laboratory. His research has focused on connections between CNS trauma and neurodegeneration with an emphasis on coagulation proteases, principally thrombin, its regulation and its expression in the CNS. Thrombin inhibitors and regulators, such as protease nexin I (PN-I) and thrombomodulin (TM,) have featured in his group's studies emphasizing neuroinflammation. He retired from the VA in October 2010 and founded pHLOGISTIX LLC, a Delaware company with strategies to harness neuroinflammation in CNS injury and other conditions.
Philip B. Gorelick, MD, MPH
Hauenstein Neuroscience Institute
Dr. Philip B. Gorelick is the Medical Director of the Hauenstein Neuroscience Center, Saint Mary's Health Care, Grand Rapids, MI (February 6, 2012–present) and previously was the John S. Garvin Professor and Head, Department of Neurology and Rehabilitation, University of Illinois College of Medicine at Chicago (2003–Jan. 2012). Dr. Gorelick attended the Cardinal Stritch School of Medicine at Loyola and graduated in 1977. He completed Neurology Residency at Loyola and Hines VAH (1978–1981). After residency, he served as a Stroke Fellow under Louis R. Caplan, M.D., at Michael Reese Hospital as part of the University of Chicago Neurology Program (1981–1982). Dr. Gorelick then served as the Director of the University of Illinois Stroke Service in the Department of Neurology (1982–1985). He was later the Director of the Stroke Service at Michael Reese Hospital (1985–1991) and during this time received a MPH in epidemiology and biostatistics at University of Illinois School of Public Health. He was the Director of the Stroke and Neurological Critical Care Service at Rush Medical Center (1991–2003) where he was awarded an endowed chair in Neurology—the Jannotta Presidential Chair. Dr. Gorelick is board-certified in Neurology and Vascular Neurology.Dr. Gorelick is well known in national and international circles as a world leader in stroke prevention. He has developed innovative studies for identification of risk factors for stroke, prevention of first and recurrent stroke, and the elucidation of risk factors and mechanisms for vascular forms of cognitive impairment (VCI). His important work has been recognized by major stroke organizations worldwide as he has received the Feinberg Award for Excellence in Clinical Stroke 2004 from the American Heart Association and the National Stroke Association (NSA) Visionary in Stroke Award. He has also held the Daniel Gainey Professorship 2005 at Mayo Clinic, the Henry Barnett 2005 Lectureship from the Canadian Stroke Network, and the Stooplemoor Visiting Lectureship in Neurology (2009) at University of Iowa. Dr. Gorelick was awarded a grant from the World Federation of Neurology in 2011 to develop a prototype registry of provision of neurological services worldwide and to develop interventions to improve neurological services and treatment in developing countries. He currently directs the Clinical Coordinating Center for the US DIAS Trial and recently 1st-authored a AHA/ASA guidance statement on the vascular burden of cognitive impairment (Gorelick PB et al. Stroke 2011; 42: 2672–2713). He also holds the distinction of continuous funding from the NIH for his research work over an 18-year period. Dr. Gorelick has published over 250 peer-reviewed articles and has edited 6 books in his field with 2 more in development.
Steven M. Greenberg, MD, PhD
Harvard Medical School
Dr. Greenberg is Director of the Hemorrhagic Stroke Research Program at Massachusetts General Hospital and Professor of Neurology at Harvard Medical School. Initiated in 1994, the Hemorrhagic Stroke Research Program has become internationally recognized as a leading authority on the causes, diagnosis, and treatment of cerebral amyloid angiopathy. Dr. Greenberg has authored over 100 research articles and 50 chapters, reviews, and editorials in the areas of hemorrhagic stroke and small vessel brain disease, served as principal investigator on multiple national research grants, and in leadership positions at national and international conferences on hemorrhagic stroke and vascular cognitive impairment. He currently serves as Chair of the International Stroke Conference, Chair of the NINDS Stroke Progress Review Group's Vascular Cognitive Impairment subsection, and Director of Faculty Development for the Massachusetts General Hospital Department of Neurology.
Costantino Iadecola, MD
Weill Cornell Medical College
Costantino Iadecola, M.D., the G. C. Cotzias Distinguished Professor of Neurology and Neuroscience and Chief of the Division of Neurobiology at Weill Cornell Medical College, is a clinician-scientist who works on the cellular and molecular mechanisms of cerebral ischemia, and on the interface between stroke and dementia. Dr. Iadecola has published over 220 peer-reviewed papers and plays a leadership role in several research organizations and funding agencies. He chairs the scientific board of the Fondation Leducq and is an advisor to the European Stroke Network and to the Institute of Stroke and Dementia Research (Munich, Germany). He is a recipient of the Willis Award, the highest honor in stroke research bestowed by the AHA, and of the Zenith Fellow Award from the Alzheimer's Association.
Kejal Kantarci, MD
Mayo Clinic
Kejal Kantarci is Associate Professor of Radiology at the division of Neuroradiology Mayo Clinic. Dr. Kantarci’s research focuses on identifying imaging markers for early diagnosis and differential diagnosis of dementia. She has authored 50 peer-reviewed publications, 8 book chapters and given invited lectures in 22 national and international courses and symposia. She is a charter member of the NIH /CSR Biomedical Imaging and Technology Study Section. She received the New Investigator Award from the Alzheimer's Association in 2003 and Paul Beeson Award in Aging from the National Institutes of Aging, American Federation of Aging Research, John Hardford Foundation, Atlantic Philantropies, and Starr Foundation in 2007. Her research program has been funded continuously by the Alzheimer’s Association and the National Institutes of Health since 2003.
Vincent Marchesi, MD, PhD
Yale School of Medicine
Vincent Marchesi is a Professor of Pathology and Director of the Boyer Center for Molecular Medicine at Yale University. He received a BA and MD from Yale and a D. Phil from Oxford University and is a member of the National Academy of Sciences and the Institute of Medicine.
Bruce R. Reed, PhD
UC Davis Alzheimer's Disease Research Center
Dr. Reed is Professor of Neurology at the University of California, Davis and serves as Associate Director of the UC Davis Alzheimer's Disease Center. Dr. Reed received his B.A. Carleton College and his Ph.D. in Clinical Psychology from SUNY Stony Brook. He has published over 100 peer-reviewed publications on the neuropsychology of cognitive aging and dementia. His work on the contributions of vascular factors to cognitive impairment in aging has been funded by NIA since 1993. He recently served as Chair of the NIH Clinical Neuroscience Neurodegeneration study section and as panel member for the NINDS Stroke Progress Review Group's Vascular Cognitive Impairment subsection.
Gustavo C. Román, MD
Methodist Neurological Institute
Prior to joining the Methodist Hospital, Dr. Román was Professor of Neurology, University of Texas Health Science Center at San Antonio (UTHSCSA), and Neurologist at the Veterans Administration Audie L. Murphy Hospital in San Antonio, Texas, USA. Dr. Román is a medical graduate from the National University of Colombia with training in Neurology at the Salpêtrière Hospital, University of Paris, France, and at the University of Vermont, Burlington, VT. Dr. Román was Interim Chairman of Neurology and Neurosurgery at Texas Tech University in Lubbock, Texas. He served as Chief of the Neuroepidemiology Branch at the prestigious US National Institutes of Health. At the NIH, he organized the international workshop that defined the criteria for Vascular Dementia for research studies (NINDS-AIREN Criteria). He created an international research network in neuroepidemiology, with participants from Latin America, Europe, India and China that to this day continues to yield data. Dr. Román received the Commendation Medal of the US Department of Health and Human Services and the Distinguished Alumnus Medal of his Alma Mater. He is Honorary Member of the neurological societies of France, Spain, Panama, Dominican Republic, Cuba, Venezuela, and Austrian Society of Tropical Medicine. Dr. Román was elected Fellow of the American Neurological Association, American Academy of Neurology, American College of Physicians, Royal Society of Medicine (London), Royal Society of Tropical Medicine (London) and the Colombian Academy of Medicine. He is Honorary President of the Pan American Society of Neuroepidemiology, and Honorary Professor, Universita degli Studi di Ferrara (Italy). He has participated in the International Affairs committee of the American Academy of Neurology and is Chair Elect of the Neuroepidemiology Section. In 2008, Dr Román was elected Trustee to the Board of Directors of the World Federation of Neurology. He has served as Associate Editor of The Journal of the Neurological Sciences, official journal of the WFN, Ad Hoc Member of the Continuing Education Committee, Chair of the Research Group (RG) on Neuroepidemiology, Secretary for the Americas of the RG on Tropical Neurology, member of the RG on Dementia, and Secretary of the Environmental Neurology RG. Dr Román is fluent in Spanish, English and French, and has published 16 books, 35 chapters in books and more than 300 journal articles. He organized the International Congress on Vascular Dementia (Geneva, 1999, Salzburg 2002) and Vas-Cog 2007 (San Antonio, Texas, USA). He is past Editor-in-Chief of Neuroepidemiology (2000-2007) and editorial board member of Dementia and Geriatric Cognitive Disorders, Clinical Neurology and Neurosurgery, Revista de Neurología, Neurología, Gaceta Médica de México, and ad-hoc reviewer for numerous journals. Dr. Román is an internationally recognized expert in vascular dementia, cognitive neurology, neuroepidemiology and tropical neurology. He served as advisor to the FDA and is a current reviewer for the Aging Systems and Geriatrics Study Section of the NIH.
Chris B. Schaffer, PhD
Cornell University
Chris Schaffer received his undergraduate degree from the University of Florida in 1995 and his PhD from Harvard University, working with Eric Mazur, in 2001. Both of his degrees are in Physics. As a post-doc at UCSD, Chris worked with David Kleinfeld in the Physics and Neuroscience departments. He is currently an Associate Professor at Cornell University in the Department of Biomedical Engineering. His research has centered on the development of optical tools for in vivo manipulation of biological structures and the use of these tools to study the role of cortical microvascular lesions in neurological disease, with a current focus on the role of microvascular disruptions in Alzheimer’s disease.
Sidney Strickland, PhD
The Rockefeller University
Sidney Strickland is Professor and Dean of the Graduate School at The Rockefeller University in New York City. He received his BS in chemistry in 1968 from Rhodes College in Memphis. He obtained his PhD in biochemistry from the University of Michigan in 1972 where he studied the biophysics of enzymology with Vincent Massey. He then was a postdoctoral fellow for two years at Rockefeller with Edward Reich, where he initiated his work on plasminogen activators. He joined the faculty of Rockefeller as an Assistant Professor and then Associate Professor. In 1983, he accepted a position as Leading Professor at the State University of New York at Stony Brook. He returned to Rockefeller in 2000 and established the Laboratory of Neurobiology and Genetics. His lab studies mechanisms of neurodegeneration.
Cheryl Wellington, PhD
University of British Columbia
Dr. Wellington obtained her PhD in Microbiology at the University of British Columbia in 1991 and did postdoctoral training at Harvard Medical School, the University of Calgary, and the University of British Columbia. She joined the Department of Pathology and Laboratory Medicine at the University of British Columbia in 2000 and was promoted to Associate Professor in 2006.
Dr. Wellington’s research interests encompass include lipid and lipoprotein metabolism in the brain and how this relates to chronic and acute neurological disorders. Dr. Wellington’s group has made key contributions to the understanding of the role of apolipoprotein E (apoE) in Alzheimer’s Disease. ApoE is the major cholesterol carrier in the brain and the best established genetic risk factor for late-onset Alzheimer’s Disease. However, the mechanisms by which apoE affects Alzheimer’s Disease pathogenesis is poorly understood. Dr. Wellington’s laboratory has shown that the amount of lipids carried on apoE affects the metabolism of Aß peptides, which are toxic species that accumulate as amyloid plaques in the brains of patients with Alzheimer’s Disease and also accumulate in individuals who have suffered traumatic brain injury. Specifically, Dr. Wellington has identified the cholesterol transporter ABCA1 as the physiological transporter of lipids onto brain apoE. Her group has shown that mice deficient in ABCA1 have poorly-lipidated apoE in the brain and develop more amyloid, whereas transgenic mice that overexpress ABCA1 have lipid-rich apoE and have virtually no amyloid deposits. Her current research projects are aimed at developing methods to increase apoE lipidation in the brain for application to both Alzheimer's Disease and traumatic brain injury.
Abstracts
Vascular Contributions to Cognitive Impairment and Dementia
Philip B. Gorelick, MD, MPH, Hauenstein Neuroscience Institute
1. Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, et al. Vascular contributions to cognitive impairment and dementia: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42: 2672–2713.
The Overlap between Neurodegenerative and Vascular Factors in Dementia
Costantino Iadecola, MD, Weill Cornell Medical College
Gain-of-Function Somatic Mutations Initiate the Vascular Damage that Leads to Alzheimer's Dementia: A Hypothesis
Vincent Marchesi, MD, PhD, Yale School of Medicine
Understanding Cerebral Amyloid Angiopathy
Steven M. Greenberg, MD, PhD, Harvard Medical School
MRI Markers of Vascular Cognitive Impairment
Bruce R. Reed, PhD, UC Davis Alzheimer's Disease Research Center
The traditional MRI markers of vascular brain injury identify infarcts and areas of altered white matter. Most models of vascular cognitive impairment emphasize a predilection of these lesions to occur in fronto-subcortical circuits with consequent cognitive executive deficits. In this talk I will present work from our laboratory that support the following points: 1) the concept of VBI should be extended to include cortical atrophy, which is a major driver of cognitive impairment in general. 2) the view that VBI causes executive dysfunction is overly simple, 3) the direct effects of VBI are most prominent and can be best differentiated from those of AD in non-demented persons, 4) VBI likely plays a very important role in MCI (and "normal" cognitive aging), independent of those of AD. These findings support an integrated model of vascular contributions to cognitive impairment that identifies VBI as having both focal and diffuse effects on brain and with cognitive consequences that change with the progression of the disorder and with comorbid AD.
The Effects of Abeta Immunotherapy on the Vasculature
Kejal Kantarci, MD, Mayo Clinic
Hypertension, Cognitive Decline and Dementia: The Hidden Role of Obstructive Sleep Apnea
Gustavo C. Román, MD, Methodist Neurological Institute
Results: The mean age was 72.9 years; 51.5% men and 48.5% women. Mean Body Mass Index was 27.5 kg/m2 [range=19 – 41]. Most patients were Caucasian (59%), followed by Hispanics (25%), African Americans (12%) and Asian (4%). The main vascular risk factors were hypertension (77%), hypercholesterolemia (45%), cardiovascular disease (33%), diabetes (28%), and prior history of stroke (22%). A third of the cases had a family history of dementia. Clinical diagnoses of the cognitive problems included Mild Cognitive Impairment (MCI) Dysexecutive type (24%), Mixed Alzheimer's disease + Vascular Dementia (20%), MCI Amnestic type (17%), Vascular Dementia (12%), Alzheimer's disease (9%) and Normal Pressure Hydrocephalus (7%). MRI revealed extensive small vessel disease in 86% of the cases including lacunar strokes in the corona radiata and basal ganglia, as well as isolated white matter hyperintensities (34%). Large-vessel strokes were found in 17% of the cases. Severe OSA was found in 31% of the patients, moderate OSA in 47%, mild OSA in 19% and 4% had normal sleep.
Conclusion: OSA appears to be a significant factor in cognitive decline in the elderly, enhancing the effects of hypertension on small vessel disease in the brain.
TBI and AD: Vascular Coag-Inflammatory Pathways and Therapeutic Targets
Barry W. Festoff, MD, University of Kansas Medical Center and pHLOGISTIX LLC
Leukocyte Plugging of Capillaries Reduces Brain Blood Flow in Mouse Models of Alzheimer's Disease
Chris B. Schaffer, PhD, Cornell University
Fibrinogen and β-amyloid Association Alters Thrombosis and Fibrinolysis: A Possible Contributing Factor to Alzheimer's Disease
Sidney Strickland, PhD, The Rockefeller University
Guarding Vascular Health with High Density Lipoproteins
Cheryl Wellington, PhD, University of British Columbia
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