eBriefing

Imaging and the Aging Brain

Imaging and the Aging Brain
Reported by
Alan Dove

Posted August 28, 2009

Presented By

New York Academy of Sciences and the American Federation for Aging Research

Overview

On May 16–17, 2006, some of the world's top neuroscientists gathered at New York University for a conference titled Imaging & the Aging Brain, which was cosponsored by the New York Academy of Sciences and the American Federation for Aging Research. The presentations focused on the recent technological revolution in brain imaging, which is transforming the way researchers understand normal and pathological aging processes.

The meeting covered an astonishing amount of territory, with major presentations from two dozen top investigators in the field, and a barrage of brief talks and posters from talented junior researchers. This eBriefing contains a sampling of the work presented, and includes full reports summarizing six of the major talks, as well as nine multimedia presentations. It provides an overview of the breadth and depth of this extraordinary gathering.

Use the tabs above to find a meeting report and multimedia from this event.


Speakers include:

Helen Benveniste (Brookhaven National Laboratory)
Wen-Biao Gan (NYU School of Medicine)
Adam Gazzaley (University of California, San Francisco)
Eric Kandel (Columbia University)
Mark A. Mintun (Washington University)
Scott A. Small (Columbia University)
Reisa A. Sperling (Harvard Medical School)
Wendy A. Suzuki (New York University)
Paul Thompson (UCLA School of Medicine)
Michael W. Weiner (University of California, San Francisco)

For proceedings from thie conference, please see volume 1097 of the Annals of the New York Academy of Sciences, Imaging and the Aging Brain.


Sponsorship

This conference and eBriefing were made possible with support from the International Brain Research Foundation, The Alzheimer's Association, GE Global Research, Anonymous, Elan, Ohio Valley Imaging Solutions, Institute for the Study of Aging, and:

           

Web Sites

Administration on Aging
This agency of the U.S. Department of Health and Human Services provides long-term, direct care to elderly persons. Their site offers a wide range of information on aging-related conditions, including an Alzheimer's Resource Room.

Alliance for Aging Research
An advocacy group working to make aging research a medical priority, and to create and disseminate information to healthcare providers and the general public.

Alzheimer's Association
An organization dedicated to promoting Alzheimer's research, communicating information about Alzheimer's and recent research developments, and providing support to patients with Alzheimer's and their caregivers.

Alzheimer's Disease Neuroimaging Initiative
A major research study, sponsored by the National Institutes of Health, to determine whether brain imaging can help predict onset and monitor progression of Alzheimer’s disease.

American Federation for Aging Research
This organization supports scientists working on aging-related diseases and promotes awareness of aging-related research among the general public.

American Parkinson Disease Association
This organization offers information for patients and physicians, and funds grants for promising research to find a cure for Parkinson's disease.

Functional MRI Research Center
The Columbia University facility run by Joy Hirsch that studies the neurocircuitry of the brain that underlies cognition, perception and action, and is developing clinical applications that enhance the goals of personalized medicine.

In Vivo Microscopy: Technologies and Applications
Publication based on a 1999 conference on imaging applications for small animal models. (PDF, 1.3 MB)

MedLine Plus
Collects links to recent articles on Alzheimer's disease, Parkinson's disease, and dementia.

The National Parkinson Foundation (NPF)
Supports Parkinson-related research, patient care, education, training, and outreach.

RadiologyInfo
A site for consumers explaining various imaging technologies in current clinical use.


Books

De Leon, M. J., E. Braak & H. Braak. 1999. An Atlas of Alzheimer's Disease. Parthenon Publishing Group, Lancashire, UK.
Amazon | Barnes & Noble

Kandel, E. R. 2006. In Search of Memory: The Emergence of a New Science of Mind. W. W. Norton, New York.
Amazon | Barnes & Noble


Journal Articles

General Resources

De Leon, M. J. & W. Klunk. 2006. Biomarkers for the early diagnosis of Alzheimer's disease. Lancet Neurol. 5: 198-199.

Glodzik-Sobanska, L., H. Rusinek, L. Mosconi, et al. 2005. The role of quantitative structural imaging in the early diagnosis of Alzheimer's disease. Neuroimaging Clin. N. Am. 15: 803-826.

Helpern, J. A., S. P. Lee, M. F. Galangola, et al. 2004. MRI assessment of neuropathology in a transgenic mouse model of Alzheimer's disease. Magn. Reson. Med. 51: 794-798.

Hilbush, B. S., J. H. Morrison, W. G. Young, et al. 2005. New prospects and strategies for drug target discovery in neurodegenerative disorders. NeuroRx 2: 627-637. FULL TEXT

Hirsch, J. 2005. Functional neuroimaging during altered states of consciousness: how and what do we measure? Prog. Brain Res. 150: 25-43.

Law, J. R., M. A. Flanery, S. Wirth, et al. 2005. Functional magnetic resonance imaging activity during the gradual acquisition and expression of paired-associate memory. J. Neurosci. 25: 5720-5729. [PubMed - in process]

Ma, Y., P. R. Hof, S. C. Grant, et al. 2005. A three-dimensional digital atlas database of the adult C57BL/6J mouse brain by magnetic resonance microscopy. Neuroscience 135: 1203-1215.

Mosconi, L., S. De Santi, H. Rusinek, et al. 2004. Magnetic resonance and PET studies in the early diagnosis of Alzheimer's disease. Expert Rev. Neurother. 4: 831-849.

Mosconi, L. W. H. Tsui, S. De Santi, et al. 2005. Reduced hippocampal metabolism in MCI and AD: automated FDG-PET image analysis. Neurology 64: 1860-1867.

Redwine, J. M., B. Kosofsky, R. E. Jacobs, et al. 2003. Dentate gyrus volume is reduced before onset of plaque formation in PDAPP mice: a magnetic resonance microscopy and stereologic analysis. Proc. Natl. Acad. Sci. USA 100: 1381-1386. FULL TEXT

Rusinek, H., S. De Santi, D. Frid, et al. 2003. Regional brain atrophy rate predicts future cognitive decline: 6-year longitudinal MR imaging study of normal aging. Radiology 229: 691-696. FULL TEXT

Rusinek, H., Y. Endo, S. De Santi, et al. 2004. Atrophy rate in medial temporal lobe during progression of Alzheimer disease. Neurology 63: 2354-2359.

Wirth, S., M. Yanike, L. M. Frank, et al. 2003. Single neurons in the monkey hippocampus and learning of new associations. Science 300: 1578-1581.

Top-down Modulation and Normal Aging

Gazzaley, A., J. W. Cooney, K. McEvoy, et al. 2005. Top-down enhancement and suppression of the magnitude and speed of neural activity. J. Cogn. Neurosci. 17: 507-517.

Gazzaley, A., J. W. Cooney, J. Rissman, et al. 2005. Top-down suppression deficit underlies working memory impairment in normal aging. Nat. Neurosci. 8: 1298-1300.

Gazzaley, A. H., S. J. Siegel, J. H. Kordower, et al. 1996. Circuit-specific alterations of N-methyl-D-aspartate receptor subunit 1 in the dentate gyrus of aged monkeys. Proc. Natl. Acad. Sci. 7: 3121-3125. (PDF, 1.67 MB) FULL TEXT

In Vivo Imaging of Synaptic Plasticity and Pathology

Feng, G., R. H. Mellor, M. Bernstein, et al. 2000. Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 28: 41-51.

PET-Based Amyloid Plaque Imaging in Humans

Fagan, A. M., M. A. Mintun, R. H. Mach, et al. 2006. Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans. Ann. Neurol. 59: 512-519.

Klunk, W. E., H. Engler, A. Nordberg, et al. 2004. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann. Neurol. 55: 306-319.

Price, J. L. & J. C. Morris. 2001. Tangles and plaques in nondemented aging and "preclinical" Alzheimer's disease. Ann. Neurol. 45: 358-368.

Dissociating Alzheimer's Disease from Aging: A Cross-Species Investigation

Small, S. A. 2001. Age-related memory decline: current concepts and future directions. Arch. Neurol. 58: 360-364.

Small, S. A., K. Kent, A. Pierce, et al. 2005. Model-guided microarray implicates the retromer complex in Alzheimer's disease. Ann. Neurol. 58: 909-919.

Small, S. A., W. Y. Tsai, R. DeLaPaz, et al. 2002. Imaging hippocampal function across the human life span: is memory decline normal or not? Ann. Neurol. 51: 290-295.

Functional MRI Studies of Associative Memory in Normal Aging and mild Alzheimer's disease

Dickerson, B. C., D. H. Salat, J. F. Bates, et al. 2004. Medial temporal lobe function and structure in mild cognitive impairment. Ann. Neurol. 56: 27-35.

Dickerson, B. C., D. H. Salat, D. N. Greve, et al. 2005. Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD. Neurology 65: 404-411.

Rand-Giovannetti, E., E. F. Chua, A. E. Driscoll, et al. 2006. Hippocampal and neocortical activation during repetitive encoding in older persons. Neurobiol. Aging 27: 173-182.

Sperling, R. A., J. F. Bates, E. F. Chua, et al. 2003. fMRI studies of associative encoding in young and elderly controls and mild Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry 74: 44-50. FULL TEXT

Sperling, R., E. Chua, A. Cocchiarella, et al. Putting names to faces: successful encoding of associative memories activates the anterior hippocampal formation. Neuromage 20: 1400-1410.

Associative Learning and the Monkey Medial Temporal Lobe

Suzuki, W. A. & D. G. Amaral.1994. Perirhinal and parahippocampal cortices of the macaque monkey: cortical afferents J. Comp. Neurol. 350: 497-533.

Anatomical and Functional Phenotyping of Mice Models of Alzheimer's Disease by MR Microscopy

Jack, C. R. Jr., T. M. Wengenack, D. A. Reyes, et al. 2005. In vivo magnetic resonance microimaging of individual amyloid plaques in Alzheimer's transgenic mice. J. Neurosci. 25: 10041-10048. FULL TEXT

Lee, S. P., M. F. Falangola, R. A. Nixon, et al. 2004. Visualization of beta-amyloid plaques in a transgenic mouse model of Alzheimer's disease using MR microscopy without contrast reagents. Magn. Reson. Med. 52: 538-544.

Ma, Y., P. R. Hof, S. C. Grant, et al. 2005. A three-dimensional digital atlas database of the adult C57BL/6J mouse brain by magnetic resonance microscopy. Neuroscience 135: 1203-1215.

McDaniel, B., H. Sheng, D. S. Warner, et al. 2001. Tracking brain volume changes in C57BL/6J and ApoE-deficient mice in a model of neurodegeneration: a 5-week longitudinal micro-MRI study. Neuroimage 14: 1244-1255.

Mueggler, T., D. Baumann, M. Rausche, et al. 2003. Age-dependent impairment of somatosensory response in the amyloid precursor protein 23 transgenic mouse model of Alzheimer's disease. J. Neurosci. 23: 8231-8236. FULL TEXT

Szema, A. M., S. A. Hamidi, S. Lyubsky, et al. 2006. Mice lacking the VIP gene show airway hyperresponsiveness and airway inflammation, partially reversible by VIP. Am. J. Physiol. Lung Cell. Mol. Physiol.

Monitoring Progression and Early Detection of Alzheimer's Disease With MRI: Alzheimer's Disease Neuroimaging Initiative

Lerch, J. P., J. C. Pruessner, A. Zijdenbos, et al. 2004. Focal decline of cortical thickness in Alzheimer's disease identified by computational neuroanatomy. Cereb. Cortex 15: 995-1001. FULL TEXT

Population-based Mapping of Brain Changes in Aging & Dementia

Carmichael, O. T., L. H. Kuller, O. L. Lopez, et al. 2006. Ventricular volume and dementia progression in the Cardiovascular Health Study. Neurobiol. Aging.

Lu, Z., J. Hu, C. K. Chen, et al. 2006. Effectiveness and safety of olanzapine in the treatment of schizophrenia among Asian patients switching from conventional antipsychotics. Prog. Neuropsychopharmacol. Biol. Psychiatry. [Epub ahead of print]

Sowell, E. R., B. S. Peterson, P. M. Thompson, et al. 2003. Mapping cortical change across the human life span. Nat. Neurosci. 6: 309-315.

Thompson, P. M., R. A. Dutton, K. M. Hayashi, et al. 2005. Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4 T lymphocyte decline. Proc. Natl. Acad. Sci. USA 102: 15647-15652. FULL TEXT

Thompson, P. M., K. M. Hayashi, S. L. Simon, et al. 2004. Structural abnormalities in the brains of human subjects who use methamphetamine. J. Neurosci. 24: 6028-6036. FULL TEXT

Thompson, P. M., C. Vidal, J. N. Giedd, et al. 2001. Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia. Proc. Natl. Acad. Sci. USA 98: 11650-11655. FULL TEXT (PDF, 1.2 MB)

Organizers

Mony J. de Leon, EdD

Department of Psychiatry
New York University
email | web site | publications

Mony de Leon is professor of psychiatry at the New York University School of Medicine. He has studied and developed imaging approaches to the early diagnosis of Alzheimer's disease for over 25 years. Among his qualifications, he has published over 175 papers and founded the Center for Brain Health, an interdisciplinary clinical research center at the New York University School of Medicine. De Leon is a reviewer and/or editorial board member for over 15 journals and has served on several recent NIH advisory panels in the area of early diagnosis of Alzheimer's disease and in the use of biomarkers for its detection.

De Leon's work is centered on the argument that the early and preclinical diagnosis of Alzheimer's is a realistic possibility. Investigators from his New York University research center wrote the first CT paper demonstrating that cortical atrophy could be measured in vivo in the disease. More recently, this group wrote the first prediction paper demonstrating that CT/MRI determined hippocampal atrophy was predictive of future Alzheimer's in subjects with mild memory impairments. De Leon and colleagues were also the first to show, using two independent imaging modalities, that imaging markers found in normal elderly can predict future MCI and Alzheimer's disease. Most recently, the New York University group has developed an automated image analysis technique called HipMask for sampling the PET scan.

Howard Federoff, MD, PhD

University of Rochester
Center for Aging and Developmental Biology
email | web site | publications

Howard Federoff is professor of neurology, medicine, microbiology, and immunology at the University of Rochester. He studies molecular mechanisms that underlie plasticity in the nervous system and looks for ways exploit these mechanisms to predictably modify the intact and damaged nervous system.

Federoff obtained his PhD and MD degrees from Albert Einstein College of Medicine. He joined the University of Rochester School of Medicine faculty as professor of neurology and became the founding chief of the division of molecular medicine and gene therapy. He went on to become director of the University of Rochester Interdepartmental Neuroscience Program, the founding director of the Center for Aging and Developmental Biology, and the senior associate dean for basic research. Federoff is a member of several editorial boards, including Brain and Mind, Experimental Neurology, and Gene Therapy. He has also acted as consultant for corporations such as Promega, Integrated Nano-Technologies, Abbott Pharmaceuticals, Avigen Inc., and Amgen Inc.

Joy Hirsch, PhD

Columbia University
Department of Psychology
email | web site | publications

Joy Hirsch is professor of psychology and functional neuroradiology at Columbia University. She was recruited to Columbia University Medical Center to build and direct the new fMRI Research Center, which is focused on the investigation of systems within the brain that govern cognition, perception, sensory and motor functions as well as disease and treatment-related neurocircuitry. Her current research interests are focused on understanding the neurocircuitry that governs early and late visual processes, second-language acquisition, cognition, emotion, neuro-rehabilitation, and treatment-related mechanisms.

Prior to joining the faculty of Columbia University, Hirsch founded the fMRI laboratory at Memorial Sloan-Kettering Cancer Center and pioneered the introduction of brain mapping procedures for clinical applications as well as neuroimaging investigations of human vision and language. She was previously a professor at Yale University in the neuroscience program and the department of ophthalmology and visual sciences. She received her PhD in psychology from Columbia University.

George M. Martin, MD

University of Washington, Seattle
Department of Pathology
email | web site | publications

George Martin is professor of pathology at the University of Washington School of Medicine. His current research interests are all related to the application of genetic concepts and methodologies to the elucidation of the pathobiology of aging in man, other mammals, and birds. He focuses on three main areas of research: the genetic basis for susceptibility and resistance to dementias of the Alzheimer type, the nature of gene action in the pathogenesis of Werner's syndrome, and DNA damage associated with aging.

Martin obtained his medical degree from the University of Washington. He has received several awards, including the National Institutes of Health Merit Award, the American Aging Association Research Medal, the Gerontological Society of America Robert W. Kleemeier Award, and the Paul Glenn Foundation Award from the Gerontological Society of America. Martin serves on the editorial board of several journals with a focus on pathology and aging and has multiple national responsibilities, such as serving on the Board of Scientific Counselors of the National Institute on Aging. He also served as vice president and president-elect of the Federation for Aging Research and acted as chairman of the American Federation for Aging Research Scientific Review Committee.

John Morrison, PhD

Mount Sinai School of Medicine
Department of Neuroscience
email | web site | publications

John Morrison is professor and chair of neuroscience and the Willard T. C. Johnson Professor of Geriatrics and Adult Development in Neurobiology at Mount Sinai School of Medicine. Morrison's research incorporates basic neurobiological research on neuronal specialization and the biochemical coding of brain circuits with human neuropathology in order to illuminate the cellular events that lead to Alzheimer's disease. He also studies the neurobiological events that accompany normal aging, as well as the differences between these events and those that accompany Alzheimer's disease. Within this context, Morrison is interested in the effects of estrogen on the cerebral cortex, the interface between endocrine and neural aging, and the effects of stress on cortical neurons.

Morrison earned his doctorate from Johns Hopkins University and completed postdoctoral study at the Salk Institute. In 1989, he joined the faculty at Mount Sinai, where he is director of the Kastor Neurobiology of Aging Laboratories. Morrison has published more than 250 scholarly works on the molecular, cellular, and neuroanatomic organization of the cerebral cortex, the cellular pathology of neurodegenerative disorders, and the neurobiology of aging. He is the recipient of numerous research awards and has served on advisory boards and review committees of multiple scientific organizations, including the National Institute of Aging, National Institute of Mental Health, Society for Neuroscience, American Federation for Aging Research, and Amyotrophic Lateral Sclerosis Association. He is also a cofounder of Neurome Inc., a biotech company dedicated to developing treatments for neurodegenerative diseases.

Al Snider, PhD

James N. Jarvie Commonweal Service
email | web site

Al Snider was appointed the executive director and CEO of the Jarvie Commonweal Service in 1997. His long-standing interest in the use of research, training, and education to attain strategic goals has enhanced Jarvie's mission.

Snider holds a PhD in sociological and anthropological studies in education from Stanford University. Prior to coming to Jarvie, he served for 13 years as deputy director of and senior research scientist at the New York State Institute for Basic Research, a neuroscience research center located on Staten Island. During that time, he received national and international acclaim for building the International Alzheimer's Disease and Related Disorders conference into the largest and most important research meeting in the world on Alzheimer's disease. The last such conference held under his leadership was in Amsterdam and attracted 3000 scientists and physicians from over 50 countries and featured over 1300 presentations. Earlier, he served as assistant commissioner for family and children's services in the New York State Department of Social Services. Snider is a member of the board of directors of the American Federation for Aging Research and a trustee of The Interchurch Center in Manhattan.

Keynote Speaker

Eric R. Kandel, MD
Columbia University College of Physicians and Surgeons
Howard Hughes Medical Institute
email | web site | publications

Eric R. Kandel is University Professor of Physiology and Psychiatry at the Center for Neurobiology and Behavior at the Columbia University College of Physicians and Surgeons. In 2000 he shared the Nobel Prize in Physiology or Medicine with Arvid Carlsson of the University of Göteborg, Sweden, and Paul Greengard of the Rockefeller University, New York, for their contributions to the field of neuroscience. A Howard Hughes Medical Institute senior investigator, he is a member of the National Academy of Sciences and the American Philosophical Society and a winner of the National Medal of Science. Among his other honors he counts the Wolf prize, the Lasker Award, the Gairdner Award, and the Harvey Prize.

Kandel's seminal work with the sea slug Aplysia clearly delineated a simple behavior that could be modified by several forms of learning and could give rise to both short- and long-term memory. He then analyzed the molecular mechanisms that lead to short- and long-term memory. The work has been essential not only for understanding the basic processes of learning and memory, but for highlighting many of the cellular processes that are targets of cognitive enhancement drugs.

In response to calls for an integrated approach to understanding the biological basis of behavior, Columbia established the Center for Neurobiology and Behavior and recruited Kandel as its director in 1975. The Center—comprising faculty with appointments in the departments of anatomy and cell biology, biochemistry and molecular biophysics, genetics and development, neurology, pathology, pharmacology, physiology and cellular biophysics, and psychiatry—applies research in these disciplines to understanding the cellular and molecular basis of behavior, perception, and learning. Throughout his career, Kandel has maintained an active interest in clinical psychiatry, as well as in fostering the interchange of ideas among diverse disciplines that examine the relationship between mind and brain. He has recently published a scientific autobiography of his life and career in science, entitled In Search of Memory: The Emergence of a New Science of Mind.

Speakers

Helene Benveniste, MD, PhD

Brookhaven National Laboratory
Medical Department
email | web site | publications

Wiesje M. van der Flier, PhD

Vrije Universiteit Medical Center, Amsterdam
email | publications

Wen-Biao Gan, PhD

New York University School of Medicine
Department of Physiology and Neuroscience
email | web site | publications

Adam Gazzaley, MD, PhD

University of California, San Francisco
Department of Neuroscience
email | web site | publications

Stephanie Lederman, EdM

American Federation for Aging Research
publications

Ken Marek, MD

Institute for Neurodegenerative Disorders
Yale University School of Medicine
email | publications

Thomas D. McRae, MD

Pfizer Global Pharmaceuticals
email | publications

Mark A. Mintun, MD

Washington University School of Medicine
Department of Radiology
email | web site | publications

Susan Molchan, MD

National Institutes of Health
National Institute on Aging
email | publications

Michael Montalto, PhD

GE Global Research Center, Biosciences
email | web site | publications

Bradford Navia, MD, PhD

Johnson & Johnson
email | publications

Maiken Nedergaard, MD, PhD

University of Rochester Medical Center
Department of Neurosurgery
email | publications

Leslie S. Prichep, PhD

New York University School of Medicine
Department of Psychiatry
Nathan S. Kline Institute
email | web site | publications/p>

Naftali Raz, PhD

Wayne State University
Institute of Gerontology
email | web site | publications

Eric M. Reiman, MD

Banner Alzheimer's Institute
University of Arizona
Translational Genomics Research Institute
Arizona Alzheimer's Disease Consortium
email | web site | publications

Marcin Sadowski, MD, PhD

New York University School of Medicine
Department of Neurology
email | web site | publications

Scott A. Small, MD

Columbia University Medical Center
Department of Neurology
email | web site | publications

Reisa A. Sperling, MD, MMSc

Brigham and Women's Hospital
Massachusetts General Hospital
Harvard Medical School
email | web site | publications

Wendy A. Suzuki, PhD

New York University
Center for Neural Science
email | web site | publications

Paul Thompson, PhD

University of California, Los Angeles School of Medicine
Department of Neurology
email | web site | publications

Kamil Ugurbil, PhD

University of Minnesota Medical School
Departments of Radiology, Neurosciences, and Medicine
email | web site | publications

Michael Weiner, MD

University of California, San Francisco
Veteran Affairs Medical Unit
email | web site | publications


Alan Dove

Alan Dove earned his PhD in microbiology from Columbia University and is now a science writer and reporter for Nature Medicine, Nature Biotechnology, and Journal of Cell Biology. He also teaches at the NYU School of Journalism.

Sponsorship

This conference and eBriefing were made possible with support from:

           

and

International Brain Research Foundation

The Alzheimer's Association

GE Global Research

Anonymous

Elan

Ohio Valley Imaging Solutions

Institute for the Study of Aging