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Scott A. Small, MD

  • Boris and Rose Katz Professor of Neurology (in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, the Gertrude H. Sergievsky Center and in Radiology)
  • Director, Alzheimer's Disease Research Center
Scott A. Small, MD

Scott A. Small M.D. is the Director of the Alzheimer’s Disease Research Center at Columbia University, where he is the Boris and Rose Katz Professor of Neurology. He is appointed in the Departments of Neurology, Radiology, and Psychiatry.

With an expertise in Alzheimer’s disease and cognitive aging, Dr. Small’s research focuses on the hippocampus, a circuit in the brain targeted by these and other disorders, notably schizophrenia. He has pioneered the development and application of high-resolution functional MRI techniques that can pinpoint parts of the hippocampus most affected by aging and disease. His lab then uses this information to try to identify causes of these disorders. Over the years, his lab has used this ‘top-down’ approach to isolate pathogenic mechanisms related to Alzheimer’s disease, cognitive aging, and schizophrenia. More recently, his lab has used this insight for drug discovery and to develop novel therapeutic interventions, some of which are currently being tested in patients.

Dr. Small has co-authored over 120 articles and his neuroimaging and molecular work has led to 7 patents. Dr. Small is the recipient of numerous awards, including the Beeson Scholar Award in Aging Research from the American Federation on Aging, the McKnight Neuroscience of Brain Disorders Award, the Derek Denny-Brown Young Neurological Scholar Award from the American Neurological Association, and the Lamport Award for Excellence in Clinical Science Research from Columbia University.

The hippocampal formation functions as a three-dimensional network. We have been developing MRI approaches that allow us to investigate the hippocampus as a circuit in humans and, most recently, in mice to understand how the hippocampus functions during normal associative memory, and how the hippocampus fails during aging and Alzheimer's disease.

We have focused on the longitudinal axis of the hippocampus in our studies of normal memory where we have human subjects process auditory and visual stimuli, in isolation or paired in time. Results from these studies suggest specific circuit mechanisms for how the hippocampus encodes and combines information during associative memory. We are currently extending this area of investigation into mice, which will allow us to uncover potential cellular and molecular mechanisms that underlie these circuit mechanisms. We have focused on the transverse axis of the hippocampal formation in our efforts to understand how the hippocampus fails in aging and Alzheimer's disease. Toward this goal, we have developed novel imaging approaches that measure hippocampal function with microscopic resolution.

These approaches allow us to assess the multiple hippocampal subregions that make up the transverse circuit—individually to pinpoint the site of dysfunction, and simultaneously to correct for circuit-wide effects. We have used this approach to generate patterns of hippocampal dysfunction in humans with Alzheimer's disease and normal aging, as well as in mouse models with Alzheimer's disease and normal aging. Taken together, the results suggest that MRI maps of hippocampal dysfunction can dissociate causes of memory decline. We are currently testing whether these MRI approaches can be used as a diagnostic tool for early Alzheimer's disease, and whether these MRI approaches can be exploited for drug development.

Departmental Appointments

  • Department of Neurology
    Division of Aging and Dementia
  • Department of Psychiatry
    Division of Cognitive Neuroscience

Education & Training

  • Columbia University College of Physicians and Surgeons
  • Residency: NewYork-Presbyterian Hospital/Columbia University Medical Center
  • Fellowship: NewYork-Presbyterian Hospital/Columbia University Medical Center

Centers/Institutes/Programs

  • Gertrude H. Sergievsky Center
  • Taub Institute for Research on Alzheimer's Disease and the Aging Brain

Lab Locations

Honors & Awards

  • Irving Center Scholar Award
  • AFAR Paul Beeson Physician Faculty Scholar in Aging Research Award: Functional analysis of the hippocampal formation in age-related memory decline
  • NIH Mentored Patient-Oriented Research Career Development Award: Longitudinal Analysis of Age Related Memory Decline
  • NIH Alzheimer's Disease Research Center Award (senior investigator): fMRI analysis of hippocampal regions in aging and Alzheimer's disease

Research Interests

  • Brain Imaging
  • Neurobiology of Disease
  • Neurobiology of Learning and Memory
  • Neural Degeneration and Repair

NIH Grants

  • GLUTAMATE REDUCING INTERVENTIONS IN SCHIZOPHRENIA (Federal Gov)

    Jul 5 2017 - Jun 30 2019

    TARGETING RETROMER DYSFUNCTION: A CONVERGENT MECHANISM IN FAMILIAL AND SPORADIC PD (Private)

    Sep 1 2014 - Aug 31 2017

    HUMAN INDUCED NEURONAL STEM CELL MODELS OF FAMILIAL ALZHEIMER S DISEASE (Federal Gov)

    Jul 1 2012 - Jun 30 2017

    LONGITUDINAL IMAGING OF PATIENTS AT CLINICAL RISK FOR PSYCHOSIS. (Federal Gov)

    Sep 22 2011 - May 31 2017

    EXERCISE, AGE-RELATED MEMORY DECLINE, AND HIPPOCAMPAL FUNCTION (Federal Gov)

    Sep 15 2010 - May 31 2017

    HIPPOCOMPAL AND COGNITIVE FUNCTION, EXERCISE, AND OVARIAN CANCER: A PILOT STUDY (Federal Gov)

    Aug 1 2014 - Jul 31 2016

    FMRI AND MOUSE MODELS OF ALZHEIMER S DISEASE (Federal Gov)

    Jul 15 2010 - Jun 30 2016

    NEURAL SIGNATURE OF FEAR OVERGENERALIZATION IN TRAUMA EXPOSED ADULTS (Federal Gov)

    Jul 1 2015 - May 31 2016

    NEUROGENESIS: BRIDGING THE GAP BETWEEN MODEL ORGANISMS AND HUMAN COGNITION (Private)

    Sep 1 2014 - Aug 31 2015

    NATIONAL ALZHEIMER S COORDINATING CENTER (Federal Gov)

    Jul 1 2014 - Jun 30 2015

    VALIDATING A RETROMER STABILIZING COMPOUND FOR ALZHEIMERS DISEASE THERAPEUTICS (Private)

    Jan 14 2013 - Jan 13 2015

    HISTONE ACETYLATION AND COGNITIVE AGING (Federal Gov)

    Sep 1 2009 - Aug 31 2014

    NATIONAL ALZHEIMER S COORDINATING CENTER (NACC) - YR 15 (Federal Gov)

    Jul 1 1999 - Jun 30 2014

    NEUROGENESIS : BRINGING THE GAP BETWEEN MODEL ORGANISM AND HUMAN COGNITION PROJECT (Private)

    Jun 1 2013 - May 31 2014

    UNDERSTANDING THE POTENTIAL ROLE OF CF WITH REGARD TO BRAIN FUNCTION AND COGNITION (Private)

    Apr 16 2009 - May 15 2014

    ADULT NEUROGENESIS: BRIDGING THE GAP BETWEEIN MACRO AND MICRO-NEUROSCIENCES (Private)

    Sep 14 2007 - Mar 14 2013

    CROSS SPECIES IMAGING OF SCHIZOPHRENIA (Federal Gov)

    Jul 15 2011 - Jun 30 2012

    CROSS-SPECIES IMAGING OF SCHIZOPHRENIA IN HUMANS AND MOUSE M ODELS OF DISEASE (Private)

    Jul 1 2008 - Jul 1 2011

    PROTEIN SORTING DEFECTS AND THE CELL BIOLOGY OF ALZHEIMER"S DISEASE (Private)

    Apr 1 2008 - Jun 1 2011

    MAGNETIC RESONANCE IMAGING AND MOUSE MODELS OF ALZHEIMER"S ISEASE AND AGING (Federal Gov)

    Feb 1 2005 - Jan 31 2010

    AMELIORATING AGE-RELATED MEMORY DECLINE (Private)

    Aug 1 2007 - Jul 31 2009

    AMELIORATING RETROMER DYSFUNCTION IN ALZHEIMER"S DISEASE (Private)

    Mar 1 2008 - Feb 28 2009

    IMAGING-GUIDED MICROARRAY APPLIED TO HUNTINGTON''S DISEASE (Private)

    Jan 1 2007 - Dec 31 2008

    ISOLATING ALZHEIMER"S DISEASE (Private)

    Jul 1 2006 - Jun 30 2008

    THE EFFECT OF PHYSICAL ACTIVITY ON NEUROGENESIS AND BEHAVIORAL PERFORMANCE FOLLOWING SLEEP DEPRIVATION (Federal Gov)

    Mar 1 2004 - Dec 31 2007

Publications

  • Small, S.A. (2002). The longitudinal axis of the hippocampal formation: Its anatomy, circuitry and role in cognitive function. Rev. Neurosci., 13: 183-194
  • Small, S.A., Tsai, W.Y., DeLaPaz, R., Mayeux, R., Stern, Y. (2002). Imaging hippocampal function across the human life span: Is memory decline normal or not? Ann. Neurol., 51: 290-295.
  • Small, S.A., Nava, A.S., Tsai, W.Y., DeLaPaz, R., Mayeux, R., Stern, Y. (2001). Circuit mechanisms underlying memory encoding and retrieval in the long axis of the hippocampal formation. Nature Neuro., 442-449.
  • Small, S.A., Wu, E.X., Bartsch, D., Perera, G.M., Lacefield, C.O., DeLaPaz, R., Mayeux, R., Stern, Y., and Kandel, E.R. (2000). Imaging physiologic dysfunction of individual hippocampal subregions in humans and genetically modified mice. Neuron, 28: 653-664.
  • Small, S.A., Perera, G.M., DeLaPaz, R., Mayeux, R., and Stern, Y. (1999). Differential regional dysfunction of the hippocampal formation among elderly with memory decline and Alzheimer’s disease. Ann. Neurol., 45: 466-472.

For a complete list of publications, please visit PubMed.gov