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 Progress in Cognitive Aging Research
  Presentation of the Cognitive Aging RFA Grant
          Award Recipients’ Research
Research Partnership on Cognitive Aging

  • Cognitive Aging Summit – 2007
  • Neural and Behavioral Profiles of Age-related
    Cognitive Change (RFA AG-09-010)
  • Interventions to Remediate Age-related
    Cognitive Decline (RFA AG-09-009)
             Seventeen awards

• One co-funded by the NIH Office of Dietary
• One co-funded by National Center for
  Complementary and Alternative Medicine
• One funded with American Recovery &
  Reinvestment Act (ARRA) funds
       Gene Expression, Compensation
   Mechanisms, and Successful Cognitive Aging
                                    • Identify possible compensatory
                                      mechanisms in aging, based on a
                                      multidisciplinary approach using
                                      microarray analyses to profile gene
                                      expression patterns associated with
                                      successful cognitive aging in brain
                                      tissues from clinically well-
       Dr. Carl Cotman                characterized humans.
University of California - Irvine   • Test whether these profiles change
                                      in either animal model systems or
                                      humans undergoing increased
                                      physical activity.
    Synaptic Function & Plasticity in CA3
     Circuits in the Aging Hippocampus
                           • Identify mechanisms that underlie
                             age-related changes in
                             hippocampal synaptic plasticity
                             associated with maintenance, or
                             loss, of cognitive function in rats.
                             Focus will be on adaptive changes
                             occurring naturally in response to
  Dr. Alfredo Kirkwood       lost functions.
Johns Hopkins University   • Understand how intervention
                             treatments that improve learning
                             in aged individuals affect synaptic
  Hippocampal Electrophysiology and
Myelinogenesis in Healthy Cognitive Aging
                          • Correlate electrophysiological and
                            genomic markers of cognitive
                            aging in the same animals and
                            relate cognitive function to myelin
                            structure and density in cross-
                            sectional and longitudinal
  Dr. Philip Landfield      analyses
 University of Kentucky
                          • Manipulate dietary iron and/or
                            treat with cuprizone to alter the
                            course of myelinogenesis
Molecular Mechanisms Regulating Age-Related
       Cognitive Decline in C. elegans
                        • Identify the genes required for long-
                          term associative memory (LTAM)
                          that change with age and with
                          decreased function, and rescue
                          function with age through
                          manipulation of candidate genes.
  Dr. Coleen Murphy     • Identify cells involved in LTAM, and
 Princeton University
                          the characterization of their roles in
                          LTAM process.
                        • Compare changes during normal
                          aging to pathological changes in two
                          C. elegans models of dementia.
Histone acetylation and cognitive aging
                      • Examine whether exercise-induced
                        improvements in hippocampal
                        dentate gyrus function is mediated by
                        systemic reductions in blood glucose
                      • Examine whether exercise-induced
                        improvements in dentate gyrus
                        function is mediated by increases in
                        molecules related to histone
  Dr. Scott Small       modification
Columbia University
                      • Test the hypothesis that histone-
                        modifying agents differentially target
                        the dentate gyrus in young mice
      Hippocampal Network Profiles of
              Memory Aging
                             • Use large-scale ensemble
                               recording methods to identify,
                               and characterize memory traces
                               in hippocampal CA1 throughout
                               major stages of memory -
                               processing, acquisition,
                               consolidation, retrieval – in
                               young adult and aging brains.
      Dr. Joe Tsien
Medical College of Georgia   • Identify network characteristics
                               that give rise to superior
                               memory function in the aged
Neural Processes Underlying Cognitive
                     • Characterize neural processes that
                       affect cognition in normal aging
                       distinct from early-stages of
                       pathological change.
                     • Determine whether disruption of
                       large-scale brain networks accounts
                       for cognitive variation in the absence
Dr. Randy Buckner      of amyloid deposition,
Harvard University
                     • Explore whether activity increases
                       are present in normal aging and
                       mitigate cognitive decline.
 Neural and Biochemical Mechanisms of
            Cognitive Aging
                                 • Characterize healthy, cognitively intact
                                   older adults for amyloid deposition,
                                   hippocampal volume, regional glucose
                                   metabolism, and cognitive function
                                 • Examine whether relationship
                                   relationship between amyloid
                                   deposition and memory is mediated by
                                   hippocampal atrophy and mitigated by
                                   higher prefrontal cortical glucose
     Dr. William Jagust            metabolism
University of California - Davis • Characterize brain activation patterns
                                   during memory performance to
                                   further define regional susceptibility to
                                   amyloid and mechanisms of functional
                                   compensation in prefrontal cortex.
High-resolution Structural and Functional Brain
    Imaging of the Medial Temporal Lobe
                                     • Collect behavioral and high-resolution
                                       neuroimaging data to test several key
                                       predictions of a neurocognitive model of
                                       age-related memory impairment.
                                     • predict that aging will result in
                                       behavioral impairments consistent with
                                       a reduction in pattern separation
                                       abilities, and that there will be neural
                                       changes in CA3/DG activity consistent
         Dr. Craig Stark
 University of California - Irvine     with this reduction.
                                     • We also predict that aging will result in
                                       changes in the connectivity within the
                                       hippocampus and between the
                                       hippocampus and surrounding cortices (
Characterizing the Behavior Profile of
      Healthy Cognitive Aging
                     • Characterize profile of healthy
                       cognitive aging defined as age-related
                       cognitive change not accounted for by
                       the presence of common
                       neuropathologies (i.e., AD, cerebral
                       infarcts) or terminal decline.
                     • Capitalize on the unique longitudinal
Dr. Patricia Boyle     cognitive and neuropathologic data
Rush University
                       available from the Religious Orders
                       Study and the Rush Memory and Aging
                       Project in order to elucidate the
                       trajectory of healthy cognitive aging
        Health Behaviors Over the Adult
         Lifecourse and Cognitive Aging
                           • Examine the combined impact of
                             health behaviors and changes in
                             health behavior on cognitive aging.
                           • Examine the bidirectional association
                             between health behaviors and
Drs. Archana Singh-Manoux
     and Mika Kivimaki
                             cognitive aging starting in midlife.
University College, London • Understand how biological changes
                             might explain the associations
                             between health behaviors and
                             cognitive aging and how SES or
                             specific genetic alleles affect this.
  Combining Exercise and Cognitive Training
      To Improve Everyday Function
                        • Establish that a combined cognitive
                          and aerobic exercise training
                          intervention will lead to
                          improvement in cognitive control
 Drs. Ellen Binder &      and objective physical performance.
  Mark McDaniel         • Evaluate whether improvements
Washington University
                          observed transfer to other cognitive
                          tasks and to activities of daily living
                          both immediately post-training and
                          six months after the end of training.
    Dose-Response Study of Exercise in
              Older Adults
                       • Examine the dose-response
                         relationship of aerobic exercise on
                         cognition in adults 75+ in a six month
                         supervised exercise program.
                       • Examine the dose-response
                         relationship of aerobic exercise on
                         aerobic function as the cause of
                         improvements in cognition.
 Dr. Jeffrey Burns     • Examine the effect of aerobic exercise
University of Kansas     on measures of physical function.
   A Brain-based Approach to Enhancing
Executive Control Functions in Healthy Aging

                            • Pilot a novel training intervention that
                              combines therapist-guided strategy
                              training plus targeted cognitive
                              process training to enhance goal-
                              directed behavior of older adults.
 Dr. Mark D’Esposito        • Evaluate the utility of functional MRI
University of California-     biomarkers in predicting behavioral
       Berkeley               and functional outcomes from the
                              proposed intervention.
   Tai Chi and Guided Autobiography for
Remediation of Age-Related Cognitive Decline
                        • Examine how structured programs in
                          Tai Chi, Guided Autobiography, or the
                          combination of both improve
                          executive function and episodic
                          memory over 12 months.
                        • Estimate inter-participant variability
 Dr. Victor Henderson
                          and effect sizes for between group
  Stanford University     differences on a composite measure
                          of executive function and episodic
Omega-3 & Blueberry Supplementation
  in Age-Related Cognitive Decline
                           • Assess whether a six month trial of
                             Omega-3 fatty acids plus blueberry
                             powder might enhance cognition
                             and daily function in older adults
                             exhibiting signs of memory decline.
                           • Collect data on metabolic
                             parameters, inflammation and RBC
                             membrane omega-3 fatty acids
 Dr. Robert Krikorian
                             during the trial to assess
University of Cincinnati     physiological changes during the
  Combined Exercise and Cognitive
Training Intervention in Normal Aging
                       • Assess the effects on cognition
                         and everyday functioning of a
                         three-month combined exercise
                         and cognitive training
                         intervention (vs. control
                       • Assess compliance with a home-
                         based version of the training
   Dr. Yaakov Stern      program over the year following
 Columbia University
                         the initial three-month trial and
                         reassess cognition and daily
                         function after that year.
   Annual Investigators Meeting

• Grantees were required to budget for the
  annual meeting to share reports of progress
• Joint meeting of awardees from both RFAs
• Opportunity for interaction between groups
  with traditionally different goals and foci

       October 6, 2010 in Bethesda, MD

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