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Cognitive Aging Summit III

Convened by the National Institute on Aging and made possible by the McKnight Brain Research Foundation through a generous grant to the Foundation for the National Institutes of Health.

View videos from the Cognitive Aging Summit III.

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Executive Summary

The third Cognitive Aging Summit, coordinated by the National Institute on Aging of the National Institutes of Health (NIH), was held on April 6-7, 2017 in Bethesda, MD. About 300 researchers and stakeholders attended. The meeting was supported by the McKnight Brain Research Foundation through a grant to the Foundation for the NIH. This Summit was devoted to discussion of age-related brain and cognitive changes, with a particular focus on issues related to cognitive resilience and reserve. Over the course of the meeting, investigators from around the world delivered presentations and engaged in discussion about some of the most important scientific questions relating to the biological, physiological, social, and behavioral aspects of reserve and resilience in aging individuals. Attendees also discussed strategies to preserve and bolster cognitive function during aging.

Session One, How Do We Operationalize Brain Reserve, Cognitive Reserve, Cognitive Resilience, and Compensation?, was devoted to issues related to the definition and measurement of brain reserve, cognitive reserve, cognitive resilience, and compensation. This session sought to define and characterize the anatomic and physiologic factors that are associated with these capacities, to examine ways that aging brains might recruit other circuits to compensate for declining function in traditional processing pathways, and to develop models of how cognitive reserve might influence neural function and enhance cognitive outcomes. Presenters considered the evidence supporting the existence of cognitive reserve as well as the promise offered by animal studies to understand the underlying mechanisms. They also discussed challenges in measuring cognitive reserve and resilience. A key message of this session was that consensus on definitions of terms and use of uniform measure was needed in order to advance the study of cognitive aging.

Session Two, What Are the Threats to Successful Brain and Cognitive Aging?, explored the ways that the structure and function of the brain changes over the lifespan. Aging brains often accumulate a variety of pathologic lesions that result in diminished cognitive ability in some, but not all, individuals. Speakers discussed factors that seem to be protective against cognitive decline, such as specific genotypes, physical activity, certain personality traits. This session also examined both fixed and modifiable factors that can threaten cognitive function in aging adults as well as approaches to modify these risks.

Session Three, What Are the Earlier Life Contributions to Reserve and Resilience?, delved into the ways that the brain's anatomy, physiology, and function arise from a combination of both developmental processes and environmental influences. Although many of the factors that contribute to the aging process are defined early in life—indeed, some before birth—choices made by individuals over the course of their lives may have considerable influence on late-life cognitive function and may provide avenues to modify the risk of cognitive decline. To better understand the early life influences on later life cognition, the presenters underscored the importance of conducting longitudinal studies with data collected at the level of the individual. Such studies are critical for understanding the sources of variation both throughout populations and within individuals over time, which may lead, in turn, to identification of effective strategies for therapeutic intervention.

Complementing the previous session, Session Four, What Are the Later Life Contributions to Reserve, Resilience, and Compensation?, explored the later life experiences and lifestyle choices that contribute to the brain's ability to protect against, respond to,  and compensate for pathological insults. Speakers discussed physiological processes and behavioral and social activities that may provide the brain with greater flexibility in confronting the challenges associated with accumulating brain pathology during aging. Further study of innate factors that affect cognitive aging, such as genetics, may lead to the development of targeted therapeutics. Researchers have also uncovered a strong association between cognitive resilience and physical and mental activity. If these associations are causal, lifestyle adjustments may also be effective interventions.

Session Five, How Do We Validate Approaches that Aim to Harness Reserve to Improve the Aging Brain?, addressed the development of accurate and reproducible ways to quantify cognitive function and reserve in aging individuals, because these measures are important both for researchers and clinicians. Approaches that integrate insights gained from animal studies, molecular biology, neuropathology, and behavioral analyses of decline and resilience are of particular interest. The development of a validated set of variables and best practices for measuring them would be useful not only in describing an individual's mental state but also in identifying promising paths for treatment.

The final session, Innovative Approaches in Cognitive Aging, explored novel approaches and models to address cognitive aging and to delay or prevent cognitive decline in older individuals. A better understanding of the molecular processes that underlie the pathologic basis of cognitive decline may lead to novel approaches to treatment. Novel therapeutic strategies may include non-invasive brain stimulation, treatment with endogenous factors that promote youthfulness, and pharmacological modification of age-related epigenetic signatures. Presenters underscored the need for studies of aging to take into account the complexity and uniqueness of each person's experience across his or her lifespan and that treatments may need to be tailored to the individual.

The themes that emerged from the multiple discussions across several sessions included the relevance of animal models and the importance of integrating insights from these studies into the overall conceptual framework of human aging research. Speakers emphasized the role of modifiable lifestyle choices—such as exercise and cognitive engagement across the lifespan—as important potential contributors to reserve and resilience later in life. Although population-based data can show overall trends in cognitive function in older adults, these analyses do not focus on the extraordinary individuals who maintain cognitive function in the face of advanced age or extreme brain pathology. Although these individuals may be atypical, understanding how they achieve resilience and reserve may nevertheless suggest therapeutic approaches for the rest of us. Ultimately, the goal of this research is to find ways to promote a healthy aging process in a diverse set of individuals.

Agenda

April 6

Introductions

Marie A. Bernard, MD Deputy Director, National Institute on Aging

Maria C. Freire, PhD President and Executive Director, Foundation for NIH

The McKnight Brain Research Foundation: Preserving Memory Enhancing Life

J. Lee Dockery, MD Chair, Board of Trustees, McKnight Brain Research Foundation

Session I: How Do We Operationalize Brain Reserve, Cognitive Reserve, Cognitive Resilience, and Compensation?

Session Chair: Naftali Raz, PhD Wayne State University

  • Yaakov Stern, PhD Columbia University
    Reserve: An Evolving Chapter
  • Carol A. Barnes, PhD University of Arizona
    Animal models of brain adaptation and compensation in aging
  • Cheryl L. Grady, PhD University of Toronto
    Age differences in the dynamic flexibility of brain activity and functional connectivity
  • Richard N. Jones, ScD Brown University
    Measurement of reserve

General Discussion

Session II: What Are the Threats to Successful Brain and Cognitive Aging?

Session Chair: Peter R. Rapp, PhD National Institute on Aging

  • Michela Gallagher, PhD Johns Hopkins University
    Contributions of neurocognitive aging to risk or resilience (in rats)
  • Ozioma C. Okonkwo, PhD University of Wisconsin, Madison
    Aerobic fitness and genetics contribute to resilience in AD
  • Susan M. Resnick, PhD National Institute on Aging
    Cognitive resilience in the face of pathology
  • William J. Jagust, MD University of California, Berkeley
    Age-related pathology, cognition, and resilience
  • Special highlight presented by Tammie Benzinger, MD, PhD Washington University

General Discussion

Session III: What Are the Earlier Life Contributions to Reserve and Resilience?

Session Chair: Carl W. Cotman, PhD University of California, Irvine

  • Kristine B. Walhovd, PhD University of Oslo
    Neurodevelopmental origins of lifespan changes in brain and cognition
  • Gareth R. Howell, PhD The Jackson Laboratories
    Protecting the neurovascular unit to promote healthy aging
  • Stuart J. Ritchie, PhD University of Edinburgh
    Predictors and mechanisms of cognitive ageing: Evidence from the Lothian Birth Cohort of 1936
  • Roger T. Staff, PhD NHS-Grampain/University of Aberdeen
    Early life conditions on late life accumulations of pathological burden and cognitive decline: Findings from the Aberdeen Birth Cohorts

General Discussion

Session IV: What Are the Later Life Contributions to Reserve, Resilience, and Compensation?

Session Chair: Denise C. Park, PhD University of Texas at Dallas

  • Sara N. Burke, PhD University of Florida
    An animal model of cognitive aging: Do compensatory neural processes confer resilience?
  • Elizabeth C. Mormino, PhD Stanford University
    Cognition and amyloid in healthy adults: Who is resilient and who declines?
  • Emily J. Rogalski, PhD Northwestern University
    Neurobiologic features of SuperAgers: Is it resilience or just luck?
  • Claudia H. Kawas, MD University of California, Irvine
    Cognitive and Brain Resilience: Is it present in the oldest old?
  • Special highlight presented by Robert Willis, PhD University of Michigan

General Discussion, Wrap-up

April 7

Session V: How Do We Validate Approaches That Aim to Harness Reserve to Improve the Aging Brain?

Session Chair: John F. Disterhoft, PhD Northwestern University

  • Lon R. White, MD, MPH Pacific Health Research and Education Institute
    Brain reserve, cognitive reserve, and brain co-morbidity burden together to determine resilience in neuropathologic Alzheimer's disease
  • Patricia A. Boyle, PhD Rush Alzheimer’s Disease Center
    Cognitive aging: a balance between neuropathology and resilience
  • Thomas C. Foster, PhD University of Florida
    On Biomarkers, Animal models, and Senescence
  • Adam H. Gazzaley MD, PhD University of California, San Francisco
    Technology meets neuroscience- A vision of the future of brain fitness

General Discussion

Session VI: Innovative Approaches in Cognitive Aging

Session Chair: Marilyn Albert, PhD Johns Hopkins University

  • Saul A. Villeda, PhD University of California, San Francisco
    Molecular Mechanisms of Brain Aging and Rejuvenation
  • Steven N. Austad, PhD University of Alabama at Birmingham
    Cognitive aging: new and improved animal models
  • Joel L. Voss, PhD Northwestern University
    Noninvasive stimulation targeting aging memory networks
  • Marcelo A. Wood, PhD University of California, Irvine
    Circadian gene regulation by histone deacetylation contributes to age-related impairments in memory and synaptic plasticity
  • Special highlight presented by Amar Sahay, PhD Harvard University

General Discussion

Closing Remarks

Richard J. Hodes, MD Director, National Institute on Aging

J. Lee Dockery, MD Chair, Board of Trustees, McKnight Brain Research Foundation