Cognitive Aging Summit IV

Dates

March 20, 2024 - March 21, 2024

Location

Bethesda North Marriott Hotel & Conference Center, 5701 Marinelli Road, North Bethesda, MD.

Purpose and Background

On March 20-21, 2024, the Cognitive Aging Summit IV was held in Bethesda, MD, 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. This fourth Summit will be devoted to scientific presentations and discussion of age-related brain and cognitive change, with a particular focus on individual differences and the development of personalized approaches to the remediation of decline and the maintenance of health.

Meeting Recordings

The fourth Cognitive Aging Summit was recorded to allow for viewers to watch the presentations at their convenience.

Steps for viewing individual sessions:

From the list below, click the link to the recording you are seeking to open it in YouTube.
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Recordings:

Agenda

Read the agenda for the first and second day of the summit below.

Wednesday, March 20, 2024

7:15 a.m. Registration (Salons A-C)

Continental Breakfast

8:15 a.m. Welcome/Opening Remarks (Salon D)

Jonathan W. King, PhD, National Institute on Aging
Richard Hodes, MD, Director, National Institute on Aging
Julie Gerberding, MD, MPH, President and Chief Executive Officer, Foundation for the National Institutes of Health
Michael L. Dockery, MD, Chair, Board of Trustees, McKnight Brain Research Foundation
Madhav Thambisetty, MD, PhD, Vice Chair, Board of Trustees, McKnight Brain Research Foundation

8:45 a.m. Session 1 I Blood, Metabolism, and Systemic Environment (Salon D)

Session Chair: Saul Villeda, PhD, University of California San Francisco

Platelet-derived factors rejuvenate the aging brain, Tara L Walker, PhD, University of Queensland
Decoding signals across the blood-brain barrier with age, Andrew Yang, PhD, University of California San Francisco
Dynamic endocrine modulation of the nervous system, Emily Jacobs, PhD, University of California Santa Barbara
Mid-Life Aging Transitions in Brain Metabolic Reprograming: Implications for Interventions to Sustain Brain Health and Resilience, Roberta Diaz Brinton, PhD, University of Arizona

10:05 a.m. General Discussion (Salon D)

10:35 a.m. Break (Salon Foyer)

10:55 a.m. Session 2 | Structural and Social Environment (Salon D)

Session Chair: Jennifer Manly, PhD, Columbia University

“The place where dangers awaits me.” Structural racism and cognitive health for older adults, Paris “AJ” Adkins-Jackson, PhD, MPH, Columbia University
Biopsychosocial pathways linking environmental factors to cognitive health, Laura Zahodne, PhD, University of Michigan
Cognitive Effects of Bilingualism: A Global Perspective, Miguel Arce Rentería, PhD, Columbia University Medical Center
How educational inequities in the U.S. South pre and post Brown shape cognitive health for Black and White older adults,Katrina M Walsemann, PhD, MPH, University of Maryland

12:15 p.m. General Discussion (Salon D)

12:45 p.m. Lunch (Salons A-C)

1:45 p.m. Session 3 | Genetic Environment (Salon D)

Session Chair: Catherine Kaczorowski, PhD, University of Michigan

X Chromosome-Derived Mechanisms in Cognitive Aging, Dena Dubal, MD, PhD, University of California San Francisco
Sex differences in risk and resilience to cognitive decline: intersections with APOE4 and beyond, Rachel Buckley, PhD, Harvard Medical School and Massachusetts General Hospital
A Synaptic Neuron-Astrocyte Program (SNAP), which varies naturally among humans, declines as we age, Steve McCarroll, PhD, Harvard Medical School and Broad Institute
Systems Genetics Identifies Novel Resilience Factor in ‘Normal’ Nonpathological Cognitive Aging, Catherine Kaczorowski, PhD, University of Michigan

3:05 p.m. General Discussion (Salon D)

3:35 p.m. Break (Salon Foyer)

3:50 p.m. Session 4 | Circuit Environment (Salon D)

Session Chair – Carol Barnes, PhD, The Evelyn F McKnight Institute, University of Arizona

Local dysregulation of the clock gene Per1 contributes to age-related memory impairments, Janine Kwapis, PhD, Pennsylvania State University
Understanding how aging impacts entorhinal spatial coding, Lisa Giocomo, PhD, Stanford University School of Medicine
Age-related changes in cognition in nonhuman primates, Elizabeth Buffalo, PhD, University of Washington
Human spatial navigation during midlife: Sex differences in behavior and circuitry, Elizabeth R Chrastil, PhD, University of California Irvine

5:10 p.m. General Discussion (Salon D)

5:40 p.m. Wrap-up, Jonathan W. King, PhD, National Institute on Aging

6:00 – 7:30 p.m. Reception (Salons A-D and Foyer)

Thursday, March 21, 2024

7:30 a.m. Registration (Salons A-C)

Continental Breakfast

8:25 a.m. Opening Remarks (Salon D)

Molly V. Wagster, PhD, Nationial Institute on Aging

8:30 a.m. Session 5 | Co-morbidities/Sleep Environment(Salon D)

Session Chair: Jennifer Bizon, PhD, The Evelyn F. and William L. McKnight Brain Institute, University of Florida

Interpretating blood-based Alzheimer’s disease biomarkers: Impact of comorbidities,Michelle Mielke, PhD, Wake Forest University
Genetic interactions with sex and environment shape sleep and cognitive function across the lifespan,Kristen O'Connell, PhD, The Jackson Laboratory
Importance of a Life Course Approach to Cognitive and Brain Aging,Kristine Yaffe, MD, UC San Francisco
Sleep features impacted by the aging environment, Gina R Poe, PhD, University of California Los Angeles

9:50 a.m. General Discussion(Salon D)

10:20 a.m. Break (Salon Foyer)

10:30 a.m. Session 6 | Study Design and Intervention Environment (Salon D)

Session Chairs: Randy Buckner, PhD, Harvard University and Michael A Yassa, PhD, University of California Irvine

Study Design

Machine Learning for Adaptive Experimental Designs, Anne Draelos, PhD, University of Michigan
Digital twin models of cognitive health in aging, Nathan Price, PhD, Thorne HealthTech, The Institute of Systems Biology

Interventions

Identifying parameters of personalized brain stimulation to improve memory in older adults, Robert M. G. Reinhart, PhD, Boston University
Hearing Intervention, Cognitive Decline, and Brain Health – Results from the ACHIEVE Randomized Trial, Frank Lin, MD, PhD, Johns Hopkins University
What we can learn from null results: Mindfulness-based stress reduction and exercise for cognitive function in healthy older adults (The MEDEX Study), Julie Wetherell, PhD, University of California San Diego
Targeting individual differences in hippocampal hyperactivity through translational studies of neurocognitive aging, Arnold Bakker, PhD, Johns Hopkins University

12:30 p.m. General Discussion (Salon D)

1:00 p.m. Closing Remarks (Salon D)

Molly V. Wagster, PhD, National Institute on Aging and Michael L. Dockery, MD, Chair, Board of Trustees, McKnight Brain Research Foundation

Executive Summary

The Cognitive Aging Summit IV was held on March 20-21, 2024. The summary below highlights findings and conclusions from the summit.

Executive Summary

The fourth Cognitive Aging Summit was held on March 20-21, 2024, in Bethesda, MD. This Summit was devoted to discussion of biological, behavioral, and social factors that affect age-related brain and cognitive changes. An international cohort of investigators presented research into the causes of aging-related neurodegeneration and discussed how this research could inform strategies and future interventions for sustaining brain health and cognitive function during aging and the importance of individualized approaches to risk reduction. The meeting was convened by the National Institute on Aging of the National Institutes of Health (NIH) and made possible by the McKnight Brain Research Foundation through a generous grant to the Foundation for the NIH. Key themes from each of the six sessions are highlighted below.

Session One, Blood, Metabolism, and Systemic Environment, explored plasma proteins and hormones that affect brain morphology and function and cognitive ability. Levels of several inflammatory proteins increase in the brain with age, which may exacerbate cognitive decline. Declining estrogen levels due to aging or menopause can also lead to cognitive decline, while higher estrogen levels during pregnancy can lead to increased brain functional connectivity. Research into the specific mechanisms by which plasma protein and hormone levels affect brain function may help inform individualized therapeutic interventions that sustain or rejuvenate brain health during aging. Speakers emphasized that because brain health and body health are intricately linked, improvements in lifestyle factors also may benefit cognition as individuals age. Understanding individual responses to such lifestyle changes can provide another individualized pathway to improving cognitive and brain health.

Session Two, Structural and Social Environment, addressed the cognitive effects of sociodemographic factors, the built environment, and interpersonal social determinants of health, all of which may contribute to individual differences across the life course. Researchers have leveraged historical and survey data by adding cognitive measures to examine how early life language development and education bolster cognitive abilities throughout life. By contrast, stressors like perceived discrimination, racial violence, and lack of equitable access to education correlate with increased inflammation in the brain as well as increased depressive symptoms and contribute to diminished cognitive ability later in life. However, resilience pathways appear to be protective of memory function in the context of such stressors. The session highlighted the need for further research to disentangle the impacts of frequently intersecting social and experiential factors on individual cognitive health outcomes. Improving our understanding of the influence of these factors on the brain and cognitive aging may illuminate promising avenues for policy and neighborhood-level interventions to ameliorate entrenched health disparities.

Session Three, Genetic Environment, focused on the role of specific chromosomes, genes, and proteins in shaping cognitive aging and disease. During hormonal changes like perimenopause, when lowered levels of circulating estrogens disrupt normal glucose metabolism, female APOE4 carriers display worse metabolic and cognitive outcomes than noncarriers. Cognitive decline also correlates with reduced gene expression throughout neuronal cells and on the X chromosome. Further research on these sex and gene interactions, including systematic comparisons of gene expression across populations, may contribute to the development of targeted and personalized interventions to prevent cognitive decline and improve individual cognitive health. Such findings could aid efforts to determine appropriate levels of hormone therapy for individuals based on gene expression, boost expression of silenced genes that may improve cognitive ability, or address barriers to preventive care.

Session Four, Circuit Environment, examined how gene expression, cellular activities, and brain morphology can affect learning, memory, and navigation. In human and animal experiments, upregulation of the Per1 gene, higher levels of estrogens, and consistency in neuronal firing patterns correspond with better ability to learn and remember spatial environments in young individuals. By contrast, aging results in loss of synaptic density and inconsistency in spatial firing patterns, leading to increased difficulty in spatial learning and memory. Further studies may help identify other genes involved in these changes in cognition, their mechanisms of action, and possible interventions to protect against age-related cognitive decline. These studies may also facilitate a greater understanding of individual differences in genes and behavior that lead to aging-related neural and brain changes.

Session Five, Co-morbidities and Sleep Environment, explored the importance of sleep, cardiovascular disease, and depression in risk for cognitive decline and dementia. Sleep plays a central role in learning and memory and helps clear the brain of misfolded proteins and other debris that could lead to neurodegeneration. Yet as individuals age, the percentage of time spent in REM sleep and slow wave sleep decreases. Sleep apnea, nocturia, and noisy environments (such as areas near airports) can exacerbate such sleep disruptions, while prevention and treatment of risk factors and co-morbidities—such as high blood pressure, depression, smoking and physical inactivity in midlife—may improve sleep quality and reduce the risk of cognitive decline. Because Alzheimer’s disease and related dementias are primarily diagnosed late in life, studies of how co-morbidities and sleep in early life and midlife affect risk for cognitive decline and dementia may rely on surrogate biomarkers of risk. These studies need to account for the fact that some co-morbidities, such as kidney disease and obesity, independently affect biomarkers of Alzheimer’s disease (e.g., phosphorylated tau 181 and amyloid beta 40) and thus require careful interpretation of the interaction among various conditions. Finally, both comorbidities and sleep are often related to lifestyle factors that interact with biological sex and genetic risk factors to determine individuals’ risk for cognitive decline. To probe such interactions in animal models, researchers must utilize genetically heterogeneous strains.

The final session, Study Design and Intervention Environment, delved into novel methods for delaying cognitive decline and reviewed the results from several recent intervention trials. These study results underscore the complexity and heterogeneity of treatment responses within interventions. For example, provision of hearing aids reduced the risk for dementia among older individuals in a community cohort with relatively elevated risk factors but not in a normal risk cohort. Speakers also explored novel approaches to intervention design. For example, use of “digital twins”—the virtual representation of real-world individuals with varying risk and protective factors for cognitive decline—may help researchers design multifactor interventions that target individuals based on genetic and lifestyle risk factors for cognitive decline and determine the appropriate size and duration for testing these interventions. In addition, machine learning and other AI-based methods can enable researchers to dynamically incorporate electrophysiological data in ongoing animal studies, dramatically reducing the amount of time required to understand neuronal responses to stimuli. Presenters discussed the importance of rate of decline, genetic variation, and exposures to social determinants of health in determining individual responses to interventions, as well as whether interventions have the largest impacts when initiated in midlife or earlier.

Several themes emerged from discussions across the sessions. Understanding the impacts and interactions of diverse biological, social, and environmental factors—ranging from genes to proteins to social structures—may help researchers and clinicians develop personalized therapeutic interventions. Additional research is required to understand the mechanisms through which these factors influence age-related brain and cognitive health. Speakers also emphasized the importance of early and midlife risk factors such as education, physical activity, cardiovascular disease, and sleep for predicting cognitive decline in later life. Finally, speakers discussed the need to conduct interventions for extended periods of time, among populations experiencing health disparities, and in midlife or earlier.

Contact Information

Please contact Dave Frankowski for questions you may have about the workshop.

Reasonable Accommodation: If you need reasonable accommodation to participate in this event, please contact the meeting organizer listed under Contact information. Please make your request no later than 1 week before the event.