Boosting Brain Health After COVID-19: A Convergence Solution

Harris Eyre, MD, PhD

,
Jessica Carson

,
Erin Smith

,
Helen Lavretsky, MD, MS

,
Charles F. Reynolds III, MD

,
Husseini K. Manji, MD

,
Walter D. Dawson, DPhil

Dr Dawson is a health policy researcher at the Global Brain Health Institute.

,
Laura Booi, PhD

Dr Booi is a social gerontologist at the Global Brain Health Institute.

,
Mark Heinemeyer

Mark Heinemeyer is CEO of PRODEO.

,
Jeffrey L. Cummings, MD

Dr Cummings is a research professor and Director of Chambers-Grundy Center for Transformative Neuroscience at the University of Nevada, Las Vegas.

,
Ernestine Fu, PhD

Dr Fu is a venture partner at Alsop Louie Partners. 

,
Eric A. Storch, PhD

,
William Hynes, DPhil

Dr Hynes is head of the OECD New Approaches to Economic Challenges Unit.

,
Eric J. Lenze, MD

,
Retsina Meyer, PhD

Dr Meyer is head of strategic projects and alliances at Delix Therapeutics.

,
Ian Macrae, PhD

Dr Macrae is a professor in the department of Integrative Structural and Computational Biology at Scripps Research Institute.

,
Antonella Santuccione Chadha, MD

Dr Santuccione is Head Stakeholder Liaison Alzheimer disease at Biogen.

,
Ryan Abbott, MD, JD

Dr Abbott is a professor of Law and Health Sciences at the University of Surrey School of Law and adjunct assistant professor of Medicine at the David Geffen School of Medicine at UCLA.

,
Sandra Bond Chapman, PhD

,
Ian Robertson, PhD

Dr Robertson is a T. Boone Pickens Distinguished Scientist at the Center for BrainHealth, a co- director at Global Brain Health Institute, professor emeritus at Trinity College Dublin, and founding director of its Institute of Neuroscience.

,
Carol Graham

Carol Graham is the Leo Pasvolsky Senior Fellow at the Brookings Institution, a College Park Professor at the University of Maryland, and a Senior Scientist at Gallup.

,
Brisa S. Fernandes, MD, MSc, PhD

Dr Fernandes is a postdoctoral researcher, Center for Precision Health School of Biomedical Informatics at the University of Texas Health Science Center at Houston.

,
David G. Angeler, PhD

Dr Angeler is Researcher at the Department of Aquatic Sciences and Assessment; Section for Ecology and Biodiversity at the Sveriges lantbruksuniversitet.

,
Adrienne Grzenda, MD, PhD

Dr Grzenda is Assistant Clinical Professor of Psychiatry and Biobehavioral Sciences at David Geffen School of Medicine at UCLA and UCLA Olive View Medical Center.

,
Agustin Ibañez, PhD

Dr Ibañez is a neuroscientist at the Global Brain Health Institute.

,
Zoltan Sarnyai, MD, PhD

Dr Sarnyai is a neuroscientist and professor at James Cook University, Australia.

,
Sofia Marcha

Sofia Marcha is director of Public Policy and Government Affairs, Europe, Canada, and Partner Markets at Biogen.

,
Michael Berk, MD, PhD

,
Patrick Brannelly

Patrick Brannelly is Director of Partnerships & Business Development at Gates Ventures, Alzheimer’s Disease Data Initiative.

How can we face the current pandemic while addressing the brain health crisis?

COMMENTARY

“Brain health conditions are a key contributor to the global burden of disease and disability. The devastating impact of these conditions is even more apparent as the world faces global challenges such as the COVID-19 pandemic, climate change, societal inequity, and more. To make progress, we need a fundamental shift in our approach. Convergence Brain Health deftly makes the case that a convergence approach is urgently needed to tackle the global brain health crisis and provides a roadmap for change.”

— Victor Dzau MD, President, National Academy of Medicine1

Even before the COVID-19 pandemic, the world was in the midst of an escalating global brain health crisis with severe physical, social, and economic ramifications. According to a recent World Health Organization report, around 450 million individuals were suffering from mental health conditions, marking mental health disorders among the leading causes of ill-health and disability worldwide.2 The Organisation for Economic Co-operation and Development (OECD) estimates that the consequences of mental ill health cost up to 4% of GDP worldwide.3

Due to social and physical distancing, unemployment and underemployment, stress and other factors, there have been significant increases in issues such as depression, anxiety, social isolation, substance abuse, loneliness, and cognitive decline in older adults.4-11 In addition, as observed after the SARS pandemic, it is expected that COVID-19 survivors may endure long term cognitive and psychiatric consequences, including suicide, posttraumatic stress disorders, and depression.12,13 Furthermore, brain health is a prototypical wicked problem14 in that it is extremely complex and textured by innumerable variables from biology, sociology, genetics, psychology, and the natural environment to economics and beyond.1,15 Compounding these issues are challenges at all levels of innovation around brain health, listed in Table 1.

Progress in the 21st century will be molded by our collective response to the global brain health crisis.16 Fortunately, beacons of hope are beginning to shine. Stigma has been reduced in high-income country settings, allowing individuals to overcome the barriers to seeking care.17 The COVID-19 pandemic has—in a positive sense—lowered the perceived and actual barriers to technology adoption, ushering in a new era of technology-driven brain health care. Some governments are beginning to increase spending on brain health, and venture capital funding for brain health start-ups has never been more in vogue. PitchBook data shows that 146 deals generated nearly $1.6 billion in venture capital investments as of December 10th, 2020. A decade ago, there were only 3 deals, worth $6.6 million, whereas last year saw a total of $893 million from 111 deals.18

However, these advances on their own cannot solve the myriad global challenges posed by the brain health emergency. A paradigm shift is needed to address the unprecedented complexities associated with the current global brain health crisis—a crisis now inextricably linked to concurrent interacting crises surrounding discrimination and inequality, mass misinformation, environmental catastrophes, accelerated climate change, entrenched economic models, population displacements and immigrant status, and more.1,15,16 Governments, employers, and healthcare systems around the world need to acknowledge the scope of the problem and embrace solutions to empower consumers to take charge of their own brain health and to protect existing levels of health, well-being, and social inclusion.

In response to the evolving issues, convergence science integrates knowledge, tools, and thought strategies from diverse fields to address challenges that exist at the interface of multiple disciplines.15,19,20 Convergence science not only recognizes the need to respond to apparent societal problems, but also emphasizes approaches which allow us to consider a myriad of the known unknowns and improves the odds of us quickly adapting to newly identified gaps.21 Acknowledging the serendipity of accidentally obtained knowledge permits open mindedness and innovation.22 Taking these approaches when investigating solutions to brain health challenges permits greater flexibility and utility when unforeseen challenges are inevitably met.23

Investments

Brains are the indispensable drivers of human progress. Why not invest more heavily in them? There are currently $40.5 trillion allocated to Environment, Sustainability, and Governance investing around the world.24 If only a portion of this amount were invested in brain health, we could produce major improvements for our society.

Raver and Altimus25 note that this present moment is a clarion call for the philanthropic community, which is uniquely positioned to lead an approach in 2 distinct ways. In the short term, the immediate mental health crisis can be mitigated by supporting interventions for the most vulnerable, the development and deployment of rapidly available mental health tools and technologies, and research to drive evidence-based responses to COVID-19-related mental health challenges. Much work is needed to address the long-term mental health impacts caused by the pandemic. There is an ongoing and urgent need for targeted investment in research to better understand and treat mental health conditions, build capacity and diversity within the mental health system, and advocate for social and policy solutions to improve the ecosystem of mental health care.

Global Economics

Given the critical need to nurture healthier, more resilient, and increasingly flexible brains worldwide, we have introduced the concept of Brain Capital—broadly defined as a form of capital which prioritizes brain skills and brain health.26

The OECD Neuroscience-inspired Policy Initiative seeks to place Brain Capital at the center of a new narrative to fuel societal resilience in mitigating economic shocks, and to create preparedness should future societies fundamentally transform, for instance through irreversible damage to the environment. The OECD’s New Approaches to Economic Challenges Unit has created the Neuroscience-inspired Policy Initiative. This initiative seeks to reconceptualize and revitalize the economy, laying the groundwork to identify relevant metrics while building a transdisciplinary network of stakeholders. The initiative will rapidly refine and advance the concept of Brain Capital via a series of research projects, economic modelling, seminars, and clear policy analyses and recommendations.

In this context, our Brain Capital Grand Strategy supports the focus of the OECD initiative. The Grand Strategy has 3 main components: considering Brain Capital in all policies, developing a comprehensive investment plan to support Brain Capital, and generating a Brain Capital Index.16

Policy

Brain health issues should be addressed in the context of improving performance within the fields of innovation and entrepreneurship. Because most new jobs are created by firms less than 5 years old,27 creative and innovative entrepreneurs are needed to drive social and economic growth at the regional and national levels. In many ways, together with unprecedented government investment in many countries, entrepreneurs stand as a critical firewall against recession and deprivation. They serve as economic first responders when (exogenous) catastrophic events produce national and global economic shocks. 

In the United States, deaths due to suicide, opioid overdoses, and other addictions and poisonings (deaths of despair) are a barrier to complete economic recovery from COVID-19.28 Approximately 20% of prime-aged males who have dropped out of the labor force are disproportionately represented in these deaths, and many of them will not take up jobs even when available due to the severity of their addiction.29

A senior economist at The Brookings Institution is leading an initiative to coordinate the many efforts to deal with this crisis. An important role for the task force would be to coordinate with the many burgeoning local level efforts to address addiction and despair, and these local organizations could greatly benefit from ties to a federal-level coordinating agency. Among other things, this agency could serve as an information clearing house.29 Without addressing the linked issues of mental health and labor market drop-out simultaneously, it will be difficult to solve the tragic mental health crisis or achieve the goal of widely shared economic prosperity.

Organizational and Building Structures

It is also essential that, given the complexity of the challenges being addressed, freedom to fail is offered liberally. Flat organizational structures, which are agile and empower individuals to make decisions in their specific areas and roles without need to constantly consult with managers at higher levels, are important. However, these decisions should be aligned with the mission and not deviate from the already traced goals and strategy. In Table 2, we provide examples of organizations and buildings which foster Convergence Brain Health activities.

Innovation Models

Existing models of innovation are not adequate—suffering from siloing and a lack of speed. There are now a number of more contemporary models which may propel the brain health field forward more quickly and effectively. 

For example, The Davos Alzheimer Collaborative (DAC) is a public-private partnership committed to a collective global response against the challenges Alzheimer disease presents to millions of families around the world.32 The DAC aims to raise around USD $700 million for a 6-year plan to accelerate and diversify innovation in Alzheimer disease research. The 3 main components of DAC include a global cohort developed to identify new targets for potential treatments, a global clinical trial support platform to reduce the cost and time to bring new treatments to market, and a healthcare system prepared to get new treatments to patients. The DAC project will enable novel biomarker development, connect global researchers using the data platform provided by the Alzheimer Disease Data Initiative, and keep individuals with the lived experience of Alzheimer disease at the center of its efforts.

Harnessing Big Data

The first big data wave occurred over a decade ago, fueled by the reduced cost of -omics techniques (eg, genomics, transcriptomics), increased access to neuroimaging equipment, and the transition to electronic medical records. Insights from this data, however, have not translated into dramatically improved outcomes for patients. Diagnostic clarity is often elusive and treatment selection remains primarily trial-and-error. A second wave of big data proliferation is already underway with the increased implementation of mobile applications and wearable devices.33 Solutions are desperately needed to resolve current bottlenecks in transforming data into insights and action. 

Furthermore, according to economist Klaus Schwab, PhD, we are on the verge of the Fourth Industrial Revolution, which will see a rise in cyber-physical systems that blur “the lines between the physical, digital, and biological spheres.”34 Virtual reality environments, brain-computer interfaces, wearable or implantable devices, and mobile applications will continue to contribute to the current data explosion. Artificial intelligence integrates knowledge from a myriad of disciplines, including computer science, data science, mathematics, engineering, physics, statistics, linguistics, signal processing, ethics, and philosophy. Artificial intelligence is no longer a novelty, but a requisite set of convergence tools for navigating the future.

As psychological disorders are mediated by complex interactions between genetic and environmental factors it will be imperative to dedicate significant effort to understanding the modifiable risk factors emerging from the environment.35 Since the environment includes biological, psychosocial, and ecological components, it is likely to be more complex than the genes, proteins, and metabolites that are currently analyzed by a variety of tools. Therefore, within the framework of convergence brain health it will be necessary to develop highly powerful and complex tools that record, measure, and analyze the myriad environmental factors. This effort will be pursued as it has been with the omics technologies but with a much larger scope, ranging from psychophysiological data collected from millions of individual smartphones to satellite tracking of air pollution in big cities. Important ethical issues, however, will have to be addressed with some urgency.

Operationalizing a convergent clinical framework will require effective direction and utilization of the continuing data explosion.36 The role of digital clinical operating systems is therefore critical for allowing effective patient care, as well as ongoing research. These clinical operating systems house data from clinical encounters, imaging, pathology, personal medical devices, wearables, and finance. Analytics methods include the use of mathematical and algorithmic-based processing of data resources, including subfields of artificial intelligence, such as machine learning, natural language processing, and visual analytics to generate descriptive, predictive, and prescriptive models to analyze and derive insight from data. Machine learning has been utilized in predictive risk assessment, clinical decision support, home health monitoring, finance, and resource allocation.36

Convergent approaches often require consideration of many different data types. Data harmonization involves creating a single consistent macro-data source from multiple, potentially disparate micro-datasets. Contributing datasets are structured to remove inconsistencies, creating harmony, such that the final dataset provides a cohesive view of a subject from many different perspectives. Machine learning enables automatization of this process, permitting integration of clinical, behavioral, -omic, imaging, neurosignals, and other datatypes for data mining and predictive modelling. Deep learning in combination with multidimensional biological data (eg, genomics, proteomics) enables examination of the impact of genetic variation or other system disturbances on transcription, translation, signaling, and resultant phenotypic variation. 

Clinical Models

Perioperative brain health is an emerging example of the need for a convergence approach in brain health science. The average individual undergoes 9 surgical procedures in his or her lifetime, typically at an older age when the brain is more vulnerable to perioperative insults such as stress, illness, and immobility.37 As such, the perioperative period is a very high-risk period for older adults, and brain health impairments are abundant with considerable negative impacts. For example, the US National Health and Aging Trends Study found clinically significant depressive and anxiety symptoms in 39% and 24% older adults in rehabilitation facilities, respectively, in older adults recently in rehabilitation facilities (vs. 10% and 9% for older adults in the community).37 Similarly, a study in the UK of postoperative Intensive Care Unit patients found rates of 40% and 46%, respectively.37 Depression and anxiety are connected to poor postoperative outcomes, including persistent pain, delirium, longer hospital stays, poor functional recovery, lower quality of life, and increased chance of both falls and rehospitalization.37,38

A new field of perioperative mental health is responding to the need to integrate mental and cognitive healthcare with surgical and postsurgical care. The increasing number of older adults undergoing surgery creates high demand for this innovation, so that care can move beyond an emphasis only on surgical success and anesthetic safety, to a convergent brain health view of outcomes, such as improved functional recovery, reduced rehospitalization, and decreased long-term morbidity. These innovations are further driven by bundled care models, which include preoperative optimization, in-hospital care, and postoperative rehabilitation. With the recent genesis of the Center for Perioperative Mental Health, funded by the National Institute of Mental Health (P50MH122351), surgeons, anesthesiologists, nurses, physical and occupational therapists, and surgical patients will work together with psychiatrists in an accelerated laboratory for translating scientific advances to practical clinical care that improves the lives of older adults.

With the emergence of so many digital innovations, care providers are presented with more tools than ever. However, such a crowd of novel options adds complexity and uncertainty. To be clinically useful, such point solutions must first be vetted and then clustered into symphonies shown to play well together to optimize collective benefit for specific conditions. In the dementia field, for example, it is encouraging to see multidomain interventions being deployed.39 In the future, a therapeutic guidance system may make sense, similar to those used to advance precision medicine, such as oncology and neurosurgery.

Intra- and Interpersonal Dynamics

To develop a workforce that can harness and deploy a convergence brain health framework, increased inclusion and empowerment of women and other traditionally under-represented populations is required. Building institutions that are both inclusive and meritocratic is health promoting in its own right. But more importantly, it is a powerful mechanism for producing the additional talent, fresh perspectives, and new ideas that are needed.

Meanwhile, certain behavioral characteristics among individual innovators should be cultivated. MacRae and Furnham40 articulated 3 dimensions of a high-potential individual suited to convergent teamwork building on Silzer and Church’s model of potential.41 There are 3 core dimensions: foundational, growth, and career dimensions. These dimensions explain how personality traits are foundational to potential because they represent fundamental and stable individual differences. Personality traits, especially conscientiousness and adjustment, contribute to success in nearly any type of work and have, “higher predictive ability of potential in roles that are more complex, challenging, and demanding such as that of the convergence practitioner.”40

Career dimensions are the unique and specific skills, expertise, and occupational knowledge required for success in a specific career or role: “Convergence practice requires sublimating one’s own objectives into the vision and the objectives of the team.”40 MacRae and Furnham explain in detail how personality traits fit within a model of convergence practitioner potential and expand on 10 behaviors that are related to career dimensions of potential.40 These behavioral and workplace cultural characteristics allow us to formulate screening criteria for potential new entrants into convergent brain health work, identify those who are high potential convergence practitioners, as well as consider training approaches for those within our existing brain health structures.

Leaders must assume a critical role in optimizing transdisciplinary collaboration and facilitating the emergence of discoveries from these endeavors.42 Gray outlined 3 responsibilities of transdisciplinary leaders: cognitive leadership, structural leadership, and processual leadership:

- Cognitive leadership. Effective cognitive leadership provides a vision that links and motivates transdisciplinary researchers to step beyond their disciplinary lens, relax old assumptions, and search for creative frame-breaking solutions.

- Structural Leadership. Effective structural leadership adds value by creating bridges and links among unconnected individuals, labs, groups, or departments.

- Processual Leadership: Effective processual leadership encourages trust and turns conflict into constructive interactions.

These leadership approaches should be kept in mind when fostering Convergence Brain Health within an organization. Other adaptive qualities of a convergence workplace include a flat organizational structure with minimal discipline silos, a culture of trust and mutual respect, and an open acceptance of the need to respectfully challenge entrenched ways of thinking.43 Teams should be humble in acknowledging that nobody has cracked the many complex problems to date, and likely never will due to unsolvable uncertainty. However, being open to novel and seemingly eccentric ideas may help navigate such problems and identify ways for their best possible management.

Teams in a convergence workplace must embrace the three somehow radical tenets outlined in Jim Dator, PhD’s laws of the future: 1) The future cannot be predicted because the future does not exist; 2) Any useful idea about the future should appear to be ridiculous; and 3) We shape our tools and thereafter our tools shape us.44 An optimal convergence science environment should have a strong guiding vision, will be capable of identifying myriad possible alternative futures, and better guide the organization toward the desired future.

Concluding Thoughts

Convergence Brain Health provides direction for transformational change in how teams could work and how organizations need to be built and operated. As we embark on building the new normal of our post-COVID-19 world, Convergence Brain Health will play a key role in this rapidly unfolding change. Indeed, Convergence Brain Health provides an opportunity to grow global Brain Capital and enter a new era of innovation and progress, leading to greater health justice for all people and preparing for the unprecedented brain health challenges of the 21st century.

Dr Eyre is cofounder of the PRODEO Institute, adjunct associate professor with IMPACT at Deakin University, instructor in brain health diplomacy at the Global Brain Health Institute, and co-lead of the OECD Neuroscience-inspired Policy Initiative. Jessica Carson is Director of Innovation at a major mental health association and expert in residence at Georgetown University, and the author of Wired This Way. Erin Smith is an associate with the PRODEO Institute and Thiel Fellow at Stanford University. Dr Lavretsky is a professor of psychiatry at University of California in Los Angeles (UCLA). Dr Reynolds is Distinguished and Emeritus Professor of Psychiatry, University of Pittsburgh, Pittsburgh, PA. Dr Manji is the global head of Science for Minds at Johnson & Johnson. Dr Dawson is a health policy researcher at the Global Brain Health Institute. Dr Booi is a social gerontologist at the Global Brain Health Institute. Mark Heinemeyer is CEO of PRODEO. Dr Cummings is a research professor and Director of Chambers-Grundy Center for Transformative Neuroscience at the University of Nevada, Las Vegas. Dr Fu is a venture partner at Alsop Louie Partners. Dr Storch is professor and vice chair of Psychiatry & Behavioral Services at Baylor College of Medicine. Dr Hynes is special advisor to the OECD secretary general and head of the OECD New Approaches to Economic Challenges Unit. Dr Lenze is the Wallace & Lucille Renard Professor of Psychiatry and the Director of the Healthy Mind Lab at Washington University School of Medicine in St. Louis, Missouri. Dr Meyer is head of strategic projects and alliances at Delix Therapeutics. Dr Macrae is a professor in the department of Integrative Structural and Computational Biology at Scripps Research Institute. Dr Santuccione is Head Stakeholder Liaison Alzheimer disease at Biogen. Dr Abbott is a professor of Law and Health Sciences at the University of Surrey School of Law and adjunct assistant professor of Medicine at the David Geffen School of Medicine at UCLA. Dr Chapman is the founding director of the Center for Brain Health at UT Dallas. Dr Robertson is a T. Boone Pickens Distinguished Scientist at the Center for BrainHealth, a co- director at Global Brain Health Institute, professor emeritus at Trinity College Dublin, and founding director of its Institute of Neuroscience. Carol Graham is the Leo Pasvolsky Senior Fellow at the Brookings Institution, a College Park Professor at the University of Maryland, and a Senior Scientist at Gallup. Dr Fernandes is a postdoctoral researcher, Center for Precision Health School of Biomedical Informatics at the University of Texas Health Science Center at Houston. Dr Angeler is Researcher at the Department of Aquatic Sciences and Assessment; Section for Ecology and Biodiversity at the Sveriges lantbruksuniversitet. Dr Grzenda is Assistant Clinical Professor of Psychiatry and Biobehavioral Sciences at David Geffen School of Medicine at UCLA and UCLA Olive View Medical Center. Dr Ibañez is a neuroscientist at the Global Brain Health Institute. Dr Sarnyai is a neuroscientist and professor at James Cook University, Australia. Sofia Marcha is director of Public Policy and Government Affairs, Europe, Canada, and Partner Markets at Biogen. Dr Berk is a professor of psychiatry at the Institute for Mental and Physical Health and Clinical Translation (IMPACT) at Deakin University. Patrick Brannelly is Director of Partnerships & Business Development at Gates Ventures, Alzheimer’s Disease Data Initiative.

Acknowledgements

MB is supported by a NHMRC Senior Principal Research Fellowship (1156072). MB has received Grant/Research Support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, Medical Benefits Fund, National Health and Medical Research Council, Medical Research Futures Fund, Beyond Blue, Rotary Health, A2 milk company, Meat and Livestock Board, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Abbot, Astra Zeneca, Janssen and Janssen, Lundbeck and Merck and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Janssen and Janssen, Lundbeck Merck, Pfizer and Servier – all unrelated to this work. HAE is an employee of PRODEO LLC. ES is an employee of PRODEO LLC. ASC is an official employee of Biogen Int and the VP of Euresearch. Her contribution to this work is based on her personal opinion and might not reflect the one of the organizations with whom she is affiliated. AI has received Grant/Research Support from ANID/FONDECYT Regular (1210195); FONCYT-PICT 2017-1820; ANID/FONDAP/15150012; Alzheimer’s Association GBHI ALZ UK-20-639295; Sistema General de Regalías [BPIN2018000100059] Universidad del Valle [CI 5316], and the Multi-Partner Consortium to Expand Dementia Research in Latin America [ReDLat, supported by National Institutes of Health, National Institutes of Aging (R01 AG057234), Alzheimer’s Association (SG-20-725707), Rainwater Charitable Foundation (Tau Consortium), and Global Brain Health Institute)]. EJL has received support from the NIH, Patient-Centered Outcomes Research Institute, Taylor Family Institute for Innovative Psychiatric Disorders, and Center for Brain Research in Mood Disorders at Washington University.

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