Helen Lavretsky, MD, MS

is Professor of Psychiatry, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA.

Videos

Dr Lavretsky invites us to use the pandemic as a chance to build good habits, explore spiritual avenues, and start new routines. 

An Opportunity for Growth

Modern mental health problems are characterized by their complexity, multi-systemic nature, and broad societal impact, hence making them poorly suited to siloed approaches of thinking and innovation. The New England Journal of Medicine recently published an article that articulated the stark limitations of an increasingly siloed focus on biologic knowledge in psychiatry.

 The article describes how the biological revolution of the 1980s has failed to live up to its therapeutic or scientific promise, with a comprehensive biologic understanding of the causes or treatments of psychiatric disorders yet to be discovered. Further, the article argues that psychiatry faces a new set of challenges, such as a professional diagnosis being reduced to a “checklist-style amalgamations of symptoms,” and an alarming degree of “trial-and-error medication management” taking over practice.

Psychiatry is characterized by multiple complex interacting, biological, social, medical, psychological, and related systems. Consequently, it is important to note that these challenges are not nostalgic arguments for a return to the insular, often unscientific psychodynamic practice of psychiatry that marked the 20th century. Instead, they indicate the need to forge a new path, one with an approach ready to meet the unprecedented and complex systemic mental health challenges of the 21st century.

Indeed, the 21st century will be largely defined by our collective response to the global mental health crisis. According to a recent World Health Organization (WHO) report, around 450 million people currently suffer from mental health conditions, making brain disorders among the leading causes of ill health and disability worldwide. The world’s failure to respond to the mental health crisis has resulted in a “

 of human capabilities and avoidable suffering.”

 Many of these issues will be magnified by COVID-19 that will result in social and physical distancing, economic hardship, and challenges in accessing care (

A paradigm shift is needed in order to solve the unprecedented complexities and challenges associated with the current global mental health crisis. Indeed, scientific progress may be seen as “a series of peaceful interludes punctuated by intellectually violent revolutions.”

 A convergence science approach is needed to address the global mental health crisis, bringing about an urgently needed revolution in science and society.

Convergence science integrates knowledge, tools, and thought strategies from various fields for tackling challenges that exist at the interfaces of multiple fields.

 In the context of mental health, convergence involves the integration of scientists, clinicians, bioinformaticists, global health experts, engineers, technology entrepreneurs, medical educators, caregivers, and patients. Synergy between government, academia, and industry is also vital. Convergence mental health is the approach used for mental health (

Innovation and entrepreneurship with convergence science

COVID-19 can provide a framework for a convergence science approach to tackling the global mental health crisis. Akin to 

 efforts, solutions to the global mental health crisis will require the traditional sciences of chemistry, biology and virology, and the new sciences of big data and artificial intelligence, computer science and statistical models, and -omics medicine. Subsequently, solutions will need sociologists, psychologists, philosophers, ethicists, scientists, media practitioners, crisis management experts, policy makers, and senior civil servants.

The demands of today’s global problems—especially the mental health crisis—also necessitate a fundamental shift in approaching education and workforce development. Individuals in a convergence science workforce must be equipped with deep expertise in their field, while also having literacy and understanding across a broad range of disciplines necessary for transdisciplinary collaborations.

We must be willing to rethink education and training for researchers, clinicians, and others within traditional health care fields. Education needs to shift toward skill sets adaptable to diverse problems. Unconventional skills and topics, such as design thinking, entrepreneurship, computer science, cryptography, and the like, could be incorporated into learning. Creative education opportunities such as mini-fellowships or exchanges may facilitate divergent thinking.

Traditional education pathways as the sole means of involvement in mental health research must also be reconsidered. To develop innovative solutions, a diverse array of solvers is needed. Collective intelligence—including citizen scientists—must be leveraged. Bansho, the Japanese method of collective problem-solving, teaches people to grasp connections and progressions of the thinking needed to develop solutions. It may provide a framework for education and training modules for convergence science researchers.

 was co-founded by Alph Bingham, PhD, and Aaron Schacht to crowdsource solutions to the most intractable solutions.

 As a space for dialogue between specialists and industry outsiders was created, fresh ideas to persistent questions were found. A chemist from Illinois, John Davies, was able to use an idea from his earlier career in construction to help solve the cleanup of the Exxon Valdez oil spill on Alaska’s coast.

 Other organizations have also utilized the InnoCentive model, including 

, which is dedicated to problems in machine learning.

 Both InnoCentive and Kaggle have methods that are currently being adapted to develop solutions for COVID-19 related issues and could be used to develop mental health solutions in the future.

In low- and middle-income settings, where there are few psychiatrists, greater deployment of community health workers is important to provide essential care. This requires transdisciplinary thinking. A recent clinical trial explored the role of lay counsellors in providing a “depression in later life” intervention in Goa, India.

 In this randomized clinical trial, lay counselors provided problem-solving therapy, brief behavioral treatment for insomnia, education in self-care of common medical disorders such as diabetes, and assistance in accessing medical and social programs. The intervention was effective for preventing episodes of major depression in older persons with subsyndromal symptoms. Furthering the reach of lay counsellors, promising trial data now show the value of internet- based behavioral activation with lay counsellor support for the treatment of depression.

A convergence workforce adept at navigating the adoption of new technological innovations is especially important. Technology will continue to fundamentally shift the way we conceptualize and treat mental health conditions. For example, Mindstrong aims to provide continuous digital biomarkers of mood and cognition to support diagnosis, prognosis, and treatment monitoring.

 Born from convergence science, Mindstrong originated from prior work of co-founder Paul Dagum, MD, PhD, in cybersecurity. Adopted for mental health conditions, it may make it possible to detect prodromal stages of mental health conditions, enabling objective measurements and the opportunity for early intervention and prevention.

The same technologies used for early detection and monitoring may also be used to deliver treatment and interventions. For example, 

 builds clinically validated cognitive therapeutics, assessments, and diagnostics that look and feel like video games and has submitted 

for people with attention-deficit/hyperactivity disorder for FDA approval.

 A recent review of the mental health technology field projected there will be 1000 mental health startups by the end of 2020.

 See the Examples of Convergence Mental Health in Action at the end of this article for more information.

The progress in technological advancements like the printing press and developments in science, art, philosophy, and trade that underpinned the Renaissance period was sparked by a convergence approach that merged science and humanities.

 A similar revolution will occur with convergence mental health solutions, ensuring greater integration of social sciences in care. Mental health is an inherently human undertaking. Indeed, convergence mental health should employ considerations from the new field of responsible innovation in mental health, which is “a collaborative endeavor wherein stakeholders commit to clarifying and meeting a set of ethical and social principles by designing solutions to sustainably address the needs and challenges of mental health systems.”

Convergence mental health must also address the social determinants of health and be mindful of the world’s immense cultural diversity. Addressing the social determinants and cultural components of mental health requires rethinking our concept of disease and integration among health systems, local community partners, and coordination at a national or international level. Ensuring that there is a place for social science is critical to achieve a convergence approach and provides an opportunity to prevent mental health disorders, improve mental health at a population level, and reduce social and health inequalities.

Psychiatry has a major opportunity to leverage convergence science that will lead to innovation and progress. Ultimately, convergence mental health will help usher in a new era of care marked by bridging the divergent fields of medical practice, integrating insights from the brain and mind. Convergence mental health holds the potential to integrate technological innovations, insights from other areas of medicine, paradigmatic research shifts that blur existing boundaries between academia and industry, social determinants of health, philanthropy, and unconventional funding mechanisms. These changes will result in better patient outcomes and ensure greater health justice for all people by preparing psychiatry to meet the unprecedented mental health challenges of the 21st century.

We hope to offer brainstorming opportunities and solutions in our forthcoming book, Convergence Mental Health: A Roadmap Towards Transdisciplinary Innovation and Entrepreneurship, scheduled for publication in late 2020. We only hope to keep up with the world that is rapidly changing in front of our eyes.

is Brain Health Venture Executive, Founder and CEO, FacePrint, and 

is Affiliate, Department of Computer Engineering Stanford University, Palo Alto, CA. 

is Distinguished and Emeritus Professor of Psychiatry, University of Pittsburgh, Pittsburgh, PA. 

is Professor of Psychiatry, Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Department of Psychiatry, ORYGEN Youth Health, The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Victoria, Australia. 

is Instructor in Entrepreneurship, Global Brain Health Institute (UCSF and Trinity College Dublin); Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Department of Psychiatry, University of Melbourne; Brainstorm Laboratory for Mental Health Innovation, Department of Psychiatry, Stanford University School of Medicine, Palo Alto, CA; and Discipline of Psychiatry, School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia. 

 is Professor of Psychiatry, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA. The authors report no conflicts of interest concerning the subject matter of this article.

—Dr Berk is supported by a NHMRC Senior Principal Research Fellowship (1059660 and 1156072).

1. Gardner C, Kleinman A. Medicine and the mind: the consequences of psychiatry’s identity crisis. 

The Lancet Commission on global mental health and sustainable development

The Structure of Scientific Revolutions. 

Chicago and London: Chicago University Press; 1962.

Convergence: Facilitating Transdisciplinary Integration of Life Sciences, Physical Sciences, Engineering, and Beyond. 

Washington, DC: National Academies Press; 2014.

The Model Thinker: What You Need to Know to Make Data Work for You.

The Great Mental Models: General Thinking Concepts. 

Minneapolis, MN: Latticework Publishing Inc; 2019.

Range: Why Generalists Triumph in a Specialized World. 

10. Dia A, Azariah F, Anderson SJ, et al. Effect of a lay counselor intervention on prevention of major depression in older adults living in low- and middle-income countries: a randomized clinical trial. 

11. Arjadi R, Nauta MH, Scholte, WF, et al. Internet-based behavioural activation with lay counsellor support versus online minimal psychoeducation without support for treatment of depression: a randomised controlled trial in Indonesia. 

12. Carey B. California tests a digital “fire alarm” for mental distress. 

14. Kollins SH, DeLoss DJ, Canadas, E, et al. A novel digital intervention for actively reducing severity of paediatric ADHD (STARS-ADHD): a randomised controlled trial. 

15. Hays S. Approaching 1000 Mental Health Startups in 2020. 

https://medium.com/what-if-ventures/approaching-1-000-mental-health-startups-in-2020-d344c822f757

16. Szaley J. The Renaissance: The Rebirth of Science and Culture. Live Science. 2016. 

https://www.livescience.com/55230-renaissance.html

17. Eyre HA, Ellsworth W, Fu E, et al. Responsible innovation in mental health. 

18. Fernandes BS, Williams LM, Steiner J, et al. The new field of precision psychiatry. 

19. Brady L, Hotopf M, Broekmans A, et al. Remote assessment of disease and relapse in major depressive disorder (RADAR-MDD). 

https://fnih.org/sites/default/files/final/pdf/CS5_RADAR%20MDD.pdf

21. Jain FA, Walsh RN, Eisendrath SJ, et al., Critical analysis of the efficacy of meditation therapies for acute and subacute phase treatment of depressive disorders: a systematic review. 

22. Cramer H, Lauche R, Langhorst J, Dobos G. Yoga for depression: a systematic review and meta-analysis. 

23. Laird K, Jain F, Lavretsky H. Convergence neuroscience of meditative mind-body therapies for mental health. Eyre HA, Lavretsky H, Reynolds III C2020, Eds. 

Convergence Mental Health: A Roadmap Towards Transdisciplinary Innovation.

 New York City: Oxford University Press; 2020.

24. Eyre HA, Robb A, Abbott R, Hopwood M. Mental health innovation diplomacy: an under-recognised soft power. 

25. Psychiatric Cell Map Initiative 01/25/20; Available from: 

26. Mind O. Health Brains Financing Initiative. 

https://onemind.org/healthy-brains-financing-initiative

27. Smith E, Au R, Mosse M, et al. Rebooting late-life mental health innovation and entrepreneurship with convergence science. 

Articles

A paradigm shift is needed in order to solve the unprecedented complexities and challenges associated with the current global mental health crisis.

Convergence Mental Health: A New Pathway for Transdisciplinary Innovation and Entrepreneurship

Society’s psychological reactions to a crisis can be predicted according to disaster response frameworks. Mental health innovators can use these frameworks to understand what to build during the evolving 

 crisis, and when those innovations will prove most vital.


	While the occurrence of disasters is largely unpredictable, the human emotional response to disasters is relatively predictable. Researchers have mapped the phases of emotional 

 based on patterns that have been consistently witnessed in times of crisis, from hurricanes to terrorism to disease.

 Although plot details differ, the same storyline can be applied to crises worldwide: the impact occurs, heroism abounds, social cohesion surges, and then, once the news crews have resided, another sentiment takes its place-disillusionment, apathy, grief, and psychological distress.

Crisis, however, does not have to be an inhibitor of innovation, but can be an invitation for innovation. Historically speaking, crisis is often followed by a creative resurgence of the human spirit that guides changes in technological and social innovation, like the 

 (1347-1350), which was soon followed by the Italian Renaissance; new societal concepts and financial institutions can bring about global restructuring that facilitates psychological adaptation and growth (similar to the concept of post-traumatic growth). We witnessed this in the last global crisis, World War II, that resulted in the complete remake of the world’s social matrix with the emergence of the US as the global leader, and significant innovations on every level of human functioning.

While facing the reality of the COVID-19 pandemic, we can anticipate far-reaching consequences that will affect our financial system in the immediate future and bring about massive changes to the way our world functions on every level. This global pause-the “quarantine”- as a self-imposed reset button has the opportunity to usher in a heightened awareness of our individual priorities, and a burst of alternative technological solutions that are likely to persist beyond the viral pandemic, such as how schools and education function, or how health care is administered.

In light of the COVID-19 crisis, we can use this historical precedent-now conveniently captured by emotional response disaster frameworks-to guide our path forward. Not only can these frameworks be used to understand how and when our world will be psychologically affected by this disaster, but they can help inform what is needed during each phase to best support mental, emotional, and spiritual well-being. Mental health innovators must come to view their work through a public health lens, not only considering what is immediately needed, but what needs will arise once the “honeymoon” phase of this crisis is over.


	Over the course of March 2020, our world traversed the heroic phase of the disaster response. This phase is characterized by high levels of activity, low levels of productivity, and a surge in altruistic, adrenaline-induced rescue behavior (think: health care providers valiantly working without personal protective equipment).

 During this phase, the mental health innovation trend was that of open-access innovations. A multitude of companies, from meditation apps to teleconferencing technologies, offered free or discounted access to their platforms in this time of limited resources and millions out of work. Examples of this include therapy app Talkspace, which now offers free therapy for health care workers and discounted subscriptions for the public, and the meditation app Headspace, which now offers free meditation recordings for all.
	• Phase: Heroic - March 2020
	• Characteristics: High activity, high altruism, low productivity
	• Innovation trend: Open-access

Throughout April 2020, we entered the honeymoon phase (

). In this phase, disaster assistance became available, community bonding was more prevalent than ever (albeit virtual), and there was a sense of collective optimism.

 This honeymoon phase seems to be characterized by the mental health innovation trend of platform innovations-the use of existing technologies (apps, websites, etc) upon which new products and services can be offered. Examples of this include the teleconferencing platform Zoom, which has created specialized resources, tools, and capabilities to meet the heightened demand and unique needs of this time; Facebook helping local governments and emergency health organizations reach people via Facebook and Messenger.
	• Phase: Honeymoon - April 2020
	• Characteristics: High assistance, high bonding, high optimism
	• Innovation trend: Platform


	However, as we move deeper into May 2020 we seem to be nearing a less hospitable phase-the disillusionment phase (

). In this phase, the public has recognized the limits of the governments in being able to control viral spread, develop vaccines, or provide disaster assistance. We are feeling a heightened sense of discouragement and distress as we see more clinical manifestations of reactions to stress including affective and emotional symptoms (anxiety, phobias, depression, irritability, apathy, withdrawal); physiological disorders, sleep disorders and dreaming disturbances, memory disorders; behaviors that reinforce and maintain the trauma in the conscience; and 

 Experts have been referring to this phase as the “mental health tsunami”-if the virus outbreak was the earthquake, then mental illness will be the storm surge that comes in its wake. In the disillusionment phase, realities like unemployment, debt, and death begin to sink in, and individuals may rely more heavily on alcohol, opioids, and the like to cope.

Disillusionment is the longest of the phases-the depth of which will largely dictate how quickly and easily we will recover-which is why it will need to be characterized by a mental health innovation trend of prevention innovation. These technologies must focus on the prevention or mitigation of mental health issues like depression, 

, and addiction, as it is through prevention that we will lessen the depth of the post-crisis crash. An example of an existing prevention technology is affective computing that can detect depression relapse or emergent suicidal ideations through the wearable devices or iPhone use, and connect individuals to mental health providers.

 can assist in detecting high-risk populations among health care workers who might be experiencing burn out, stressed caregivers, or students with high levels of pre-existing anxiety. Technologies oriented toward rebalancing of stress response (eg, meditation and breathing apps, music and art therapy, promoting sleep, proper nutrition, and facilitating immune response) could be developed to guide those in distress.
	• Phase: Disillusionment (including post-crisis crash) - May 2020 - ?
	• Characteristics: Low optimism, high distress, high illness
	• Innovation trend: Prevention


	Although we cannot say for certain how long the disillusionment phase will last-the range is from months to years, especially with the looming financial crisis-we will eventually emerge into the calmer waters of the reconstruction phase.

 During this phase, individuals feel a sense of recovery, responsibility, and capacity for rebuilding-there is a greater acceptance of and adjustment to the new normal. With the new normal must come novel solutions, which is why mental health innovation will need to be characterized by frontier innovations, novel technologies based on significant scientific advances, and engineering innovation. Examples of frontier technologies include innovations like AI, sensors, -omics, imaging, synthetic biology, smart devices, digital therapeutics, and the like. While this is not to suggest that frontier technologies should not be built throughout the crisis, it’s also useful for mental health innovators to consider what tools are most crucial and when they are most needed. For instance, frontier technologies may not be readily adopted during the disillusionment phase if they are too costly or complex to use during a time of great uncertainty.
	• Phase: Reconstruction - timing unknown
	• Characteristics: Return to recovery and responsibility
	• Innovation trend: Frontier

Although these stages of response to disasters are true for the population at large, patients with serious mental illness are more vulnerable to profound levels of depression, anxiety, and distress, and may not reach recovery without additional help from practitioners.


	The COVID-19 pandemic is forcing us to face the reality that our world has shifted-climate change, natural disasters, and pandemics are part of our new normal. What seemed stable is now uncertain, our hope in the government’s ability to manage all disasters is diminishing, and we are turning to each other and to our neighbors for solutions. The phrase “we are in this together” rings true for us and has left us to ask: What can each of us do to contribute to the solution and solvency of our society and the planet 

? How can we innovate to continue to enjoy our planet, and leave it to our children to enjoy and develop further? What should be guiding the development of technologies during crises of global proportions such as COVID-19?

To guide innovation at every level, we should anticipate the spiritual and psychological needs of the population at large, as well as those of the most vulnerable patients. Maintaining hope, focusing on well-being, and rebalancing the stress response, as well as improving infrastructure for mental health care can help reduce burnout in the health care workforce and improve the lives of all individuals. We encourage you to consider the following questions with us:
	1. How can we inspire, encourage, and retrain those who have been cast aside as “non-essential” in this time? If retraining 20 million people can be quickly achieved, what scalable technological or vocational training can be offered immediately?
	2. In an increasingly non-religious world, what scalable spiritual alternatives can be offered to provide individuals with answers to existential questions like meaning, purpose, destiny, control, and role of the self at this time?
	3. How can we cultivate resilience to ensure society of its capacity to rebuild and redesign our collective new normal?


	4. How can we train individuals to live simpler lives with enhanced self-reliance, and how can technological innovation help?

Armed with the knowledge of the human emotional response to disaster, we can anticipate and potentially bypass psychological lows by preparing humanity to be more flexible, proactively deal with disasters, and honor their own strength and ability to fight adversity. Mental health innovators will represent a group of humble, perhaps unsung heroes in this crisis, and it’s through collaboration, urgency, optimism, and trust that we will get through this together.

 It’s time for us to get to work-to help, heal, and harness the innovative potential inherent in crisis.

, Expert in Residence at Georgetown University, and author of Wired This Way; 

 is Brain Health Venture Executive and Innovation Diplomat, Instructor in Entrepreneurship at the Global Brain Health Institute (UCSF and Trinity College Dublin), Advisor to Brainstorm Lab for Mental Health Innovation, Stanford University, Honorary Fellow with IMPACT, Deakin University, Australia; 

 is Professor of Psychiatry, Department of Psychiatry, University of California Los Angeles. We’d like to hear from you, you can email Jessica Carson (jessica@jessicacarson.co), Harris Eyre (harris.eyre@gmail.com), or Helen Lavretsky (hlavrets@ucla.edu) with questions, comments, or if you’d like more information on mental health innovation ideas. The authors report no conflicts on interest concerning the subject matter of this article.

1. DeWolfe DJ. Training manual for mental health and human service workers in major disasters. US Department of Health and Human Services. Substance Abuse and Mental Health Services Administration, Center for Mental Health Services; 2000.
	2. Washington E. 

. 2020. 
	3. LÃ³pez-Ibor Jr JJ. Disasters and mental health: new challenges for the psychiatric profession. 

. 2006;7:171-182.
	4. Laird KT, Krause B, Funes C, Lavretsky H. Psychobiological factors of resilience and depression in late life. 

. 2019;9:1-18.
	5. Smith E, Au R, MossÃ© M, et al. Rebooting late-life mental health innovation and entrepreneurship with convergence science. 

. 2020; In press.
	6. Ternes K, Iyengar V, Lavretsky H, et al. Brain health Innovation Diplomacy: a model binding diverse disciplines to manage the promise and perils of technological innovation. 

Lockdown is the world’s biggest psychological experiment - and we will pay the price

. World Economic Forum. 2020.
	3. Collins F. 

Dealing with Stress, Anxiety, and Grief during COVID-19

Society’s psychological reactions to a crisis can be predicted according to disaster response frameworks, which can be used to understand what to build during the evolving COVID-19 crisis, and when those innovations will prove most vital.

Dear Mental Health Innovators: The COVID-19 Honeymoon Is Almost Over

Dr. Lavretsky is Professor of Psychiatry, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles.

This Special Report on Geriatric Psychiatry addresses a variety of clinical issues in the rapidly growing diverse population of older adults. With the increase in the population of adults over age 65 years expected to reach 22% of the general population by 2040, neuropsychiatric disorders of aging will become a challenge for many practicing health care providers. This demographic trend has led to an intensive search for effective strategies to diagnose, treat, and prevent mental, cognitive, and physical disorders of aging.

The stigma of mental illness still overshadows proper diagnosis and management of neuropsychiatric symptoms and disorders in the elderly. The boundaries between neuropsychiatric and physical illnesses are often blurred, especially in the acute medical and in long-term care settings, because of frequently comorbid mood, anxiety, cognitive, and physical disorders in older adults. Aging-related physiological changes lead to the increased risk of adverse events such as falls and drug toxicity with pharmacological management.

The growing population of aging baby boomers brings to light new challenges characteristic of this cohort, such as increasing rates of drug abuse and higher rates of depression and anxiety, sleep disorders, and PTSD compared with previous generations. The issue of gender identity and the aging LGBTQ community is coming to the forefront of public and professional awareness of the unique health care needs of its members. It is also becoming more obvious that multiple diseases of aging share common risk factors and may benefit from shared treatment and preventive strategies, such as heart disease, diabetes, and Alzheimer disease.

The 7 articles in this section highlight common clinical dilemmas and outline the nuances of diagnosis, management, and outcomes-and provide helpful practical tips for clinicians. We hope that readers will find the information in this Special Report clinically relevant and helpful in the diagnosis and treatment of neuropsychiatric conditions in older adults.

Dr. Lavretsky reports that she has received research grants from Forest/Allergan.

This work was supported by the NIH grants MH97892, AT009198, and AT008383.

This Special Report on Geriatric Psychiatry addresses a variety of clinical issues in the rapidly growing diverse population of older adults.

Introduction: Neuropsychiatric Disorders of Aging

Meet Helen Lavretsky, Professor of Psychiatry at UCLA, who speaks about a 

 in older adults with subjective memory complaints and mild cognitive impairment.

Patients assigned to yoga practice for 12 weeks with daily meditation for 12 minutes in weekly one hour classes did better than those who participated in memory training classes in verbal and visual memory, executive function, mood resilience, anxiety, and connectivity of the brain.

Results suggest that yoga can be a cognitive enhancement or brain fitness exercise that can confer similar or even more extensive cognitive resilience than memory training-the gold standard-in older adults.

Meditation in this study was practiced with music recorded on the 

 album, which received a Grammy award this year.

Dr Lavretsky is Professor of Psychiatry at UCLA. She also directs the Late Life Mood, Stress, and Wellness Research Program at the Semel Institute at UCLA. She is a member of the Editorial Board of 


	
	1.Eyre HA1, Siddarth P1, Acevedo B1, et al. A randomized controlled trial of Kundalini yoga in mild cognitive impairment. 

https://www.cambridge.org/core/journals/international-psychogeriatrics/article/randomized-controlled-trial-of-kundalini-yoga-in-mild-cognitive-impairment/138A3EB97520CE72B01D17059B7AA286

.
	
	2. Yang H, Leaver AM, Siddarth P, et al. Neurochemical and Neuroanatomical Plasticity Following Memory Training and Yoga Interventions in Older Adults with Mild Cognitive Impairment. 

 http://journal.frontiersin.org/article/10.3389/fnagi.2016.00277/full

In this pilot study, older adults who practiced yoga did better on measures of verbal and visual memory and executive function than those in memory training classes.

Cognitive Enhancement-With Yoga

Dementia, also referred to as major neurocognitive disorder (including Alzheimer disease [AD]), is a growing problem because of increased lifespan. There is no known cure. Several drugs are FDA-approved for the treatment of dementia, including acetylcholinesterase inhibitors (eg, donepezil, rivastigmine, galantamine) and an 

-methyl-D-aspartate (NMDA) receptor antagonist, but these have limited efficacy, adverse effects, and significant cost-all of which contribute to the search for alternative therapies to improve cognition.

In this article, we look at several natural products used to improve cognitive impairment or cognitive symptoms of dementia (

A popular supplement for cognition is ginkgo biloba, which is extracted from the leaf of the Maidenhair tree. Although it has been used as a supplement in the US, in many European countries it is part of mainstream medical care and requires a prescription. A standardized extract called EGb 761 is prescribed in many countries outside of the US.

 examined the mechanisms of ginkgo biloba that provide neurocognitive benefits and defined its 3 main active agents: ginkgolides, bilobalide, and flavonoids. The ginkgolides are thought to inhibit platelet-activating factor, thereby preventing clotting, promoting blood flow, and inhibiting inflammatory mediators such as cyclooxygenase-2, nitric oxide synthase, and tumor necrosis factor. Bilobalide is thought to inhibit platelet-activating factor receptors and

9 Natural Supplements for Cognitive Impairment

reduce the excitotoxic effects of glutamate. Finally, the flavonoids serve as antioxidants that reduce the damage caused by free radicals.

The majority of trials that show the benefits of ginkgo biloba pertain to improved cognition in persons who already have a major neurocognitive disorder or dementia. However, the data regarding a benefit in cognitively intact individuals are mixed. The most rigorous study by Mix and Crews

 examined the effect of a 180-mg dose of ginkgo biloba on community-dwelling individuals without neurocognitive disorders. Full neuropsychological testing showed some small improvements in memory, but intergroup differences limited the results. The dosage was lower than typically recommended, which is generally about 120 mg to 240 mg, 2 or 3 times daily. Another randomized clinical trial (RCT), which used a 240-mg dose of ginkgo biloba, demonstrated some small effects in immediate and delayed recall.

 In summary, there is no compelling evidence to support the use of ginkgo biloba to improve memory functioning in individuals who are cognitively intact.

Can ginkgo biloba prevent major neurocognitive impairment? Four well-designed studies show differing results. The Ginkgo Evaluation of Memory (GEM) study examined more than 3000 individuals aged over 75 years with either normal cognition or mild cognitive impairment.

 The study failed to show any protective effect of ginkgo biloba in preventing dementia.

Another study looked at the prevention of AD in adults aged 72 to 96 years with either normal cognition or mild cognitive impairment.

 The study used EGb 761 (a ginkgo biloba extract) at a dosage of 120 mg twice daily over the course of 6 years. No risk reduction was found.

The GuidAge study looked at the prevention of dementia with ginkgo biloba in more than 2000 community-dwelling older adults over a 5-year period.

 Like the GEM study, the GuidAge study did not show a benefit of ginkgo biloba in preventing dementia over 4 years; however, after 5 years, it started to show an improvement. A limitation of the GuidAge study is the especially low incidence of dementia in the participant population (1.2/100 to 1.4/100), which makes it more difficult to show statistical significance. The large, 20-year PAQUID study showed that ginkgo biloba prevented dementia. However, important characteristics such as dosage and duration of ginkgo treatment were not documented.

These studies include both epidemiological studies as well as RCTs, which make it difficult to compare findings. Epidemiological studies do not control for confounding variables, such as comorbid risk factors that might contribute to the development of dementia. Moreover, there is insufficient evidence to support the use of ginkgo biloba in the prevention of dementia. Studies that focus on dosage and duration of ginkgo biloba administration are needed to remove the potential confounding effects.

Some evidence supports the use of ginkgo biloba in those already affected by a major neurocognitive disorder. Thus, given that more traditional agents do not generally show superiority, ginkgo biloba is a reasonable option for such patients. The data on ginkgo biloba for improving cognition in patients with dementia are more extensive than the data on prevention of cognitive impairment. Birks and Grimley Evans

 evaluated 36 trials on the effects of ginkgo biloba on cognition in persons with cognitive impairment and determined that the results were inconsistent, although they noted that ginkgo biloba is fairly safe.

A smaller but more recent meta-analysis demonstrated a potential benefit of ginkgo biloba on cognition in those who already had cognitive impairment.

 The standard mean difference calculated between ginkgo biloba and placebo was -0.89 (95% confidence interval, -1.82 to 0.04), and there was a statistically significant but not necessarily clinically significant benefit on Alzheimer Disease Assessment Scale-cognitive (ADAS-cog) scores of 2.65. Significant improvement in cognitive functioning in outpatients with mild to moderate AD or vascular dementia occurred with 240 mg of EGb 761.

 In addition, ginkgo biloba has an antidepressant effect in patients with dementia.

 Other studies have shown that ginkgo biloba was not inferior to donepezil and may provide added benefit when both are given to individuals with AD.

Ginkgo biloba must be used with caution in patients who are at increased risk for hemorrhage because it may potentiate bleeding. However, studies of its effect on bleeding function found ginkgo biloba to be safe alone and in combination with antiplatelet drugs.

Persons who are most likely to benefit from ginkgo biloba include those who already have dementia.

 identified omega-3 fatty acids as one of the most common complementary and alternative medicines. Nutritional sources of omega-3 fatty acids are primarily fish, nuts, algae, and krill. The 2 main forms of omega-3 fatty acids are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). DHAs are important in neuronal development; DHA deficiency increases the risk of developmental delays.

 Beyond neurodevelopmental effects, omega-3 fatty acids may serve a neuroprotective role through antioxidant, anti-inflammatory, and antiamyloid effects.

 the consumption of fish reduced the development of AD. In APOE-4 non-carriers, eating fish 2 or 3 times per week reduced the development of dementia by 50% over 4 years.

 In a prospective follow-up study, 899 individuals without dementia were studied over 9 years. There was a 47% reduction in the development of AD in participants with high plasma levels of DHA.

Supplementation with omega-3 fatty acids has been less promising than the consumption of fish. A meta-analysis showed that omega-3 fatty acid supplementation is helpful for mild cognitive impairment but not for dementia or prevention of dementia.

 Both attention and processing speed improved with supplementation.

The APOE-4 allele is a genetic predisposition for the development of AD. Individuals who have this genetic susceptibility to AD do not appear to benefit in the same way from omega-3 fatty acid supplementation as do individuals without the APOE-4 allele. Older adults who seek to prevent AD might benefit from a diet rich in omega-3 fatty acids, including fish; whereas older adults who already have mild cognitive impairment might benefit from omega-3 fatty acid supplementation to improve attention and memory.

Omega-3 fatty acid supplements, primarily EPA, also provide an antidepressant effect.

 Thus, it is possible that supplementation for the purpose of cognitive impairment might have unforeseen benefits on mood. Similarly, the confounding effect of omega-3 fatty acids might be improved cognition with the improvement of depression, since depression in geriatric patients often adversely affects cognition.

Ginseng may have cognitive-enhancing effects. In a study that compared Korean red ginseng with placebo, significant improvement was seen in ADAS-cog scores in participants who received 9 g of ginseng.

 Another study used 150 mg of Panax ginseng as well as other cognitive-enhancing agents, including 120 mg of ginkgo biloba and royal jelly.

 Statistically significant improvement in cognitive function was observed, as measured by about 2 points on the Mini-Mental State Examination (MMSE); however, such improvement is not always considered clinically significant.

Huperzine A is a bioactive constituent of 

, which has been suggested to have cognitive-enhancing effects. Huperzine has several mechanisms of action similar to those of traditional cognitive-enhancing medications, such as acetyl cholinesterase inhibitors, and the antagonistic effects on the NMDA receptor. The common dose range is from 200 to 400 µg.

An RCT showed an improvement in activities of daily living with 100 µg of huperzine twice daily.

 However, a larger US study demonstrated less significant effects. The study compared 200 µg and 400 µg of huperzine twice daily. A modest effect on cognition was observed with 400 µg of huperzine in patients with AD.

 The most common adverse effect of huperzine is nausea. For individuals with dementia who cannot tolerate or afford traditional cognitive-enhancing medications, huperzine may be an effective alternative.

Deficiencies in cyanocobalamin (vitamin B

) can cause cognitive impairment. Therefore, it is standard practice to evaluate levels of these vitamins in anyone who presents with cognitive impairment.

, as evidenced by elevations in methylmalonate and homocysteine, are related to deficiencies in memory and decreases in perceptual speed and brain volume.

Data do not support a cognitive-enhancing effect in individuals with normal vitamin B levels.

 The doses of vitamin supplements in the study were 5 mg of folate, 25 mg of vitamin B

; the duration of treatment was 18 months. Another study that included individuals older than 60 years with AD or vascular dementia and normal vitamin B levels also failed to show a therapeutic effect with vitamin B supplementation.

 may have a cognitive-enhancing effect in persons with normal cognition. Therapeutic benefits on immediate and delayed recall were observed with vitamin B supplementation in adults aged 60 to 74 years.

 Although there is insufficient evidence to show the benefit of vitamin B supplementation on cognition in persons with dementia and normal vitamin B levels, the data suggest some benefit in cognitively intact individuals. Adverse effects include induction of mania and burning sensations.

Vitamin D stimulates macrophage-induced phagocytosis of beta-amyloid protein.

 In a population study of 171 individuals, an increased incidence of all-cause dementia was seen in those who had vitamin D deficiency compared with those who had normal levels.

Beyond cognition, vitamin D appears to have a therapeutic window to strive for in optimizing treatment. Optimal levels of vitamin D (25-hydroxyvitamin D) are greater than 25 nmol/L and less than 50 nmol/L. Michaelsson and colleagues

 reported increased mortality related to low vitamin D levels (< 46 nmol/L) and high vitamin D levels (> 98 nmol/L). An RCT of older women who had normal vitamin D levels demonstrated an increased risk of falls and fractures when participants were given a large bolus of vitamin D.

 High levels of vitamin D (> 56 mmol/L) also increase mortality risk.

Here: a look at several natural products used to improve cognitive impairment or cognitive symptoms of dementia.

Helen Lavretsky, MD, MS

Articles

An Opportunity for Growth

Convergence Mental Health: A New Pathway for Transdisciplinary Innovation and Entrepreneurship

Dear Mental Health Innovators: The COVID-19 Honeymoon Is Almost Over

Introduction: Neuropsychiatric Disorders of Aging

Cognitive Enhancement-With Yoga

Natural Supplements and Vitamins for Treatment and Prevention of Dementia and Cognitive Decline

Positive Psychiaty, Resilience, and Aging

Treatment Options in Late-Life Treatment-Resistant Depression

All to Do About Aging!

Convergence Science: Shaping 21st Century Psychiatry