Q&A with Jonathan Rosand, MD, MSC

Jonathan Rosand, MD, MSC is Co-Founder of the Henry and Allison McCance Center for Brain Health, Emeritus Chief, Division of Neurocritical Care and Emergency Neurology and Emeritus Medical Director, Neuroscience Intensive Care Unit at Massachusetts General Hospital (Mass General). Dr. Rosand is also a Professor of Neurology at Harvard, holds the J.P. Kistler Endowed Chair in Neurology at Massachusetts General Hospital, and is an Associate Member of the Broad Institute of MIT and Harvard. An internationally renowned scientist, clinician, educator and organizational leader, he has created a legacy of multidisciplinary teams that tackle some of the most pressing challenges in brain disease. Dr. Rosand graduated from Columbia College with a degree in Greek and Latin, and earned his medical degree from the Vagelos College of Physicians and Surgeons at Columbia University. He completed his clinical and research training at Mass General, the Harvard School of Public Health, and the Whitehead Institute Center for Genome Research. Dr. Rosand’s world-class research program in cerebrovascular health has been the training ground for a generation of top investigators in stroke and brain health. Dr. Rosand founded the International Stroke Genetics Consortium, which brings together over 100 pre-eminent investigators from 6 continents, and also launched the NIH-funded investigator training program in Recovery and Restoration of Central Nervous System function following injury. He continues to care for patients in the Neuroscience Intensive Care Unit and the McCance Center's outpatient practice. Prior to co-founding the McCance Center, Dr. Rosand founded and built Mass General’s Division of Neurocritical Care into the country’s preeminent Neurocritical Care team.

Meredith Callanan: Jonathan Rosand – thank you for speaking with us.

Martin Goldstein: The McCance Center mission – stopping brain disease before it develops – is bold, meaningful, and important, particularly as we face a mental health crisis in our country. Please speak to the vision.

Jonathan Rosand: Our goal is simple – to reduce the rates of the three most common and debilitating age-related brain conditions: 10% fewer cases of dementia, stroke, and depression in 10 years, and 30% fewer by 2050. Achieving our goal depends on reliably measuring the rates of these conditions annually and demonstrating progress from our clinical innovations.

Our vision is to reduce the rates of those three most common and debilitating age-related brain conditions. It is to improve brain health long before symptoms are visible. We know that modifying risk factors could prevent up to 40% of dementia, more than 50% of all strokes, and at least 35% of depression. Converting this knowledge to practice is our immediate priority. In parallel, we will develop new approaches and medicines to protect and improve brain health thatcan be rapidly integrated as they become available. To be successful, we must work beyond traditional healthcare, across both the developed and developing world.

We are approaching our work by selecting populations and communities, pockets, if you will, in which to get started, establishing strong sustainable programs, learning from our experiences, and expanding over time. How do we get started? By identifying leaders from academic medicine who share our vision and are ready to act on behalf of the patients and communities they serve and study. This is about leveraging the trust and collegiality of colleagues generated over our careers. While we are jumping in to make change right now, we are also focused on developing low-cost, safe, and effective drugs that will someday be available as preventive treatments particularly for neurodegenerative diseases worldwide. We focus on lifestyle and risk modification for the current generation, while developing medicines that will be added to benefit future generations.

Callanan: Please define “brain care” and “brain health,” and where mental health fits in?

Rosand: Let's start with how we're approaching the brain. My co-founders, Rudy Tanzi, a neuroscientist and geneticist, and Greg Fricchione, a psychiatrist, and I approach the brain as one organ. Considering neurologic diseases, like Alzheimer's, independently of psychiatric diseases, like depression or anxiety, doesn’t make sense biologically. Start with the biology when it comes to discovering new medicines. Start with the risk factors when it comes to advocating, encouraging, and sustaining lifestyle change. If conditions such as depression and stroke share modifiable risk factors, then it makes sense to integrate them when approaching lifestyle modification. Resilience to stress plays an enormous role in mental health and in susceptibility to stroke and dementia.

Our focus has shifted from brain health to brain care. This is fundamental to the McCance Center’s approach and that of our collaborators globally. It’s about the stigmatizing impact of labeling ourselves as healthy, healthier, or less healthy.Several classic questions I receive from someone who has recovered from a stroke (or their partner): “Is there a permanent change to my brain? Will my brain never be as healthy as someone who has not had a stroke?” More heartbreaking is when the parent of a someone with schizophrenia asks, “Will my son/daughter’s brain always be unhealthy?” We realized early on that labeling a brain as “unhealthy” was a trap, potentially exacerbating stigma rather than reducing it, and running the risk of turning people away from continuing to engage in a helpful way with the healthcare system. We have come to view stigma as a key barrier to an individual’s adopting and maintaining healthy behaviors. Reducing stigma is therefore a key component of our overall strategy.

After many conversations with patients and practitioners, it became clear that taking care of oneself is critical. Everybody can carry out brain care, regardless of their starting point, their social and cultural background, or the state of their brains. “Brain care” is our way of introducing people to what they can do to take good care of their brain. We created a simple score, the Brain Care Score, grounded in robust scientific data, to answer that question.

Callanan: Tell us about this tool you’ve created: the Brain Care Score (BCS). How did it come about and how are you using it?

Rosand: The origins of patient scores go back decades when epidemiologists began to build risk scores. Once we learned about different risk factors for a disease, we started to compute scores to combine the risk factors and estimate cumulative risk. All these scores were about risk, so the higher your score, the worse things looked. The objective generally has been to get the score down. The Brain Care Score takes a different approach. It reflects steps patients and doctors can take to reduce risk, and it rises as risk goes down. Higher numbers are more reassuring as opposed to more alarming.

We want to make brain care a daily part of life. The score grew out of conversations with patients and families confronting severe disability from brain hemorrhages or strokes, or family members of people who died with related brain disease. They were asking what they could do for themselves and their children to prevent the brain diseases that had caused them and their loved ones so much suffering. In constructing the BCS, we identified steps for which the evidence was incontrovertible. We wanted a tool that would be acceptable to the most skeptical doctor, the most skeptical scientist, or a skeptical grandmother. We focused on simplicity and sought to avoid controversy.

Goldstein: Thinking about the brain as a single organ, consider a family with a genetic disorder such as frontotemporal disorder (FTD). How does McCance address genetic disorders?

Rosand: Brain care applies to everyone, including those of us who have inherited gene variants that put us at high risk of developing a brain disease such as FTD or other dementias. Data suggests a high Brain Care Score can neutralize a substantial proportion of the risk conferred by APOE4, a common genetic risk factor for Alzheimer’s. A research team at the Broad Institute affiliated with the McCance Center, led by Sonya Vallabh and Eric Minikel, are developing treatments,including gene therapies, to prevent a rare genetic condition in which carriers of a mutation have a 100% chance of developing dementia at a young age. Even in these rare circumstances, there is growing evidence that lifestyle interventions can postpone the development of dementia.

Callanan: You have described the issues related to brain aging as a tsunami. Could you explain that?

Rosand: Between 2000 and 2050, the proportion of the world's population over 60 years will double from about 11% to 22%. The absolute number of people aged 60 years and over is projected to increase from 605 million to 2 billion. In parallel we see dropping birth rates across the developed world. The growth in the elderly population means the number of people affected by age-related depression, dementia, and stroke will skyrocket. The costs associated with taking care of the afflicted elderly will threaten to bankrupt our economies, increasing the strain on the younger generations who are working to support the older generations.

Goldstein: The latest predictions of brain disease in the US are daunting – 71+ million American adults experiencing brain disease; Alzheimer's increasing four-fold by 2050; and cases of strokes and dementia doubling. Costs are projected to be $935 billion due to the delay in the onset of Alzheimer's disease. Healthcare costs constitute between 20-25% of our GDP. If you're a healthy 20-year-old functioning at high levels, you may have an underlying disease or potential for one of these diseases. How will McCance Center impact that in a proactive as opposed to reactive treatment?

Rosand: That question could be asked about almost any disease in modern medicine. We are essentially a reactive healthcare system. The Framingham Heart Study, launched 60-70 years ago, showed that elevated cholesterol levels preceded heart attacks by decades or more. The introduction of effective cholesterol-lowering treatments is one example of successful preventive care.

The model for the McCance Center is heart disease. At one time, heart attacks were seen as inevitable. Now they're seen as preventable. A lot of primary care focus is on heart attack prevention through monitoring cholesterol, blood pressure and prescribing drugs that lower cholesterol. Similarly, cancer screening and prevention have had success.

We envision the same approach for brain care. Many of the risk factors for cancer and heart disease are also risk factors for Alzheimer's, dementia, depression, and stroke. While preventing heart disease or cancer, we could also bepreventing brain disease. We can unify prevention under one approach.

Goldstein: Is there data suggesting the components of the brain score may differ for each disease and for different populations?

Rosand: We recently published a study that a higher Brain Care Score is associated with a substantial reduction in risk of dementia and stroke. We evaluated 360,000 participants in the UK Biobank, a population study tracking the development of various diseases over time and were able to reconstruct the Brain Care Score at the time individuals entered the study and then chart their disease risk over time. For people under the age of 50 when their BCS was measured, a five-point higher BCS at baseline was associated with a 59% lower risk of dementia and 48% lower risk of stroke. For those whose BCS was calculated when they were between 50 and 59, the figures were 32% and 52%. Even people older than 60 when their BCS was calculated had a substantial reduction in risk of dementia and stroke. We have also conducted analyses for risk of depression, and a higher BCS has a similar effect. We currently have manuscripts under review that demonstrate a similar relationship for the Brain Care Score not only with risk of depression, which is a key focus of ours, but also heart disease, lung cancer, breast cancer and colorectal cancer. What is good for the brain is good for the heart and the body. Importantly, the message is: Putting brain care at the center of primary care could be a simple, effective approach that could transform individual preventive healthcare. Implementing this approach is a key challenge and one that we are committed to meeting.

Goldstein: The COVID pandemic increased the incidence of anxiety and depression with a disparate impact on people of color and people of low socioeconomic status. What steps are being taken to address that brain health disparity?

Rosand: The Brain Care Score was designed to help people take simple steps for their brain health. Social determinants of health play a significant role in our health. The health care system itself also is a major factor, often interacting with social determinants. Socioeconomic status, for example, has a big impact on access to healthcare. With the Brain Care Score, we start with the foundation of seeking to meet people where they are. Recall that we launched the BCS in response to questions from our patients and families. Meeting people where they are means considering their cultural background, socioeconomic status, level of education, and, perhaps most important, their access to health care. We envision adapting the BCS to different groups, different populations as we build more collaborations locally, nationally, and globally. So many of us are at substantially higher risk of dementia, stroke, and depression because of adversesocial determinants of health. We must therefore engage and rigorously study broad and diverse populations if we are to be successful in our mission. Narrowing health care disparities is the cornerstone of our mission. We believe that brain care will engage everyone, provided we engage everyone where they are currently at.

Goldstein: Is the data on blood pressure and its impact on dementia, stroke, and Alzheimer's disease applicable to all populations?

Rosand: Reducing blood pressure could have a huge impact on the brain disease crisis. Eliminating hypertension could prevent 40-50% of all strokes, perhaps 30% of dementias and a substantial proportion of age-related depression. The challenge is that we have generally not been able to achieve blood pressure control for more than half of all patients with high blood pressure. To solve this challenge, we have launched a national study of patients recovering from stroke that is examining a key question: What are the barriers and facilitators for patients and practitioners to engage with effective blood pressure control strategies? The pressing question is no longer how to get blood pressure controlled. It is how to ensure that patients and doctors get the job done.

Goldstein: So much of brain care seems to be about exercise and diet. Is that right?

Rosand: The truth is that it is up to each one of us where to start. For me, the most powerful BCS component to improve brain care starts with blood pressure. I want to ask everyone, “Have you measured your blood pressure today?” You could imagine an ideal world in which every adult at the age of 18 is given a home blood pressure cuff and educated on the role of blood pressure in their health. Not only are blood pressure data the strongest, but the effect size is the largest. The epidemiological data for physical activity is strong. The effect of diet is always hard to measure. Recent studies of curated, healthy lifestyles, show mixed results for reducing the risk of dementia, but most of the scientific community agree that diet can have a substantial impact on reducing disease risk. Data on sleep is becoming more and more convincing, and we have begun working with sleep researchers on the best way to engage people to improve sleep.

But, when it comes to a patient’s choices, it is not up to me. It is up to them. People in our practice decide what steps to start with. It can be diet, exercise, blood pressure, or any of the other components of the Brain Care Score. What is important is that patients have a choice and pick what they find most motivating. The good news is that many of the BCS components are interrelated. For example, both physical activity and diet are likely to influence blood pressure as well as sleep.

We have found that early success improving Brain Care Scores will motivate people to use it by giving them choices to find something they are good at. Success experiences are reinforcing – reducing blood pressure by taking a pill may be followed by starting to exercise using a treadmill and so on.

Callanan: What are the next steps towards achieving adoption of the Brain Care Score and achieving the McCance Center’s vision?

Rosand: We are building a global coalition of partners who are committed to achieving 10% fewer cases of dementia, stroke, and depression in 10 years and 30% by 2050. The coalition starts with patients and families. By our estimates, up to 75% of all adults have personal experience with dementia, stroke, or depression themselves or through a close loved-one. With so many adults exposed to the suffering these conditions cause, there is great motivation to protect ourselves and our loved ones from ever becoming afflicted.

The key leaders in the coalition are from academic medical centers who share our vision. It has been gratifying to recruit distinguished physicians from around the world to the coalition. They will be the backbone of our success with the experience and confidence to take on the challenges that must be overcome to achieve success. These leaders are choosing to take a risk on an unproven direction using the Brain Care Score to prevent neurologic and psychiatric disease. They have joined us from leading medical centers in US, Canada, Asia, Europe, and Africa. Theseaccomplished individuals are drawn to our commitment to science and implementation to improve the lives of patients and families. Another crucial group of contributors are data scientists. One of the greatest limitations we face is the lack of reliable data on rates of new cases of dementia, stroke and depression for cities, regions, and nations. We can only be sure of our success if we can measure it!

In parallel, we are recruiting a new generation of researchers with skills in community-based research and collaborations with community experts who are academic health scientists. We have started engaging insurers, the private and government sectors as well. As leaders realize that the brain health crisis is really a pandemic, and that we are bringing together a global community to address it, they begin to ask how they can help.

We were launched by a circle of visionary physicians, scientists, community experts and philanthropists. Our work has a 10-to-30-year timeline. It is driven by a broad coalition of accomplished leaders in academic medicine with shared vision. It requires these leaders to step out of their traditional comfort zones and work closely with a diverse range of partners, all the while training the next generation of clinician-scientists to continue the work. Philanthropy is the cornerstone for supporting our novel vision and high-risk high reward studies. Traditional sources of research and innovation such as the federal government tend to focus on low-risk science with a shorter-term horizon.

Finally, each of us can take the first step in caring for our brain and monitoring our progress using the Brain Care Score! Share it with your own circle of friends and family. Imagine if each of us adopts a group of people to join together to improve our Brain Care Score. Surely, we will get to 10% fewer cases in 10 years in no time!

About the Authors:

Meredith Callanan was a senior leader at T. Rowe Price Group for many years, focusing on marketing and communications, corporate responsibility, and philanthropy, before participating in the Harvard Advanced Leadership Initiative as a Fellow in 2019. As a Senior Fellow in 2020 and 2021, she conducted national research on leadership diversity and development in the U.S. early care and education (ECE) sector which culminated in her establishing the Early Years Leadership Diversity Initiative to address barriers to advancement for rising leaders in ECE.

Martin Goldstein is a 2020 Harvard ALI Senior Fellow and Senior Editor for the Social Impact Review. Martin has thirty plus years in biopharma, initially at Hoffmann-La Roche; followed by Genentech; subsequently, as founder and CEO of ViroLogic, Inc., a clinical laboratory guiding therapy of HIV-infected patients; and more recently working with venture to build biotech companies pursuing cutting edge science to develop therapeutics to treat disease.

This Q&A has been edited for length and clarity.