Dr. Andre Machado heads the Neurological Institute at Cleveland Clinic and is leading the largest ever clinical study for brain disease. His goal is to identify early signs of brain diseases to improve diagnosis and, better yet, lead to prevention.
Read the Q&A with Dr. Andre Machado below.
WAM: You are launching the world’s largest brain health study, hoping to follow tens of thousands of individuals over 20 years. Why so many—and why over such a long period of time?
Dr. Machado: By launching a longitudinal study of this magnitude, we have the potential to discover the causes of brain disorders and what happens before symptoms appear – during the so-called silent phase. This is the first study of this scale, depth and detail to explore the underpinnings of brain disease by following healthy individuals without neurological disease over many years as they age. Our ultimate objective is to identify early causes for brain disease, new treatment targets and new biomarkers that will predict who will develop disease. We are hoping to change the course of neurodegeneration, with the long-term goal of curing diseases in their earliest stages, years before clinical symptoms manifest. We can make neurological care better for our children and our grandchildren.
WAM: How will all the data you are collecting from thousands of volunteers undergoing tests such as sleep studies, eye retina scans and MRIs help you to uncover why millions of people from around the world suffer from brain diseases?
Dr. Machado: We do not fully understand what happens during the silent phase of disease. By periodically testing individuals as they age with all these tests, in addition to blood work and neurological exams, we cast a wide net to understand biological processes that may lead to neurological disease. Collectively, these data points will form a trendline that will predict the occurrence of disease and its likely causes.
WAM: Do you have a sense of why so many people, 1 in 6, end up diagnosed with a neurological disease, including Alzheimer’s?
Dr. Machado: With the great advancements in heart care over the past decade, we have reached the point of outliving our brains. The risk of being affected by a neurological disorder increases progressively with age, reaching a peak annual incidence of approximately 15% in healthy individuals aged 75 and older. While the medical community has learned to manage some symptoms of brain disorders, it remains challenging to predict who will become sick. Furthermore, we do not yet know the early causes of disease as well as the biological processes that occur in the very initial stages. This is a major limitation for developing effective drugs that will allow our brains to age healthier.
WAM: When you look at the landscape of medical research and speak to your colleagues, what’s the prevailing theory on how and why sex comes into play as it relates to the disproportionate number of women who are diagnosed with neurological diseases, including Alzheimer’s?
Some brain disorders are more common in women and some brain disorders are more common in men. Our problem is not so much that we do not know what happens to the female brain. Our challenge is that we do not yet understand the impact of sex on brain disease. The Cleveland Clinic Brain Study will be impactful and will help us to gain important insight into what happens to women and men as we age. It’s one thing to learn why women have more Alzheimer’s than men. It is another level to learn why some women develop Alzheimer’s and some do not. The same questions apply to stroke, depression, obsessive-compulsive disorder, multiple sclerosis, Parkinson’s disease, neuromuscular disorders and so on.
WAM: You speak of wanting a glimpse into “the silent phase” of neurological diseases. What does that mean, and how will this study help?
The biological events that lead to a neurological disorder happen well before the symptoms begin, during the silent phase. There are devastating events occurring for years – probably many years – before we suspect a neurological problem. By the time a disease like Parkinson’s disease is diagnosed, half of the brain cells that produce dopamine in the brain may already be lost. The disease is already accelerated and the brain already significantly damaged. It is hard to implement treatments at this stage that will stop the progression or reverse what has already happened. This is the crucial problem of the silent phase. The Cleveland Clinic Brain Study will study individuals who are still neurologically healthy – without any symptoms. We will follow all these individuals with the many tests previously mentioned over a long period of time. Once we know which individuals developed disease and which didn’t, we can rewind the data to find out what happened in the silent phase of those who eventually became sick compared to those who did not develop disease. The silent phase will be the most valuable time to try new interventions. Imagine a day when we can treat disease before it happens!
WAM: Do you think that at the heart of the wide variety of these diseases that there might be a common denominator? (Increasingly we hear that inflammation may be at the root cause of many neurological diseases.)
That is still speculative. It may be that inflammation is a common path across many neurological diseases but that does not mean that they all start with an inflammatory change. Our suspicion is that neurological disease happens as a result of multiple contributors and the very large data set stemming from the study will help us understand that. One of our aims is to identify biomarkers to predict the onset of various neurological problems. These could be blood biomarkers, such as inflammatory biomarkers, or they could involve the structure of the brain, as revealed by MRI imaging, or they could be at the neurophysiological level or the neuropsychological or cognitive levels. I suspect that the biomarkers will be a combination of factors.