For Muhammad Ali, who died at age 74 after suffering from Parkinson’s disease, there couldn’t have been a crueler condition to haunt his later years. For the self-proclaimed Greatest, known for his ability to float like a butterfly around his opponents, Parkinson’s slowly stole his capacity to control his own muscles and put a stop to his once voluble commentary on everything from his opponents to his religion to race.
But how much of what made him great—those three decades of hit after hit to the head—contributed to his condition? His family believes boxing wasn’t the cause, that the cruel intrusion of Parkinson’s was the result of his genes and his exposure to pesticides while training outdoors.
They may be partly right. There are genes associated with a higher risk of Parkinson’s, though it’s not clear if Ali possessed them. And some studies point to toxins from pesticides that target the delicate motor nerves in the brain. But there is also undeniable evidence that repeated trauma to the brain can damage those same neurons.
Since the 1920s, doctors have known about the correlation between a career in boxing and a series of symptoms that include slurred speech and tremors. The connection was compelling enough for them to dub the syndrome dementia pugilistica. It’s now known as chronic traumatic encephalopathy (CTE), and scientists today have a deeper understanding of how trauma to the brain might contribute to Parkinson’s as well as to other brain diseases like Alzheimer’s. (CTE is still hard to diagnose; for now, it can only be done posthumously.)
“Almost everybody in the neurodegenerative-diseases world believes the reason Ali wound up with Parkinson’s is because of brain trauma over the course of his career,” says Dr. Robert Cantu, professor of neurosurgery at Boston University and a leading CTE researcher.
Proving that hunch is more challenging. So far, about a dozen studies have concluded that repeated head trauma is a risk factor for Parkinson’s. But Dr. Michael Okun, medical director for the National Parkinson Foundation, notes that “there is still a big gap in our knowledge. Researchers have found that people hit in the head repeatedly are more likely to develop Parkinson’s, so there is something to it. But to assign causation is still too premature.”
Scientists do not fully understand how the buildup of proteins in the brain—like one called tau, a telltale sign of Alzheimer’s and other neurodegenerative diseases—is triggered when the brain is injured. It’s likely that no single answer will ever explain what the occupational hazards of boxing do to the brain. There is a chance that head injuries could magnify or accelerate underlying problems and contribute to the progression of Parkinson’s, the same way it’s possible that exposure to pesticide chemicals could play a part.
Both may have been the case with Ali, who was already showing signs of Parkinson’s—slurred speech and uncoordinated movements—before his last fight. And the punches to the head from that fight could have heightened any damage that had already occurred.
What will clarify these questions are studies of brain tissue from people like Ali, who both experienced repeated brain trauma and developed Parkinson’s. But those studies don’t yet exist. It’s expensive to follow people over the many years it takes for Parkinson’s to develop, but the National Institutes of Health recently begun a study looking back at the medical records of people who developed Parkinson’s. Much more research will be needed to know with any certainty if there is a causal link between head trauma and brain disorders.
Perhaps that’s yet another legacy Ali will leave. Having raised awareness about Parkinson’s, as he did in his later years, his death may inspire ever deeper studies into the terrible condition that claimed his life.
For much more on Muhammad Ali, see TIME’s ALI: The Greatest, a 112-page, fully illustrated commemorative edition. Available at retailers and at AMAZON.COM