Scientists have discovered a link between dementia, white matter in the brain, and the neurodegenerative disease CTE in former American football players.
When it comes to our brain health, both gray and white stuff matter, researchers say. White matter is made up of all the connections linking together the brain’s working neuron cells, collectively known as gray matter.
Scientists have long known that traumatic brain injuries and concussions contribute to white matter injury, which breaks down the connections between the brain’s neurons and associate with dementia.
But more recently, researchers have attributed subconcussive repetitive head impacts—like the kind of hits football players experience—to causing white matter injury.
A new study in JAMA Neurology is one of the first to reveal the biological mechanisms that link years of playing football to white matter injury, which might contribute to dementia in people with CTE.
Here, lead researcher Michael Alosco, assistant professor of neurology and codirector of the clinical cores at the Alzheimer Disease Center and the Chronic Traumatic Encephalopathy (CTE) Center at Boston University School of Medicine, talks about the connection between CTE and dementia:
Many former football players who suspect they have CTE—as well as their family members—have said dementia is one of the symptoms that made them concerned about their brain health. How does this study provide solid evidence that the dementia seen in CTE patients truly is caused by years of football play?
CTE is characterized by an abnormal buildup in the brain of a protein known as p-tau. Consistent with some of our past findings, we found a greater amount of p-tau in the brain was associated with dementia and the number of years a person had played football.
But one of the really cool and new findings about this study is the white matter piece. Scientific literature has long shown that white matter changes can be the result of traumatic brain injury and/or concussion.
However, in this study, we found a direct association between the number of years someone played American football and the severity of white matter changes; the more years of football someone had played, the more likely they were to have more severe white matter changes, which contributed to dementia. Based on this study, we know that p-tau is not the whole story.
We also found other factors contributing to dementia in people with CTE that were not related to a person’s exposure to repetitive head impacts. Specifically, we found that arteriolosclerosis, a hardening of the brain’s small vessels due to cardiovascular disease risk factors like high blood pressure, also contributed to dementia.
Do these findings mean that football can directly lead to dementia?
It’s really the first study to bring together the buildup of p-tau, white matter changes, as well as arteriolosclerosis and link them all together as contributing to dementia in people with CTE. Years of American football play was indeed associated with dementia through its relationship with p-tau and the white matter changes.
From clinical interviews, you found that nearly two-thirds of the study participants, who were all diagnosed with CTE, also had dementia. Why doesn’t everyone who has CTE also have dementia?
We do see a lot of variability between individuals in how CTE develops and who gets dementia. Our study suggests that this is likely a result of several different factors that can affect people with CTE, such as a combination of p-tau buildup, white matter changes, as well as arteriolosclerosis.
From clinical interviews, you found that nearly two-thirds of the study participants, who were all diagnosed with CTE, also had dementia. Why doesn’t everyone who has CTE also have dementia?
We do see a lot of variability between individuals in how CTE develops and who gets dementia. Our study suggests that this is likely a result of several different factors that can affect people with CTE, such as a combination of p-tau buildup, white matter changes, as well as arteriolosclerosis.
What do these findings mean for the bigger picture of CTE research? Is this another huge strike against football?
Our study provides concrete support for the link between head impacts, white matter changes, buildup of p-tau, CTE, and dementia, bringing all these factors together into one story. But there’s still a lot left to do.
There are important limitations to consider—we only looked at the brains of football players that have already been diagnosed with CTE. In that group, we looked at white matter brain disease using a subjective scale.
What we really need to do is get more granular assessments of white matter to see the extent of white matter injuries and better understand the relationship between head impacts and dementia.
We also need to bring in people from other comparison groups, such as looking at how people with Alzheimer’s might have a different white matter story than people with CTE. We expect, for example, that we would see more white matter damage in people with CTE.
Most importantly, although these pathology studies—where we are looking at the brains of deceased people—are really informative in terms of understanding disease symptoms and the biological mechanisms that cause them, we really need to have more longitudinal studies in living people—following someone throughout their life to see how symptoms change over the course of time. Some factors we’ve identified, like having arteriolosclerosis, could accelerate the course of CTE and make the symptoms more severe.
For you, what are the biggest takeaways from these findings?
P-tau is one contributor to CTE, but we need to consider what’s a consequence of that. How much of dementia and other clinical outcomes are due to tau, and how much to white matter changes or other factors like arteriolosclerosis?
It’s a more complex story that we need to understand. We also have to be mindful of the limitations of this study—these findings can’t be generalized to look at the broader population since we only looked at former football players with CTE.
The National Institute on Aging, the National Institute of Neurological Disorders and Stroke, a Department of Veterans Affairs Merit Award, the Nick & Lynn Buoniconti Foundation, the National Center for Advancing Translational Sciences, the Fonds de recherche du Québec–Santé, and the Alzheimer’s Association funded the work.
Source: Boston University
