When I was the treating neurologist for professional football players, I took a lot of heat from many quarters for keeping men off the field. A player would pass the standard concussion checks, and the pressure to send him back onto the field came from many directions. I had a high level of suspicion that these players were more wounded than our standard measures could show, and I believed that, as a treating physician, it was my job to hold them out even when the pressure to return them was intense. That position was not popular. A study published today suggests it was the right one.
What the New JAMA Network Open Study Found
On October 28, 2026, a Boston University team led by first author Julia Gallini and senior author Yorghos Tripodis, PhD, published "Bias-Adjusted Prevalence of Chronic Traumatic Encephalopathy Among Deceased National Football League Players" in JAMA Network Open. The researchers used the National Death Index to identify 2,362 former NFL players who died between January 2008 and December 2023, then compared them with the 396 who had donated their brains to the UNITE brain bank. Among the 387 donors whose CTE status could be determined, 362, or 93.5 percent, had chronic traumatic encephalopathy (CTE) at autopsy.
That 93.5 percent figure has always come with a fair objection. Families who watched a father or husband lose his memory are more likely to donate his brain, so a brain bank will overrepresent the sickest players. The Boston University team estimated that effect and found that players with cognitive symptoms were about five times more likely to be donated. After adjusting for it, they estimated that 74.5 percent of all 2,362 deceased players had CTE at death (95% confidence interval, 69.6 to 78.3 percent). Their most conservative analysis still produced 63.7 percent (95% confidence interval, 57.2 to 68.9 percent). They also estimated that 27.2 percent of the players had dementia during life, a figure the authors consider an underestimate. For comparison, Gallini noted in Boston University's announcement of the study that CTE has consistently been found in fewer than 1 percent of donors to community brain banks.
The estimate applies to former players who died in that 15-year window, not to living retirees or to men playing today under newer concussion rules. CTE at autopsy means the pathology was present, which is different from saying it caused symptoms or death, since many cases were likely early stage. And the diagnosis can still only be confirmed after death. The authors' conclusion is that selection bias inflates the old brain bank numbers but cannot explain away the burden of disease.
Why Standard Concussion Measures Missed So Much
The sideline tools we used, and still largely use, ask whether a player has symptoms and whether he can perform a short cognitive screen. They were never designed to detect what is happening inside the cells. A player can feel fine and test at baseline while his brain is still running an injury response, and that gap between how a player looks and what his tissue is doing is the reason I kept players out. I go into more of what we look for in a sports concussion evaluation that goes beyond the sideline and in our page on traumatic brain injury and concussion treatment.
The pushback I received over those years taught me something I had already learned once as a resident, which I wrote about in why I became a neurologist and why I practice differently. When the incentives of an institution point one way and the patient's brain points the other, the physician has to choose the brain. That conviction started me on a search I am still on today, which is to build care protocols that address the underlying pathophysiology of chronic brain disease rather than waiting for symptoms to declare themselves.
The Pathophysiology Underneath CTE: Inflammation, Mitochondria, and the Endoplasmic Reticulum
CTE is defined by an abnormal buildup of tau protein, but tau is the end of a longer chain of events, and three processes upstream of it have shaped how I treat brain injury.
The first is chronic inflammation. In 2016, Jonathan Cherry, Thor Stein, Ann McKee, and colleagues at Boston University examined the brains of 66 deceased American football players and 16 non-athlete controls in Acta Neuropathologica Communications. Longer exposure to repetitive head impacts was associated with greater density of activated microglia, the brain's resident immune cells, independent of age at death, and that inflammation accounted for a modest part of the link between head impacts and tau. Those brains were examined at a single point after death, so the study cannot show the timing directly, but it is consistent with my suspicion that injured players were more wounded than they appeared, because the immune response to injury does not necessarily switch off when the symptoms fade.
The second is mitochondrial failure. After a brain injury, excess glutamate drives calcium into neurons, mitochondria take up more calcium than they can handle, and their ability to produce energy falls. A 2025 review in Frontiers in Cellular Neuroscience by Olusola Olatona and colleagues describes how damaged mitochondria release signals that activate microglia, which in turn produce more inflammatory stress, creating a cycle that can sustain itself into chronic neurodegeneration. It is worth noting that most of this mechanistic evidence comes from animal and cell models, and human data are still limited. I have written about the energy side of brain health in depression as a brain energy problem and in what the evidence shows about NAD+ therapy.
The third is what I describe to patients as endoplasmic reticulum fatigue, which researchers call ER stress. The endoplasmic reticulum folds the proteins a neuron needs, and when injury overwhelms it, the cell activates an alarm system called the unfolded protein response. In a 2017 study in the Journal of Neurotrauma, Brandon Lucke-Wold and colleagues at West Virginia University showed in rats that blast injury switched on ER stress markers within 30 minutes, followed by abnormal tau within six hours and learning deficits at 21 days. A drug that blocks part of this ER stress response, salubrinal, lowered the ER stress markers and improved one anxiety-related behavior in the rats, though its effect on tau and learning was not tested. That work was done in animals and has not been tested as a treatment in people, but it points to a step between the impact and the tau that medicine could one day intervene on.
How We Translate This Into Care at NGP
Because CTE cannot yet be diagnosed in a living person, I do not try to label anyone with it. I try to measure what the brain is doing now and treat the processes that drive decline. For a former player, a veteran, or anyone with years of head impacts, that starts with a full precision workup through our Intensive Brain Health Program in St. Marys, Georgia. That evaluation can include diffusion tensor imaging to look for white matter injury, NeuroQuant volumetric MRI to track regional brain volume over time, brain PET imaging when memory is involved, and brain health lab panels that look at inflammation, metabolism, and markers of neurodegeneration. I explain why a single test is never enough in why your brain workup needs six data streams.
Treatment follows the biology. None of these treatments has been shown to prevent, slow, or reverse CTE, and I do not present them that way. We use them to support brain energy, inflammation, and function in people with a history of head impacts, and we track whether each patient actually responds. For mitochondrial support, we use physician-supervised infusions such as NAD+ IV therapy and Niagen (nicotinamide riboside) IV therapy, and for oxidative stress, glutathione IV therapy. For mood, impulse control, and the cognitive habits that injury erodes, we pair medical care with neurocoaching. For properly consented patients who want to consider regenerative approaches, our Cellular Rejuvenation Initiative offers options whose evidence is still early, and we discuss that evidence openly before anyone decides. Nutritional support for the same pathways is available through our sister company, Action Potential Supplements. Veterans with blast exposure face many of the same questions, and our veterans brain health page covers how we approach them.
What Former Players and Their Families Should Do Now
If you played football at any level and you or your family have noticed changes in memory, mood, temper, or sleep, do not wait for those changes to get worse before having them evaluated. Today's study is about men who have already died, and the most useful thing it can do for the living is to move them toward evaluation sooner. I would rather see a former player at 50 with mild symptoms than at 70 with dementia, because there is far more we can do to protect the brain in the earlier window. You can request an Intensive Brain Health evaluation or read more about how our direct-care model gives us the time this kind of workup requires.
I took the heat for holding players out because I believed their brains were worth more than one more game. In the Neuroeconomy, where a person's cognition is the asset that supports a career, a family, and a legacy, that belief applies to everyone who has taken repeated hits to the head, and protecting that asset early is the work we do every day.
This article was drafted with the assistance of AI writing tools, then reviewed, edited, and approved by Dr. Sean C. Orr, M.D., who holds full editorial responsibility for its content.
Sources
- Gallini J, Alosco ML, Abdolmohammadi B, Weuve J, McKee AC, Stein TD, Stern RA, Daneshvar DH, Mez J, Nowinski C, Tripodis Y. Bias-adjusted prevalence of chronic traumatic encephalopathy among deceased National Football League players. JAMA Netw Open. 2026;9(10):e2640884. doi:10.1001/jamanetworkopen.2026.40884.
- Cherry JD, Tripodis Y, Alvarez VE, et al. Microglial neuroinflammation contributes to tau accumulation in chronic traumatic encephalopathy. Acta Neuropathol Commun. 2016;4:112. doi:10.1186/s40478-016-0382-8.
- Olatona OA, Sterben SP, Kansakar BS, Symes AJ, Liaudanskaya V. Mitochondria: the hidden engines of traumatic brain injury-driven neurodegeneration. Front Cell Neurosci. 2025;19:1570596. doi:10.3389/fncel.2025.1570596.
- Lucke-Wold BP, Logsdon AF, Turner RC, Huber JD, Rosen CL. Endoplasmic reticulum stress modulation as a target for ameliorating effects of blast induced traumatic brain injury. J Neurotrauma. 2017;34(Suppl 1):S62-S70. doi:10.1089/neu.2016.4680.