Repeated Head Impacts, Inflammation and Memory Loss Connected

Summary: Higher levels of inflammation in former college and professional football players were associated with changes in brain white matter that were, in turn, linked to worse memory performance. Blood and spinal fluid markers of inflammation correlated with reduced structural integrity in limbic system pathways, regions critical for emotion and cognition.

The study found that inflammation itself was not directly tied to cognitive scores, but its relationship with white matter microstructure suggests a biological pathway connecting repetitive head impacts to later-life symptoms. These associations were strongest in players with the greatest exposure and most severe symptoms consistent with traumatic encephalopathy syndrome. The findings highlight inflammation as a potential therapeutic target for reducing long-term brain changes related to repetitive head injuries.

Key Facts

Inflammation–Brain Structure Link: Higher inflammatory biomarkers were associated with poorer white matter microstructure in the limbic system.
Memory Connection: White matter damage, not inflammation alone, was tied to worse memory performance.
Stronger in High-Risk Players: Associations were greatest in those with the most head-impact exposure and severe symptoms.
Majority With Symptoms: 59% of former players showed cognitive impairment and 58% had neurobehavioral dysregulation.
Association, Not Causation: The study identified biological links but did not prove cause and effect.

Source: AAN

In former college and professional football players, a new study has found higher levels of inflammation were associated with worse brain structure, which in turn was related to worse memory.

The study was published February 25, 2026, in Neurology.

The study does not prove cause and effect; it only shows associations.

Repetitive head impacts are multiple jolts to the head that may not cause symptoms right away but could cause brain problems over time. These impacts can increase the risk of chronic traumatic encephalopathy (CTE), a neurodegenerative disease that can lead to cognitive changes and dementia.

This shows a football player and a brain. — Higher inflammation levels were associated with reduced white matter integrity in limbic pathways tied to memory and behavior. Credit: Neuroscience News

“Experiencing repetitive head impacts during contact sports like American football has been found in previous research to increase the risk for neurodegenerative diseases like CTE,” said study author Breton M. Asken, PhD, of the University of Florida in Gainesville. “However, the paths linking these head impacts to symptoms later in life are not well understood. Our study found that higher levels of inflammation were associated with brain changes that were, in turn, related to poorer cognition.”

The study was conducted using data from the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of CTE (DIAGNOSE CTE) Research Project. It involved 223 male participants, including 170 who played college or professional football with an average age of 57, and 53 who had no history of contact sports, military service or concussion with an average age of 59.

Researchers measured participants’ levels of three biomarkers in the blood and spinal fluid related to inflammation: interleukin-6, tumor necrosis factor alpha and glial fibrillary acidic protein. Participants had brain scans to evaluate brain structure. Researchers used the scans to measure fractional anisotropy, the direction of water movement in the brain, and mean diffusivity, how freely water moves through the brain.

Since CTE can be confirmed only in autopsy, participants were also evaluated for traumatic encephalopathy syndrome, symptoms associated with potential CTE. Of football players in the study, 59% had cognitive impairment and 58% had neurobehavioral dysregulation, an impaired ability to manage emotions and behavior. Participants who were not football players reported that they had no cognitive concerns, and few, 2%, reported they had neurobehavioral dysregulation.

Researchers found in football players, higher levels of inflammation biomarkers were associated with worse microstructure in the white matter of the brain, specifically the limbic system. The limbic system is a set of brain structures that regulate emotions, motivation, memory, and other behaviors.

Inflammation was more strongly related to worse brain microstructure in football players than in those who did not play football.

Researchers then found that worse brain microstructure in football players was, in turn, associated with worse memory. However, they found no direct link between inflammation and cognition.

When researchers looked at a subgroup of 57 football players who were considered most likely to have CTE based on the severity of their symptoms and amount of head impact exposure, most of the associations were stronger.

“Because the limbic system influences both cognition and behavior, targeting inflammation could offer a way to potentially reduce the risk for developing brain changes that lead to worsening symptoms associated with repetitive head injuries,” said Asken. “We are excited to continue to explore this path in future research.”

A limitation of the study was it looked at male athletes who played football, so the results may not be the same for female athletes, athletes in other contact sports or at lower levels of play.

Funding: The DIAGNOSE CTE Research Project was supported by the National Institute of Neurological Disorders and Stroke.

Key Questions Answered:

Q: What is the main brain pathway linking inflammation to memory problems in former football players?

A: Higher inflammation levels were associated with damage to white matter in the limbic system, and this structural disruption was linked to worse memory performance.

Q: Did inflammation directly cause cognitive decline in this study?

A: No, inflammation was not directly tied to cognition; instead, it was related to brain microstructure changes that were associated with poorer memory.

Q: Why are these findings important for understanding CTE risk?

A: They identify inflammation as a potential biological step connecting repetitive head impacts to later brain changes, suggesting a possible target for future treatments or monitoring.