Inflammation may play a key role in brain changes in former football players

GAINESVILLE, Fla. — Among former college and professional football players, higher levels of inflammation were associated with microstructural changes in the brain’s white matter, particularly in regions involved in memory and emotion, according to a new study led by investigators at the University of Florida and Boston University.

The findings appear in Neurology, the medical journal of the American Academy of Neurology, and they offer new insight into the biological pathway linked to memory problems among some former football players. The research also suggests inflammation as a potential target for reducing the risk for brain degeneration in people who experience repeated hits to the head.

“Repetitive head impacts from popular sports like American football are a known risk factor for dementia later in life, but how these impacts increase dementia risk is not well understood,” said lead author Olivia Emanuel, a Ph.D. candidate in clinical and health psychology at the UF College of Public Health and Health Professions. “Our findings suggest that inflammation and changes to the brain’s white matter might be important contributors to cognitive and behavior changes with aging.”

Repeated head collisions are common in football and other contact sports. These frequent jolts may not cause concussion or other immediate symptoms but can accumulate over time, potentially leading to problems with memory, mood and behavior later in life, as well as a degenerative condition known as chronic traumatic encephalopathy, or CTE.

“Not all former football players experience problems later in life. For those who do, chronic inflammation may be a critical step in between sustaining repetitive head impacts and developing cognitive decline several years later,” said Breton Asken, Ph.D., one of the study’s senior authors and an assistant professor and neuropsychologist in the UF Department of Clinical and Health Psychology. “Clarifying these biological links will help us improve earlier detection and identify who is at greatest risk before too much brain change has occurred.”

The memory issues reported by some former football players suggest they may not be experiencing typical age-related memory lapses, Emanuel said.

“The frequency and severity of concerns reported by some people raise the possibility of something more than age-related changes, such as a neurodegenerative disease,” she said. “We often hear complaints about frequently forgetting details about recent events or conversations, needing constant reminders, or being told they repeat themselves. However, the types of memory symptoms can vary widely.”

For the study, researchers analyzed data from the Diagnostics, Imaging and Genetics Network for the Objective Study and Evaluation of CTE Research Project, or DIAGNOSE CTE, a study supported by the National Institute of Neurological Disorders and Stroke.

The study included 223 men over age 50. Of those, 170 had played college or professional football and were recruited for the study because they were concerned about their cognitive functioning. The other 53 participants had no history of contact sports, military service or concussion and were cognitively healthy.

Investigators measured biomarkers associated with inflammation in participants’ blood and spinal fluid and conducted brain scans to evaluate microstructure of limbic white matter, a network of nerve fibers that connects brain regions involved in memory, emotions and behavior.

Among the former football players, 59% showed objective cognitive impairment on formal testing and 58% had neurobehavioral dysregulation, characterized as difficulty managing emotions and behavior. Higher levels of inflammation were associated with worse brain microstructure.

“The study builds on the growing evidence that shows inflammation is a chronic consequence of repetitive head impacts,” said Michael Alosco, Ph.D., an associate professor of neurology at the Boston University Chobanian & Avedisian School of Medicine and the study’s other senior author. “We are excited to continue to explore this path through the DIAGNOSE CTE Research Project-II, which is following people from the original study as well as actively recruiting new people.”

Inflammation plays a central role in the body’s ability to heal and is not all bad, the researchers say. Future studies are needed to determine when brain inflammation can cause damage and how it can be prevented.

“We need to continue refining our understanding of how, if and when the brain’s inflammatory response becomes problematic, and which parts of that inflammatory cascade are responsible for that shift,” Emanuel said. “That said, we can rely on the well-established research in other areas of dementia that show the significant brain health benefits of interventions like optimal nutrition and physical activity, which we think act through pathways that keep inflammation under control.”