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Researchers examine potential causes of dementia in CTE

Key clinical point: In deceased patients with CTE, more years of football play are associated with more severe white matter rarefaction and greater phosphorylated tau accumulation.

Major finding: The odds ratio for dementia was 1.69 among participants with more severe white matter rarefaction.

Study details: A cross-sectional study of 180 deceased former football players with CTE.

Disclosures: The study was funded by grants from the National Institute on Aging, National Institute of Neurological Disorders and Stroke, the Department of Veterans Affairs, the Nick and Lynn Buoniconti Foundation, and the National Center for Advancing Translational Sciences. Some of the authors reported financial ties to the pharmaceutical industry and serving on professional sports committees.


Alosco ML et al. JAMA Neurol. 2019 Aug 5. doi: 10.1001/jamaneurol.2019.2244.


The study by Alosco et al. provides new insights into the pathogenesis of dementia in deceased former football players with chronic traumatic encephalopathy (CTE), Julie A. Schneider, MD, professor of neuropathology at Rush University, Chicago, wrote in an accompanying editorial (JAMA Neurol. 2019 Aug 5. doi: 10.1001/jamaneurol.2019.1089).

Significant and widespread white matter injury is an established result of head trauma resulting from acceleration-deceleration injuries. In addition, studies of single and repetitive traumatic brain injury have shown disruption of axons and white matter. The findings of Alosco et al. “underscore the importance of studying the risk factors and mechanisms for the white matter rarefaction, in addition to the tauopathy, in individuals who have played U.S. football and have CTE,” Dr. Schneider wrote.

The comprehensive neuropathologic examinations, advanced statistical techniques, and multiple sensitivity analyses that the investigators performed are among the study’s strengths. An important limitation, however, is selection bias. “The frequency of pathologic characteristics in this group should not be generalized to estimate the prevalence of neuropathologic conditions in living individuals who have played or are playing U.S. football,” Dr. Schneider wrote. “Moreover, individuals who played football who were selected for autopsy and found to have CTE may differ in other important ways from those who did not undergo autopsy or did not have CTE.” Recall bias could alter associations between years of play and dementia diagnosis, and the study’s semiquantitative assessments could result in decreased power to observe relevant associations, she said.

“In spite of these limitations, the authors should be applauded for elegant work and compelling support for multiple pathologic pathways to dementia in football players with CTE,” Dr. Schneider concluded.

Dr. Schneider is with the Rush Alzheimer’s Disease Center at Rush University, Chicago. She has been an expert consultant for the National Football League and the National Hockey League.