Advanced CTE Associated With Dementia in Veterans Study

A study in veterans has found a link between dementia and severe chronic traumatic encephalopathy (CTE)—a degenerative brain disorder diagnosed after death that typically affects contact sports athletes and military personnel. Brain donors with advanced CTE (stage 4) were nearly 4.5 times more likely to have developed dementia than those without CTE. Individuals with stage 3 CTE had more than double the risk of dementia. The study was published in January in Alzheimer's and Dementia. 

CTE stages 1 and 2 were not associated with dementia, cognitive impairment, or functional decline. Researchers also did not observe mood or behavioral symptoms at any stage of the disease. Researchers from the Boston University CTE Center and Veterans Affairs Boston Healthcare System (VABHS) led the study, which was funded by grants from the National Institutes of Health (NIH).

“This study proves that CTE is not a benign brain disease and that it has a significant impact on people’s lives,” coauthor Ann C. McKee, MD, chief of neuropathology at VABHS and director of the Boston University CTE Center, told Federal Practitioner. 

McKee added that this research “provides evidence of a robust association between CTE and dementia, as well as cognitive symptoms, supporting our suspicions of CTE being a possible cause of dementia.”

Because CTE can only be diagnosed after death, researchers analyzed 614 donated brains from individuals with known exposure to repetitive head impacts. Among these donors, 366 (59.6%) had CTE and 248 (40.4%) did not. Most donors were male (97%), and most played American football (80.3%). Of the 614 donated brains, 20 (3.3%) were female. The average age of death from these 614 was 52 years, ranging from 13 to 98 years.

None of the donors had any of the 3 most common neurodegenerative causes of dementia: Alzheimer disease, dementia with Lewy bodies, or frontotemporal lobar degeneration.

Researchers also collected clinical information from individuals close to the donors. Typically, these are family members or close contacts through retrospective evaluations that combined online surveys, telephone interviews, and medical records. 

Data collected included demographics; educational attainment; athletic history (including sport, level of play, position, age at first exposure, and duration); military history; traumatic brain injury history; substance use; and medical, social, and family histories. 

CTE is often misdiagnosed as Alzheimer disease. In this study, among those diagnosed with dementia, 40% were informed they had Alzheimer, yet autopsy findings later showed no evidence of the disease. Another 38% were told the cause of dementia was unknown or could not be specified.

“In cases of dementia, when there is a history of repetitive head impacts from contact sports, military activities, or other exposures, CTE should be considered in the differential diagnosis,” McKee said. “Efforts should be made to distinguish CTE from Alzheimer disease and other causes of dementia during life.”

CTE shares features with Alzheimer, specifically the accumulation of abnormal tau protein. In healthy brains, tau helps maintain the stability and proper function of nerve cells. In CTE, however, tau accumulates in small clumps inside nerve cells that eventually form larger tangles.

Normally, the body clears excess tau protein, but in neurodegenerative diseases this process fails. The ensuing buildup damages brain cells, leading to cell death and the progressive symptoms of dementia.

Understanding how brain changes, including those related to CTE, relate to symptoms is of “paramount importance,” said Heather M. Snyder, PhD, senior vice president of medical and scientific relations at the Alzheimer’s Association in Chicago, who was not involved in the study.

Snyder described the research as “the first study to definitely demonstrate that brain changes caused by CTE are associated with the presence of dementia symptoms.” She also noted that the findings suggest a dose-response relationship, with more severe brain changes linked to worse cognitive symptoms.

The findings “open up new paths of research,” Snyder told Federal Practitioner, but also emphasized that improved tools are needed to detect these CTE-related brain changes in living individuals. 

“While we have made significant progress in understanding the diseases that cause dementia, we have much to learn,” Snyder said. “Continued and steadfast investment in research remains a priority to improve early detection during life and develop personalized approaches.”

Ann McKee reported that she is a member of the Mackey-White Committee of the National Football League Players Association and received funding from the National Institutes of Health, US Department of Veteran Affairs, the Buoniconti Foundation and the MacParkman Foundation during the conduct of the study. She reports honorarium for speaking engagements.

Heather Snyder is a full-time employee of the Alzheimer’s Association, Chicago, IL and has a spouse who is employed by Abbott in an unrelated area. She has no financial conflicts to disclose.