funded by the National Institutes of Health (NIH) provides the clearest evidence to date to link severe chronic traumatic encephalopathy (CTE) to dementia risk. CTE is a degenerative brain disorder in some people who have had repeated head impacts over time. It can only be diagnosed after death by examining brain tissue. While researchers were able to link severe CTE (stages III and IV) to dementia risk, they did not find any measurable link between less severe CTE (stages I and II) and changes in thinking, mood, or daily functioning.
The research, led by scientists at Boston University CTE Center and the U.S. Department of Veterans Affairs Boston Healthcare System, analyzed 614 donated brains from people with known exposure to repetitive head impacts. None of the donors had Alzheimer's disease, Lewy body disease, or frontotemporal lobar degeneration, three of the most common neurodegenerative diseases that cause dementia.
CTE is marked by the buildup of abnormal tau protein - which in healthy brains helps keep nerve cells stable and working properly. In CTE, tau forms small, brownish tangles clustered around tiny blood vessels deep in the brain's grooves and spreads more widely as the disease advances.
"By examining hundreds of brains and ruling out other common neurodegenerative diseases, the team could look at CTE alone and linked it to symptoms reported during life," said Dr. Amy Bany Adams, acting director of the NIH's National Institute of Neurological Disorders and Stroke (NINDS), which funded the research.
The researchers found that individuals with stage IV CTE were 4.5 times more likely to have had dementia during life than donors without CTE. Stage III CTE was also associated with higher dementia risk. In contrast, stages I-II were not found to be associated with dementia, cognitive impairment, or functional decline. Mood and behavioral symptoms were not observed at any stage of CTE.
Dr. Richard Hodes, director of the NIH's National Institute on Aging (NIA), which also funded the research, noted important implications for dementia research. "Understanding which brain changes drive cognitive decline is essential," he said. "This study shows that only severe CTE has a clear link to dementia, which provides an important distinction for researchers, healthcare providers, and families."
The study also indicates that mood or behavior changes commonly attributed to CTE may instead come about from other brain effects of repetitive head impacts or from unrelated medical or environmental factors.
The new results build on NIH-funded work published earlier this year showing that repetitive head impacts in young athletes can trigger early cellular changes - such as immune activation, blood vessel alterations, and loss of certain brain cells - well before tau buildup in the brain appears. However, it is still not clear whether these early brain changes cause any symptoms or lead to CTE later in life. Together, the two studies outline a more complete picture of how repetitive head impacts affect the brain over time.
This work was supported by grants from NINDS and NIA. Long-term federal investment enabled analysis of one of the largest CTE cohorts ever assembled, allowing researchers to untangle the specific effects of CTE on brain function and disease for the first time.
This research was supported by NINDS through grant U54 NS115266 and NINDS and NIA through grants R01NS122854 and R01NS139383.
