A longer duration of exposure to repetitive head impacts is associated with more severe white matter rarefaction and greater phosphorylated tau accumulation in the brains of former footballers diagnosed with chronic traumatic encephalopathy (CTE).

A US study of 180 brains, from mostly professional and college-level football players, found more years of play was also associated with high CTE stage. About 80% of the men were staged at CTE III or IV compared to 20% at stage I or II.

More severe white matter rarefaction and dorsolateral frontal cortex neurofibrillary tangles (DLFC NFT) subsequently and independently corresponded to an increased likelihood for dementia.

For example, deceased men with a high DLFC NFT burden were about 2.65 times more likely to have dementia than men with a low DLFC NFT burden, after controlling for age and race.

Overall, two-thirds of the men had been diagnosed with dementia before their deaths. The average age at death in the cohort was 68 years.

The study found arteriolosclerosis, a marker of ageing and CVD, was not associated with years of football play, but was independently associated with dementia.

The researchers said CTE often presents with various cognitive and neuropsychiatric changes that can progress to dementia.

“The extent to which these symptoms are accounted for by phosphorylated tau is unclear, especially behavioural and mood changes that occur early in life.”

“Non tau pathologic changes, including white matter degeneration associated with repetitive head impacts and arteriolosclerosis associated with ageing or CVD, may affect the clinical expression of CTE and contribute to clinical hetereogeneity,” they wrote.

“Increased understanding of comorbid contributors to the pathogenesis and symptom profile of CTE is imperative to fully diagnose, treat, and prevent this progressive brain disease.”

An accompanying editorial said the study provides “intriguing data” regarding the importance of both the white matter and tau pathways.

“The authors show that the association between years of play and dementia was completely mediated by the white matter rarefaction and tauopathy. Moreover, the magnitude of the association on dementia from the white matter injury and tauopathy was similar across these 2 pathways,” wrote Dr Julie Scheider of the Rush Alzheimer’s Disease Center, Chicago.

“These findings 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 US football and have CTE.”

She said further study was also required on the risk factors for arteriolosclerosis and the mechanisms by which it affects the brain and cognition in people who have played football and are ageing.

Two cases of CTE in elite rugby league players in Australia were reported recently.