Can CTE be diagnosed during life?

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Scientists are currently unable to diagnose CTE during life. This is similar to other neurodegenerative diseases, including Alzheimer’s disease, that cannot accurately be diagnosed during life and require postmortem examination of brain tissue. However, over the past decade, there have been tremendous advances in the ability to diagnose these types of diseases during life due to the creation and refinement of objective biological tests of the underlying changes in the brain. These types of tests, called biomarkers, include measurements of proteins and other molecules in the cerebrospinal fluid and, more recently, in blood, as well as the use of MRI scans to examine the structures and functioning of the brain. None of these tests is yet validated or approved for the diagnosis of CTE and requires additional research. There is a special type of PET scan that is approved to help doctors rule out Alzheimer’s disease as the cause of an individual’s cognitive decline. That PET scan measures the amount of amyloid-beta plaque buildup in the brain. Because amyloid-beta plaque is a necessary part of the diagnosis of Alzheimer’s disease, if a patient with significant cognitive impairment does not exhibit the elevated amyloid-beta on the PET scan, they would likely not be diagnosed with Alzheimer’s disease as the cause of the problems. Rather, other conditions (including CTE in an individual with extensive history of repetitive head impact exposure) would have to be considered.

More recently, an experimental PET scan that detects the amount and location of abnormal tau protein in the brain has been studied as a possible biomarker for CTE. Preliminary findings published in the New England Journal of Medicine showed that former NFL players with cognitive, mood, and behavioral symptoms had significantly higher amounts of abnormal tau detected on the PET scan than same-aged men without any history of traumatic brain injury, and the tau accumulations were in areas in the brain seen in neuropathological examinations of CTE brains. Moreover, the amount of abnormal tau detected on the PET scan was associated with the total number of years playing tackle football. Although these results are promising, this PET scan remains experimental and requires a great deal of additional research before it might be able to be used to diagnose individual patients. Researchers are hopeful that diagnosing CTE during life will be possible within a few years, based on a combination of increased research, validation of provisional clinical diagnostic criteria, and advances in biomarker development.

On May 2nd, 2019, the New England Journal of Medicine published a new study written by several members of the DIAGNOSE CTE Research Project team. An experimental brain PET scan developed to detect abnormal tau protein and an FDA-approved PET scan that detects amyloid plaque were used to assess 26 former NFL players (ages 40-69, with cognitive, mood, and behavior symptoms), and 31 control participants (same-age men without symptoms or a history of brain trauma). Results showed that the tau PET levels were significantly higher in the former NFL players than in the controls, and the tau was seen in areas of the brain where tau is found in Dr. McKee’s studies of deceased individuals with chronic traumatic encephalopathy (CTE). Another important finding is that there were no differences between the two groups on the amyloid PET scan, suggesting that the former players’ symptoms were not due to Alzheimer’s disease, and possibly due to CTE. The full publication can be found here.