A research team from the UK and Sweden has used dynamic flortaucipir-PET imaging to show that single moderate-to-severe traumatic brain injury (TBI) can trigger signs of accumulation of neurodegenerative tau protein and lead to cognitive decline.

The researchers found significant tau build-up in a brain region associated with object recognition, and they observed a correlation between the increased deposits that reduced cognitive abilities among patients with a more severe TBI almost 20 years after their injury (Sci. Transl Med. 10.1126/scitranslmed.aaw1993).

“The ability to detect tau pathology in vivo after TBI has major potential implications for diagnosis and prognostication of clinical outcomes after TBI,” wrote the study authors, led by Nikos Gorgoraptis, from the department of brain sciences at Imperial College London in the UK. “It is also likely to assist in patient selection and stratification for future treatment trials targeting tau.”

Flortaucipir (Avid Radiopharmaceuticals) has recently shown promise in binding to tau neurofibrillary tangles in postmortem brain tissue of Alzheimer’s patients. It has also been shown to build up in brain regions associated with chronic traumatic encephalopathy (CTE) among former professional football players who experience multiple head traumas.

Tau deposition also is known to occur after one TBI, with “abundant and widely distributed neurofibrillary tangles [having] been found postmortem in about one-third of patients with TBI,” Gorgoraptis and colleagues noted.

What remains unexplored is flortaucipir-PET’s role in quantifying tau accumulation many years after a single TBI, and how much that injury might affect a patient’s health?

To answer the question, the researchers looked at 21 patients (median age, 49 years; range, 29–72 years) with one moderate-to-severe TBI. Examinations of their injuries, primarily from traffic accidents (86%), occurred at a median age of 32 years (range, 18–51 years). For comparison purposes, 11 age- and demographically matched healthy controls were included in the study.

All participants underwent dynamic PET imaging for 90 minutes with an average intravenous bolus (250 MBq) of flortaucipir, as well as structural 3-tesla diffusion-tensor MR imaging (DTI-MRI) to assess white-matter integrity through fractional anisotropy.

Additional assessments included the Glasgow Outcome Scale-Extended (GOS-E) index, which measures brain function after an injury on a scale of 1 (brain dead) to 8 (good recovery), and a Mini-Mental State Examination (MMSE). An MMSE score of less than 12 is considered severe dementia, while a score greater than 24 is normal.

The researchers then divided TBI patients into two groups: a “disabled” subgroup of subjects with a GOS-E index of 6 or less and a “good recovery” subgroup with an index greater than 6. Longitudinal data was available for 15 TBI patients beginning at a mean of 17 years before the current clinical assessments.

Flortaucipir-PET images showed significantly greater tracer binding to tau deposits in the right lateral occipital cortex (p < 0.05) of TBI patients, compared with the healthy controls. In addition, white-matter integrity, as measured by fractional anisotropy, was significantly reduced in TBI patients (p = 0.04), compared with healthy controls.

The researchers also found evidence of a cognitive decline in MMSE scores (average, -1.3; -0.073 MMSE points per year) in the disabled TBI subgroup, compared with the good outcome TBI subgroup, which actually improved its collective MMSE scores (average, 1; 0.058 MMSE points per year), creating a statistically significant difference between the two subgroups (p = 0.041).

Given flortaucipir-PET’s ability to detect tau in patients after a single TBI, Gorgoraptis and colleagues suggested the technique could help in the design of future trials of tau-targeting therapies.

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