An array of tests that combines functional assessment with blood tests and brain scans promises more sensitive and objective estimation of brain degeneration in human veterans exposed to battlefield improvised explosive device (IED) blasts, according to research led by doctors at the Icahn School of Medicine at Mount Sinai and the James J. Peters VA Medical Center. The study was published in Molecular Psychiatry on Tuesday, February 25, and featured on the journal's cover.

Traumatic brain injury (TBI) is associated with acute brain destruction at the time of the injury and is also a risk factor for developing neurodegenerative diseases later in life. It is estimated that 10 to 20 percent of veterans returning from the conflicts in Iraq and Afghanistan sustained mild TBI resulting from IED and other blast exposures. The true prevalence may be even higher, given that many blast-related injuries go undocumented. Symptoms of mild TBI frequently resolve in days to months following injury, but in a subset of patients, symptoms persist and evolve into a chronic syndrome. Veterans who had sustained TBIs may suffer subtle, yet important, endocrine and neuropsychiatric dysfunction. Given the fact that suicide rates have jumped substantially among young military veterans in recent years, it is imperative to develop earlier, more objective and sensitive methods to detect brain damage.

Using advanced methods of clinical neuropsychological and neurocognitive assessment, brain imaging, and blood biomarker measurement in veterans of the Middle East conflicts, together with modeling of mild repeated blast injury in laboratory rats, the researchers found changes in the brains and blood of those subjected to blasts. Specifically, they performed neuroimaging and blood analysis of human veterans who were exposed to IED blasts on the battlefield and on rats exposed to repetitive, low-level blasts in a shock tube. All veterans reported histories of between 1 and 50 blast exposures, and all had chronic behavioral and cognitive complaints.
Two chemical changes that occur during neurodegeneration involve clumping of a brain protein called tau and leakage of another protein called neurofilament protein-light chain (Nf-L) from the brain into the blood. The research team used positron emission topography (PET) and the [18F]AV1451 (flortaucipir) tau ligand, a molecule which produces a signal by binding to a site on the tau protein that "lights up" on a PET image, and found that 5 of the 10 veterans exhibited excessive retention of [18F]AV1451 at the white/gray matter junction in frontal, parietal, and temporal brain regions, a typical localization where tau protein clumps tend to accumulate after TBI. In healthy brains, tau is essential for normal cell functioning, helping stabilize the internal skeleton of nerve cells in the brain, but when tau proteins build up and clump together, it causes the internal skeleton to collapse and form twisted tau tangles that promote brain cell damage.

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