FDDNP-PET Tau Brain Protein Binding Patterns in Military Personnel with Suspected Chronic Traumatic Encephalopathy1

Since the 1920s, it has been known that the repetitive brain trauma associated with boxing may produce a progressive neurological deterioration, originally termed dementia pugilistica, and more recently, chronic traumatic encephalopathy (CTE). We review 48 cases of neuropathologically verified CTE recorded in the literature and document the detailed findings of CTE in 3 profession althletes, 1 football player and 2 boxers. Clinically, CTE is associated with memory disturbances, behavioral and personality changes, parkinsonism, and speech and gait abnormalities. Neuropathologically, CTE is characterized by atrophy of the cerebral hemispheres, medial temporal lobe, thalamus, mammillary bodies, and brainstem, with ventricular dilatation and a fenestrated cavum septum pellucidum. Microscopically, there are extensive tau-immunoreactive neurofibrillary tangles, astrocytic tangles, and spindle-shaped and threadlike neurites throughout the brain. The neurofibrillary degeneration of CTE is distinguished from other tauopathies by preferential involvement of the superficial cortical layers, irregular patchy distribution in the frontal and temporal cortices, propensity for sulcal depths, prominent perivascular, periventricular, and subpial distribution, and marked accumulation of tau-immunoreactive astrocytes. Deposition of beta-amyloid, most commonly as diffuse plaques, occurs in fewer than half the cases. Chronic traumatic encephalopathy is a neuropathologically distinct slowly progressive tauopathy with a clear environmental etiology.

The objective of this article is to report the proportion of soldiers in a Brigade Combat Team (BCT) with at least 1 clinician-confirmed deployment-acquired traumatic brain injury (TBI) and to describe the nature of sequelae associated with such injuries. Members of an Army unit (n = 3973) that served in Iraq were screened for history of TBI. Those reporting an injury (n = 1292) were further evaluated regarding sequelae. Of the injuries suffered, 907 were TBIs and 385 were other types of injury. The majority of TBIs sustained were mild. Postdeployment, responses to the Warrior Administered Retrospective Casualty Assessment Tool (WARCAT) facilitated clinical interviews regarding injury history and associated somatic (ie, headache, dizziness, balance) and neuropsychiatric symptoms (ie, irritability, memory). Traumatic brain injury diagnosis was based on the American Congress of Rehabilitation Medicine mild TBI criteria, which requires an injury event followed by an alteration in consciousness. A total of 22.8% of soldiers in a BCT returning from Iraq had clinician-confirmed TBI. Those with TBI were significantly more likely to recall somatic and/or neuropsychiatric symptoms immediately postinjury and endorse symptoms at follow-up than were soldiers without a history of deployment-related TBI. A total of 33.4% of soldiers with TBI reported 3 or more symptoms immediately postinjury compared with 7.5% at postdeployment. For soldiers injured without TBI, rates of 3 or more symptoms postinjury and postdeployment were 2.9% and 2.3%, respectively. In those with TBI, headache and dizziness were most frequently reported postinjury, with irritability and memory problems persisting and presenting over time. Following deployment to Iraq, a clinician-confirmed TBI history was identified in 22.8% of soldiers from a BCT. Those with TBI were significantly more likely to report postinjury and postdeployment somatic and/or neuropsychiatric symptoms than those without this injury history. Overall, symptom endorsement decreased over time.

Mild traumatic brain injury (mTBI) includes concussion, subconcussion, and most exposures to explosive blast from improvised explosive devices. mTBI is the most common traumatic brain injury affecting military personnel; however, it is the most difficult to diagnose and the least well understood. It is also recognized that some mTBIs have persistent, and sometimes progressive, long-term debilitating effects. Increasing evidence suggests that a single traumatic brain injury can produce long-term gray and white matter atrophy, precipitate or accelerate age-related neurodegeneration, and increase the risk of developing Alzheimer's disease, Parkinson's disease, and motor neuron disease. In addition, repetitive mTBIs can provoke the development of a tauopathy, chronic traumatic encephalopathy. We found early changes of chronic traumatic encephalopathy in four young veterans of the Iraq and Afghanistan conflict who were exposed to explosive blast and in another young veteran who was repetitively concussed. Four of the five veterans with early-stage chronic traumatic encephalopathy were also diagnosed with posttraumatic stress disorder. Advanced chronic traumatic encephalopathy has been found in veterans who experienced repetitive neurotrauma while in service and in others who were accomplished athletes. Clinically, chronic traumatic encephalopathy is associated with behavioral changes, executive dysfunction, memory loss, and cognitive impairments that begin insidiously and progress slowly over decades. Pathologically, chronic traumatic encephalopathy produces atrophy of the frontal and temporal lobes, thalamus, and hypothalamus; septal abnormalities; and abnormal deposits of hyperphosphorylated tau as neurofibrillary tangles and disordered neurites throughout the brain. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently unknown. Chronic traumatic encephalopathy has clinical and pathological features that overlap with postconcussion syndrome and posttraumatic stress disorder, suggesting that the three disorders might share some biological underpinnings.