Amyloid and Tauopathy PET Imaging in Acute and Chronic Traumatic Brain Injury
Condition: Traumatic Brain Injury; Chronic Traumatic Encephalopathy; Mild Cognitive Impairment
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Brain Diseases; Chronic Traumatic Encephalopathy; Wounds and Injuries; Cognitive Dysfunction
Study type: Observational

Summary: 
      The potential long-term effects of Traumatic Brain Injury (TBI) are poorly understood.
      Repeated concussions have been associated with an elevated incidence of Alzheimer's disease
      (AD) along with a reduced age of onset. As repetitive TBI has been studied, a syndrome has
      now been identified: chronic traumatic encephalopathy (CTE). There are growing concerns about
      the long-term neurologic consequences of head impact exposure from routine participation in
      contact sports (e.g., boxing, football). Brain autopsies of athletes with confirmed CTE have
      demonstrated tau-immunoreactive neurofibrillary tangles and neuropil threads (known as
      tauopathy). The relationship between exposure to repetitive head impact and the subsequent
      development of chronic neurodegenerative disease has not been established. Further, as the
      diagnosis of CTE (defined by the presence of tauopathy) is presently made after death at
      autopsy, clinical tools and biomarkers for detecting it remain to be defined.

      With the advent of FDA-approved PET amyloid imaging, clinicians and researchers are now able
      to estimate plaque density in the brains of living patients. However, there are critical
      limitations to amyloid imaging. Current evidence suggests that markers of the presence and
      severity of tauopathy may be able to address these limitations. The study will utilize both
      [18F] Florbetapir and [18F]-T807 PET imaging to investigate amyloid and tau accumulation in
      subjects with a history of concussions. In order to determine whether problems with cognition
      and memory are seen within the populations defined for the study, the researchers will
      administer a core battery of neurocognitive testing. This battery will assess cognitive
      abilities commonly affected by TBI, including processing speed, reaction time, new
      problem-solving, executive functions, attention and concentration, and learning and memory.
      These tests, in conjunction with the imaging, will be able to determine whether regional
      brain activity is associated with specific cognitive problems. The researchers will obtain
      PET and neurocognitive data in 3 cohorts: subjects with a history of TBIs, subjects with mild
      cognitive impairment (MCI) and no TBI history, and healthy controls.

      The investigators aim to determine whether individuals with TBI are on the same trajectory of
      neurodegenerative disease seen in AD or in CTE. Because of the overlap in clinical/cognitive
      and some behavioral symptoms in AD and CTE, an additional biomarker tool is needed to prevent
      misdiagnosis. Accurate diagnosis is crucial in order to provide patients with appropriate
      treatment.
    

Detailed description: 
      The study involves two days of study visits. Subjects will be given a copy of the consent
      form on the morning of their first visit, and sign consent in a private room at Mount Sinai
      before any research related procedures are conducted. Subjects will then be brought to the
      Hess Center for Science in Medicine for injection for the [18F] AV-45 (or Amyvid) PET scan.
      On the second visit, which is to be conducted the day after the first visit, subjects will
      have the [18F]AV-1451 (or T807) PET scan and complete the neuropsychological testing battery.

      Both PET scans will be done entirely for the purpose of research. The scans will be read by
      nuclear medicine physicians and a clinical report will be sent to the PI. Any clinically
      relevant findings will be sent to the treating physician and will be communicated to
      patients. During both visits, subjects will be allowed time for meals and breaks between
      study procedures.

      Details of procedures:

      Amyvid PET scan: At the first visit, each participant will have an Amyvid PET scan. The scan
      involves use of a "tracer", which is a radioactive sugar-like substance. This type of PET
      scan involves a tracer called AV-45 (also known as Florbetapir, and by the trade name of
      Amyvid). It has been approved by the FDA for use in PET imaging. It binds to beta-Amyloid
      plaques that may or may not be present in the brain. Amyloid plaque is a sticky substance
      (protein) that accumulates in the brain in larger amounts in people who may have Alzheimer's
      disease. A thin line will be inserted into a vein in one arm for the injection of the tracer.
      Subjects will begin the Amyvid PET scan 50-60 minutes after the injection of the tracer, and
      scanned for about 20 minutes.

      T807 PET scan: On the day of the second visit, each participant will have an [F18] AV-1451
      PET scan, also known as a T807 PET scan. This type of PET scan is being studied by the FDA as
      a diagnostic tool. This PET scan involves a very similar procedure to the Amyvid PET scan the
      day before. Like the Amyvid scan, a thin line will be inserted into a vein in one arm for the
      injection of the AV-1451 radiotracer. This tracer binds to clusters of Tau protein inside the
      brain called neurofibrillary tangles. These tangles are associated with both Alzheimer's
      disease and memory problems that may be related to multiple head injuries or concussions.
      Scanning will begin 80 minutes after the injection of the tracer, and last for about 20
      minutes.

      Neuropsychological testing battery: The neuropsychological assessment is a battery of pencil
      and paper tests that measure memory and thinking abilities. In total it takes about two hours
      to complete.
    

Intervention name(s): Amyvid PET Scan; T807 PET scan
Intervention type(s): Drug; Drug
Intervention description(s): A thin line will be inserted into a vein in one arm for the injection of the tracer. Subjects will begin the Amyvid PET scan 50-60 minutes after the injection of the tracer, and scanned for about 20 minutes.; Scanning will begin 80 minutes after the injection of the tracer, and last for about 20 minutes.
Other intervention name(s): [F18] AV-45; Florbetapir; Amyvid; [F18] AV-1451
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Subjects will be recruited through the Mount Sinai's Alzheimer's Disease Research Center
        (ADRC), the Memory and Aging Center (MAC), Center for Cognitive Health (CCH), and the NFL
        Neurological Program at the Icahn School of Medicine at Mount Sinai.
      
Keywords: Traumatic Brain Injury; Chronic Traumatic Encephalopathy; Mild Cognitive Impairment; PET imaging; tauopathy; amyloid