Amyloid and Tauopathy PET Imaging in Acute and Chronic Traumatic Brain Injury

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.

Conditions

• Traumatic Brain Injury
• Chronic Traumatic Encephalopathy
• Mild Cognitive Impairment

Interventions

DRUG

Amyvid PET Scan

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.

DRUG

T807 PET scan

Scanning will begin 80 minutes after the injection of the tracer, and last for about 20 minutes.

Sponsors & Collaborators

• Samuel Gandy

  lead OTHER

Principal Investigators

• Sam Gandy, MD, PhD · Icahn School of Medicine at Mount Sinai

• Dara Dickstein, PhD · Icahn School of Medicine at Mount Sinai

Eligibility

Min Age

40 Years

Max Age

85 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2015-01-31

Primary Completion

2017-12-21

Completion

2017-12-21

FDA Drug

Yes

Countries

• United States

Study Locations