title: Tauopathy PET and amyloid PET in the diagnosis of chronic traumatic encephalopathies: studies of a retired NFL player and of a man with FTD and a severe head injury.
abstract: Single, severe traumatic brain injury (TBI) which elevates CNS amyloid, increases the risk of Alzheimer's disease (AD); while repetitive concussive and subconcussive events as observed in athletes and military personnel, may increase the risk of chronic traumatic encephalopathy (CTE). We describe two clinical cases, one with a history of multiple concussions during a career in the National Football League (NFL) and the second with frontotemporal dementia and a single, severe TBI. Both patients presented with cognitive decline and underwent [(18)F]-Florbetapir positron emission tomography (PET) imaging for amyloid plaques; the retired NFL player also underwent [(18)F]-T807 PET imaging, a new ligand binding to tau, the main constituent of neurofibrillary tangles (NFT). Case 1, the former NFL player, was 71 years old when he presented with memory impairment and a clinical profile highly similar to AD. [(18)F]-Florbetapir PET imaging was negative, essentially excluding AD as a diagnosis. CTE was suspected clinically, and [(18)F]-T807 PET imaging revealed striatal and nigral [(18)F]-T807 retention consistent with the presence of tauopathy. Case 2 was a 56-year-old man with personality changes and cognitive decline who had sustained a fall complicated by a subdural hematoma. At 1 year post injury, [(18)F]-Florbetapir PET imaging was negative for an AD pattern of amyloid accumulation in this subject. Focal [(18)F]-Florbetapir retention was noted at the site of impact. In case 1, amyloid imaging provided improved diagnostic accuracy where standard clinical and laboratory criteria were inadequate. In that same case, tau imaging with [(18)F]-T807 revealed a subcortical tauopathy that we interpret as a novel form of CTE with a distribution of tauopathy that mimics, to some extent, that of progressive supranuclear palsy (PSP), despite a clinical presentation of amnesia without any movement disorder complaints or signs. A key distinguishing feature is that our patient presented with hippocampal involvement, which is more frequently seen in CTE than in PSP. In case 2, focal [(18)F]-Florbetapir retention at the site of injury in an otherwise negative scan suggests focal amyloid aggregation. In each of these complex cases, a combination of [(18)F]-fluorodeoxyglucose, [(18)F]-Florbetapir and/or [(18)F]-T807 PET molecular imaging improved the accuracy of diagnosis and prevented inappropriate interventions.
authors.affiliation: 1] Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA [2] Mount Sinai's Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA [3] James J. Peters VA Medical Center, Bronx, NY, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Mitsis
authors.affiliation: 1] Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA [2] James J. Peters VA Medical Center, Bronx, NY, USA [3] Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA [4] The NFL Neurological Program, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Riggio
authors.affiliation: Department of Nuclear Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: L
authors.initials: L
authors.lastname: Kostakoglu
authors.affiliation: 1] Mount Sinai's Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA [2] Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Dickstein
authors.affiliation: Department of Nuclear Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Machac
authors.affiliation: Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: B
authors.initials: B
authors.lastname: Delman
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Goldstein
authors.affiliation: Institute for Neurodegenerative Disorders, Yale University, New Haven, CT, USA.
authors.forename: D
authors.initials: D
authors.lastname: Jennings
authors.affiliation: Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: E
authors.initials: E
authors.lastname: D'Antonio
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Martin
authors.affiliation: Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: T P
authors.initials: TP
authors.lastname: Naidich
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Aloysi
authors.affiliation: 1] Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA [2] Mount Sinai's Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA [3] James J. Peters VA Medical Center, Bronx, NY, USA.
authors.forename: C
authors.initials: C
authors.lastname: Fernandez
authors.affiliation: Institute for Neurodegenerative Disorders, Yale University, New Haven, CT, USA.
authors.forename: J
authors.initials: J
authors.lastname: Seibyl
authors.affiliation: Department of Neurology, University of Virginia, Charlottesville, VA, USA.
authors.forename: S T
authors.initials: ST
authors.lastname: DeKosky
authors.affiliation: 1] Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA [2] James J. Peters VA Medical Center, Bronx, NY, USA [3] Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Elder
authors.affiliation: Institute for Neurodegenerative Disorders, Yale University, New Haven, CT, USA.
authors.forename: K
authors.initials: K
authors.lastname: Marek
authors.affiliation: 1] The NFL Neurological Program, Icahn School of Medicine at Mount Sinai, New York, NY, USA [2] Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: W
authors.initials: W
authors.lastname: Gordon
authors.affiliation: 1] Mount Sinai's Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA [2] Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: P R
authors.initials: PR
authors.lastname: Hof
authors.affiliation: 1] Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA [2] Mount Sinai's Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA [3] James J. Peters VA Medical Center, Bronx, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Sano
authors.affiliation: 1] Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA [2] Mount Sinai's Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA [3] James J. Peters VA Medical Center, Bronx, NY, USA [4] Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA [5] The NFL Neurological Program, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Gandy
mesh_terms: D000368:Aged; D000814:Aniline Compounds; D001921:Brain / Q000000981:diagnostic imaging; D001924:Brain Concussion / Q000150:complications; D020208:Brain Injury, Chronic / Q000150:complications / Q000000981:diagnostic imaging*; D006259:Craniocerebral Trauma / Q000150:complications / Q000000981:diagnostic imaging*; D005026:Ethylene Glycols; D005538:Football; D057180:Frontotemporal Dementia / Q000150:complications / Q000000981:diagnostic imaging*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D024801:Tauopathies / Q000000981:diagnostic imaging
chemical_list: D000814:Aniline Compounds; D005026:Ethylene Glycols; D019275:Radiopharmaceuticals; C545186:florbetapir