FDDNP Protocol for Visualizing Brain Proteinopathies to Assist in the Diagnosis of Persons With Suspected CTE and AD

Inclusion Criteria

• •Participants enrolling in the trial must meet all of the following criteria:
• •Participant may be male or female and of any race/ethnicity
• •Age 18 to 80 years at the time of study drug dosing
• •Female participants must be either surgically sterilized or post-menopausal, defined as at least one-year without menses as reported by the participant or have a negative serum pregnancy test
• •Participant or participant's legally acceptable representative (when appropriate) provides informed consent
• •Participant is capable of complying with study procedures
• •Participant is capable of communicating with study personnel
• •Participant is willing to undergo longitudinal follow-up at 1 and 2 years after the Imaging Visit
• •All participants will meet criteria for mild cognitive impairment (Petersen et al, 2014) or Mild Neurocognitive Disorder (APA, 2013):
• •Patient awareness of a memory problem, preferably confirmed by another person who knows the patient
• •Memory impairment detected with standard assessment tests
• •Ability to perform normal daily activities
• •For a broad definition of mild cognitive impairment, we also use guidelines to identify those with other mild cognitive impairment subtypes, including those with memory impairment and/or additional cognitive deficits (Winblad et al, 2004). The diagnosis will be corroborated by clinical judgment and include participants who score 1 standard deviation or more below the age-corrected norms because this threshold for impairment yields high sensitivity for predicting dementia (de Jager et al, 2005). To balance increased sensitivity with specificity, impairment on at least 2 neuropsychological tests will be required (Jak et al., 2009).
• •Participants with suspected CTE enrolling in the trial must meet all of the following criteria:
• •Participant must meet the most recently proposed clinical criteria for suspected CTE (termed possible traumatic encephalopathy syndrome or TES; Reams et al, 2016). These proposed diagnostic criteria for possible TES include the following features:
• •Required Features:
• •Persistence of symptoms for longer than 2 years; no other neurologic disorder that is more likely to account for all the clinical features; history of head trauma exposure; progressive course; and at least 1 supportive feature
• •History of head trauma exposure, typically associated with history of concussion, although may be limited to subconcussive trauma
• •Head trauma exposure is repetitive in nature
• •Demonstrated progressive course
• •Delayed symptom onset
• •Self-report or observer report of cognitive dysfunction, confirmed with objective cognitive decline documented by results of formal neuropsychological testing. Cognitive decline typically affects more than 1 domain (executive, visuospatial, memory, and language).
• •Supportive Features (only 1 required):
• •Emotional dysregulation: including depression, anxiety, agitation, aggression, paranoid ideation, deterioration of interpersonal relationships, and suicidality
• •Behavioral change: including violence, poor impulse control, socially inappropriate behavior, avolition, apathy, change in personality, and comorbid substance abuse
• •Motor disturbance: including bradykinesia, tremor, rigidity, gait instability, dysarthria, dysphagia, and ataxia
• •Participants with suspected AD enrolling in the trial must meet all of the following criteria:
• •Cognitive deficits do not occur exclusively in the context of a delirium.
• •Cognitive deficits are not better explained by another mental disorder (e.g., major depressive disorder, schizophrenia).
• •There is insidious onset and gradual progression of impairment in one or more cognitive domains.
• •The participant has documented memory problems in one or more other cognitive domains, such as language, visual-spatial functioning, executive functioning, etc. (Busse et al., 2006).