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

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).

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

What this study is about

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

What this study is about