Visualizing Brain Proteinopathies Using [F-18]Flornaptitril-PET in the Prediction of Clinical Progression of Mild Cognitive Impairment With Either Suspected Chronic Traumatic Encephalopathy or Alzheimer's Disease

Participants with MCI enrolling in the trial must meet all the following criteria:

a. All of the following features are required: i) 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 ii) History of head trauma exposure, typically associated with history of concussion, although may be limited to subconcussive trauma iii) Head trauma exposure is repetitive in nature iv) Demonstrated progressive course v) Delayed symptom onset vi) 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 (neuropsychological tests, visuospatial, memory, and language) b. Only 1 of the following supportive features is required: i) Emotional dysregulation: including depression, anxiety, agitation, aggression, paranoid ideation, deterioration of interpersonal relationships, or suicidality ii) Behavioral change: including violence, poor impulse control, socially inappropriate behavior, avolition, apathy, change in personality, or comorbid substance abuse iii) Motor disturbance: including bradykinesia, tremor, rigidity, gait instability, dysarthria, dysphagia, or ataxia 9. Participants with MCI due to suspected AD must meet all the following criteria:

1. Diagnosis of MCI due to suspected AD according to workgroups of the Diagnostic Guidelines of the National Institute on Aging and Alzheimer's Association (NIA-AA)

2. Documented evidence of memory decline with gradual onset and slow progression for at least 1 year. If medically documented evidence is not available, an informant may provide confirmatory evidence

3. An MMSE-2 score of 22 to 30, inclusive, at the Screening Visit

4. Biomarker positive based on predefined plasma p-tau cutoff

5. Modified Hachinski Ischemic Score of ˂4 at the Screening Visit

6. Cognitive deficits do not occur exclusively in the context of delirium

7. Cognitive deficits are not better explained by another mental disorder (e.g., major depressive disorder, schizophrenia), or other medical condition (e.g., hypothyroidism)

8. Treated with a stable dosage regimen of acetylcholinesterase inhibitors (AchEI) and/or memantine for at least 4 months prior to the Screening Visit. Participants should be expected to remain on a stable dosage regimen of these medications for the duration of the trial. Participants who are not being treated with AchEI and/or memantine at the time of the Screening Visit due to contraindications or previous failed treatment with these medications are also eligible for inclusion, if it is expected that participants will not be treated with these medications for the duration of the trial.

1. Medically healthy, at the age within 3 years of any participants with MCI due to suspected CTE or AD in Part A, and with no clinically relevant findings on physical examination or laboratory results

2. Participants must have a trial partner who has frequent interaction with them (approximately \>3-4 times per week), will be present for all clinic visits, and can assist in compliance with trial procedures

3. No cognitive impairment based upon cognitive assessment and as evaluated by the Investigator

4. No first-degree family history of early-onset AD or other neurodegenerative diseases (prior to age 65)

5. An MMSE-2 score ≥27.

Visualizing Brain Proteinopathies Using [F-18]Flornaptitril-PET in the Prediction of Clinical Progression of Mild Cognitive Impairment With Either Suspected Chronic Traumatic Encephalopathy or Alzheimer's Disease

What this study is about

Visualizing Brain Proteinopathies Using [F-18]Flornaptitril-PET in the Prediction of Clinical Progression of Mild Cognitive Impairment With Either Suspected Chronic Traumatic Encephalopathy or Alzheimer's Disease

What this study is about