Cognitive Decline and Alzheimer's Disease in the Dallas Lifespan Brain Study
Condition: Alzheimer Disease; Cognitive Decline
MeSH terms: Alzheimer Disease; Cognitive Dysfunction
Intervention: [18F]AV-1451; Positron Emission Tomography
Intervention description: The subject will receive up to a target dose of 370 megabecquerel (MBq) as a single IV bolus of [18F]AV-1451.; Approximately 80 minutes after injection subjects will be placed in the UTSW PET/CT scanner for a 20-minute brain scan.
Phase: Phase 2
Study type: Interventional
Primary purpose: Diagnostic
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 125.0
Sex: All
Minimum age: 38 Years
Maximum age: 96 Years
Healthy volunteers: No
Keywords: Positron Emission Tomography

Summary:

      The investigators will conduct tau positron emission tomography (PET) scans on 125 adults
      using the radiopharmaceutical Flortaucipir F18 ([18F]AV-1451). This will allow the
      investigators to determine tau deposition across adults of different ages and assess the
      relationship of current tau burden to cognitive function and amyloid deposition collected
      over the previous 10-year interval.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participated in Wave 1 or 2 of the DLBS study.

          -  Subjects must indicate that they are not currently pregnant if they are women of
             child-bearing potential. Women of child-bearing potential and men must agree to use
             adequate contraception (hormonal or barrier method of birth control; abstinence) prior
             to study entry, for the duration of study participation, and for 90 days following
             completion of therapy. Should a woman become pregnant or suspect she is pregnant while
             participating in this study, she should inform her treating physician immediately. A
             female of child-bearing potential is any woman (regardless of sexual orientation,
             having undergone a tubal ligation, or remaining celibate by choice) who meets the
             following criteria: 1) Has not undergone a hysterectomy or bilateral oophorectomy; or
             2) Has not been naturally post-menopausal for at least 12 consecutive months (i.e.,
             has had menses at any time in the preceding 12 consecutive months).

          -  Volumetric Brain MRI Image (T-1 Weighted MPRage) collected as part of DLBS Wave 1, 2,
             or 3 protocol.

          -  Completed at least 9 years of formal education, or the equivalent of freshman year of
             high school.

          -  Fluent English speakers.

          -  Tolerate laying 20 minutes on a flat table for the PET scan.

          -  Ability to understand and the willingness to sign a written informed consent.

        Exclusion Criteria:

          -  Mini-Mental State Examination (MMSE) score lower than 22; all DLBS participants at the
             time of initial Wave 1 enrollment between 2008 - 2014 had an MMSE score of 26 or
             above, indicating normal cognitive function. However, in the time interval between
             Wave 1 and Wave 3, it is possible that mental capacity may have deteriorated. The
             investigators will exclude all participants in Wave 3 testing who have an MMSE lower
             than 22.

          -  Taking some types of sedatives, benzodiazepines, or anti-psychotics.

          -  Currently undergoing chemotherapy or radiation for cancer.

          -  New history of substance abuse.

          -  Has a history of drug or alcohol dependence within the last year, or prior prolonged
             history of dependence.

          -  Recreational drug use in past six months.

          -  Central nervous systems disease or brain injury that would preclude participation in
             the study.

          -  Psychiatric or neurological disorder that would preclude participation in this study.

          -  Has clinically significant hepatic, renal, pulmonary, metabolic or endocrine
             disturbances which pose safety risk.

          -  Has a current clinically significant cardiovascular disease that poses a safety risk.

          -  Has a current clinically significant infectious disease or a medical comorbidity which
             poses a safety risk.

          -  Has either: 1) Screening electrocardiogram (ECG) with corrected QT Interval (QTc) >
             450 millisecond (msec) if male, or QTc > 470 msec if female; or 2) A history of
             additional risk factors for Torsades de Pointes (TdP) (e.g., hypokalemia, family
             history of Long QT syndrome) or are taking drugs that are known to cause QT
             prolongation (a list of prohibited and discouraged medications is provided by the
             Sponsor); Patients with a prolonged QTc interval in the setting of intraventricular
             conduction block (examples right bundle branch block or left bundle branch block), may
             be enrolled with sponsor approval.

          -  Has received or will receive investigational medication within the 30 days of PET/CT
             scan.

          -  Has received or will receive a radiopharmaceutical for imaging or therapy within 24
             hours of PET/CT scan.

          -  Is a participant who, in the opinion of the investigator(s), is otherwise unsuitable
             for a study of this type.