Cognitive Decline and Alzheimer's Disease in the Dallas Lifespan Brain Study
Condition: Alzheimer Disease; Cognitive Decline
MeSH terms: Alzheimer Disease; Cognitive Dysfunction
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      Alzheimer's disease (AD) is a highly prevalent disorder of dementia in older adults. AD
      neuropathology is marked by the presence of amyloid plaques and tau neurofibrillary tangles.
      Autopsy studies, as well as magnetic resonance imaging (MRI) studies in living persons, have
      established that the neurodegenerative changes in AD begin in medial temporal lobe structures
      and later progress to adjacent temporal, parietal and frontal neocortical regions. Magnetic
      resonance image studies of AD consistently reveal volumetric loss in the hippocampus using
      both cross-sectional and longitudinal approaches. The primary symptom of early-stage AD is
      memory impairment possibly accompanied by deficits in attentional control. Normal aging,
      however, is also marked by cognitive decline, as well as structural brain changes. Autopsy
      data had shown in the past that about 30% of older adults with no obvious cognitive
      impairment show some degree of the neuropathology typically associated with dementia at
      autopsy.

      Importantly, the recent ability to image beta-amyloid and tau deposits in vivo using positron
      emission tomography (PET) scanning has revolutionized our understanding of early stages of
      AD. Evidence suggests that amyloid deposits may be detected 10 - 15 years before memory
      symptoms appear. These findings are leading to the ability to diagnose AD years before
      symptoms begin. Much less is known about the impact and developmental course of tau
      deposition as compared to beta-amyloid because the ligand to image tau was only recently
      invented. There is increasing evidence that tau is particularly toxic to the brain and is a
      later precursor of AD than amyloid deposits. Additional research on beta-amyloid and tau
      deposition in aging is crucial, as much work suggests that treatment of AD may be most
      effective when implemented early in the time course of the disease. Understanding the impact
      of tau deposits and its interactions with amyloid deposition allows the investigators to see
      the development of early markers of AD, which are important in understanding the trajectory
      of the disease. An important approach to understand the amyloid/tau puzzle and its
      relationship to AD is a large-scale longitudinal study of normal aging that integrates
      extensive neuroimaging and cognitive assessments along with tau imaging. A key aspect in
      understanding pathological aging is the need to be able to clearly differentiate normal aging
      from early pathology. The present Tau imaging study described here is an important component
      of the Dallas Lifetime Brain Study (DLBS).

      The Dallas Lifespan Brain Study (DLBS) began in 2008 and was designed to utilize the new in
      vivo imaging techniques to address uncertainty regarding how AD pathology relates to the
      developmental process of aging and cognition, fueled in part by the partial overlap of
      pathological markers and decline in mnemonic function observed in a substantial proportion of
      'normal' aged individuals. A total of 296 participants were recruited for Wave 1 from 2008 to
      2014 to the DLBS and they received cognitive testing, structural and functional MRI, as well
      as a scan for beta amyloid using the radioligand AV-45 Florbetapir F 18 (also known as
      "[18F]AV-45"). A total of 183 returning participants were tested four years later in Wave 2,
      and they received the same battery as in Wave 1. In addition, 60 of these were also scanned
      with Flortaucipir F 18 (also known as "[18F]AV-1451"). [18F]AV-1451 is a newly-developed
      Phase II ligand that measures tau deposit in the human brain and this drug was provided to
      the DLBS by Avid Radiopharmaceuticals.

      The objective of the current study is to test 125 DLBS participants with [18F]AV-1451
      (Flortaucipir F 18) at the University of Texas Southwestern Medical Center (UTSW). The
      inclusion of tau imaging in Wave 3 will allow the investigators to relate tau deposition in
      the brain to the 10-year history of amyloid deposition and cognitive decline in the DLBS
      participants and understand the independent and joint contributions of tau to cognitive
      decline and early AD at different ages.
    

Intervention name(s): [18F]AV-1451; Positron Emission Tomography
Intervention type(s): Drug; Procedure
Intervention description(s): 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.
Other intervention name(s): Flortaucipir F18; PET
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Positron Emission Tomography