Alzheimer's Disease Neuroimaging Initiative 3 (ADNI3)
Overview
- Phase
- Not Applicable
- Intervention
- Cognitively Normal (CN)
- Conditions
- Mild Cognitive Impairment (MCI)
- Sponsor
- University of Southern California
- Enrollment
- 1141
- Locations
- 59
- Primary Endpoint
- Rate of change in cognition as measured by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog13)
- Status
- Completed
- Last Updated
- last month
Overview
Brief Summary
Since its launch in 2004, the overarching aim of the Alzheimer's Disease Neuroimaging Initiative (ADNI) has been realized in informing the design of therapeutic trials in AD. ADNI3 continues the previously funded ADNI-1, ADNI-GO, and ADNI-2 studies that have been combined public/private collaborations between academia and industry to determine the relationships between the clinical, cognitive, imaging, genetic and biochemical biomarker characteristics of the entire spectrum of Alzheimer's disease (AD). The overall goal of the study is to continue to discover, optimize, standardize, and validate clinical trial measures and biomarkers used in AD research.
Detailed Description
The overall goal of ADNI3 is to determine the relationships among the clinical, cognitive, imaging, genetic and biochemical biomarker characteristics of the entire spectrum of Alzheimer's disease (AD), as the pathology evolves from normal aging through very mild symptoms, to mild cognitive impairment (MCI), to dementia. ADNI3 continues the previously funded AD Neuroimaging Initiative (ADNI1, ADNI-GO, and ADNI-2), and remains a public/private collaboration between academia and industry to study biomarkers of AD. ADNI will continue to inform the neuroscience of AD, identify diagnostic and prognostic markers, identify outcome measures that can be used in clinical trials, and help develop the most effective clinical trial scenarios. This is multi-center, a non-randomized, natural history, non-treatment study. 1,070-2,000 total participants will be enrolled across three cohorts: cognitively normal\* (CN), mild cognitive impairment (MCI) and mild Alzheimer's Disease (AD) dementia. Participants between the ages of 55-90 (inclusive) will be enrolled at 59 sites in the United States and Canada. Approximately, 700 - 800 will be rollover participants from previous ADNI studies, and 370 - 1200 will be newly enrolled. Clinical/cognitive, imaging, biomarker, and genetic characteristics will be assessed across the three cohorts. Participants will undergo longitudinal clinical and cognitive assessments, computerized cognitive batteries, biomarker and genetic tests, PET (FDG, amyloid and tau) and MRI scans and cerebral spinal fluid (CSF) collection for up to 5 years. \*currently recruiting non-Caucasian participants only for the cognitively normal cohort.
Investigators
Paul S. Aisen
Director, Alzheimer's Therapeutic Research Institute
University of Southern California
Eligibility Criteria
Inclusion Criteria
- •(all CN participants):
- •Participant with or without subjective memory complaints, verified by a study partner, beyond what one would expect for age
- •Normal memory function documented by scoring above education adjusted cutoffs on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale -Revised (the maximum score is 25):
- •9 for 16 or more years of education
- •5 for 8-15 years of education
- •3 for 0-7 years of education
- •Mini-Mental State Exam score between 24 and 30 inclusive (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director)
- •Clinical Dementia Rating =
- •Memory Box score must be 0
- •Cognitively normal, based on an absence of significant impairment in cognitive functions or activities of daily living
Exclusion Criteria
- •(all CN participants):
- •Any significant neurologic disease, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities
- •Exclusion Criteria (all MCI participants):
- •1\. Any significant neurologic disease other than suspected incipient Alzheimer's disease, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities.
- •Exclusion Criteria (all AD participants):
- •1\. Any significant neurologic disease other than Alzheimer's disease, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities.
- •Exclusion Criteria (all participants):
- •The following additional exclusion criteria apply to all diagnostic categories:
- •Screening/Baseline MRI brain scan with evidence of infection, infarction, or other focal lesions or multiple lacunes or lacunes in a critical memory structure
- •Subjects that have any contraindications for MRI studies, including the presence of cardiac pacemakers, or metal fragments or foreign objects in the eyes, skin or body.
Arms & Interventions
Cognitively Normal (CN)
135-500 newly enrolled participants with no apparent memory problems, and 295-300 cognitively normal participants followed from the ADNI2 study. Currently recruiting non-Caucasian participants only for the normal cognition group.
Mild Cognitive Impairment (MCI)
150 - 515 newly enrolled participants with mild cognitive impairment (MCI), and 275-320 MCI participants followed from the ADNI2 study.
Mild Alzheimer's Disease (AD) dementia
85 - 185 newly enrolled participants with mild Alzheimer's disease (AD) dementia, and 130 - 150 mild AD participants followed from the ADNI2 study.
Outcomes
Primary Outcomes
Rate of change in cognition as measured by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog13)
Time Frame: 5 years
The ADAS-Cog is an in-person examiner-administered, structured scale that evaluates memory (word recall, word recognition), reasoning (following commands), language (naming, comprehension), orientation, ideational praxis (placing letter in envelope) and constructional praxis (copying geometric designs). Ratings of spoken language, language comprehension, word finding difficulty, and ability to remember test instructions are also obtained.
Rate of change in cognition as measured by the Logical Memory Test I and II
Time Frame: 5 years
Rate of change in cognition as measured by the Mini-Mental State Examinations (MMSE)
Time Frame: 5 years
The MMSE scale evaluates orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two overlapping pentagons.
Secondary Outcomes
- Rate of change in cognition as measured by the Cogstate Brief Battery (CBB)(5 years)
- Rate of change in cognition as measured by the Rey Auditory Verbal Learning Test(5 years)
- Rate of change in cognition as measured by the American National Adult Reading Test (ANART)(5 years)
- Rate of change in cognition as measured by the Trail Making Test: A and B(5 years)
- Change in tau deposition as measured by 18F-AV-1451(5 years)
- Change in amyloid deposition as measured by Florbetapir(5 years)
- Change in amyloid deposition as measured by Florbetaben(5 years)
- Rate of change in cognition as measured by the Montreal Cognitive Assessment (MoCA)(5 years)
- Rate of conversion to MCI or dementia due to AD(5 years)
- Rates of change of glucose metabolism (FDG-PET)(5 years)
- Change in Cerebral Spinal Fluid (CSF) Tau Biomarkers(5 years)
- Change in brain structure using magnetic resonance imaging (MRI)(5 years)