Alzheimer's Disease Neuroimaging Initiative Grand Opportunity
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Mild Cognitive Impairment
- Sponsor
- Alzheimer's Disease Cooperative Study (ADCS)
- Enrollment
- 342
- Locations
- 55
- Primary Endpoint
- Rate of Decline as measured by: Cognitive tests, Activities of Daily Living, and CDR Sum of Boxes
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
The purpose of this study is to build upon the information obtained in the original Alzheimer's Disease Neuroimaging Initiative (ADNI1), to examine how brain imaging technology can be used with other tests to measure the progression of mild cognitive impairment (MCI) and early Alzheimer's disease (AD). ADNI-GO seeks to define and characterize the mildest symptomatic phase of AD, referred to in this study as early amnestic MCI (EMCI). This information will aid in the early detection of AD, and in measuring the effectiveness of treatments in future clinical trials.
Detailed Description
This project continues the work from ADNI1, the goal of which is to test whether serial magnetic resonance imaging (MRI), positron emission tomography (PET), other biological markers, and clinical and neuropsychological assessments can be combined to measure the progression of mild cognitive impairment (MCI) and early Alzheimer's disease (AD). The goal of the study is to determine relationships among the clinical, cognitive, imaging, genetic, and biochemical biomarker characteristics of the stage of the AD spectrum that precedes MCI, the mildest symptomatic phase of AD, referred to here as EMCI. The ADNI-GO model posits that AD begins with amyloid β (Aβ) deposition in the cortex, which leads to synaptic dysfunction, neurodegeneration, and cognitive/ functional decline. Some of the leading-edge technologies under study are brain-imaging techniques, such as positron emission tomography (PET), including FDG-PET (which measures glucose metabolism in the brain); PET using a radioactive compound (F-AV-45) that measures brain beta-amyloid; and structural MRI. Brain scans are showing scientists how the brain's structure and function change as AD starts and progresses. Biomarkers in cerebrospinal fluid are revealing other changes that could identify which patients with MCI will develop Alzheimer's. Scientists are looking at levels of beta-amyloid and tau in cerebrospinal fluid. (Abnormal amounts of the amyloid and tau proteins in the brain are hallmarks of Alzheimer's disease.) All participants from ADNI1 who are in the normal and MCI stages will continue to be followed in ADNI-GO. The next step is to scan and analyze the brains of people with EMCI; 200 EMCI participants will be enrolled to narrow the gap between cognitively normal (CN) and "late MCI (LMCI)" participants currently enrolled in ADNI. The overall impact of this study will be increased knowledge concerning the sequence and timing of events leading to MCI and AD, development of better clinical and imaging/fluid biomarker methods for early detection and for monitoring the progression of these conditions, and facilitation of clinical trials of treatments to slow disease progression, ultimately contributing to the prevention of AD.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Between 55 and 90 years of age
- •Study partner to accompany patient to all clinic visits for the duration of the protocol
- •Memory complaint by patient and/or study partner
- •Abnormal memory function score on Wechsler Memory Scale (adjusted for education)
- •Mini-Mental State Exam score between 24 and 30 (inclusive)
- •Clinical Dementia Rating = 0.5; Memory Box score at least 0.5
- •General cognition and functional performance sufficiently preserved such that a diagnosis of Alzheimer's disease cannot be made by the site physician at the time of the screening visit
- •Stability of the following permitted medications for 4 weeks (unless stated otherwise):
- •Antidepressants lacking significant anticholinergic side effects
- •Estrogen replacement therapy
Exclusion Criteria
- •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 defaults or known structural brain abnormalities
- •Screening/baseline MRI scans with evidence of infection, infarction, or other focal lesions; multiple lacunes or lacunes in a critical memory structure
- •Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body
- •Major depression, bipolar disorder as described in DSM-IV within the past 1 year
- •Psychotic features, agitation or behavioral problems within the last 3 months which could lead to difficulty complying with the protocol
- •History of schizophrenia
- •History of alcohol or substance abuse or dependence within the past 2 years
- •Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol
- •Clinically significant abnormalities in B12, or TFTs that might interfere with the study
- •Residence in skilled nursing facility
Outcomes
Primary Outcomes
Rate of Decline as measured by: Cognitive tests, Activities of Daily Living, and CDR Sum of Boxes
Time Frame: at screening, baseline, 6 (EMCI only) and 12 months
Secondary Outcomes
- Group differences for each imaging and biomarker measurement(at screening, baseline, 6 (EMCI only) and 12 months)
- Correlations among biomarkers and biomarker change(at screening, baseline, 6 (EMCI only) and 12 months)
- Rates of change on each specified biochemical biomarker(at baseline, 6 (EMCI only) and 12 months)
- Extent of amyloid deposition as measured by 18F-AV-45(at baseline)
- Rate of volume change of whole brain, hippocampus, and other structural MRI measures(at screening and 3, 6, and 12 months (EMCI); at baseline and 12 months (follow-up patients))
- Rate of conversion will be evaluated among all four groups(at screening , baseline, 6 (EMCI only) and 12 months)
- Rates of change of glucose metabolism (FDG-PET)(at baseline)
- Subgroups analyses: APOE genotype, low CSF Aβ42, positive amyloid imaging with 18F-AV-45(at baseline)