ADNI 1

Cohort
200 elderly controls
400 MCI
200 AD

The first phase of ADNI launched in October 2004 with a 6-year, $67 million contributions from the National Institute on Aging, 13 pharmaceutical companies and two foundations. Originally designed to find more sensitive and accurate biomarkers for the early detection and tracking of AD, the ADNI1 study gathered and analyzed thousands of brain scans, genetic profiles, and blood and cerebrospinal fluid biomarkers.

The study included 400 subjects diagnosed with mild cognitive impairment (MCI), 200 subjects with the early AD, and 200 elderly control subjects.

As with all ADNI phases, ADNI1 researchers used brain imaging measures including structural MRI and PET (both FDG-PET, which measures glucose metabolism in the brain, and a pilot study using amyloid PET using a radioactive compound “Pittsburgh Compound B” which measures brain amyloid accumulation).

Further Reading
The Alzheimer’s Disease Neuroimaging Initiative: Progress report and future plans
The Alzheimer’s Disease Neuroimaging Initiative: A review of papers published since its inception

ADNI GO

Cohort

• 200 EMCI (new)
• 500 Normal Controls and MCI (rollover from ADNI1)

Objectives:

1. Define and characterize the stage of the AD spectrum that precedes MCI by enrolling 200 subjects in the mildest symptomatic phase of AD (EMCI).
2. Perform F18 amyloid imaging on the CN and LMCI subjects from ADNI1 and the newly enrolled EMCI subjects. FDG PET will be performed in association with F18 amyloid imaging.
3. Establish a national network for F18 amyloid imaging and test hypotheses concerning the prevalence and severity of brain amyloid accumulation and its relationship to current and previous changes of clinical state, MRI, FDG-PET, CSF and plasma biomarkers from ADNI1.
4. Collect 3T MRI on all newly enrolled subjects at Baseline, Month 3, Month 6, and Month 12.
5. Continue longitudinal clinical/cognitive and 1.5T MRI studies of approximately 500 LMCI and Cognitively Normal subjects from ADNI1 for an additional 2 years.
6. Collect and analyze blood and CSF biomarkers from all newly enrolled EMCI and follow-up subjects.
7. Collect blood samples for DNA and RNA extraction. Newly enrolled subjects will also have samples collected for Cell Immortalization and APOE genotyping.

ADNI 2

Cohort

• 150 Normal Controls (new)
• 450-500 CN and MCI (rollover from ADNI1; approximate)
• 150 EMCI (new)
• 200 EMCI (rollover from ADNI GO; approximate)
• 150 LMCI (new)
• 200 mild AD (new)

Objectives:

1. Determine the relationships among clinical, imaging, genetic, and biochemical biomarker characteristics of the entire spectrum of Alzheimer’s disease (AD) as the pathology evolves.
2. Inform the neuroscience of AD, identify diagnostic and prognostic markers and outcome measures that can be used in clinical trials, and help develop the most effective clinical trial scenarios.
3. Develop uniform standards for acquiring longitudinal multisite MRI and PET data on patients with AD, MCI, and elderly controls.
4. Perform longitudinal clinical, cognitive, MRI, PET (18F-Florbetapir and FDG), and blood and CSF biomarker studies on 550 newly enrolled subjects in addition to continuing these studies for approximately 700 subjects from ADNI1 and ADNI GO for an additional 5 years.
5. Collect blood samples for DNA and RNA extraction. Newly enrolled subjects will also have samples collected for Cell Immortalization and APOE genotyping.
6. Validate the clinical diagnoses and imaging and biomarker surrogates through neuropathological examination of ADNI1, ADNI GO, and ADNI2 participants who come to autopsy.

ADNI 3

Cohort

• 135-500 Normal Controls (new)
• 295-330 Normal Controls (rollover from ADNI2; approximate)
• 150-515 Mild Cognitive Impairment (MCI) (new)
• 275-320 Mild Cognitive Impairment (MCI) (rollover from ADNI2; approximate)
• 85-185 Mild Alzheimer’s Disease dementia (AD) (new)
• 130-150 Mild Alzheimer’s Disease dementia (AD) (rollover from ADNI2; approximate)

 Objectives:

1. Longitudinal changes in cognition and associated biomarkers

Determine and define those measures of cognition and function, including composite measures, and those biomarker measures, which capture longitudinal change with the highest statistical power to detect treatment effects in clinical trials. Longitudinal change of cerebral tau measured with 18F-AV-1451 PET (AV-1451) will be correlated/compared with other measures.

2. Prediction of cognitive decline

Determine which clinical, cognitive, and biomarker measures that best predict decline of cognition in CN, MCI, and AD participants. In addition, determine which biomarker changes correlate with cognitive decline, with focus on AV-1451 PET.

3. Validation

Validate biomarker measures obtained at Baseline and longitudinally by correlating results with ‘gold standard’ clinical measurements and pathology.

4. Clinical trial design

Determine the optimum outcome measures with attention to cognitive decline and AV-1451 PET (tau PET) , predictors of cognitive decline, and inclusion/exclusion criteria for clinical trials of cognitively normal participants (for secondary preclinical AD trials), MCI patients (for prodromal AD trials) and participants with early dementia due to AD.

5. Discovery

To determine the effects of other known disease proteins found in AD brains and genes, as well as newly discovered genes, proteins, and analytes that provide useful information concerning the pathogenesis/diagnosis of AD.

Further Reading

• The Alzheimer’s Disease Neuroimaging Initiative: Progress report and future plans
• The Alzheimer’s Disease Neuroimaging Initiative: A review of papers published since its inception
• Impact of the Alzheimer’s Disease Neuroimaging Initiative, 2004 to 2014.
• The Alzheimer’s Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement