1. Alzheimer’s Disease Neuroimaging Initiative STEERING COMMITTEE April 20 2015
Michael W. Weiner

2. The “Big” News
The highly encouraging Biogen phase 1b results, showing reduction of brain amyloid load and slowing of cognitive decline, provide POC for anti-amyloid treatments
This encourages
more clinical trial activity
more NIH funding
interest in AD biomarkers detection and monitoring
Potential problems in enrolling ADNI 3 subjects

3. THE BIG PICTURE Overall, ADNI is doing very well
We have 15 months left for ADNI2
Two tau PET studies funded in past year
DOD Tau PET, includes ADNI subjects
ADNI competitive supplement for tau PET
Should allow tau PET on all ADNI and DOD ADNI subjects and longitudinal studies
Expect to submit ADNI3 mid October 2015

4. PLANS FOR ADNI 3 SPECIFIC AIMS
Overall goal: validation of biomarkers for AD
Longitudinal change of cognition and biomarkers: measures that capture longitudinal change with highest statistical power
Prediction of cognitive decline:
Clinical trial design: Optimum outcome measures, predictors, and inclusion/exclusion criteria for clinical trials
Discovery: new markers, new targets

5. ADNI 3 STUDY DESIGN About 900 subjects planned
40% cognitively normal, 40% MCI, 20% dementia (from converted MCI)
Most subjects will be roll-overs, but some new subjects will be enrolled
Annual visits: Clinical, cognitive, MRI, amyloid PET, tau PET, FDG PET?, LP/CSF, genetics, omics

6. NEW FEATURES IN ADNI 3
Use of Brain Health Registry for recruitment, assessment and longitudinal monitoring
Includes on-line cognitive testing for screening, F/U
Tau PET: AVID 1451, and others to be considered
Amyloid PET centaloid project: AVID, Pirimal, ?
Advanced, Connectome, multi-modal MRI
New Platform for CSF analysis, Mass Spec
Systems Biology, Omics, and Data Mining

7. DISCLOSING RESULTS TO PATIENTS
Some clinicans request to disclose results to patients. Request change in ADNI policy
Advantages
Patients have a “right to know”
Will facilitate recruitment/retention
Disadvantages
This action will change the outcome
Not using “CLIA-approved labs”
Amyloid PET, CSF results, tau results, genetics?
Current plan is not to include in grant application

8. PROBLEM: COMPETITIVE SPACE
Selection of ADNI 3 Biomarker platform
Review of all possibilities: consultation with PPSB
Selection of tau tracer by PET Core
Currently AVID 1451 is only tracer widely available, piloted in ADNI2
All possible tau tracers to be considered
Selection of on-line cognitive tests
Compelling data in grant required: goal is to be funded
ADNI 3 begins 16 months after grant submission
ADNI 3 enrollment will compete with many trials

9. COLLABORATION WITH INDUSTRY PARTNERS
ADNI is a grant submitted to NIA, must be reviewed and funded
ADNI investigators responsible for scientific conduct
UO-1 or UO-19 requires close NIA oversight: For example, NIA decides on sample release
Industry supports 30% of funds. The overall goal is to facilitate industry and academic trials. We greatly value PPSB input and collaboration

10. OTHER COLLABORATIONS Joint analysis with DIAN
Joint analysis of ADNI and PPMI data sponsored by Michael J Fox
SAGE Challange

11. GOVERNANCE
Grant is submitted to NIA from the Northern California Institute for Research and Education (NCIRE), Michael Weiner PI
In the event that the PI cannot function as PI, Bill Jagust , at UC Berkeley, will become PI and assume an NCIRE appointment
After that future decisions will be made by NIA, NCIRE, ADNI Executive Committee , in consultation with the PPSB

12. LONG TERM FUTURE OF ADNI
If ADNI 3 proceeds, what would happen after ADNI 3?
Depending on success of treatments, it may not be possible to enroll subjects with preclinical, prodromal or , dementia due to AD in an observational trial
Shift to study of younger amyloid negative subjects at long term risk for developing amyloid positivity: primary prevention trials to prevent amyloid /tau formation
And/or a study of “normal aging”

13. OPPORTUNITY
ADNI 3 may be the “last” large observational study of the natural history of AD progression
Availability of treatments will prevent study of populations without treatment
High excitement about AD clinical trials provides compelling rationale for ADNI3 to inform better trial design

14. MANY THANKS NIA for strong support
Industry Partners, Foundations, and FNIH
Site PIs, study coordinators
ADCS staff
Subjects and their families