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

2. 10 TH YEAR ANNIVERSARY Discussions about ADNI began in 2001 ADNI funded in 2004 We still have 2 ½ years of ADNI2 Encouraged to submit an ADNI2

3. THE BIG PICTURE Overall, ADNI is doing very well –We are more than half-way through ADNI2 We have overenrolled Drop outs are low Many publications: widespread data sharing Clinical trials use ADNI results and methods High interest in a renewal: ADNI3 –Very high interest in longitudianal tau PET! –High interest in studying the “earliest stages”

4. SPECIFIC ACCOMPLISHMENTS First and largest multisite study: amyloid phenotyping: –PIB –Florbetapir –CSF amyloid These measurements, together with clinical, cognitive, MRI, FDG PET, genetic make for a huge resource Clifford Jack’s “model” of progression

5. Disease progression Seminal paper by Jack et al (2010) proposed a model for disease progression that formed the basis of many subsequent studies.

6. 500… or 15.3 inches (38cm), double-sided. Over 3200 publications mention “Alzheimer’s Disease Neuroimaging Initiative” (Google Scholar) Plus > 300 submitted

7. PROBLEMS Very large, complex project, difficult to understand all activities Projected budget deficit: –Plan is to eliminate: –ADs, Control and SMC alternate years, MRIs of MCI on alternate years, all FDG PET –Formal notification to sites coming soon Delay in data upload from sites: –Major Problem: difficult to track drop outs

8. TAU PET Very promising because tau –Correlates with symptoms much better than amyloid (based on autopsy) –Is a potential “surrogate outcome” for clinical trials because Autopsy has shown that tangle accumulation closely correlates with neurodegeneration Thus slowing of tau tangle accumulation may be a valid surrogate for slowing of disease progression Tau PET may have higher power than cognition

9. GRANT SUBMISSIONS FOR TAU PET (T807) Department of Defense: –Multisite tau PET add-on to DOD ADNI: Effects of TBI and PTSD on AD in Vietnam Veterans. Includes some ADNI subjects NIA: Competitive supplement to ADNI2: –Longitudinal multisite tau PET: all 5 subject groups. Will be reviewed in June 2014 AVID has offered T807 without cost for these grants

10. WHAT IS NEXT ADNI 3 submission could be as early as June 2015, depending on advise from NIA –Overall goal: Validation of biomarkers for AD trials A focus will be on longitudinal tau PET Strong interest in early development of AD –Possibly enroll younger subjects –Consider less emphasis on demented subjects We need input from Site PIs, NIA, Pharma, Foundations, and others to plan ADNI3

11. OTHER HIGHLIGHTS Emerging longitudinal data of ADNI2 Mass Spectroscopy analysis of CSF amyloid –May reduce the problems of quantification Whole genome sequencing Multimodal MRI

12. COMPARISON OF ASL- PERFUSION MRI, FDG PET, sMRI Philp Insel, Duygu Tosun, Niklas Mattsson, Norbert Schuff, Michael Weiner VA Medical Center, UCSF

13. GOAL AND METHODS To compare the sensitivity of ASL-MRI, FDG PET, and sMRI to detect changes due to AD at different disease stages All comparisons are performed against amyloid negative normal controls Amyloid positive subjects: –Controls, EMCI, LMCI, AD Used both CSF and Florbetapir for phenotyping

14. [unpublished data] FDG CBF STR Aβ+ Early MCIAβ+ MCIAβ+ AD Aβ+ CN Aβ+ CN vs Aβ- CNAβ+ eMCI vs Aβ- CNAβ+ MCI vs Aβ- CNAβ+ AD vs Aβ- CN ACCSENSSPECACCSENSSPECACCSENSSPECACCSENSSPEC FDG0.84± 0.07 0.58± 0.26 0.95± 0.10 0.74± 0.04 0.66± 0.11 0.82± 0.07 0.70± 0.09 0.42± 0.17 0.89± 0.15 0.75± 0.09 0.66± 0.10 0.82± 0.15 CBF0.81± 0.12 0.66± 0.16 0.88± 0.10 0.72± 0.07 0.68± 0.13 0.79± 0.11 0.72± 0.09 0.49± 0.14 0.87± 0.12 0.69± 0.09 0.61± 0.22 0.63± 0.10 STR0.95± 0.05 0.92± 0.08 0.94± 0.05 0.92± 0.06 0.92± 0.08 0.92± 0.11 0.86± 0.04 0.82± 0.10 0.89± 0.10 0.94± 0.02 0.94± 0.06 0.93± 0.04 VOXEL BASED COMPARISONS: USED FLORBETAPIR

15. NL+ vs. NL- : All Modalities

16. EMCI+ vs. NL- : All Modalities

17. LMCI+ vs. NL- : All Modalities

18. AD+ vs. NL- : All Modalities

19. ASL: All DX

20. FDG: All DX

21. Volume: All DX

22. Headings

23. SUMMARY AND CONCLUSION Cerebral blood flow, measured by ASL MRI, favorably compares with FDG PET and sMRI –Especially in earlest stages Changes in CBF occur in same/different regions than FDG PET, the techniques are complementary ASL appears particularly useful to detect early changes in controls and EMCI 3D ASL sequences are expected to provide improved results

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