Alzheimer’s Disease Neuroimaging Initiative

STEERING COMMITTEE

Michael W. Weiner

10TH 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

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”

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

Disease progression

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

500…

or 15.3 inches (38cm), double-sided.

Over 3200 publications mention “Alzheimer’s Disease Neuroimaging Initiative” (Google Scholar)

Plus > 300 submitted

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

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

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

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

OTHER HIGHLIGHTS

• Emerging longitudinal data of ADNI2• Mass Spectroscopy analysis of CSF amyloid

– May reduce the problems of quantification

• Whole genome sequencing• Multimodal MRI

COMPARISON OF ASL-PERFUSION MRI, FDG PET, sMRI

Philp Insel, Duygu Tosun, Niklas Mattsson, Norbert Schuff, Michael Weiner

VA Medical Center, UCSF

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

[unpublished data]

FDG

CBF

STR

Aβ+ Early MCI Aβ+ MCI Aβ+ ADAβ+ CN

Aβ+ CN vs Aβ- CN Aβ+ eMCI vs Aβ- CN Aβ+ MCI vs Aβ- CN Aβ+ AD vs Aβ- CN

ACC SENS SPEC ACC SENS SPEC ACC SENS SPEC ACC SENS SPEC

FDG 0.84±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

CBF 0.81± 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

STR 0.95±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

NL+ vs. NL- : All Modalities

EMCI+ vs. NL- : All Modalities

LMCI+ vs. NL- : All Modalities

AD+ vs. NL- : All Modalities

ASL: All DX

FDG: All DX

Volume: All DX

Headings

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

MANY THANKS

• NIA for strong support• Industry Partners, Foundations, and FNIH• Site PIs, study coordinators• ADCS staff• Subjects and their families