1. ADNI PiB Amyloid Imaging Chet Mathis University of Pittsburgh

2. Enrollment in ADNI PiB Studies to June 2010 ( All Data Are Available On The LONI Website) Baseline – 103 Subjects at 14 PET Sites NL: 19, 78±5 y/o, MMSE 29±1 MCI: 65, 75±8 y/o, MMSE 27±2 AD: 19, 73±9 y/o, MMSE 22±3 1 Yr Longitudinal Studies – 80 Subjects NL: 17/19 (89%) MCI: 50/65 (77%) AD: 13/19 (68%) PiB Baseline Entry Times 20 subjects at ADNI true baseline 69 subjects at ADNI 12 months 14 subjects at ADNI 24 months 3 Yr Longitudinal Studies – 2 Subjects NL: 2 MCI: 0 AD: 0 2 Yr Longitudinal Studies – 39 Subjects NL: 11 MCI: 26 AD: 2 Total 224 PiB Scans

3. Baseline PiB Studies: 103 Subjects (19 NL, 65 MCI, 19 AD)

4. SUVR 50-70 1.0 1.5 2.0 2.5 3.0 3.5 ACGFC PAR PRC NeoC4 Ave Baseline ADNI PiB Subjects NL MCI AD 10 9 47 18 17 2 Cut-Off: Aizenstein et al., Arch Neurol 2008; 65:1509-17 Cut-off PiB(+)

5. SUVR 50-70 1.0 1.5 2.0 NLMCI AD PiB(-) PiB(+) PiB NeoC4 SUVR Baseline Values by Subject Group n = 10 9 18 47 17 2

6. 1 Year Longitudinal PiB Follow-Up Studies: 80 Subjects (17 NL, 50 MCI, 13 AD)

7. 1 Year Changes in PiB NeoC4 SUVR Values by Subject Group Baseline 1 year Baseline 1 year N = 916 1 8 34 12

8. 2 Year Changes in PiB NeoC4 SUVR Values by Subject Group N = 711 4 15 2 Baseline 2 year Baseline 2 year

9. Logan DVR 1.0 2.0 Baseline 1 Yr 2 Yr Longitudinal PiB Studies Cognitively Normal Elderly Subject

10. PiB NeoC4 Reliable Change Index (RCI) Defined Using Test-Retest Scans 0% 5% 10% 15% 20% 25% 30% -0.3 -0.25 -0.2 -0.15 -0.1 +/-0.05 0.1 0.15 0.2 0.25 0.3 Delta SUVR Frequency +1.645  (one-tailed) p=0.05 >0.215  -SUVR

11. ADNI PiB Longitudinal RCI Data PiB(-) 9 2 16 0 1 0 PiB(+) 8 3 34 5 12 3 Ctrl # >0.215 MCI # >0.215 AD # >0.215 All PiB(-) 2/26 = 8% All PiB(+) 11/54 = 20% 1 Yr Significant PiB NeoC4 RCI Changes

12. ADNI PiB Longitudinal RCI Data PiB(-) 6 011 0 0 0 PiB(+) 5 115 32 0 Ctrl # >0.215 MCI # >0.215 AD # >0.215 All PiB(-) 0/17 = 0% All PiB(+) 4/22 = 18% 2 Yr Significant PiB NeoC4 RCI Changes

13. Mild Cognitive Impairment: Predictive Value of PiB Scanning

14. Lopresti et al., J Nuclear Medicine 2005 MCI’s Cover the Range of Amyloid Load

15. Does PiB-Positivity Predict Clinical Conversion of MCI to AD? Three Published Studies To Date: Forsberg et al., Neurobiol Aging 2008 Wolk et al., Annals of Neurology 2009 Okello et al., Neurology 2009 Over 1-2 Years of Follow-Up PiB(+) MCI  AD Converters: 26/44 (59%) PiB(-) MCI  AD Converters: 1/21 (5%)

16. Does PiB-Positivity Predict Clinical Conversion of MCI to AD? ADNI PiB MCI Conversion Data Over 1-2 Years of Follow-Up PiB(+) MCI  AD Converters: 21/47 (45%) PiB(-) MCI  AD Converters: 3/18 (16%)

17. 2.11 2.26 2.54 PiB NeoC4 SUVR: PiB(+) 3.0 1.0 ADNI PiB Converters from MCI to AD PiB(-) 1.21 1.22 1.43 PiB NeoC4 SUVR: “abnormal FDG scan with an FTD-like pattern” “severely abnormal FDG scan with an FTD-like pattern; highly confident of FTD” “not clearly abnormal, although borderline abnormalities are limited to frontal regions”

18. Use of Pons as Reference Region

19. SUVR 50-70 0.0 0.80 1.6 2.4 ACGFC PAR PRC NeoC4 Ave Baseline ADNI PiB Subjects (PONS) NL MCI AD 10 9 45 20 17 2 Cut-off PiB(+)

20. SUVR 50-70 1.0 1.5 2.0 2.5 3.0 3.5 ACGFC PAR PRC NeoC4 Ave Baseline ADNI PiB Subjects NL MCI AD 10 9 47 18 17 2 Cut-Off: Aizenstein et al., Arch Neurol 2008; 65:1509-17 Cut-off PiB(+)

21. ADNI PiB Summary Results from baseline ADNI PiB scans are generally consistent with other groups and the literature Year 1 and 2 longitudinal PiB scans show small or no group increases, but ~20% of individual PiB(+) subjects show significant increases over 1-2 year ADNI PiB MCI to AD conversion data show ~3X as many PiB(+) conversions than PiB(-) conversions. More ADNI PiB(-) converted compared to literature data, but the n is low for ADNI and 2 of 3 PiB(-) subjects had an FDG pattern consistent with FTD not AD Use of Pons as the reference region made little difference in data analysis results and interpretation ADNI PiB data contain more noise than data collected at one site, but provide a useful, open database for investigators

22. Acknowledgements ADNI PiB Funding Alzheimer’s Association GEHC Collaborators Bill Jagust, UC Berkeley Bob Koeppe, U Michigan Norm Foster, U Utah Bill Klunk, U Pittsburgh Julie Price, U Pittsburgh

23. Reliable Change Index (RCI) Jacobson & Truax, J Consult Clin Psychol 59:12-19 (1991) Compares the change in an individual over time to “noise” measured in test-retest experiments Noise = SD diff = RCI = (SUVR t2 – SUVR t1 ) / SD diff (i.e., a z-score) Significant at p=0.05 when RCI > 1.645  (one-tailed because interested in significant increases)

24. PiB Reliable Change Index (RCI) Defined at Pittsburgh [Retest –Test] PiB value determined for: 7 Control, 9 MCI, and 6 AD subjects within 28 days Values did not differ by diagnostic group, so all 22 subjects were combined SD diff was calculated for each individual ROI and NeoC4 average RCI then calculated for each subject at 1 or 2 years

25. ADNI PiB Longitudinal RCI Data (PONS) PiB(-) 9 0 17 0 1 0 PiB(+) 8 1 33 6 12 3 Ctrl # >0.114 MCI # >0.114 AD # >0.114 All PiB(-) 0/27 = 0% All PiB(+) 10/53 = 19% 1 Yr Significant PiB NeoC4 RCI Changes

26. ADNI PiB Longitudinal RCI Data (PONS) PiB(-) 7 010 0 0 0 PiB(+) 4 016 42 0 Ctrl # >0.114 MCI # >0.114 AD # >0.114 All PiB(-) 0/17 = 0% All PiB(+) 4/22 = 18% 2 Yr Significant PiB NeoC4 RCI Changes