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ADNI PiB Amyloid Imaging Chet Mathis University of Pittsburgh. 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.
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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%) 2 Yr Longitudinal Studies – 39 Subjects • NL: 11 • MCI: 26 • AD: 2 3 Yr Longitudinal Studies – 2 Subjects • NL: 2 • MCI: 0 • AD: 0 • PiB Baseline Entry Times • 20 subjects at ADNI true baseline • 69 subjects at ADNI 12 months • 14 subjects at ADNI 24 months Total 224 PiB Scans
Baseline PiB Studies: 103 Subjects (19 NL, 65 MCI, 19 AD)
9 47 17 10 2 18 Baseline ADNI PiB Subjects 3.5 NL MCI 3.0 AD 2.5 SUVR 50-70 PiB(+) 2.0 Cut-off 1.5 1.0 NeoC4 Ave ACG FC PRC PAR Cut-Off: Aizenstein et al., Arch Neurol 2008; 65:1509-17
PiB(-) PiB(+) 18 9 47 n = 10 17 2 PiB NeoC4 SUVR Baseline Values by Subject Group 2.0 SUVR 50-70 1.5 1.0 NL MCI AD
1 Year Longitudinal PiB Follow-Up Studies: 80 Subjects (17 NL, 50 MCI, 13 AD)
1 Year Changes in PiB NeoC4 SUVR Values by Subject Group Baseline 1 year Baseline 1 year 8 1 12 N = 9 16 34
2 Year Changes in PiB NeoC4 SUVR Values by Subject Group Baseline 2 year Baseline 2 year 4 N = 7 11 2 15
Logan DVR 2.0 1.0 Longitudinal PiB Studies Cognitively Normal Elderly Subject Baseline 1 Yr 2 Yr
30% +1.645 (one-tailed) p=0.05 25% 20% >0.215 -SUVR Frequency 15% 10% 5% 0% 0.1 0.2 0.3 -0.1 -0.3 -0.2 0.15 0.25 -0.25 -0.15 +/-0.05 Delta SUVR PiB NeoC4 Reliable Change Index (RCI)Defined Using Test-Retest Scans
ADNI PiB Longitudinal RCI Data 1 Yr Significant PiB NeoC4 RCI Changes All PiB(-) 2/26 = 8% All PiB(+) 11/54 = 20%
ADNI PiB Longitudinal RCI Data 2 Yr Significant PiB NeoC4 RCI Changes All PiB(-) 0/17 = 0% All PiB(+) 4/22 = 18%
Mild Cognitive Impairment: Predictive Value of PiB Scanning
MCI’s Cover the Range of Amyloid Load Lopresti et al., J Nuclear Medicine 2005
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 Neurology2009 Okello et al., Neurology 2009 Over 1-2 Years of Follow-Up PiB(+) MCI AD Converters: 26/44 (59%) PiB(-) MCI ADConverters: 1/21 (5%)
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 ADConverters: 3/18 (16%)
PiB(-) 3.0 1.21 PiB NeoC4 SUVR: 1.22 1.43 1.0 PiB NeoC4 SUVR: 2.11 2.26 2.54 ADNI PiB Converters from MCI to AD “not clearly abnormal, although borderline abnormalities are limited to frontal regions” “severely abnormal FDG scan with an FTD-like pattern; highly confident of FTD” “abnormal FDG scan with an FTD-like pattern” PiB(+)
Baseline ADNI PiB Subjects (PONS) 9 45 17 10 2 20 2.4 NL MCI AD 1.6 PiB(+) SUVR 50-70 Cut-off 0.80 0.0 NeoC4 Ave ACG FC PRC PAR
9 47 17 10 2 18 Baseline ADNI PiB Subjects 3.5 NL MCI 3.0 AD 2.5 SUVR 50-70 PiB(+) 2.0 Cut-off 1.5 1.0 NeoC4 Ave ACG FC PRC PAR Cut-Off: Aizenstein et al., Arch Neurol 2008; 65:1509-17
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
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