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
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
Baseline PiB Studies: 103 Subjects (19 NL, 65 MCI, 19 AD)
SU
VR
50-
70
1.0
1.5
2.0
2.5
3.0
3.5
ACG FC PAR PRC NeoC4 Ave
Baseline ADNI PiB Subjects
NL
MCI
AD
109 47
18172
Cut-Off: Aizenstein et al., Arch Neurol 2008; 65:1509-17
Cut-offPiB(+)
SU
VR
50-
70
1.0
1.5
2.0
NL MCI AD
PiB(-)PiB(+)
PiB NeoC4 SUVR Baseline Values by Subject Group
n = 10 9 18 47 172
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
Baseline1 year
N = 9 16 1 8 34 12
2 Year Changes in PiB NeoC4 SUVR Values by Subject Group
N = 7 11 4 15 2
Baseline
2 year
Baseline2 year
Logan DVR
1.0
2.0
Baseline 1 Yr 2 Yr
Longitudinal PiB Studies Cognitively Normal Elderly Subject
PiB NeoC4 Reliable Change Index (RCI)Defined Using Test-Retest Scans
0%
5%
10%
15%
20%
25%
30%-0
.3
-0.2
5
-0.2
-0.1
5
-0.1
+/-
0.0
5
0.1
0.1
5
0.2
0.2
5
0.3
Delta SUVR
Fre
qu
ency
+1.645+1.645 (one-tailed) (one-tailed)p=0.05p=0.05
>0.215-SUVR
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
ADNI PiB Longitudinal RCI Data
PiB(-) 6 0 11 0 0 0
PiB(+) 5 1 15 3 2 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
Mild Cognitive Impairment: Predictive Value of PiB Scanning
Lopresti et al., J Nuclear Medicine 2005
MCI’s Cover the Range of Amyloid Load
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%)
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%)
2.11 2.26 2.54PiB NeoC4 SUVR:
PiB(+)
3.0
1.0
ADNI PiB Converters from MCI to AD
PiB(-)
1.21 1.22 1.43PiB 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”
Use of Pons as Reference Region
SU
VR
50-
70
0.0
0.80
1.6
2.4
ACG FC PAR PRC NeoC4 Ave
Baseline ADNI PiB Subjects (PONS)
NL
MCIAD
109 45
20172
Cut-offPiB(+)
SU
VR
50-
70
1.0
1.5
2.0
2.5
3.0
3.5
ACG FC PAR PRC NeoC4 Ave
Baseline ADNI PiB Subjects
NL
MCI
AD
109 47
18172
Cut-Off: Aizenstein et al., Arch Neurol 2008; 65:1509-17
Cut-offPiB(+)
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 FundingAlzheimer’s Association
GEHC
CollaboratorsBill Jagust, UC Berkeley
Bob Koeppe, U Michigan
Norm Foster, U Utah
Bill Klunk, U Pittsburgh
Julie Price, U Pittsburgh