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