adni pib amyloid imaging chet mathis university of pittsburgh

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