landau- mci slides

8/13/2019 Landau- Mci Slides

1/15

Amyloid, Glucose Metabolism, and Longitudinal Change

Susan Landau

Helen Wills Neuroscience Institute

University of California, Berkeley

Lawrence Berkeley National Lab


2/15

Disclosures

Biogen

Synarc

Avid Radiopharmaceuticals

Janssen AI


3/15

Biomarker agreement in disease development

How are fibrillar amyloid and glucose metabolism related to

longitudinal cognitive decline?

What is the relationship between longitudinal amyloid andglucose metabolism measurements?


4/15

Agreement between florbetapir and FDG

FDG metaROI mean

Both

positive

Both

negative

Corticalflorbetap

irmean

Normal

Subj Mem Compl

Early MCI

Late MCI

AD

N265

50

299

217

171

p-value0.05

ns

0.003


5/15

Normals N=90

ADAS-cog

ADAS-c

og

-6 -5 -4 -3 -2 -1 0Time (yrs) relative to scan

Florbetapir -

Florbetapir +

FDG -

FDG +

Time (yrs) relative to scan

0.22 pts/yr greater decline 0.50 pts/yr greater decline


6/15

ADAS-cog

Normals N=90

Time (yrs) relative to scan Time (yrs) relative to scan

FDG - / Florbetapir - FDG - / Florbetapir +

ADAS-c

og FDG + / Florbetapir - FDG + / Florbetapir +

N = 45, 7 ApoE4+

0.0 pts/yr decline

N = 13, 3 ApoE4+

0.3 pts/yr decline

N = 14, 5 ApoE4+

0.6 pts/yr decline

N = 18, 7 ApoE4+

0.2 pts/yr decline


7/15


8/15

MCI N=99

Time (yrs) relative to scan Time (yrs) relative to scan

FDG + / Florbetapir +

ADAS-cog

FDG + / Florbetapir -

ADAS-cog

FDG - / Florbetapir - FDG - / Florbetapir +

N = 22, 3 ApoE4+, 2 converters

0.1 pts/yr decline

N = 16, 2 ApoE4+, 8 converters1.4 pts/yr decline

N = 17, 9 ApoE4+, 3 converters

0.4 pts/yr decline

N = 44, 32 ApoE4+, 31 converters2.5 pts/yr decline


9/15

Amyloid change

SUVRannual

change

Baseline SUVR


10/15

Amyloid change

SUVRannual

change

Baseline SUVR

Villemagne et al. Lancet Neurol (2013)

Villain N et al. Brain 2012

Jack et al. Neurology (2013)


11/15

L Angular

GyrusR Angular

Gyrus

R Inf

Temporal

Gyrus

L Inf

Temporal

Gyrus

Post

Cingulate

Gyrus

Decreasing AV45 Increasing AV45Annual florbetapir change

Baseline

Florbetapir +

N

EMCI

Baseline

Florbetapir -

FDG

change

Longitudinal florbetapir and glucose metabolism

MetaROI


12/15

Decreasing AV45 Increasing AV45Annual florbetapir change

Longitudinal florbetapir and glucose metabolism

N

EMCI

Voxelwise results:

Baseline florbetapir +/- status X

florbetapir change

FDG

change

Baseline

Florbetapir -

BaselineFlorbetapir +


13/15


14/15

Summary

MCI patients who were abnormal for both abnormal

florbetapir & FDG-PET had the greatest

retrospective decline

Combining amyloid and FDG-PET tells us more about

progression than either marker individually

AD-related FDG changes may not be unidirectional,

complicating interpretation of


15/15

Thank you

Michael Weiner

Bob Koeppe

Eric Reiman

Kewei Chen

Norman Foster

Danielle Harvey

Les Shaw

John Trojanowski

Laurel Beckett

Cliff Jack

Chet Mathis

Andrew Saykin

Ron Petersen

Michael Donohue

Anthony Gamst

Art Toga

Karen Crawford

Paul Aisen

ADNI

ADNI participants & staff

UC Berkeley

Bill Jagust

Suzanne Baker

Allison Fero

Cindee Madison

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