landau mci 2014- final slides

8/13/2019 Landau MCI 2014- Final Slides

1/22

Amyloid, Glucose Metabolism, and Longitudinal Change

Susan Landau

Helen Wills Neuroscience Institute

University of California, Berkeley

Lawrence Berkeley National Lab


2/22


3/22


4/22

Methods

ADNI 1/GO/2 subjects (Normal, Early MCI, Late MCI, AD)

ADNI 1: Up to 9 years of cognitive followup, concurrent FDG & florbetapir

ADNI GO/2: Baseline and 2-year florbetapir & FDG scans

Florbetapir

Cortical retention across Freesurfer-definedtemporal, parietal, cingulate, frontal regions

(composite reference)

FDG

AD-specific MetaROI(pons/vermis reference)

Cognitive

ADAS-cog, AVLT free recall

Longitudinal associations: Mixed effects regression

L Angular

GyrusR Angular

Gyrus

R Inf

Temporal

Gyrus

L Inf

Temporal

Gyrus

Post

Cingulate

Gyrus MetaROI

Landau et al. Neurobiol of Aging 2009

composite

reference region


5/22


6/22

Agreement between florbetapir and FDG

FDG metaROI mean

Both

positive

Both

negative

Corticalflorbetap

irmean

Normal

Subj Mem Compl

Early MCI

Late MCI

AD

Total

N265

50

299

217

171

1002

p-value0.05

ns

0.003


7/22

ADNI timeline

Cognitive testing

FDG

Florbetapir

ADNI 1 Year 0 1 2 3 4 5 6 7

How are florbetapir & FDG status related to longitudinal cognitive decline?


8/22

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


9/22

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


10/22

MCI N=99

ADAS-cog

ADAS-c

og


Florbetapir -

Florbetapir +

FDG -

FDG +

1.9 pts/yr greater decline 1.3 pts/yr greater decline


11/22

MCI N=99


FDG + / Florbetapir +

ADAS-cog

FDG + / Florbetapir -

ADAS-cog


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


12/22

So far

Normal aging Amyloid+ status linked to decline

MCI FDG+ status linked to decline

In MCI, combining amyloid and FDG tells us more

about progression than either marker individually


13/22

ADNI timeline

Cognitive testing

FDG

Florbetapir

ADNI 1

FDG

Florbetapir

ADNI GO/2

Year 0 1 2 3 4 5 6 7

Cognitive testing

Year 0 1 2

What is the relationship between longitudinal florbetapir and FDG

measurements?


14/22

Florbetapir change over 2 years

CorticalS

UVR

(compositeref)

Age

Normal

N=68

Early MCI

N=84

Late MCI

N=28

AD

N=15

Total N = 195


15/22

Amyloid change N=195

SUVRannualchange

Baseline SUVR


16/22

Amyloid change

SUVRannual

change

Baseline SUVR

Villemagne et al. Lancet Neurol (2013)

Villain N et al. Brain 2012

Jack et al. Neurology (2013)


17/22

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 N=68

EMCI N=84

Baseline

Florbetapir -

FDG

change

Longitudinal florbetapir and glucose metabolism

MetaROI

p=0.03

p=0.02


18/22

Longitudinal florbetapir and glucose metabolism

N N=68

EMCI N=84

AnnualFDG

SUVR

change Baseline

Florbetapir -

Baseline

Florbetapir +

Voxelwise SPM analysis:

Baseline florbetapir +/-

X florbetapir change

p


19/22

N

Baseline

Florbetapir +

Increasing florbetapir memory decline

Normals only, regardless of baseline florbetapir status (p = 0.03)

Longitudinal florbetapir and episodic memory change

Decreasing AV45 Increasing AV45Annual florbetapir change

N

EMCI

AVLTcha

nge

Decliningmemory

Im

provingmemory

Baseline

Florbetapir -


20/22

Summary

Cognitive decline in normal aging linked to amyloid status, decline inMCI linked to FDG

Increasing florbetapir is related to increasing FDG in normal aging andearly MCI; Normals also experience memory decline

Hypermetabolism related to amyloid and AD development has beenreported previously in cross-sectional studies, may be compensatory

(Cohen et al 2009, Oh et al 2012, Ossenkoppele et al 2013, Benzinger et al 2013)

Timing of hypermetabolism relative to other biomarker changes isunclear

Bidirectional FDG changes may complicate detection of metabolicabnormalities early in disease


21/22

AD

AS-cog

Normals N=90



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


22/22

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

landau mci 2014- final slides

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