Amyloid, Glucose Metabolism, and Longitudinal Change

Susan Landau

Helen Wills Neuroscience Institute University of California, Berkeley Lawrence Berkeley National Lab

Disclosures

Biogen Synarc Avid Radiopharmaceuticals Janssen AI

Biomarker agreement in disease development

How are fibrillar amyloid and glucose metabolism related to longitudinal cognitive decline?

What is the relationship between longitudinal amyloid and glucose metabolism measurements?

Agreement between florbetapir and FDG

Both positive
Normal Subj Mem Compl Early MCI Late MCI AD

Cortical florbetapir mean

N 265 50 299 217 171

p-value 0.05 ns 0.003 <0.001 ns

Both negative

FDG metaROI mean

Normals N=90

ADAS-cog

FDG -

Florbetapir -

FDG +
ADAS-cog
0.22 pts/yr greater decline

Florbetapir +
0.50 pts/yr greater decline

-6

-5

-4

-3

-2

-1

Time (yrs) relative to scan

Time (yrs) relative to scan

Normals N=90

ADAS-cog

FDG - / Florbetapir N = 45, 7 ApoE4+ 0.0 pts/yr decline

FDG - / Florbetapir +
N = 14, 5 ApoE4+ 0.6 pts/yr decline

ADAS-cog

FDG + / Florbetapir N = 13, 3 ApoE4+ 0.3 pts/yr decline

FDG + / Florbetapir +
N = 18, 7 ApoE4+ 0.2 pts/yr decline

Time (yrs) relative to scan

Time (yrs) relative to scan

MCI N=99

ADAS-cog

FDG -

Florbetapir -

FDG +
ADAS-cog
0.22 pts/yr greater decline

Florbetapir +
0.50 pts/yr greater decline

Time (yrs) relative to scan

Time (yrs) relative to scan

MCI N=99

FDG - / Florbetapir ADAS-cog

N = 22, 3 ApoE4+, 2 converters 0.1 pts/yr decline

FDG - / Florbetapir +
N = 17, 9 ApoE4+, 3 converters 0.4 pts/yr decline

FDG + / Florbetapir ADAS-cog

N = 16, 2 ApoE4+, 8 converters 1.4 pts/yr decline

FDG + / Florbetapir +
N = 44, 32 ApoE4+, 31 converters 2.5 pts/yr decline

Time (yrs) relative to scan

Time (yrs) relative to scan

Amyloid change

SUVR annual change

Baseline SUVR

Amyloid change

Jack et al. Neurology (2013)

Villemagne et al. Lancet Neurol (2013)

Villain N et al. Brain 2012

SUVR annual change

Baseline SUVR

Longitudinal florbetapir and glucose metabolism

Meta ROIs
Post Cingulate Gyrus

Baseline Florbetapir FDG change

MetaROI
L Inf Temporal Gyrus R Angular Gyrus

L Angular Gyrus

R Inf Temporal Gyrus

N EMCI

Baseline Florbetapir +

Decreasing AV45 Increasing AV45 Annual florbetapir change

Longitudinal florbetapir and glucose metabolism

Baseline Florbetapir FDG change

N EMCI

Voxelwise results: Baseline florbetapir +/- status X florbetapir change

Baseline Florbetapir +

Decreasing AV45 Increasing AV45 Annual florbetapir change

Longitudinal florbetapir and episodic memory change

AVLT change Declining memory Improving memory

Baseline Florbetapir -

N EMCI N

Baseline Florbetapir +

Decreasing AV45 Increasing AV45 Annual florbetapir change Increasing florbetapir memory decline Normals only, regardless of baseline florbetapir status (p = 0.03)

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

Thank you
ADNI
ADNI participants & staff 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

UC Berkeley
Bill Jagust Suzanne Baker Allison Fero Cindee Madison