Jeffrey R. Petrella, MD Jeffrey R. Petrella, MD Associate Professor of Radiology Associate Professor of Radiology Director, Alzheimer’s Imaging Research Director, Alzheimer’s Imaging Research Laboratory Laboratory Duke University Medical Center, Durham NC Duke University Medical Center, Durham NC From Molecules to Networks to From Molecules to Networks to Behavior Behavior behavior The W isconsin C ard S orting Task cognition temperment
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Jeffrey R. Petrella , MD Associate Professor of Radiology
From Molecules to Networks to Behavior. cognition. behavior. Jeffrey R. Petrella , MD Associate Professor of Radiology Director, Alzheimer’s Imaging Research Laboratory Duke University Medical Center, Durham NC. temperment. Clinical Progression of AD and MCI. Time (y). 1-10 y. 0 y. - PowerPoint PPT Presentation
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Jeffrey R. Petrella, MDJeffrey R. Petrella, MD
Associate Professor of RadiologyAssociate Professor of Radiology
Director, Alzheimer’s Imaging Research LaboratoryDirector, Alzheimer’s Imaging Research Laboratory
Duke University Medical Center, Durham NCDuke University Medical Center, Durham NC
From Molecules to Networks to BehaviorFrom Molecules to Networks to Behavior
behavior
The Wisconsin Card Sorting Task
cognition
temperment
Clinical Progression of AD and MCI
Clinical Progression of AD and MCI
Co
gn
itiv
e fu
nct
ion
•Forgetfulness
•Repetitive questions
•Daily function impaired
•Progression of cognitive deficits
•Short-term memory loss
•Word-finding difficulties
•Agitation
•Altered sleep patterns
•Total dependence: dressing, feeding, bathing
MCIMMSE 24–30 Mild AD
MMSE 20–23
Moderate ADMMSE 10–19
Severe ADMMSE 0–9
•Mild subjective/objective memory loss
•Normal function
10 y0 yTime (y)
1-10 y
Early Stage Middle StageAdapted from: Braak H, Braak E. Acta Neuropathol (Berl). 1991;82:239-259
Evolution of the Disease Evolution of the Disease Neurofibrillary Changes in Early AD
Amyloid Accumulation Plateaus EarlyAmyloid Accumulation Plateaus Early
Distribution of Left and Right Hippocampal Voxel Counts (normalized, Distribution of Left and Right Hippocampal Voxel Counts (normalized, age-adjusted) and MMSE (age-adjusted) in MCI and Control subjectsage-adjusted) and MMSE (age-adjusted) in MCI and Control subjects
-1
-0.5
0
0.5
1
1.5
Control MCI AD
Pa
ram
ete
r E
sti
mat
e (
PM
C c
lus
ter)
y = -0.1002x + 0.5029
2R = 0.2524
-2
-1
0
1
2
3
-1 4 9 14 19
Control
MCI
AD
(Petrella et al, Radiology, 2007) CVLT-II delayed recall score
Sign
al I
nten
sity
-1
-0.5
0
0.5
1
1.5
ONS MCI-Nonconverter MCI-Converter AD
Act
ivat
ion
Par
amet
er
Est
ima
te
-1
-0.5
0
0.5
1
1.5
MCI-Nonconverter MCI-Converter
PMC region of interest
-1
-0.5
0
0.5
1
1.5
Control MCI AD
Act
iva
tion
Pa
ram
ete
r E
stim
ate
(Petrella, et al., PLoS ONE Oct 2007)
APOE E3 – E4
Rieman EM et al, PNAS 2004
Cortical “Hubs”
Buckner et al., Journal of Neuroscience (2009)
Cortical Connectivity and Amyloid Deposition
Buckner et al., Journal of Neuroscience (2009)
DMN Integrity and Amyloid Burden
Sperling RA et al. Neuron 2009
Neurodegenerative Diseases Target Large-Scale Human Brain Networks