webinar presented on AlzForum January 5, 2012

1. Relationships between beta-amyloid and
functional connectivity in different components
of the default mode network in aging
Mormino EC, Smiljic A, Hayenga AO, Onami S, Greicius
MD, Rabinovici GD, Janabi M, Baker SL, Yen I, Madison
CM, Miller BL, Jagust WJ
Cerebral Cortex, 2011

2. Introduction:
• Aβ is common in cognitively normal elderly subjects.
• May reflect preclinical AD1.
• Initial downstream effects at level of synaptic function2.
Overall Aim: Combine PIB-PET imaging with resting state
fMRI to examine early effects of Aβ in normals.
1Morris 2009 Arch Neurol; 2Selkoe 2002, Science

3. The Default Mode Network
Buckner et al., 2005; J Neurosci
• Highly active ‘at rest’.
• Implicated in episodic memory, future planning, mind wandering, considering
thoughts of others, self-referential processing…
• Overlap with pattern of Aβ deposition.

4. Subjects & Methods
• 44 cognitively normal elderly
• PIB-PET imaging
– Measure of Aβ
• Resting State fMRI
– functional connectivity (spontaneous fluctuations)
– Decomposed via ICA (FSL MELODIC)
– Selected DMN component (template matching procedure)
• Higher level Analysis
– Global PIB versus voxelwise DMN FC

5. PIB and DMN Overlap
PIB
DMN
Overlap
Thresholded at p<0.001, k=100

6. PIB versus Voxelwise DMN
p<0.05, k=50
More PIB, less FC
More PIB, more FC
RSC: Lower connectivity, worse EM (p=0.08)

7. FC versus Regional PIB?
PIB DMN Overlap Decreased FC Increased FC
No pattern between regional PIB and differences in functional connectivity.

8. Different subnetworks within DMN, different vulnerabilities to Aβ?
Medial temporal system: EM
Dorsal medial PFC system: self-referential
Midline core: binds subsystems
Andrews-Hanna 2010, Neuron

9. Summary & Conclusions
• Misalignment between regional PIB levels and FC differences.
• Elevated A is associated with FC decreases in EM-relevant regions of
the DMN.
– Impacted in AD
– Supports preclinical relevance of A in normals
– Consistent with results from other labs (Hedden 2009; Sheline 2010 )
• Elevated A is associated with increases in the dorsal medial PFC
subsystem.
– Compensation for failing episodic memory regions?
– Difficult to interpret resting state connectivity increases

10. Thank you!
Jagust LAβ
Bill Jagust
Gil Rabinovici
Beth Kuczynski
Cindee Madison
Research Assistants
Suzanne Baker
Michael Brandel
Susan Landau Andre Smiljic
Audrey Perrotin Irene Yen
Hwamee Oh Susan Onami
Shawn Marks Ron Liu
Amynta Hayenga
Candace Markley
Henry Schwimmer
Adi Alkalay
Neha Agarwal
Linh Dang
Miranka Wirth
Bénédicte Rossi
Natalie Marchant
Raymond Lo
Tad Haight
And the Berkeley Aging Cohort Subjects!
Funding: NIH (AG027859, AG032814), Alzheimer’s Association (ZEN-08-87090)