O1-04-08 PIB AND MRI PROVIDE COMPLEMENTARY INFORMATION IN IMAGING OF AD AND MCI Clifford R. Jack, Val Lowe, Bradley Kemp, Maria Shiung, Stephen Weigand, David Knopman, Bradley Boeve, Ronald Petersen, Mayo Clinic, Rochester, MN, USA. Contact e-mail: jack.clifford@mayo.edu Background: The development of amyloid plaque (or plaque and tangle) labeling compounds like Pittsburgh Compound -B (PIB) has revolutionized the approach to diagnosis of Alzheimer’s Disease (AD). Early diagnostic imaging comparisons have been between PIB and FDG PET with only a single published PIB - Magnetic Resonance Imaging (MRI) comparison report to date. We report preliminary results of an ongoing study comparing MRI and PIB in the same subjects spanning the cognitive spectrum from normal to demented. Objective: To com- pare structural MRI and PIB measures in prevalent normal aging, amnestic Mild Cognitive Impairment (aMCI), and AD. Methods: Thir- teen cognitively normal (CN) elderly, 13 aMCI, and 7 AD subjects underwent PIB and structural MRI. We measured global PIB cortical to cerebellar uptake ratio and hippocampal volumes (HV) corrected for age, gender, and head size in all subjects. Results: PIB ratios were ordered AD  aMCI  CN, and group-wise ordering of HV was reversed. Group-wise separation by PIB and HV was comparable. Mean (SD) PIB ratios in CN, aMCI, and AD were 1.1 (0.1), 1.5 (0.3), 1.9 (0.3), respectively. HV were 0.0 (1.3), - 0.9 (0.6), -2.2 (0.6), respec- tively. For both modalities, CN and AD subjects were completely separated while aMCI subjects overlapped both the CN and AD range. There was a single exception - one CN subject whose HV was in the AD range. All pair-wise comparisons (CN vs aMCI, CN vs AD, aMCI vs AD) were significant (p  0.05) for both PIB and MRI. Conclusions: The two modalities supply independent information about mechanisms relevant to dementia: PIB is an in vivo measure of plaque burden, and structural MRI a measure of neuronal and synaptic damage. Although the inverse correlation was high (r -0.65, p = 0.003), ranking of individual subjects by PIB ratio and HV was not monotonically inverse, indicating that the two modalities provide complimentary diagnostic information. And, combining the two modalities should provide unique insight into the multifactorial mechanisms underlying dementias. Acknowledgments: AG11378, AG06786, AG16574, Robert and Clarice Smith and Abigail Van Buren AD Research Program SUNDAY, JUNE 10, 2007 ORAL O1-05 EARLY DETECTION AND DIAGNOSIS 2 O1-05-01 CORTICAL AMYLOID DEPOSITION RELATED TO FAILURE OF HIPPOCAMPAL ACTIVATION Reisa Sperling 1 , Pete LaViolette 2 , Eli White 1 , J. Alex Becker 2 , Erin Moran 2 , Matt Gregas 3 , William Klunk 4 , Chet Mathis 4 , Julie Price 4 , Alan Fischman 2 , Dennis Selkoe 1 , Dorene Rentz 1 , Keith Johnson 2 , 1 Brigham and Women’s Hospital, Boston, MA, USA; 2 Massachusetts General Hospital, Boston, MA, USA; 3 Harvard School of Public Health, Boston, MA, USA; 4 University of Pittsburgh, Pittsburgh, PA, USA. Contact e-mail: reisa@rics.bwh.harvard.edu Background: Amyloid is thought to be an inciting factor in the patho- physiological process of Alzheimer’s disease (AD). Autopsy data, how- ever, has revealed relatively weak correlations between the amount and location of amyloid plaque burden and dementia severity, while in vitro assays of synaptic function and animal experiments have suggested that amount of amyloid may acutely modulate memory function. Our previous fMRI studies have shown that AD patients demonstrate significantly de- creased hippocampal activation compared to normal older controls. In this study, we wanted to examine the relationship of amyloid burden to the hippocampal activation across a spectrum of cognitive impairment. Ob- jective(s): To investigate the relationship of amyloid deposition, as as- sessed by positron emission tomography (PET) with Pittsburgh Imaging Compound B (PIB), to memory-related functional magnetic resonance imaging (fMRI) patterns of activation. Methods: Seventeen older subjects (seven controls (CDR 0); five subjects with mild cognitive impairment (MCI; CDR 0.5) and five mild AD patients (CDR 1.0)) were imaged with both fMRI during an associative face-name encoding task and PIB-PET acquired over 60 minutes after injection of 10-15 mCi C11-PIB. fMRI datasets were analyzed with two-sample t-tests in SPM2. Functional con- nectivity was assessed with psychophysiological interactions (PPI). Spe- cific PIB binding was calculated using the Logan graphical analysis method yielding a distribution volume ratio (DVR) with cerebellar gray as reference. Subjects were classified as PIB+ if the cortical DVR was 1.05 and PIB- if only non-specific binding was present. Level of PIB binding was entered as a regressor into the functional connectivity maps. Results: Ten of the 17 subjects were PIB+, while seven subjects were PIB-. PIB+ subjects showed significantly decreased activation in the right hippocam- pus (p0.003), compared to PIB- subjects. This finding remained signif- icant, even when CDR score was entered as a co-variate. Furthermore, the level of PIB binding in cortical regions, in particular the precuneus, was correlated with decreased connectivity between precuneus and hippocam- pal regions (p0.007). Conclusions: These preliminary results support the hypothesis that cortical amyloid deposition, particularly in medial parietal regions, is related to hippocampal dysfunction. O1-05-02 AGE AND ALZHEIMER’S DISEASE RELATED EFFECTS ON CEREBRAL BLOOD FLOW AND ARTERIAL TRANSIT TIME OF POSTERIOR CINGULATE CORTEX WITH SERIAL ARTERIAL SPIN LABELING MRI Xiaoping Zhu 1,2 , Norbert Schuff 1,2 , Matthias Gunther 3 , David Feinberg 3 , Yu Zhang 1,2 , Geon-ho Jahng 1,2 , Michael W. Weiner 1,2 , 1 Department of Radiology, UCSF, San Francisco, CA, USA; 2 Center for Imaging of Neurodegenerative Diseases, VA Medical Center, San Francisco, CA, USA; 3 Advanced MRI Technologies, Sebastopol, CA, USA. Contact e-mail: Xiaoping.Zhu@ucsf.edu Background: Previous studies using PET and SPECT reported substantial reduction of cerebral blood flow (CBF) of the posterior cingulate (PC) in Alzheimer disease (AD) and mild cognitive impairment (MCI). However, these methods use ionizing radiation and quantification of CBF remains a S176 Oral O1-05-01: Early Detection and Diagnosis 2