[11C]PIB positron emission tomography - Alzheimer's & Dementia

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University School of Medicine, St Louis, Missouri, United States; 2Avid ... Mental Health; Anzhen Hospital, Capital University of Medical Sciences,. Beijing, China ...

Poster Presentations P1 deposition, but this increase was significantly higher in PiB+ within a large network. This finding may reflect the fact that PiB- do have slower rates of Aß accumulation, or that they are less numerous to show a significant PiB accumulation. Arguing for the later hypothesis, the distribution of individual rates of neocortical Aß accumulation revealed to be bimodal, and clustering analyses led to a consistent threshold to separate these two subgroups into “PiB non-accumulators” vs. “PiB accumulators”. The voxelwise 3-way ANCOVA was then re-computed with the “PiB accumulators” only and the results were almost unchanged (see Figure). Conclusions: This study highlighted that rates of Aß accumulation increased as the PiB load increased. It thus suggests that Aß deposition does not reach a plateau when cognitive decline occurs but is instead an on-going mechanism over the course of AD. Besides, this is the first study to take into account the fact that Aß accumulation may not increase in all individuals which might offer the possibility to identify the earliest stages of brain Aß accumulation in PiB- accumulators subjects.

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FREESURFER IN REGIONAL ANALYSIS OF BETAAMYLOID DEPOSITION WITH [11C]PIB POSITRON EMISSION TOMOGRAPHY

Yi Su1, Andrei Vlassenko1, Tammie Benzinger1, Gina D’Angelo1, Tyler Blazey1, Shivangi Vora1, John Morris1, Mark Mintun2, 1Washington University School of Medicine, St Louis, Missouri, United States; 2Avid Radiopharmaceuticals, Philadelphia, Pennsylvania, United States. Background: [11C]PIB and other positron emission tomography (PET) tracers are currently available for the imaging of the amyloid-beta (Aß) plaque deposition in the brain, the hallmark of Alzheimer’s disease (AD). Due to non-specific binding of tracers to white matter, careful separation of gray matter is critical and typical quantitative analysis of PIB images involves manually-derived MRI-based regions of interests (ROIs). However, defining ROIs manually is time consuming, labor intensive, and usually restricted to a limited number of ROIs. In this study, we evaluated the feasibility of using FreeSurfer, a software package that provides automatic segmentation of the brain, to facilitate the regional analysis of [11C] PIB images. Methods: Automated segmentation of the brain was performed based on MRI data using FreeSurfer v5.0. After registration of MRI and the PIB PET images using in house software, for each FreeSurfer ROI, Logan graphical analysis was performed to calculate the binding potential (BP) using cerebellar cortex as the reference region. Standard PIB data analysis was also performed with manually drawn MRI-based ROIs in representative brain regions including precuneus, prefrontal, gyrus rectus, temporal, anterior cingulate, occipital cortex and caudate nucleus. Mean cortical binding potential (MCBP) was calculated from the first four regions and used as a global measure of brain Aß deposition. We then analyzed the consistency between [11C] PIB BP values derived from best matched FreeSurfer and manual ROIs. Results: Strong correlation between the FreeSurfer and manual ROI based results was observed for MCBP (R2 ¼ 0.97, p ¼ 5.8 x 1030) and for regional [11C] PIB BPs in the group of 39 individuals (24 females; mean age 71 6 6.8 yo). The correlation was also high in different subgroups separated based on [11C] PIB levels (PIB+/-, MCBP ¼ 0.18 as cutoff), APOE status (APOE4+/-) and gender. Conclusions: Our data suggest that gray matter regions defined with FreeSurfer segmentation may be used in the evaluation of Aß deposition at different stages of AD pathology.

P1-358

WHITE MATTER INTEGRITY IN FIRST-EPISODE LATE-ONSET DEPRESSION USING TRACT-BASED SPATIAL STATISTICS 1

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Huali Wang , Daniel Chang , Na Zhang , Yi He , Huishu Yuan , Orhan Nalcioglu2, Xin Yu3, Min-Ying Su2, 1Dementia Care & Research Center, Peking University Institute of Mental Health; Key Laboratory for Mental Health, Ministry of Health (Peking University), Beijing, China; 2Tu & Yuen Center for Functional Onco-Imaging, University of California, Irvine, Irvine, California, United States; 3Peking University Institute of Mental Health; Anzhen Hospital, Capital University of Medical Sciences,

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Beijing, China; 4Dementia Care & Research Center, Peking University Institute of Mental Health, Beijing, China; 5Peking University Third Hospital, Beijing, China. Background: The relationship between depression and cognitive impairment is very complex. Previous studies have demonstrated that late-onset depression (LOD) is associated with multi-domain cognitive impairment, including memory, executive function and attention. However, the mechanism of cognitive impairment in LOD remains unclear. In mild cognitive impairment, abnormalities of white matter (WM) measured with diffusion tensor imaging (DTI) technique have been reported. This study was designed to, using tract-based-spatial-statistics (TBSS), explore the whole-brain differences in white matter integrity in first-episode LOD. Methods: A total of 58 subjects were scanned with a Siemens 3T MRI scanner. The diffusion tensor images were acquired with a spinecho single-shot EPI sequence with 64 encoding directions. The demographic characteristics were matched between the two groups. The NC subjects (n ¼ 30; 17 male, 13 female) had a mean age 6 stdev of 72.167.5, and the LOD subjects (n ¼ 28; 13 male, 15 female) had a mean age 6 stdev of 70.467.0. All preprocessing and statistical analysis were performed with the FSL software package from Oxford’s Analysis Group (http://fsl.fmrib.ox.ac.uk/fsl). The FA maps from 58 brains were analyzed with TBSS, with registration of individual FA maps to the most representative FA map within the cohort. MD maps were processed using the same nonlinear registration and projection vectors as the FA maps. Once the skeletonized maps were obtained, the FA and MD values were compared in a voxel-wise fashion between the NC and LOD group using a permutation test with threshold-free cluster enhancement. All tests were taken to be significant at p < 0.05. Results: Group-wise voxel-based comparisons between the NC and LOD revealed significantly decreased FA values in LOD subjects corresponding to the neural tracts of the corpus callosum and the forceps minor of the cingulate gyrus. Significant decreases in FA were also found in the inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and uncinate fasciculus of the sagittal stratum and anterior corona radiata. No significant differences were noted for comparison of MD maps. Conclusions: The comparison of FA and MD maps between the NC and LOD groups revealed significant differences in FA maps corresponding to white matter tracts associated with the limbic, parietal, frontal, and temporal lobes. The inferior fronto-occipital fasciculus, which integrates auditory and visual association cortices with the prefrontal cortex, the inferior longitudinal fasciculus, which is involved in the integration of auditory and speech nuclei, and the uncinate fasciculus, which plays a role in memory integration, are all associated with cognitive emotional function. Decreased FA values in these tracts indicate a possible change in neuron cell integrity or fiber degeneration relative to NC subjects, while no significant changes in MD values suggest conservation of cell-matrix integrity between the two groups. These findings are in agreement with the increasing body of evidence from literature, which hypothesizes that LOD may be associated with acute microstructural WM changes. However, the relationship between microstructural WM changes and the cognitive impairment warrants further investigations.

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COGNITIVELY NORMAL INDIVIDUALS WITH ALZHEIMER’S DISEASE PARENTS MAY BE AT RISK FOR DEVELOPING AGING-RELATED CORTICAL THINNING PATTERNS CHARACTERISTIC OF ALZHEIMER’S DISEASE

Katherine Reiter1, John Csernansky1, John Morris2, Lei Wang1, 1 Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States; 2Washington University, St. Louis, Missouri, United States. Background: Alzheimer’s Disease (AD) is a neurodegenerative disorder in which neuroanatomical changes precede behavioral symptoms. Children of AD patients are at heightened risk of developing AD due to genetic influences, including the apolipoprotein E4 (ApoE4) allele. Studying MR scans of cognitively healthy, adult children of AD patients (AD offspring) and

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