Human Neurodegenerative Disorders
Thursday 23 April 2009
Room 311 16:00-18:00


Caroline A. Sage and Claudia A. M. Wheeler-Kingshott

16:00 729. Differential Diagnosis of Neurodegenerative Dementias Using Structural MRI
    Prashanthi Vemuri1, Kejal Kantarci1, Matthew L. Senjem1, Jeffrey L. Gunter1, Jennifer L. Whitwell1, Keith A. Josephs1, David S. Knopman1, Bradley F. Boeve1, Ronald C. Peterson1, Clifford R. Jack Jr. 1
Mayo Clinic and Foundation, Rochester, MN, USA
    We have developed a framework where antemortem structural MRI scans of pathologically confirmed “pure” cases of each dementia can be used to train an algorithm to recognize the structural abnormalities related to the specific dementia disease process. This knowledge can then be applied to provide differential diagnosis of dementia prospectively for unique individual patients based on the analysis of the subject’s structural MRI scan. The proposed system can also be used to determine the relative contribution of several different dementia disease processes underlying the clinical presentation of dementia in an individual subject.
16:12 730. Brain Alternations in Alzheimer Disease and Frontotemporal Dementia: A Multimodal MRI Analysis
    Yu Zhang1,2, Norbert Schuff1,2, Christopher Ching1,2, Duygu Tosun1,2, Marzieh Nezamzadeh1,2, Wang Zhan1,2, Howard J. Rosen3, Joel H. Kramer3, Maria Luisa Gorno-Tempini3, Bruce L. Miller3, Michael W. Weiner1,2
CIND, VA Medical Center, San Francisco, CA, USA; 2Radiology, UC San Francisco, San Francisco, CA, USA; 3Neurology, UC San Francisco, San Francisco, CA, USA
    We report initial attempts of utilizing structural, perfusion and diffusion MRI together toward a comprehensive analysis of brain alterations in Alzheimer’s disease (AD) and frontotemporal dementia (FTD). We found that gray matter damage, reflected by cortical atrophy and hypoperfusion, dominated the alterations in AD, whereas damage to gray matter and white matter, as measured by diffusion MRI, characterized FTD. These tissue specific patterns may shine a light on the differential pathologies underlying AD and FTD. They may also aid a differential diagnosis between the diseases and emphasize the benefit of multimodality MRI.
16:24 731. Diffusivity Changes Are Predominantly Proportional Along All Axes with Early Neurodegeneration in Alzheimer's Disease
    Julio Acosta-Cabronero1, Guy B. Williams1, George Pengas1, Peter J. Nestor1
Department of Clinical Neurosciences, University of Cambridge, Cambridge, Cambridgeshire, UK
    Diffusion tensor imaging has become a major research focus in neurodegenerative diseases such as Alzheimer’s disease (AD). Most studies have concentrated on fractional anisotropy (FA) reductions. Using tract-based spatial statistics, we found that increases in axial, radial and mean diffusivity in AD were concordant and far more sensitive than FA reductions. The former three measures identified largely confluent white matter abnormalities in parahippocampal gyrus and posterior cingulum, extending laterally into adjacent temporoparietal regions as well as splenium and fornix. This study offers a very plausible and comprehensive view of the landscape of white-matter tract degeneration in early-stage AD.
16:36 732. Comparing APOE Subgroups in Alzheimer's Disease Using Structural and Diffusion MRI
    Nicola Filippini1,2, Achim Gass3, Andreas U. Monsch4, Anil Rao5, Brandon Whitcher5, Paul M. Matthews5, Stephen Smith1
Oxford University FMRIB Centre, Oxford, Oxon, UK; 2Dept. Psychiatry, Oxford University, UK; 3Depts. Neurology and Neuroradiology, University Hospital Basel, Switzerland; 4Memory Clinic Basel, Switzerland; 5GlaxoSmithKline, Clinical Imaging Centre, London, UK
    The APOE4 allele is considered the strongest genetic risk factor for sporadic early and late onset Alzheimer’s disease. While the association between grey matter changes and the presence of APOE4 has been fairly well studied, little is known about the effect of APOE4 on white matter in AD.  To better define specific influences on neurodegenerative processes played by APOE4, we studied grey matter and white matter changes in a group of AD patients, finding meaningful, consistent differences from both structural and diffusion imaging of the 3 relevant APOE subgroups.
16:48 733. Aricept® Treatment Enhances Hippocampal Connectivity in Subjects with Mild Alzheimer’s Disease
    Wenjun Li1, Chunming Xie1,2, Zhilin Wu1, Jennifer Jones3, Piero Antuono3, Thomas McRae4, Shi-Jiang Li1,5
Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA; 2Neurology, School of Clinical Medicine, Southeaset University, Nanjing, Jiang Su, China; 3Neurology, Medical College of Wisconsin, Milwaukee, WI, USA; 4Pfizer, Inc.; 5Psychiatry, Medical College of Wisconsin, Milwaukee, WI, USA
    Cholinergic inhibitor (Aricept®) has proven to be successful in improving the cognitive function of adults with Alzheimer’s disease (AD). We hypothesize that since the cortical and hippocampal areas receive major cholinergic input from the basal forebrain nuclei, treatment with Aricept® can improve the cholinergic activity of AD; it will improve connectivity of the hippocampus network.
17:00 734. Cerebrovascular Reactivity as a Novel Marker in Assessing Vascular Dysfunction in Alzheimer’s Disease
    Uma Yezhuvath1, Jinsoo Uh1, Yamei Cheng1, Kristin Martin-Cook2, Myron Weiner2, Matthias van Osch3, Hanzhang Lu1
Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; 2Alzheimer’s Disease Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; 3Department of Radiology, Leiden University Medical Center, Leiden, Netherlands
    Hypercapnic BOLD (5% CO2 breathing) and baseline PCASL scans were carried out in AD patients and elderly normal controls to obtain whole brain distributions of cerebrovascular reactivity (CVR) and cerebral blood flow (CBF), respectively. AD patients revealed an anterior distribution for CVR deficits along with a posterior distribution of CBF deficits. Regions of CBF deficits did not have any underlying CVR deficits. BOLD functional MRI shows great potential as a marker of dynamic vessel reactivity as compared to CBF measurements that reflect neuronal metabolic changes.
17:12 735. Amplitude of Low Frequency Fluctuation of BOLD Signal and Resting-State Functional Connectivity Analysis of Brains of Parkinson's Disease
    Qin Chen1, Su Lui2, Shu-Shan Zhang1, He-Han Tang2, Jian-Gang Wang3, Xiao-Qi Huang2, Qi-Yong Gong2, Dong Zhou1, Hui-Fang Shang1
Department of Neurology, West China Hospital of Sichuan University, Chengdu, Sichuan, China; 2Huaxi MR Research Center (HMRRC)£Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China; 3Department of Rheumatology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
    Previous studies revealed that PD is associated with abnormal activity in spatially distributed neural systems by PET or SPECT. The present study aims to apply resting state fMRI to examine both regional cerebral function and functional integration in patients with PD. Eleven right handed PD patients and ten healthy controls were recruited in this study. Amplitude of low-frequency (0.01¨C0.8 Hz) fluctuations (ALFF) of the blood oxygenation level-dependent (BOLD) signal and functional connectivity based on a seed-voxel correlation approach was used to investigate the brain function alteration and correlation with UPDRS-III scores.
17:24 736. Tract-Based Spatial Statistics (TBSS) Study in Parkinson’s Disease Identifies Focal Microstructural Abnormality
    Martyn Ezra1, V Gontu2, Maryam Abaei1, Paul S. Morgan1, Nin Bajaj2, Dorothee P. Auer1
Academic Radiology, University of Nottingham, Nottingham, UK; 2Neurology, Derby Royal Infirmary, Derby, UK
    This study aimed to investigate microstructural abnormalities in Patients with Parkinson’s Disease (PwPD). Tract Based Spatial Statistics (TBSS) analysis was performed on Diffusion Tensor Imaging (DTI) data for 26 PwPD and 16 matched controls. We demonstrated focal reduction in Fractional Anisotrophy in the Postural Instability Gait Difficulty (PIGD) subgroup in the left temporo-parietal white matter (WM). Posthoc region of interest (ROI) analysis confirmed a subgroup concordance. Location & subgroup concordance point towards an association with cognitive symptoms in PwPD.
17:36 737. Exploratory 7T MRS in Huntington’s Disease Gene Carriers
    Wouter Teeuwisse1, Eve M. Dumas2, Simon J. van den Bogaard2, Hermien E. Kan1, Raymund A. Roos2, Mark A. van Buchem1, Jeroen van der Grond1
Radiology, Leiden University Medical Center, Leiden, Netherlands; 2Neurology, Leiden University Medical Center, Leiden, Netherlands
    Huntington’s Disease (HD) is a hereditary genetic disease which presents clinically with motor, cognitive and behavioural symptoms. Single voxel MRS (STEAM, TR/TE/TM = 2000/19/25 ms) was performed in frontal lobe, hypothalamus, thalamus, caudate nucleus (CN) and putamen in 8 gene carriers and 11 healthy controls on a Philips 7 Tesla Achiva system. In CN, patients with Huntington’s disease showed decreased NAA concentration and NAA/Cre ratio. Also, Choline levels in thalamus and mI/Cre ratio in the hypothalamus were elevated in patients. No significant differences between patients and controls were found for metabolite concentrations or metabolite/Cre ratios in putamen and frontal lobe.
17:48 738. Quantification of Neurodegeneration in Amyotrophic Lateral Sclerosis (ALS) Using DTI and Iron Mapping
    Christian Langkammer1, Christian Enzinger1, Stefan Quasthoff1, Paula Grafenauer1, Michaela Soellinger1, Franz Fazekas1, Stefan Ropele1
Department of Neurology, Medical University of Graz, Graz, Austria
    The study sought to better characterise disease related brain tissue changes in amyotrophic lateral sclerosis (ALS) using tract based spatial statistics (TBSS) and regional analyses both on DTI and R2* data. The latter served to quantify iron deposition in deep gray and white matter, focussing on changes along the corticospinal tract. R2* measurements appeared to be more sensitive over DTI in detecting tissue abnormalities.