Malo Gaubert1,2, Catharina Lange3,4, Gaël Chételat5, Miranka Wirth6, Antoine Garnier-Crussard7,8, Theresa Köbe1, Salma Bougacha7, Julie Gonneaud7, Robin de Flores7, Clémence Tomadesso7, Florence Mézenge7, Brigitte Landeau7, Vincent de la Sayette9. 1. German Center for Neurodegenerative Diseases, Dresden, Germany. 2. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, LMU University Hospital Munich, Ludwig-Maximilians-Universität, Munich, Germany. 3. German Center for Neurodegenerative Diseases, Dresden, Germany. catharina.lange@charite.de. 4. Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany. catharina.lange@charite.de. 5. Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany. chetelat@cyceron.fr. 6. German Center for Neurodegenerative Diseases, Dresden, Germany. miranka.wirth@dzne.de. 7. Inserm UMR-S U1237, Caen-Normandie University, GIP Cyceron, Caen, France. 8. Clinical and Research Memory Center of Lyon, Lyon Institute for Elderly, Hospices Civils de Lyon, Lyon, France. 9. Normandy University, UNICAEN, PSL Research University, EPHE, INSERM, U1077, CHU of Caen, Neuropsychology and Imaging of Human Memory, Caen, France.
Abstract
BACKGROUND: White matter hyperintensities (WMH) are frequently found in Alzheimer's disease (AD). Commonly considered as a marker of cerebrovascular disease, regional WMH may be related to pathological hallmarks of AD, including beta-amyloid (Aβ) plaques and neurodegeneration. The aim of this study was to examine the regional distribution of WMH associated with Aβ burden, glucose hypometabolism, and gray matter volume reduction. METHODS: In a total of 155 participants (IMAP+ cohort) across the cognitive continuum from normal cognition to AD dementia, FLAIR MRI, AV45-PET, FDG-PET, and T1 MRI were acquired. WMH were automatically segmented from FLAIR images. Mean levels of neocortical Aβ deposition (AV45-PET), temporo-parietal glucose metabolism (FDG-PET), and medial-temporal gray matter volume (GMV) were extracted from processed images using established AD meta-signature templates. Associations between AD brain biomarkers and WMH, as assessed in region-of-interest and voxel-wise, were examined, adjusting for age, sex, education, and systolic blood pressure. RESULTS: There were no significant associations between global Aβ burden and region-specific WMH. Voxel-wise WMH in the splenium of the corpus callosum correlated with greater Aβ deposition at a more liberal threshold. Region- and voxel-based WMH in the posterior corpus callosum, along with parietal, occipital, and frontal areas, were associated with lower temporo-parietal glucose metabolism. Similarly, lower medial-temporal GMV correlated with WMH in the posterior corpus callosum in addition to parietal, occipital, and fontal areas. CONCLUSIONS: This study demonstrates that local white matter damage is correlated with multimodal brain biomarkers of AD. Our results highlight modality-specific topographic patterns of WMH, which converged in the posterior white matter. Overall, these cross-sectional findings corroborate associations of regional WMH with AD-typical Aß deposition and neurodegeneration.
BACKGROUND: White matter hyperintensities (WMH) are frequently found in Alzheimer's disease (AD). Commonly considered as a marker of cerebrovascular disease, regional WMH may be related to pathological hallmarks of AD, including beta-amyloid (Aβ) plaques and neurodegeneration. The aim of this study was to examine the regional distribution of WMH associated with Aβ burden, glucose hypometabolism, and gray matter volume reduction. METHODS: In a total of 155 participants (IMAP+ cohort) across the cognitive continuum from normal cognition to AD dementia, FLAIR MRI, AV45-PET, FDG-PET, and T1 MRI were acquired. WMH were automatically segmented from FLAIR images. Mean levels of neocortical Aβ deposition (AV45-PET), temporo-parietal glucose metabolism (FDG-PET), and medial-temporal gray matter volume (GMV) were extracted from processed images using established AD meta-signature templates. Associations between AD brain biomarkers and WMH, as assessed in region-of-interest and voxel-wise, were examined, adjusting for age, sex, education, and systolic blood pressure. RESULTS: There were no significant associations between global Aβ burden and region-specific WMH. Voxel-wise WMH in the splenium of the corpus callosum correlated with greater Aβ deposition at a more liberal threshold. Region- and voxel-based WMH in the posterior corpus callosum, along with parietal, occipital, and frontal areas, were associated with lower temporo-parietal glucose metabolism. Similarly, lower medial-temporal GMV correlated with WMH in the posterior corpus callosum in addition to parietal, occipital, and fontal areas. CONCLUSIONS: This study demonstrates that local white matter damage is correlated with multimodal brain biomarkers of AD. Our results highlight modality-specific topographic patterns of WMH, which converged in the posterior white matter. Overall, these cross-sectional findings corroborate associations of regional WMH with AD-typical Aß deposition and neurodegeneration.
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Authors: Rutger Heinen; Martijn D Steenwijk; Frederik Barkhof; J Matthijs Biesbroek; Wiesje M van der Flier; Hugo J Kuijf; Niels D Prins; Hugo Vrenken; Geert Jan Biessels; Jeroen de Bresser Journal: Sci Rep Date: 2019-11-14 Impact factor: 4.379
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Authors: Miranka Wirth; Malo Gaubert; Theresa Köbe; Antoine Garnier-Crussard; Catharina Lange; Julie Gonneaud; Robin de Flores; Brigitte Landeau; Vincent de la Sayette; Gaël Chételat Journal: Front Integr Neurosci Date: 2022-04-26
Authors: Antoine Garnier-Crussard; Salma Bougacha; Miranka Wirth; Sophie Dautricourt; Siya Sherif; Brigitte Landeau; Julie Gonneaud; Robin De Flores; Vincent de la Sayette; Denis Vivien; Pierre Krolak-Salmon; Gaël Chételat Journal: Alzheimers Dement Date: 2021-07-28 Impact factor: 16.655
Authors: Liu Shi; Colin R Buchanan; Simon R Cox; Robert F Hillary; Riccardo E Marioni; Archie Campbell; Caroline Hayward; Aleks Stolicyn; Heather C Whalley; Mathew A Harris; Jennifer Waymont; Gordon Waiter; Ellen Backhouse; Joanna M Wardlaw; Douglas Steele; Andrew Mcintosh; Simon Lovestone; Noel J Buckley; Alejo J Nevado-Holgado Journal: Alzheimers Dement (Amst) Date: 2021-09-27