title: Hippocampal shape alterations are associated with regional Aβ load in cognitively normal elderly individuals.
abstract: Aβ deposition is a driving force of Alzheimer's disease pathology and can be detected early by amyloid positron emission tomography. Identifying presymptomatic structural brain changes associated with Aβ deposition might lead to a better understanding of its consequences and provide early diagnostic information. In this respect we analyzed measures of cortical thickness and subcortical volumes along with hippocampal, thalamic and striatal shape and surface area by applying novel analysis strategies for structural magnetic resonance imaging. We included 69 cognitively normal elderly subjects after careful clinical and neuropsychological workup. Standardized uptake value ratios (cerebellar reference) for uptake of 11-C-Pittsburgh Compound B (PiB) were calculated from positron emission tomographic data for a cortical measurement and for bilateral hippocampus, thalamus and striatum. Associations to shape, surface area, volume and cortical thickness were tested using regression models that included significant predictors as covariates. Left anterior hippocampal shape was associated with regional PiB uptake (P < 0.05, FDR corrected), whereas volumes of the hippocampi and their subregions were not associated with cortical or regional PiB uptake (all P > 0.05, FDR corrected). Within the entorhinal cortical region of both hemispheres, thickness was negatively associated with cortical PiB uptake (P < 0.05, FDR corrected). Hence, localized shape measures and cortical thickness may be potential biomarkers of presymptomatic Alzheimer's disease.
authors.affiliation: Institute for Regenerative Medicine, University of Zurich, Wagistrasse 12, CH-8952, Schlieren, Switzerland.
authors.forename: Clemens
authors.initials: C
authors.lastname: Schroeder
authors.affiliation: Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.|Cerebral Imaging Centre, Douglas Mental Health University Institute, McGill University, Montréal, QC, Canada.
authors.forename: Min Tae M
authors.initials: MTM
authors.lastname: Park
authors.affiliation: Cerebral Imaging Centre, Douglas Mental Health University Institute, McGill University, Montréal, QC, Canada.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Germann
authors.affiliation: Cerebral Imaging Centre, Douglas Mental Health University Institute, McGill University, Montréal, QC, Canada.|Departments of Psychiatry and Biomedical Engineering, McGill University, Montreal, QC, Canada.
authors.forename: M Mallar
authors.initials: MM
authors.lastname: Chakravarty
authors.affiliation: Institute of Neuroradiology, University of Zurich, Zurich, Switzerland.
authors.forename: Lars
authors.initials: L
authors.lastname: Michels
authors.affiliation: Institute of Neuroradiology, University of Zurich, Zurich, Switzerland.
authors.forename: Spyros
authors.initials: S
authors.lastname: Kollias
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich, Zurich, Switzerland.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Kroll
authors.affiliation: Department of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Alfred
authors.initials: A
authors.lastname: Buck
authors.affiliation: Department of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Valerie
authors.initials: V
authors.lastname: Treyer
authors.affiliation: Clinic for Gerontopsychiatry, Psychiatric University Hospital Zurich, Zurich, Switzerland.
authors.forename: Egemen
authors.initials: E
authors.lastname: Savaskan
authors.affiliation: Institute for Regenerative Medicine, University of Zurich, Wagistrasse 12, CH-8952, Schlieren, Switzerland.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Unschuld
authors.affiliation: Institute for Regenerative Medicine, University of Zurich, Wagistrasse 12, CH-8952, Schlieren, Switzerland.
authors.forename: Roger M
authors.initials: RM
authors.lastname: Nitsch
authors.affiliation: Institute for Regenerative Medicine, University of Zurich, Wagistrasse 12, CH-8952, Schlieren, Switzerland.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Kälin
authors.affiliation: Institute for Regenerative Medicine, University of Zurich, Wagistrasse 12, CH-8952, Schlieren, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hock
authors.affiliation: Institute for Regenerative Medicine, University of Zurich, Wagistrasse 12, CH-8952, Schlieren, Switzerland.
authors.forename: Anton F
authors.initials: AF
authors.lastname: Gietl
authors.affiliation: Institute for Regenerative Medicine, University of Zurich, Wagistrasse 12, CH-8952, Schlieren, Switzerland.|Clinic for Gerontopsychiatry, Psychiatric University Hospital Zurich, Zurich, Switzerland.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Leh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D052160:Benzothiazoles; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging* / Q000254:growth & development; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D019275:Radiopharmaceuticals; D013844:Thiazoles
keywords: Alzheimer's disease; beta-amyloid; hippocampal shape; magnetic resonance imaging; positron emission tomography