title: White matter pathology isolates the hippocampal formation in Alzheimer's disease.
abstract: Prior work has demonstrated that the memory dysfunction of Alzheimer's disease (AD) is accompanied by marked cortical pathology in medial temporal lobe (MTL) gray matter. In contrast, changes in white matter (WM) of pathways associated with the MTL have rarely been studied. We used diffusion tensor imaging (DTI) to examine regional patterns of WM tissue changes in individuals with AD. Alterations of diffusion properties with AD were found in several regions including parahippocampal WM, and in regions with direct and secondary connections to the MTL. A portion of the changes measured, including effects in the parahippocampal WM, were independent of gray matter degeneration as measured by hippocampal volume. Examination of regional changes in unique diffusion parameters including anisotropy and axial and radial diffusivity demonstrated distinct zones of alterations, potentially stemming from differences in underlying pathology, with a potential myelin specific pathology in the parahippocampal WM. These results demonstrate that deterioration of neocortical connections to the hippocampal formation results in part from the degeneration of critical MTL and associated fiber pathways.
authors.affiliation: MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA 02129-2060, United States. salat@nmr.mgh.harvard.edu
authors.forename: D H
authors.initials: DH
authors.lastname: Salat
authors.forename: D S
authors.initials: DS
authors.lastname: Tuch
authors.forename: A J W
authors.initials: AJ
authors.lastname: van der Kouwe
authors.forename: D N
authors.initials: DN
authors.lastname: Greve
authors.forename: V
authors.initials: V
authors.lastname: Pappu
authors.forename: S Y
authors.initials: SY
authors.lastname: Lee
authors.forename: N D
authors.initials: ND
authors.lastname: Hevelone
authors.forename: A K
authors.initials: AK
authors.lastname: Zaleta
authors.forename: J H
authors.initials: JH
authors.lastname: Growdon
authors.forename: S
authors.initials: S
authors.lastname: Corkin
authors.forename: B
authors.initials: B
authors.lastname: Fischl
authors.forename: H D
authors.initials: HD
authors.lastname: Rosas
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology*; D016880:Anisotropy; D001921:Brain / Q000473:pathology; D056324:Diffusion Tensor Imaging; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology; D009434:Neural Pathways / Q000473:pathology; D009929:Organ Size; D020534:Parahippocampal Gyrus / Q000473:pathology