title: White Matter Changes are Associated with Ventricular Expansion in Aging, Mild Cognitive Impairment, and Alzheimer's Disease.
abstract: White matter lesions are highly prevalent in individuals with Alzheimer's disease (AD). Although these lesions are presumed to be of vascular origin and linked to small vessel disease in older adults, little information exists about their relationship to markers of classical AD neurodegeneration. Thus, we examined the link between these white matter changes (WMC) segmented on T1-weighted MRI and imaging markers presumed to be altered due to primary AD neurodegenerative processes. Tissue microstructure of WMC was quantified using diffusion tensor imaging and the relationship of WMC properties and volume to neuroimaging markers was examined in 219 cognitively healthy older adults and individuals with mild cognitive impairment and AD using data from the Alzheimer's Disease Neuroimaging Initiative. No significant group differences in WMC properties were found. However, there were strong associations between diffusivity of WMC and ventricular volume, volume of WMC and total WM volume. In comparison, group differences in parahippocampal white matter microstructure were found for all diffusion metrics and were largely explained by hippocampal volume. Factor analysis on neuroimaging markers suggested two independent sets of covarying degenerative changes, with potentially age- and vascular-mediated tissue damage contributing to one factor and classical neurodegenerative changes associated with AD contributing to a second factor. These data demonstrate two potentially distinct classes of degenerative change in AD, with one factor strongly linked to aging, ventricular expansion, and both volume and tissue properties of white matter lesions, while the other factor related to classical patterns of cortical and hippocampal neurodegeneration in AD.
authors.affiliation: MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.|Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Coutu
authors.affiliation: MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.|Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Goldblatt
authors.affiliation: MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.|Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: H Diana
authors.initials: HD
authors.lastname: Rosas
authors.affiliation: MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.|Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.|Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, MA, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Salat
mesh_terms: D000368:Aged; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D005163:Factor Analysis, Statistical; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D008609:Mental Status Schedule; D009483:Neuropsychological Tests; D066127:White Matter / Q000473:pathology*
keywords: Alzheimer’s disease; cerebral ventricles; diffusion tensor imaging; hippocampus; leukoaraiosis; mild cognitive impairment; white matter