White Matter Changes are Associated with Ventricular Expansion in Aging, Mild Cognitive Impairment, and Alzheimer’s Disease

Article type: Research Article

Authors: Coutu, Jean-Philippe^{a; b; *} | Goldblatt, Alison^{a; c} | Rosas, H. Diana^{a; d} | Salat, David H.^{a; c; e} | the Alzheimer’s Disease Neuroimaging Initiative (ADNI)¹

Affiliations: [a] MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA | [b] Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA | [c] Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [d] Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [e] Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, MA, USA

Correspondence: [*] Correspondence to: Jean-Philippe Coutu, Division of Health Sciences and Technology, Massachusetts Institute of Technology, Building E25-518, 77 Massachusetts Avenue, Cambridge, 02139-4307 MA, USA. Tel.: +1 857 318 9617; Fax: +1 617 253 6692; E-mail: [email protected]

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing ofthis report. A complete listing of ADNI investigators can be foundat http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

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.

Keywords: Alzheimer’s disease, cerebral ventricles, diffusion tensor imaging, hippocampus, leukoaraiosis, mild cognitive impairment, white matter

DOI: 10.3233/JAD-150306

Journal: Journal of Alzheimer's Disease, vol. 49, no. 2, pp. 329-342, 2016