White matter changes in familial Alzheimer's disease. (12th March 2015)

• Record Type: Journal Article
• Authors: Li, X.; Westman, E.; Ståhlbom, A. K.; Thordardottir, S.; Almkvist, O.; Blennow, K.; Wahlund, L.‐O.; Graff, C.
• Is Part Of: Journal of internal medicine. Volume 278:Number 2(2015:Aug.)
• Page Start: 211
• Page End: 218
• Publication Date: 2015-03-12
• Subjects: Internal medicine -- Periodicals; Medicine -- Periodicals; 616
• DOI: 10.1111/joim.12352
• Languages: English
• ISSNs: 0954-6820

Abstract

<abstract abstract-type="main" id="joim12352-abs-0001"> <title>Abstract</title> <sec id="joim12352-sec-0001" sec-type="section"> <title>Background</title> <p>Familial Alzheimer's disease (FAD) resulting from gene mutations in <italic>PSEN1</italic>, <italic>PSEN2</italic> and <italic>APP</italic> is associated with changes in the brain.</p> </sec> <sec id="joim12352-sec-0002" sec-type="section"> <title>Objective</title> <p>The aim of this study was to investigate changes in grey matter (GM), white matter (WM) and the cerebrospinal fluid (CSF) in FAD.</p> </sec> <sec id="joim12352-sec-0003" sec-type="section"> <title>Subjects</title> <p>Ten mutation carriers (MCs) with three different mutations in <italic>PSEN1</italic> and <italic>APP</italic> and 20 noncarriers (NCs) were included in the study. Three MCs were symptomatic and seven were presymptomatic (pre‐MCs).</p> </sec> <sec id="joim12352-sec-0004" sec-type="section"> <title>Methods</title> <p>Whole‐brain GM volume as well as fractional anisotropy (FA) and mean diffusivity (MD) using voxel‐based morphometry and tract‐based spatial statistics analyses, respectively, were compared between MCs and NCs. FA and MD maps were obtained from diffusion tensor imaging.</p> </sec> <sec id="joim12352-sec-0005" sec-type="section"> <title>Results</title> <p>A significant increase in MD was found in the left inferior longitudinal fasciculus, cingulum and bilateral superior longitudinal fasciculus in pre‐MCs compared with NCs. After inclusion of the three symptomatic MCs in the analysis, the regions became wider. The mean MD of these regions showed significant negative correlation with the CSF level of Aβ42, and positive correlations with P‐tau<sub>181p</sub> and T‐tau. No differences were observed in GM volume and FA between the groups.</p> </sec> <sec id="joim12352-sec-0006" sec-type="section"> <title>Conclusions</title> <p>The results of this study suggest that FAD gene mutations affect WM diffusivity before changes in GM volume can be detected. The WM changes observed were related to changes in the CSF, with similar patterns previously observed in sporadic Alzheimer's disease.</p> </sec> </abstract>