White matter changes in familial Alzheimer's disease

• DOI: 10.1111/joim.12352
• Publication Date: 2015-01-31T06:52:36Z
• Authors: X. Li; E. Westman; A. K. Ståhlbom; S. Thordardottir; O. Almkvist; K. Blennow; L.‐O. Wahlund; C. Graff
• Keywords: Adult; Male; Middle Aged; Neuropsychological Tests; White Matter; 3. Good health; 03 medical and health sciences; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; 0302 clinical medicine; Alzheimer Disease; Humans; Female

AbstractBackgroundFamilial Alzheimer's disease (FAD) resulting from gene mutations in PSEN1, PSEN2 and APP is associated with changes in the brain.ObjectiveThe aim of this study was to investigate changes in grey matter (GM), white matter (WM) and the cerebrospinal fluid (CSF) in FAD.SubjectsTen mutation carriers (MCs) with three different mutations in PSEN1 and APP and 20 noncarriers (NCs) were included in the study. Three MCs were symptomatic and seven were presymptomatic (pre‐MCs).MethodsWhole‐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.ResultsA 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‐tau181p and T‐tau. No differences were observed in GM volume and FA between the groups.ConclusionsThe 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.