Volumetric reduction of the corpus callosum in Alzheimer's disease in vivo as assessed with voxel-based morphometry Tiffany M. Chaim a , Fábio L.S. Duran a , Ricardo R. Uchida a,c , Cintia A.M. Périco a , Claudio C. de Castro b , Geraldo F. Busatto a, ⁎ a Department of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil b Department of Radiology, University of São Paulo Medical School, São Paulo, Brazil c Department of Psychiatry, Santa Casa Medical School, São Paulo, Brazil Received 20 October 2005; received in revised form 11 March 2006; accepted 2 April 2006 Abstract Several recent magnetic resonance imaging studies have employed voxel-based morphometry (VBM) to detect regional gray matter volume abnormalities in Alzheimer's disease (AD). However, investigations of corpus callosum (CC) abnormalities in AD using this automated methodology have been scarce, and no VBM study investigated correlations between regional CC atrophy and cognitive measurements in AD subjects at mild disease stages. We used VBM to compare the topography of CC volume differences between 14 AD subjects (MMSE 14–25) and 14 healthy volunteers. Images were acquired using a 1.5-Telsa scanner, and were spatially normalized and segmented using optimized VBM. Statistical comparisons were performed using the general linear model. Significant CC atrophy was detected in the antero-superior portion of the splenium, the isthmus, the anterior and posterior portions of the CC body, and the rostral portion of the genu. Voxels showing peak statistical difference were all left-sided (P b 0.001, uncorrected for multiple comparisons). A cluster of significant positive correlation with MMSE scores was seen on the left anterior CC body. Our results confirm previous findings of diffuse volumetric CC reductions early in the course of AD, and warrant further evaluation of the relevance of atrophic changes in anterior CC portions to the cognitive impairments that characterize the disorder. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Magnetic resonance imaging; Cerebral volumetry; Dementia; Memory 1. Introduction Structural brain abnormalities in Alzheimer's disease (AD) include macroscopic brain atrophy and neuropath- ological degenerative changes, which particularly affect medial temporal structures early during the course of the illness, and neocortical regions subsequently (Baron et al., 2001; Galton et al., 2001; Busatto et al., 2003). Several in vivo brain morphometric studies using magnetic reso- nance imaging (MRI) have shown volumetric reductions in AD subjects compared to healthy elderly controls involving not only gray matter cortical areas (Salat et al., 1999; Baron et al., 2001), but also white matter tracts, especially the corpus callosum (CC) (Janowsky et al., 1996; Hampel et al., 1998; Pantel et al., 1999; Black et al., 2000; Meguro et al., 2003; Teipel et al., 2003). Such callosal abnormalities are thought to be due mainly to Wallerian degeneration, secondary to AD-related patho- logical changes in the cortical association areas interconnected by CC fibers (Leys et al., 1991; Bozzali Psychiatry Research: Neuroimaging 154 (2007) 59 – 68 www.elsevier.com/locate/psychresns ⁎ Corresponding author. Rua Ovídio Pires Campos, s/n-CEP 05403- 010, São Paulo, Brazil. Tel./fax: +55 11 30643567. E-mail address: geraldo.busatto@hcnet.usp.br (G.F. Busatto). 0925-4927/$ - see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.pscychresns.2006.04.003