When, where, and how the corpus callosum changes in MCI and AD: a multimodal MRI study.

BACKGROUND: The corpus callosum (CC) has been shown to be susceptible to atrophy in Alzheimer disease (AD) as a correlate of wallerian degeneration or retrogenesis. However, when and where these 2 mechanisms intervene is still unclear. METHODS: In 3 memory clinics, we recruited 38 patients with amnestic mild cognitive impairment (MCI), 38 patients with mild AD, and 40 healthy controls (HC). Combining voxel-based morphometry and diffusion tensor imaging, we investigated CC white matter (WM) density and fractional anisotropy (FA), radial diffusivity (DR), and axial diffusivity (DA). RESULTS: Compared with HC, patients with amnestic MCI showed reduced WM density in the anterior CC subregion; however, FA, DR, and DA did not differ between the 2 groups. Significant changes were found in patients with mild AD compared with HC in the anterior and posterior CC regions. These differences were evident in both voxel-based morphometry and diffusion tensor imaging analyses. Specifically, we found reduced callosal WM density in the genu, posterior body, and splenium; decreased FA and increased DR in the anterior CC subregion; and increased DA, with no difference in the FA, in the posterior CC subregion. CONCLUSIONS: Callosal changes are already present in patients with amnestic mild cognitive impairment (MCI) and mild Alzheimer disease (AD). The precocious involvement of the anterior callosal subregion in amnestic MCI extends to posterior regions in mild AD. Two different mechanisms might contribute to the white matter changes in mild AD: wallerian degeneration in posterior subregions of the corpus callosum (suggested by increased axial diffusivity without fractional anisotropy modifications) and a retrogenesis process in the anterior callosal subregions (suggested by increased radial diffusivity without axial diffusivity modifications).