title: The cholinergic system in mild cognitive impairment and Alzheimer's disease: an in vivo MRI and DTI study.
abstract: Few studies have investigated in vivo changes of the cholinergic basal forebrain in Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI), an at risk stage of AD. Even less is known about alterations of cortical projecting fiber tracts associated with basal forebrain atrophy. In this study, we determined regional atrophy within the basal forebrain in 21 patients with AD and 16 subjects with MCI compared to 20 healthy elderly subjects using deformation-based morphometry of MRI scans. We assessed effects of basal forebrain atrophy on fiber tracts derived from high-resolution diffusion tensor imaging (DTI) using tract-based spatial statistics. We localized significant effects relative to a map of cholinergic nuclei in MRI standard space as determined from a postmortem brain. Patients with AD and MCI subjects showed reduced volumes in basal forebrain areas corresponding to anterior medial and lateral, intermediate and posterior nuclei of the Nucleus basalis of Meynert (NbM) as well as in the diagonal band of Broca nuclei (P < 0.01). Effects in MCI subjects were spatially more restricted than in AD, but occurred at similar locations. The volume of the right antero-lateral NbM nucleus was correlated with intracortical projecting fiber tract integrity such as the corpus callosum, cingulate, and the superior longitudinal, inferior longitudinal, inferior fronto-occipital, and uncinate fasciculus (P < 0.05, corrected for multiple comparisons). Our findings suggest that a multimodal MRI-DTI approach is supportive to determine atrophy of cholinergic nuclei and its effect on intracortical projecting fiber tracts in AD.
authors.affiliation: Department of Psychiatry, University of Rostock, Rostock, Germany. stefan.teipel@med.uni-rostock.de
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Teipel
authors.forename: Thomas
authors.initials: T
authors.lastname: Meindl
authors.forename: Lea
authors.initials: L
authors.lastname: Grinberg
authors.forename: Michel
authors.initials: M
authors.lastname: Grothe
authors.forename: Jose L
authors.initials: JL
authors.lastname: Cantero
authors.forename: Maximilian F
authors.initials: MF
authors.lastname: Reiser
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Möller
authors.forename: Helmut
authors.initials: H
authors.lastname: Heinsen
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis*; D016880:Anisotropy; D001931:Brain Mapping; D018678:Cholinergic Agents / Q000378:metabolism*; D003072:Cognition Disorders / Q000175:diagnosis*; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016548:Prosencephalon / Q000378:metabolism / Q000473:pathology*
chemical_list: D018678:Cholinergic Agents