The cholinergic system in mild cognitive impairment and Alzheimer's disease: An in vivo MRI and DTI study

Authors

  • Stefan J. Teipel,

    Corresponding author
    1. Department of Psychiatry, University of Rostock, Rostock, Germany
    2. DZNE, German Center for Neurodegenerative Disorders, Rostock, Germany
    • Department of Psychiatry and Psychotherapy, University Rostock, Gehlsheimer Str. 20, Rostock 18147, Germany
    Search for more papers by this author
  • Thomas Meindl,

    1. Department of Clinical Radiology, University Hospitals-Grosshadern, Ludwig-Maximilian University, Munich, Germany
    Search for more papers by this author
  • Lea Grinberg,

    1. Department of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil
    Search for more papers by this author
  • Michel Grothe,

    1. Department of Psychiatry, University of Rostock, Rostock, Germany
    2. Laboratory of Functional Neuroscience, Spanish Network of Excellence in Neurodegenerative Diseases (CIBERNED), University Pablo de Olavide, Seville, Spain
    Search for more papers by this author
  • Jose L. Cantero,

    1. Laboratory of Functional Neuroscience, Spanish Network of Excellence in Neurodegenerative Diseases (CIBERNED), University Pablo de Olavide, Seville, Spain
    Search for more papers by this author
  • Maximilian F. Reiser,

    1. Department of Clinical Radiology, University Hospitals-Grosshadern, Ludwig-Maximilian University, Munich, Germany
    Search for more papers by this author
  • Hans-Jürgen Möller,

    1. Department of Psychiatry, Ludwig-Maximilian University, Munich, Germany
    Search for more papers by this author
  • Helmut Heinsen,

    1. Morphological Brain Research Unit, Department of Psychiatry, University Würzburg, Würzburg, Germany
    Search for more papers by this author
  • Harald Hampel

    1. Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience (TCIN), Laboratory of Neuroimaging & Biomarker Research, Trinity College Dublin, The Adelaide and Meath Hospital Incorporating the National Children's Hospital (AMiNCH), Dublin, Ireland
    2. Department of Psychiatry, University of Frankfurt, Frankfurt/Main, Germany
    Search for more papers by this author

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. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc.

Ancillary