Subregional basal forebrain atrophy in alzheimer's disease: A multicenter study

Ingo Kilimann, Michel Grothe, Helmut Heinsen, Eduardo Joaquim Lopez Alho, Lea Grinberg, Edson Amaro, Gláucia Aparecida Bento Dos Santos, Rafael Emídio Da Silva, Alex J. Mitchell, Giovanni B. Frisoni, Arun L W Bokde, Andreas Fellgiebel, Massimo Filippi, Harald Hampel, Stefan Klöppel, Stefan J. Teipel

Research output: Contribution to journalArticlepeer-review


Histopathological studies in Alzheimer's disease (AD) suggest severe and region-specific neurodegeneration of the basal forebrain cholinergic system (BFCS). Here, we studied the between-center reliability and diagnostic accuracy of MRI-based BFCS volumetry in a large multicenter data set, including participants with prodromal (n = 41) or clinically manifest AD (n = 134) and 148 cognitively healthy controls. Atrophy was determined using voxel-based and region-of-interest based analyses of high-dimensionally normalized MRI scans using a newly created map of the BFCS based on postmortem in cranio MRI and histology. The AD group showed significant volume reductions of all subregions of the BFCS, which were most pronounced in the posterior nucleus basalis Meynert (NbM). The mild cognitive impairment-AD group showed pronounced volume reductions in the posterior NbM, but preserved volumes of anterior-medial regions. Diagnostic accuracy of posterior NbM volume was superior to hippocampus volume in both groups, despite higher multicenter variability of the BFCS measurements. The data of our study suggest that BFCS morphometry may provide an emerging biomarker in AD.

Original languageEnglish
Pages (from-to)687-700
Number of pages14
JournalJournal of Alzheimer's Disease
Issue number3
Publication statusPublished - 2014


  • Atrophy
  • biomarker
  • cholinergic system
  • dementia
  • European DTI Study on Dementia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology
  • Medicine(all)


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