Brain structural profile of multiple system atrophy patients with cognitive impairment

Eleonora Fiorenzato, Luca Weis, Klaus Seppi, Marco Onofrj, Pietro Cortelli, Stefano Zanigni, Caterina Tonon, Horacio Kaufmann, Timothy Michael Shepherd, Werner Poewe, Florian Krismer, Gregor Wenning, Angelo Antonini, Roberta Biundo

Research output: Contribution to journalArticlepeer-review


Current consensus diagnostic criteria for multiple system atrophy (MSA) consider dementia a non-supporting feature, although cognitive impairment and even frank dementia are reported in clinical practice. Mini-Mental State Examination (MMSE) is a commonly used global cognitive scale, and in a previous study, we established an MSA-specific screening cut-off score <27 to identify cognitive impairment. Finally, MSA neuroimaging findings suggest the presence of structural alterations in patients with cognitive deficits, although the extent of the anatomical changes is unclear. The aim of our multicenter study is to better characterize anatomical changes associated with cognitive impairment in MSA and to further investigate cortical and subcortical structural differences versus healthy controls (HC). We examined retrospectively 72 probable MSA patients [50 with normal cognition (MSA-NC) and 22 cognitively impaired (MSA-CI) based on MMSE <27] and compared them to 36 HC using gray- and white-matter voxel-based morphometry and fully automated subcortical segmentation. Compared to HC, MSA patients showed widespread cortical (bilateral frontal, occipito-temporal, and parietal areas), subcortical, and white-matter alterations. However, MSA-CI showed only focal volume reduction in the left dorsolateral prefrontal cortex compared with MSA-NC. These results suggest only a marginal contribution of cortical pathology to cognitive deficits. We believe that cognitive dysfunction is driven by focal fronto-striatal degeneration in line with the concept of “subcortical cognitive impairment”.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalJournal of Neural Transmission
Publication statusE-pub ahead of print - 2016


  • Cognition
  • Dementia
  • Mini-Mental State Examination (MMSE)
  • Multiple system atrophy (MSA)
  • Neuroimaging
  • Voxel-based morphometry

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry


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