Journal of Neurology

, Volume 267, Issue 1, pp 87–94 | Cite as

Cognitive impairment and structural brain damage in multiple system atrophy-parkinsonian variant

  • Francesca Caso
  • Elisa Canu
  • Milica Jecmenica Lukic
  • Igor N. Petrovic
  • Andrea Fontana
  • Ivan Nikolic
  • Vladimir S. Kostic
  • Massimo Filippi
  • Federica AgostaEmail author
Original Communication


In this multiparametric, cross-sectional study, we aimed to investigate cognitive impairment and brain structural changes in patients with multiple system atrophy (MSA)-parkinsonian variant (MSA-p). Twenty-six MSA-p patients and 19 controls underwent clinical and neuropsychological evaluation and 1.5 T brain MRI scan. Cortical thickness measures and volumes of deep grey matter structures were obtained. A regression analysis correlated MRI metrics with clinical features in MSA-p patients. Almost 46% of MSA-p patients showed a mild cognitive impairment involving mainly attentive–executive and memory domains. Apathy and depression were found in half of MSA-p patients. MSA-p patients showed significant cortical thinning of fronto-temporal–parietal regions and atrophy of periaqueductal grey matter, left cerebellar hemisphere, left pallidum and bilateral putamen, compared to controls. Cortical thinning in temporal regions correlated with global cognitive status and memory impairment. Grey matter cerebellar atrophy correlated with motor deficits. MSA-p patients showed a multidomain cognitive impairment with a prominent cortical damage in anterior more than posterior brain regions and grey matter volume reduction in subcortical structures. Cortical and subcortical structural changes might lead to cognitive dysfunction in MSA-p.


Multiple system atrophy-parkinsonian variant MRI Cortical thickness Cognition Grey matter damage 



The authors thank the patients and their families for the time and effort they dedicated to the research.

Author contributions

FC: study concept/design; analysis/interpretation of data; drafting the manuscript for content. EC and AF: analysis/interpretation of data; revising the manuscript for content. MJL, INP and IN: acquisition of data; analysis/interpretation of data; revising the manuscript for content. VSK: interpretation of data; revising the manuscript for content; obtaining funding. MF: interpretation of data; revising the manuscript for content; obtaining funding. FA: study concept/design; analysis/interpretation of data; study supervision and coordination; revising the manuscript for content.


This study was partially supported by the Ministry of Education, Science, and Technological Development of the Republic of Serbia (project no. 175090).

Compliance with ethical standards

Conflicts of interest

F. Caso, M. Jecmenica-Lukic, I. Nikolic, and A. Fontana report no conflicts of interest. E. Canu has received research supports from the Italian Ministry of Health. I. Petrovic has received speaker honoraria from Actavis. V.S. Kostic has received speaker honoraria from Actavis and Solveo. M. Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). F. Agosta is Section Editor of NeuroImage: Clinical; has received speaker honoraria from Novartis, Biogen Idec and Philips; and receives or has received research supports from the Italian Ministry of Health, AriSLA (Fondazione Italiana di Ricerca per la SLA), and the European Research Council.

Ethical approval

The study was approved by local ethics committee and written informed consent was obtained from all participants. The stuady was therefore performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Neuroimaging Research Unit, Institute of Experimental Neurology, Division of NeuroscienceIRCCS San Raffaele Scientific InstituteMilanItaly
  2. 2.Neurology UnitIRCCS San Raffaele Scientific InstituteMilanItaly
  3. 3.Clinic of Neurology, School of MedicineUniversity of BelgradeBelgradeSerbia
  4. 4.Unit of BiostatisticsFondazione IRCCS Casa Sollievo Della SofferenzaFoggiaItaly
  5. 5.MRI Centre, Clinical Centre of SerbiaBelgradeSerbia
  6. 6.Vita-Salute San Raffaele UniversityMilanItaly

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