Cognitive impairment and structural brain damage in multiple system atrophy-parkinsonian variant
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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.
KeywordsMultiple 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.
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.
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.
- 1.Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, Wood NW, Colosimo C, Durr A, Fowler CJ, Kaufmann H, Klockgether T, Lees A, Poewe W, Quinn N, Revesz T, Robertson D, Sandroni P, Seppi K, Vidailhet M (2008) Second consensus statement on the diagnosis of multiple system atrophy. Neurology 71:670–676CrossRefGoogle Scholar
- 2.Stankovic I, Krismer F, Jesic A, Antonini A, Benke T, Brown RG, Burn DJ, Holton JL, Kaufmann H, Kostic VS, Ling H, Meissner WG, Poewe W, Semnic M, Seppi K, Takeda A, Weintraub D, Wenning GK, Movement Disorders Society MSASG (2014) Cognitive impairment in multiple system atrophy: a position statement by the neuropsychology task force of the MDS multiple system atrophy (MODIMSA) study group. Mov Disord 29:857–867CrossRefGoogle Scholar
- 14.Leentjens AF, Dujardin K, Marsh L, Richard IH, Starkstein SE, Martinez-Martin P (2011) Anxiety rating scales in Parkinson's disease: a validation study of the Hamilton anxiety rating scale, the Beck anxiety inventory, and the hospital anxiety and depression scale. Mov Disord 26:407–415CrossRefGoogle Scholar
- 17.Litvan I, Goldman JG, Troster AI, Schmand BA, Weintraub D, Petersen RC, Mollenhauer B, Adler CH, Marder K, Williams-Gray CH, Aarsland D, Kulisevsky J, Rodriguez-Oroz MC, Burn DJ, Barker RA, Emre M (2012) Diagnostic criteria for mild cognitive impairment in Parkinson's disease: movement disorder society task force guidelines. Mov Disord 27:349–356CrossRefGoogle Scholar
- 18.Bak TH, Crawford LM, Hearn VC, Mathuranath PS, Hodges JR (2005) Subcortical dementia revisited: similarities and differences in cognitive function between progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA). Neurocase 11:268–273CrossRefGoogle Scholar
- 21.Desikan RS, Segonne F, Fischl B, Quinn BT, Dickerson BC, Blacker D, Buckner RL, Dale AM, Maguire RP, Hyman BT, Albert MS, Killiany RJ (2006) An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage 31:968–980CrossRefGoogle Scholar
- 24.Siri C, Duerr S, Canesi M, Delazer M, Esselink R, Bloem BR, Gurevich T, Balas M, Giladi N, Santacruz P, Marti F, Tolosa E, Rubino A, Meco G, Poewe W, Pezzoli G, Wenning G, Antonini A (2013) A cross-sectional multicenter study of cognitive and behavioural features in multiple system atrophy patients of the parkinsonian and cerebellar type. J Neural Transm (Vienna) 120:613–618CrossRefGoogle Scholar
- 25.Auzou N, Dujardin K, Biundo R, Foubert-Samier A, Barth C, Duval F, Tison F, Defebvre L, Antonini A, Meissner WG (2015) Diagnosing dementia in multiple system atrophy by applying Movement Disorder Society diagnostic criteria for Parkinson's disease dementia. Parkinsonism Relat Disord 21:1273–1277CrossRefGoogle Scholar
- 27.Fiorenzato E, Weis L, Seppi K, Onofrj M, Cortelli P, Zanigni S, Tonon C, Kaufmann H, Shepherd TM, Poewe W, Krismer F, Wenning G, Antonini A, Biundo R, Movement Disorders Society MSAN, Imaging Study G (2017) Brain structural profile of multiple system atrophy patients with cognitive impairment. J Neural Transm (Vienna) 124:293–302CrossRefGoogle Scholar