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Journal of Neural Transmission

, Volume 124, Issue 3, pp 293–302 | Cite as

Brain structural profile of multiple system atrophy patients with cognitive impairment

  • Eleonora FiorenzatoEmail author
  • 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
  • On behalf of the Movement Disorders Society MSA (MODIMSA) Neuropsychology and Imaging Study Groups
Neurology and Preclinical Neurological Studies - Original Article

Abstract

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”.

Keywords

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

Notes

Acknowledgements

The authors thank the MSA patients who kindly participated in this study.

Compliance with ethical standards

All authors gave the final approval of this version of the manuscript to be published. We can assure that there is no one else who fulfills the criteria but has not been included as an author.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the Venice Research Ethics Committee (Venice, Italy) and with the 1964 Helsinki declaration. For this type of study, formal consent is not required.

Conflict of interest

The authors have no competing interest to declare.

References

  1. Abe O, Takao H, Gonoi W, Sasaki H, Murakami M, Kabasawa H, Kawaguchi H, Goto M, Yamada H, Yamasue H, Kasai K, Aoki S, Ohtomo K (2010) Voxel-based analysis of the diffusion tensor. Neuroradiology 52(8):699–710CrossRefPubMedGoogle Scholar
  2. Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 9:357–381CrossRefPubMedGoogle Scholar
  3. Antonini A, Kazumata K, Feigin A, Mandel F, Dhawan V, Margouleff C, Eidelberg D (1998) Differential diagnosis of parkinsonism with [18F] fluorodeoxyglucose and PET. Mov Disord 13(2):268–274CrossRefPubMedGoogle Scholar
  4. Asi YT, Ling H, Ahmed Z, Lees AJ, Revesz T, Holton JL (2014) Neuropathological features of multiple system atrophy with cognitive impairment. Mov Disord 29(7):884–888CrossRefPubMedGoogle Scholar
  5. 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(10):1273–1277CrossRefPubMedGoogle Scholar
  6. Barbagallo G, Sierra-Pena M, Nemmi F, Traon AP, Meissner WG, Rascol O, Peran P (2016) Multimodal MRI assessment of nigro-striatal pathway in multiple system atrophy and Parkinson disease. Mov Disord 31(3):325–334CrossRefPubMedGoogle Scholar
  7. Biundo R, Weis L, Antonini A (2016) Cognitive decline in Parkinson’s disease: the complex picture. NPJ Parkinsons Dis 2:16018CrossRefGoogle Scholar
  8. Brenneis C, Seppi K, Schocke MF, Muller J, Luginger E, Bosch S, Loscher WN, Buchel C, Poewe W, Wenning GK (2003) Voxel-based morphometry detects cortical atrophy in the Parkinson variant of multiple system atrophy. Mov Disord 18(10):1132–1138CrossRefPubMedGoogle Scholar
  9. Brown RG, Marsden CD (1988) ‘Subcorttcal dementia’: the neuropsychological evidence. Neuroscience 25(2):363–387CrossRefPubMedGoogle Scholar
  10. Chang CC, Chang YY, Chang WN, Lee YC, Wang YL, Lui CC, Huang CW, Liu WL (2009) Cognitive deficits in multiple system atrophy correlate with frontal atrophy and disease duration. Eur J Neurol 16(10):1144–1150CrossRefPubMedGoogle Scholar
  11. Ciolli L, Krismer F, Nicoletti F, Wenning GK (2014) An update on the cerebellar subtype of multiple system atrophy. Cerebellum Ataxias 1:14CrossRefPubMedPubMedCentralGoogle Scholar
  12. Colosimo C, Vanacore N, Bonifati V, Fabbrini G, Rum A, De Michele G, De Mari M, Bonuccelli U, Nicholl DJ, Meco G (2001) Clinical diagnosis of multiple system atrophy: level of agreement between Quinn’s criteria and the consensus conference guidelines. Acta Neurol Scand 103(4):261–264CrossRefPubMedGoogle Scholar
  13. Cummings JL (1986) Subcortical dementia. Neuropsychology, neuropsychiatry, and pathophysiology. Br J Psychiatry 149(6):682–697CrossRefPubMedGoogle Scholar
  14. Dale AM, Fischl B, Sereno MI (1999) Cortical surface-based analysis. I. Segmentation and surface reconstruction. Neuroimage 9(2):179–194CrossRefPubMedGoogle Scholar
  15. 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(3):968–980CrossRefPubMedGoogle Scholar
  16. Filoteo JV, Reed JD, Litvan I, Harrington DL (2014) Volumetric correlates of cognitive functioning in nondemented patients with Parkinson’s disease. Mov Disord 29(3):360–367CrossRefPubMedGoogle Scholar
  17. Fiorenzato E, Weis L, Falup-Pecurariu C, Diaconu S, Siri C, Reali E, Pezzoli G, Bisiacchi P, Antonini A, Biundo R (2016) Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) performance in progressive supranuclear palsy and multiple system atrophy. J Neural Transm. doi: 10.1007/s00702-016-1589-3 Google Scholar
  18. Fischl B, Sereno MI, Dale AM (1999) Cortical surface-based analysis. II: Inflation, flattening, and a surface-based coordinate system. Neuroimage 9(2):195–207CrossRefPubMedGoogle Scholar
  19. Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state. J Psychiatr Res 12(3):189–198CrossRefPubMedGoogle Scholar
  20. Fortea J, Sala-Llonch R, Bartres-Faz D, Bosch B, Llado A, Bargallo N, Molinuevo JL, Sanchez-Valle R (2010) Increased cortical thickness and caudate volume precede atrophy in PSEN1 mutation carriers. J Alzheimers Dis 22(3):909–922PubMedGoogle Scholar
  21. Fortea J, Sala-Llonch R, Bartres-Faz D, Llado A, Sole-Padulles C, Bosch B, Antonell A, Olives J, Sanchez-Valle R, Molinuevo JL, Rami L (2011) Cognitively preserved subjects with transitional cerebrospinal fluid ss-amyloid 1-42 values have thicker cortex in Alzheimer’s disease vulnerable areas. Biol Psychiatry 70(2):183–190CrossRefPubMedGoogle Scholar
  22. Franciotti R, Delli Pizzi S, Perfetti B, Tartaro A, Bonanni L, Thomas A, Weis L, Biundo R, Antonini A, Onofrj M (2015) Default mode network links to visual hallucinations: a comparison between Parkinson’s disease and multiple system atrophy. Mov Disord 30(9):1237–1247CrossRefPubMedGoogle Scholar
  23. 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(9):670–676CrossRefPubMedPubMedCentralGoogle Scholar
  24. Iglesias JE, Van Leemput K, Bhatt P, Casillas C, Dutt S, Schuff N, Truran-Sacrey D, Boxer A, Fischl B, Alzheimer’s Disease Neuroimaging I (2015) Bayesian segmentation of brainstem structures in MRI. Neuroimage 113:184–195CrossRefPubMedPubMedCentralGoogle Scholar
  25. Jenkinson M, Beckmann CF, Behrens TE, Woolrich MW, Smith SM (2012) Fsl. Neuroimage 62(2):782–790CrossRefPubMedGoogle Scholar
  26. Kawai Y, Suenaga M, Takeda A, Ito M, Watanabe H, Tanaka F, Kato K, Fukatsu H, Naganawa S, Kato T, Ito K, Sobue G (2008) Cognitive impairments in multiple system atrophy: MSA-C vs MSA-P. Neurology 70:1390–1396CrossRefPubMedGoogle Scholar
  27. Kim JS, Yang JJ, Lee DK, Lee JM, Youn J, Cho JW (2015) Cognitive impairment and its structural correlates in the Parkinsonian subtype of multiple system atrophy. Neurodegener Dis 15(5):294–300CrossRefPubMedGoogle Scholar
  28. Kitayama M, Wada-Isoe K, Irizawa Y, Nakashima K (2009) Assessment of dementia in patients with multiple system atrophy. Eur J Neurol 16(5):589–594CrossRefPubMedGoogle Scholar
  29. Lee MJ, Shin JH, Seoung JK, Lee JH, Yoon U, Oh JH, Jung DS, Kim EJ (2016) Cognitive impairments associated with morphological changes in cortical and subcortical structures in multiple system atrophy of the cerebellar type. Eur J Neurol 23(1):92–100CrossRefPubMedGoogle Scholar
  30. Lyoo CH, Jeong Y, Ryu YH, Lee SY, Song TJ, Lee JH, Rinne JO, Lee MS (2008) Effects of disease duration on the clinical features and brain glucose metabolism in patients with mixed type multiple system atrophy. Brain 131:438–446CrossRefPubMedGoogle Scholar
  31. Messina D, Cerasa A, Condino F, Arabia G, Novellino F, Nicoletti G, Salsone M, Morelli M, Lanza PL, Quattrone A (2011) Patterns of brain atrophy in Parkinson’s disease, progressive supranuclear palsy and multiple system atrophy. Parkinsonism Relat Disord 17(3):172–176CrossRefPubMedGoogle Scholar
  32. Minnerop M, Specht K, Ruhlmann J, Schimke N, Abele M, Weyer A, Wullner U, Klockgether T (2007) Voxel-based morphometry and voxel-based relaxometry in multiple system atrophy-a comparison between clinical subtypes and correlations with clinical parameters. Neuroimage 36(4):1086–1095CrossRefPubMedGoogle Scholar
  33. Minnerop M, Luders E, Specht K, Ruhlmann J, Schimke N, Thompson PM, Chou YY, Toga AW, Abele M, Wullner U, Klockgether T (2010) Callosal tissue loss in multiple system atrophy—a one-year follow-up study. Mov Disord 25(15):2613–2620CrossRefPubMedPubMedCentralGoogle Scholar
  34. Mori S, Wakana S, Van Zijl PCM, Nagae-Poetscher LM (2005) MRI atlas of human white matter. Elsevier, AmsterdamGoogle Scholar
  35. Quinn N (1989) Multiple system atrophy—the nature of the beast. J Neurol Neurosurg Psychiatry 52(Suppl):78–89CrossRefPubMedCentralGoogle Scholar
  36. Rolls ET, Joliot M, Tzourio-Mazoyer N (2015) Implementation of a new parcellation of the orbitofrontal cortex in the automated anatomical labeling atlas. Neuroimage 122:1–5CrossRefPubMedGoogle Scholar
  37. Rosas HD, Salat DH, Lee SY, Zaleta AK, Pappu V, Fischl B, Greve D, Hevelone N, Hersch SM (2008) Cerebral cortex and the clinical expression of Huntington’s disease: complexity and heterogeneity. Brain 131(4):1057–1068CrossRefPubMedPubMedCentralGoogle Scholar
  38. Salvesen L, Winge K, Brudek T, Agander TK, Lokkegaard A, Pakkenberg B (2015) Neocortical neuronal loss in patients with multiple system atrophy: a stereological study. Cereb Cortex. doi: 10.1093/cercor/bhv228 PubMedGoogle Scholar
  39. Scherfler C, Gobel G, Muller C, Nocker M, Wenning GK, Schocke M, Poewe W, Seppi K (2016) Diagnostic potential of automated subcortical volume segmentation in atypical parkinsonism. Neurology 86(13):1242–1249CrossRefPubMedGoogle Scholar
  40. Schmidt R, Enzinger C, Ropele S, Schmidt H, Fazekas F (2003) Progression of cerebral white matter lesions: 6-year results of the Austrian Stroke Prevention Study. The Lancet 361(9374):2046–2048CrossRefGoogle Scholar
  41. Schwarz CG, Reid RI, Gunter JL, Senjem ML, Przybelski SA, Zuk SM, Whitwell JL, Vemuri P, Josephs KA, Kantarci K, Thompson PM, Petersen RC, Jack CR Jr, Alzheimer’s Disease Neuroimaging Initiative (2014) Improved DTI registration allows voxel-based analysis that outperforms tract-based spatial statistics. Neuroimage 94:65–78CrossRefPubMedPubMedCentralGoogle Scholar
  42. Shigemoto Y, Matsuda H, Kamiya K, Maikusa N, Nakata Y, Ito K, Ota M, Matsunaga N, Sato N (2013) In vivo evaluation of gray and white matter volume loss in the parkinsonian variant of multiple system atrophy using SPM8 plus DARTEL for VBM. Neuroimage Clin 2:491–496CrossRefPubMedPubMedCentralGoogle Scholar
  43. 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(4):613–618CrossRefGoogle Scholar
  44. Smith SM (2002) Fast robust automated brain extraction. Hum Brain Mapp 17(3):143–155CrossRefPubMedGoogle Scholar
  45. Smith SM, Brady JM (1997) SUSAN—A new approach to low level image processing. Int J Comput Vis 23(1):45–78CrossRefGoogle Scholar
  46. 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(7):857–867CrossRefPubMedPubMedCentralGoogle Scholar
  47. Tekin S, Cummings JL (2002) Frontal–subcortical neuronal circuits and clinical neuropsychiatry. J Psychosom Res 53(2):647–654CrossRefPubMedGoogle Scholar
  48. Wenning GK, Ben-Shlomo Y, Magalhaes M, Daniel SE, Quinn NP (1995) Clinicopathological study of 35 cases of multiple system atrophy. J Neurol Neurosurg Psychiatry 58(2):160–166CrossRefPubMedPubMedCentralGoogle Scholar
  49. Wenning GK, Tison F, Ben Shlomo Y, Daniel SE, Quinn NP (1997) Multiple system atrophy: a review of 203 pathologically proven cases. Mov Disord 12(2):133–147CrossRefPubMedGoogle Scholar
  50. Worker A, Blain C, Jarosz J, Chaudhuri KR, Barker GJ, Williams SC, Brown RG, Leigh PN, Dell’Acqua F, Simmons A (2014) Diffusion tensor imaging of Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy: a tract-based spatial statistics study. PLoS One 9(11):e112638CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Eleonora Fiorenzato
    • 1
    • 2
    Email author return OK on get
  • Luca Weis
    • 1
  • Klaus Seppi
    • 3
  • Marco Onofrj
    • 4
  • Pietro Cortelli
    • 5
    • 6
  • Stefano Zanigni
    • 6
    • 7
  • Caterina Tonon
    • 6
    • 7
  • Horacio Kaufmann
    • 8
  • Timothy Michael Shepherd
    • 8
  • Werner Poewe
    • 3
  • Florian Krismer
    • 3
  • Gregor Wenning
    • 3
  • Angelo Antonini
    • 1
  • Roberta Biundo
    • 1
  • On behalf of the Movement Disorders Society MSA (MODIMSA) Neuropsychology and Imaging Study Groups
  1. 1.Parkinson Disease and Movement Disorders UnitIRCCS San Camillo Hospital FoundationVenice-LidoItaly
  2. 2.Department of General PsychologyUniversity of PaduaPaduaItaly
  3. 3.Department of NeurologyMedical University of InnsbruckInnsbruckAustria
  4. 4.Department of Neuroscience, Imaging and Clinical Sciences“G. d’Annunzio” UniversityChietiItaly
  5. 5.IRCCS Institute of Neurological Sciences of BolognaBolognaItaly
  6. 6.Department of Biomedical and Neuromotor Sciences (DIBINEM)University of BolognaBolognaItaly
  7. 7.Functional MR UnitS. Orsola-Malpighi HospitalBolognaItaly
  8. 8.Department of Neurology, Dysautonomia CenterNew York UniversityNew YorkUSA

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