Top

Published in:

01-03-2017 | Neurology and Preclinical Neurological Studies - Original Article

Brain structural profile of multiple system atrophy patients with cognitive impairment

Authors: 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, On behalf of the Movement Disorders Society MSA (MODIMSA) Neuropsychology and Imaging Study Groups

Published in: Journal of Neural Transmission | Issue 3/2017

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”.

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):699–710CrossRefPubMed

Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 9:357–381CrossRefPubMed

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):268–274CrossRefPubMed

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):884–888CrossRefPubMed

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):1273–1277CrossRefPubMed

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):325–334CrossRefPubMed

Biundo R, Weis L, Antonini A (2016) Cognitive decline in Parkinson’s disease: the complex picture. NPJ Parkinsons Dis 2:16018CrossRef

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):1132–1138CrossRefPubMed

Brown RG, Marsden CD (1988) ‘Subcorttcal dementia’: the neuropsychological evidence. Neuroscience 25(2):363–387CrossRefPubMed

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):1144–1150CrossRefPubMed

Ciolli L, Krismer F, Nicoletti F, Wenning GK (2014) An update on the cerebellar subtype of multiple system atrophy. Cerebellum Ataxias 1:14CrossRefPubMedPubMedCentral

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):261–264CrossRefPubMed

Cummings JL (1986) Subcortical dementia. Neuropsychology, neuropsychiatry, and pathophysiology. Br J Psychiatry 149(6):682–697CrossRefPubMed

Dale AM, Fischl B, Sereno MI (1999) Cortical surface-based analysis. I. Segmentation and surface reconstruction. Neuroimage 9(2):179–194CrossRefPubMed

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):968–980CrossRefPubMed

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):360–367CrossRefPubMed

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

Fischl B, Sereno MI, Dale AM (1999) Cortical surface-based analysis. II: Inflation, flattening, and a surface-based coordinate system. Neuroimage 9(2):195–207CrossRefPubMed

Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state. J Psychiatr Res 12(3):189–198CrossRefPubMed

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):909–922PubMed

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):183–190CrossRefPubMed

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):1237–1247CrossRefPubMed

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):670–676CrossRefPubMedPubMedCentral

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 113:184–195CrossRefPubMedPubMedCentral

Jenkinson M, Beckmann CF, Behrens TE, Woolrich MW, Smith SM (2012) Fsl. Neuroimage 62(2):782–790CrossRefPubMed

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 70:1390–1396CrossRefPubMed

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):294–300CrossRefPubMed

Kitayama M, Wada-Isoe K, Irizawa Y, Nakashima K (2009) Assessment of dementia in patients with multiple system atrophy. Eur J Neurol 16(5):589–594CrossRefPubMed

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):92–100CrossRefPubMed

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 131:438–446CrossRefPubMed

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):172–176CrossRefPubMed

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):1086–1095CrossRefPubMed

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):2613–2620CrossRefPubMedPubMedCentral

Mori S, Wakana S, Van Zijl PCM, Nagae-Poetscher LM (2005) MRI atlas of human white matter. Elsevier, Amsterdam

Quinn N (1989) Multiple system atrophy—the nature of the beast. J Neurol Neurosurg Psychiatry 52(Suppl):78–89CrossRefPubMedCentral

Rolls ET, Joliot M, Tzourio-Mazoyer N (2015) Implementation of a new parcellation of the orbitofrontal cortex in the automated anatomical labeling atlas. Neuroimage 122:1–5CrossRefPubMed

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):1057–1068CrossRefPubMedPubMedCentral

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 PubMed

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):1242–1249CrossRefPubMed

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):2046–2048CrossRef

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 94:65–78CrossRefPubMedPubMedCentral

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 2:491–496CrossRefPubMedPubMedCentral

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):613–618CrossRef

Smith SM (2002) Fast robust automated brain extraction. Hum Brain Mapp 17(3):143–155CrossRefPubMed

Smith SM, Brady JM (1997) SUSAN—A new approach to low level image processing. Int J Comput Vis 23(1):45–78CrossRef

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):857–867CrossRefPubMedPubMedCentral

Tekin S, Cummings JL (2002) Frontal–subcortical neuronal circuits and clinical neuropsychiatry. J Psychosom Res 53(2):647–654CrossRefPubMed

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):160–166CrossRefPubMedPubMedCentral

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):133–147CrossRefPubMed

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):e112638CrossRefPubMedPubMedCentral

Title: Brain structural profile of multiple system atrophy patients with cognitive impairment
Authors: 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
On behalf of the Movement Disorders Society MSA (MODIMSA) Neuropsychology and Imaging Study Groups
Publication date: 01-03-2017
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 3/2017
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-016-1636-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Brain structural profile of multiple system atrophy patients with cognitive impairment

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2017

Attention in Parkinson’s disease with fatigue: evidence from the attention network test

Higher levels of different muscarinic receptors in the cortex and hippocampus from subjects with Alzheimer’s disease

A prospective evaluation of taste in Parkinson’s disease

Influence of the selective antagonist of the NR2B subunit of the NMDA receptor, traxoprodil, on the antidepressant-like activity of desipramine, paroxetine, milnacipran, and bupropion in mice

Relationship between the plasma levels of neurodegenerative proteins and motor subtypes of Parkinson’s disease

Thr105Ile (rs11558538) polymorphism in the histamine-1-methyl-transferase (HNMT) gene and risk for restless legs syndrome