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Clinical and neuroimaging investigations of language disturbance in frontotemporal dementia–motor neuron disease patients

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Abstract

This study systematically investigated the neuropsychological profile of language disturbance in frontotemporal dementia–motor neuron disease (FTD–MND) using a data-driven approach. Neuroanatomical correlates of language profiles were also examined. Patients with FTD–MND (N = 26), pure motor neuron disease (N = 34), progressive non-fluent aphasia (N = 30), semantic dementia (N = 17), and controls (N = 31) underwent comprehensive language assessments. Clinical assessments were complemented with the Sydney Language Battery (SYDBAT), to assess semantic abilities, and the Test for Reception of Grammar (TROG), to assess syntactic comprehension. Two-step cluster analysis examined patterns of language impairment in FTD–MND and voxel-based morphometry investigated neuroanatomical differences between clusters. Almost all (88.5%) FTD–MND patients had language impairment, with anomia in 73.1% and impaired sentence comprehension in 56%. Cluster analysis revealed two main profiles of language impairment in FTD–MND; a mild mixed semantic and syntactic impairment (mild mixed subgroup) seen in 12 cases and a subgroup with more marked impairment particularly of syntactic comprehension (PNFA-like subgroup) seen in 7 cases. VBM revealed disproportionate atrophy of the caudate head and putamen bilaterally in the PNFA-like subgroup. In conclusion, language disturbances in FTD–MND are heterogeneous and more mixed than seen in FTD language phenotypes. Atrophy of the caudate and putamen was correlated with disproportionate impairment of syntactic comprehension. A pure semantic dementia like syndrome appears to be rare in FTD–MND.

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References

  1. Elamin M, Bede P, Byrne S, Jordan N, Gallagher L, Wynne B, O’Brien C, Phukan J, Lynch C, Pender N (2013) Cognitive changes predict functional decline in ALS A population-based longitudinal study. Neurology 80(17):1590–1597

    Article  PubMed  Google Scholar 

  2. Montuschi A, Iazzolino B, Calvo A, Moglia C, Lopiano L, Restagno G, Brunetti M, Ossola I, Presti AL, Cammarosano S (2015) Cognitive correlates in amyotrophic lateral sclerosis: a population-based study in Italy. J Neurol Neurosurg Psychiatry 86(2):168–173

    Article  PubMed  Google Scholar 

  3. Burrell JR, Kiernan MC, Vucic S, Hodges JR (2011) Motor neuron dysfunction in frontotemporal dementia. Brain 134(9):2582–2594. https://doi.org/10.1093/brain/awr195

    Article  PubMed  Google Scholar 

  4. Burrell JR, Halliday GM, Kril JJ, Ittner LM, Götz J, Kiernan MC, Hodges JR (2016) The frontotemporal dementia-motor neuron disease continuum. Lancet 388(10047):919–931

    Article  PubMed  Google Scholar 

  5. Brettschneider J, Del Tredici K, Irwin DJ, Grossman M, Robinson JL, Toledo JB, Fang L, Van Deerlin VM, Ludolph AC, Lee VM-Y (2014) Sequential distribution of pTDP-43 pathology in behavioral variant frontotemporal dementia (bvFTD). Acta Neuropathol 127(3):423–439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Brettschneider J, Del Tredici K, Toledo JB, Robinson JL, Irwin DJ, Grossman M, Suh E, Deerlin VM, Wood EM, Baek Y (2013) Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol 74(1):20–38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ringholz G, Appel SH, Bradshaw M, Cooke N, Mosnik D, Schulz P (2005) Prevalence and patterns of cognitive impairment in sporadic ALS. Neurology 65(4):586–590

    Article  CAS  PubMed  Google Scholar 

  8. Gibbons ZC, Richardson A, Neary D, Snowden JS (2008) Behaviour in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 9(2):67–74

    Article  PubMed  Google Scholar 

  9. Phukan J, Elamin M, Bede P, Jordan N, Gallagher L, Byrne S, Lynch C, Pender N, Hardiman O (2012) The syndrome of cognitive impairment in amyotrophic lateral sclerosis: a population-based study. J Neurol Neurosurg Psychiatry 83(1):102–108

    Article  PubMed  Google Scholar 

  10. Saxon JA, Thompson JC, Jones M, Harris JM, Richardson AM, Langheinrich T, Neary D, Mann DM, Snowden JS (2017) Examining the language and behavioural profile in FTD and ALS-FTD. J Neurol Neurosurg Psychiatry 88(8):675–680. https://doi.org/10.1136/jnnp-2017-315667

    Article  PubMed  Google Scholar 

  11. Taylor LJ, Brown RG, Tsermentseli S, Al-Chalabi A, Shaw CE, Ellis CM, Leigh PN, Goldstein LH (2013) Is language impairment more common than executive dysfunction in amyotrophic lateral sclerosis? J Neurol Neurosurg Psychiatry 84(5):494–498

    Article  PubMed  Google Scholar 

  12. Leslie FV, Hsieh S, Caga J, Savage SA, Mioshi E, Hornberger M, Kiernan MC, Hodges JR, Burrell JR (2015) Semantic deficits in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 16(1–2):46–53

    Article  PubMed  Google Scholar 

  13. Kamminga J, Leslie FV, Hsieh S, Caga J, Mioshi E, Hornberger M, Ballard KJ, Kiernan MC, Hodges JR, Burrell JR (2016) Syntactic comprehension deficits across the FTD-ALS continuum. Neurobiol Aging 41:11–18

    Article  PubMed  Google Scholar 

  14. Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, Freedman M, Kertesz A, Robert P, Albert M (1998) Frontotemporal lobar degeneration A consensus on clinical diagnostic criteria. Neurology 51(6):1546–1554

    Article  CAS  PubMed  Google Scholar 

  15. Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, Van Swieten JC, Seelaar H, Dopper EG, Onyike CU (2011) Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain J Neurol 134(9):2456–2477

    Article  Google Scholar 

  16. Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa S, Ogar J, Rohrer J, Black S, Boeve BF (2011) Classification of primary progressive aphasia and its variants. Neurology 76(11):1006–1014

    Article  PubMed  PubMed Central  Google Scholar 

  17. Brooks BR, Miller RG, Swash M, Munsat TL (2000) El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Mot Neuron Disord 1(5):293–299

    Article  CAS  Google Scholar 

  18. de Carvalho M, Dengler R, Eisen A, England JD, Kaji R, Kimura J, Mills K, Mitsumoto H, Nodera H, Shefner J (2008) Electrodiagnostic criteria for diagnosis of ALS. Clin Neurophysiol 119(3):497–503

    Article  PubMed  Google Scholar 

  19. Strong MJ, Abrahams S, Goldstein LH, Woolley S, Mclaughlin P, Snowden J, Mioshi E, Roberts-South A, Benatar M, HortobáGyi T (2017) Amyotrophic lateral sclerosis-frontotemporal spectrum disorder (ALS-FTSD): Revised diagnostic criteria. Amyotroph Lateral Scler Frontotemporal Degener 18(3–4):153–174

    Article  PubMed  PubMed Central  Google Scholar 

  20. Gorno-Tempini ML, Brambati SM, Ginex V, Ogar J, Dronkers NF, Marcone A, Perani D, Garibotto V, Cappa S, Miller B (2008) The logopenic/phonological variant of primary progressive aphasia. Neurology 71(16):1227–1234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mioshi E, Dawson K, Mitchell J, Arnold R, Hodges JR (2006) The Addenbrooke’s Cognitive Examination Revised (ACE-R): a brief cognitive test battery for dementia screening. Int J Geriatr Psychiatry 21(11):1078–1085

    Article  PubMed  Google Scholar 

  22. Hsieh S, Schubert S, Hoon C, Mioshi E, Hodges JR (2013) Validation of the Addenbrooke’s Cognitive Examination III in frontotemporal dementia and Alzheimer’s disease. Dement Geriatr Cogn Disord 36(3–4):242–250

    Article  PubMed  Google Scholar 

  23. So MFD, Kumfor F, Murray C, Hsieh S, Savage G, Ahmed RM, Burrell JR, Hodges JR, Irish M, Piguet O (2018) The Addenbrooke’s Cognitive Examination III: psychometric characteristics and relations to functional ability in dementia. J Int Neuropsychol Soc 24(8):854–863. https://doi.org/10.1017/S1355617718000541

    Article  PubMed  Google Scholar 

  24. Mioshi E, Hsieh S, Savage S, Hornberger M, Hodges JR (2010) Clinical staging and disease progression in frontotemporal dementia. Neurology 74(20):1591–1597. https://doi.org/10.1212/WNL.0b013e3181e04070

    Article  CAS  PubMed  Google Scholar 

  25. Strauss E, Sherman EM, Spreen O (2006) A compendium of neuropsychological tests: administration, norms, and commentary. American Chemical Society

  26. Hodges JR (2007) Cognitive assessment for clinicians. Oxford University Press, Oxford

    Google Scholar 

  27. Lezak M, Howieson D, Bigler E, Tranel D (2012) Neuropsychological assessment, 5th edn. Oxford University Press, New York

    Google Scholar 

  28. Bowie CR, Harvey PD (2006) Administration and interpretation of the trail making test. Nat Protoc 1(5):2277–2281

    Article  CAS  PubMed  Google Scholar 

  29. Benton AL, Hamsher Kd (1983) Multilingual aphasia examination: manual of instructions. Dept. of Neurology and Psychology, University of Iowa, Iowa

    Google Scholar 

  30. Ogar J, Slama H, Dronkers N, Amici S, Luisa Gorno-Tempini M (2005) Apraxia of speech: an overview. Neurocase 11(6):427–432

    Article  PubMed  Google Scholar 

  31. Savage S, Hsieh S, Leslie F, Foxe D, Piguet O, Hodges JR (2013) Distinguishing subtypes in primary progressive aphasia: application of the Sydney language battery. Dement Geriatr Cogn Disord 35(3–4):208–218

    Article  PubMed  Google Scholar 

  32. Croot K, Hodges JR, Patterson K (1999) Evidence for impaired sentence comprehension in early Alzheimer’s disease. J Int Neuropsychol Soc 5(05):393–404

    Article  CAS  PubMed  Google Scholar 

  33. Mooi E, Sarstedt M (2011) Cluster analysis. A concise guide to market research. Springer, Berlin

    Book  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  35. Zhang Y, Brady M, Smith S (2001) Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Trans Med Imaging 20(1):45–57

    Article  CAS  PubMed  Google Scholar 

  36. Andersson JL, Jenkinson M, Smith S (2007) Non-linear registration, aka Spatial normalisation FMRIB technical report TR07JA2. FMRIB Anal Group Univ Oxf 2:1–21

    Google Scholar 

  37. Nichols TE, Holmes AP (2002) Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum Brain Mapp 15(1):1–25

    Article  PubMed  Google Scholar 

  38. Irish M, Addis DR, Hodges JR, Piguet O (2012) Considering the role of semantic memory in episodic future thinking: evidence from semantic dementia. Brain 135(7):2178–2191

    Article  PubMed  Google Scholar 

  39. Onyike CU, Diehl-Schmid J (2013) The epidemiology of frontotemporal dementia. Int Rev Psychiatry (Abingdon Engl) 25(2):130–137. https://doi.org/10.3109/09540261.2013.776523

    Article  Google Scholar 

  40. Hodges JR, Davies R, Xuereb J, Kril J, Halliday G (2003) Survival in frontotemporal dementia. Neurology 61(3):349–354

    Article  CAS  PubMed  Google Scholar 

  41. Sarstedt M, Mooi E (2014) Cluster analysis. A concise guide to market research. STBE. Springer, Heidelberg

    Google Scholar 

  42. Bak TH, Hodges JR (2004) The effects of motor neurone disease on language: further evidence. Brain Lang 89(2):354–361

    Article  PubMed  Google Scholar 

  43. Tsermentseli S, Leigh PN, Taylor LJ, Radunovic A, Catani M, Goldstein LH (2016) Syntactic processing as a marker for cognitive impairment in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 17(1–2):69–76

    Article  Google Scholar 

  44. Yoshizawa K, Yasuda N, Fukuda M, Yukimoto Y, Ogino M, Hata W, Ishizaka I, Higashikawa M (2014) Syntactic comprehension in patients with amyotrophic lateral sclerosis. Behav Neurol 2014:230578. https://doi.org/10.1155/2014/230578

    Article  PubMed  PubMed Central  Google Scholar 

  45. Ash S, Menaged A, Olm C, McMillan CT, Boller A, Irwin DJ, McCluskey L, Elman L, Grossman M (2014) Narrative discourse deficits in amyotrophic lateral sclerosis. Neurology 83(6):520–528

    Article  PubMed  PubMed Central  Google Scholar 

  46. Ash S, Olm C, Mcmillan CT, Boller A, Irwin DJ, Mccluskey L, Elman L, Grossman M (2015) Deficits in sentence expression in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 16(1–2):31–39

    Article  PubMed  Google Scholar 

  47. Rakowicz WP, Hodges JR (1998) Dementia and aphasia in motor neuron disease: an underrecognised association? J Neurol Neurosurg Psychiatry 65(6):881–889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Bak TH, O’donovan DG, Xuereb JH, Boniface S, Hodges JR (2001) Selective impairment of verb processing associated with pathological changes in Brodmann areas 44 and 45 in the motor neurone disease–dementia–aphasia syndrome. Brain 124(1):103–120

    Article  CAS  PubMed  Google Scholar 

  49. Abrahams S, Goldstein L, Simmons A, Brammer M, Williams S, Giampietro V, Leigh P (2004) Word retrieval in amyotrophic lateral sclerosis: a functional magnetic resonance imaging study. Brain 127(7):1507–1517

    Article  CAS  PubMed  Google Scholar 

  50. Gorno-Tempini ML, Dronkers NF, Rankin KP, Ogar JM, Phengrasamy L, Rosen HJ, Johnson JK, Weiner MW, Miller BL (2004) Cognition and anatomy in three variants of primary progressive aphasia. Ann Neurol 55(3):335–346

    Article  PubMed  PubMed Central  Google Scholar 

  51. Grahn JA, Parkinson JA, Owen AM (2008) The cognitive functions of the caudate nucleus. Prog Neurobiol 86(3):141–155

    Article  PubMed  Google Scholar 

  52. Crosson B, Benefield H, Cato MA, Sadek JR, Moore AB, Wierenga CE, Gopinath K, Soltysik D, Bauer RM, Auerbach EJ (2003) Left and right basal ganglia and frontal activity during language generation: contributions to lexical, semantic, and phonological processes. J Int Neuropsychol Soc 9(7):1061–1077

    Article  PubMed  Google Scholar 

  53. Ford A, Triplett W, Sudhyadhom A, Gullett JM, McGregor K, FitzGerald D, Mareci T, White K, Crosson B (2013) Broca’s area and its striatal and thalamic connections: a diffusion-MRI tractography study. Front Neuroanat 7:8

    Article  PubMed  PubMed Central  Google Scholar 

  54. Teichmann M, Rosso C, Martini JB, Bloch I, Brugières P, Duffau H, Lehéricy S, Bachoud-Lévi AC (2015) A cortical–subcortical syntax pathway linking Broca’s area and the striatum. Hum Brain Mapp 36(6):2270–2283

    Article  PubMed  PubMed Central  Google Scholar 

  55. Viñas-Guasch N, Wu YJ (2017) The role of the putamen in language: a meta-analytic connectivity modeling study. Brain Struct Funct 222(9):3991–4004

    Article  PubMed  Google Scholar 

  56. Brambati SM, Amici S, Racine CA, Neuhaus J, Miller Z, Ogar J, Dronkers N, Miller BL, Rosen H, Gorno-Tempini ML (2015) Longitudinal gray matter contraction in three variants of primary progressive aphasia: a tenser-based morphometry study. NeuroImage Clin 8:345–355

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported in part by funding to Forefront, a collaborative research group dedicated to the study of frontotemporal dementia and motor neuron disease, from the National Health and Medical Research Council of Australia (NHMRC) program grant (#1037746) and the Australian Research Council (ARC) Centre of Excellence in Cognition and its Disorders Memory Program (#CE110001021). MI is supported by an ARC Future Fellowship (FT160100096). OP is supported by a NHMRC Senior Research Fellowship (APP1103258). JRB is supported by a NHMRC Early Career Fellowship (#1072451). We are grateful to the research participants involved with the ForeFront research studies.

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Authors and Affiliations

  1. Sydney Medical School, The University of Sydney, Sydney, NSW, Australia

    Zhe Long, Matthew C. Kiernan & John R. Hodges

  2. Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia

    Zhe Long, Muireann Irish, Olivier Piguet, Matthew C. Kiernan, John R. Hodges & James R. Burrell

  3. ARC Centre of Excellence in Cognition and Its Disorders, Sydney, Australia

    Muireann Irish, Olivier Piguet, John R. Hodges & James R. Burrell

  4. School of Psychology, The University of Sydney, Sydney, NSW, Australia

    Muireann Irish & Olivier Piguet

  5. The University of Sydney Concord Clinical School, Sydney, NSW, Australia

    James R. Burrell

  6. Institute of Clinical Neurosciences, Royal Prince Alfred Hospital, Sydney, NSW, Australia

    Matthew C. Kiernan

  7. Neurosciences 5 West, Concord General Hospital, Sydney, NSW, 2139, Australia

    James R. Burrell

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  1. Zhe Long
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  2. Muireann Irish
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  3. Olivier Piguet
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Correspondence to James R. Burrell.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

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This study was approved by the South Eastern Sydney Local Health District and the ethics committees of the University of New South Wales and University of Sydney.

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Written informed consent was obtained from all participants, or their caregivers, in accordance with the Declaration of Helsinki.

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Long, Z., Irish, M., Piguet, O. et al. Clinical and neuroimaging investigations of language disturbance in frontotemporal dementia–motor neuron disease patients. J Neurol 266, 921–933 (2019). https://doi.org/10.1007/s00415-019-09216-0

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  • DOI: https://doi.org/10.1007/s00415-019-09216-0

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