Movement Disorders in Frontotemporal Dementia

  • Emma Devenney
  • John HodgesEmail author


Our understanding of frontotemporal dementia (FTD) and its related syndromes has advanced significantly in recent years. One of the most prominent areas of progress is in the overlap syndromes of FTD and movement disorders, at a clinicopathological and genetic level. The aim of this chapter is to discuss the clinical, pathological, and genetic complexities of disorders of movement typically seen in FTD.


Frontotemporal dementia Movement disorder Parkinsonism Apraxia Dystonia Myoclonus Amyotrophic lateral sclerosis 



Amyotrophic lateral sclerosis


Behavioral variant frontotemporal dementia


Corticobasal syndrome


Dementia with Lewy bodies


Frontotemporal dementia


Progressive nonfluent aphasia


Progressive supranuclear palsy


Semantic dementia


Voxel-based morphometry


  1. Baba Y, Tsuboi Y, Baker MC, Uitti RJ, Hutton ML, Dickson DW, et al. The effect of tau genotype on clinical features in FTDP-17. Parkinsonism Relat Disord. 2005;11(4):205–8.PubMedCrossRefGoogle Scholar
  2. Baker M, Mackenzie IR, Pickering-Brown SM, Gass J, Rademakers R, Lindholm C, et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature. 2006;442(7105):916–9.PubMedCrossRefGoogle Scholar
  3. Beck J, Rohrer JD, Campbell T, Isaacs A, Morrison KE, Goodall EF, et al. A distinct clinical, neuropsychological and radiological phenotype is associated with progranulin gene mutations in a large UK series. Brain. 2008;131(3):706–20.PubMedCentralPubMedCrossRefGoogle Scholar
  4. Béland R, Ska B. Interaction between verbal and gestural language in progressive aphasia: a longitudinal case study. Brain Lang. 1992;43(3):355–85.PubMedCrossRefGoogle Scholar
  5. Boeve BF. Links between frontotemporal lobar degeneration, corticobasal degeneration, progressive supranuclear palsy, and amyotrophic lateral sclerosis. Alzheimer Dis Assoc Disord. 2007;21(4):S31–8. Epub 2007/12/20.PubMedCrossRefGoogle Scholar
  6. Boeve BF, Hutton M. Refining frontotemporal dementia with parkinsonism linked to chromosome 17: introducing FTDP-17 (MAPT) and FTDP-17 (PGRN). Arch Neurol. 2008;65(4):460–4. Epub 2008/04/17.PubMedCentralPubMedCrossRefGoogle Scholar
  7. Boeve BF, Baker M, Dickson DW, Parisi JE, Giannini C, Josephs KA, et al. Frontotemporal dementia and parkinsonism associated with the IVS1+ 1G → A mutation in progranulin: a clinicopathologic study. Brain. 2006;129(11):3103–14.PubMedCrossRefGoogle Scholar
  8. Boeve BF, Boylan KB, Graff-Radford NR, DeJesus-Hernandez M, Knopman DS, Pedraza O, et al. Characterization of frontotemporal dementia and/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72. Brain. 2012;135(Pt 3):765–83. Epub 2012/03/01.PubMedCentralPubMedCrossRefGoogle Scholar
  9. Caviness JN, Wszolek ZK. Myoclonus in pallido-ponto-nigral degeneration. Adv Neurol. 2002;89:35–9.PubMedGoogle Scholar
  10. Claassen DO, Parisi JE, Giannini C, Boeve BF, Dickson DW, Josephs KA. Frontotemporal dementia mimicking dementia with Lewy bodies. Cogn Behav Neurol. 2008;21(3):157–63.PubMedCrossRefGoogle Scholar
  11. Clinical and neuropathological criteria for frontotemporal dementia. The Lund and Manchester Groups. J Neurol Neurosurg Psychiatry. 1994;57(4):416–8.Google Scholar
  12. Cooper-Knock J, Frolov A, Highley JR, Charlesworth G, Kirby J, Milano A, et al. C9ORF72 expansions, parkinsonism, and Parkinson disease: a clinicopathologic study. Neurology. 2013;81(9):808–11. Epub 2013/07/26.PubMedCentralPubMedCrossRefGoogle Scholar
  13. Craenhals A, Raison-Van Ruymbeke A, Rectem D, Seron X, Laterre E. Is slowly progressive aphasia actually a new clinical entity? Aphasiology. 1990;4(5):485–509.CrossRefGoogle Scholar
  14. Cruts M, Gijselinck I, van der Zee J, Engelborghs S, Wils H, Pirici D, et al. Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature. 2006;442(7105):920–4.PubMedCrossRefGoogle Scholar
  15. Czarnecki K, Kumar N, Josephs K. Parkinsonism and tardive antecollis in frontotemporal dementia–increased sensitivity to newer antipsychotics? Eur J Neurol. 2008;15(2):199–201.PubMedCrossRefGoogle Scholar
  16. Davies RR, Hodges JR, Kril JJ, Patterson K, Halliday GM, Xuereb JH. The pathological basis of semantic dementia. Brain. 2005;128(Pt 9):1984–95. Epub 2005/07/08.PubMedCrossRefGoogle Scholar
  17. DeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron. 2011;72(2):245–56.PubMedCentralPubMedCrossRefGoogle Scholar
  18. Diehl-Schmid J, Schulte-Overberg J, Hartmann J, Forstl H, Kurz A, Haussermann P. Extrapyramidal signs, primitive reflexes and incontinence in fronto-temporal dementia. Eur J Neurol. 2007;14(8):860–4.PubMedCrossRefGoogle Scholar
  19. Espay AJ, Litvan I. Parkinsonism and frontotemporal dementia: the clinical overlap. J Mol Neurosci. 2011;45(3):343–9. Epub 2011/09/06.PubMedCentralPubMedCrossRefGoogle Scholar
  20. Evans JJ, Heggs AJ, Antoun N, Hodges JR. Progressive prosopagnosia associated with selective right temporal lobe atrophy. A new syndrome? Brain. 1995;118(Pt 1):1–13.PubMedCrossRefGoogle Scholar
  21. Forman MS, Farmer J, Johnson JK, Clark CM, Arnold SE, Coslett HB, et al. Frontotemporal dementia: clinicopathological correlations. Ann Neurol. 2006;59(6):952–62.PubMedCentralPubMedCrossRefGoogle Scholar
  22. Foster NL, Wilhelmsen K, Sima AA, Jones MZ, D’Amato CJ, Gilman S. Frontotemporal dementia and parkinsonism linked to chromosome 17: a consensus conference. Conference participants. Ann Neurol. 1997;41(6):706–15.PubMedCrossRefGoogle Scholar
  23. Gass J, Cannon A, Mackenzie IR, Boeve B, Baker M, Adamson J, et al. Mutations in progranulin are a major cause of ubiquitin-positive frontotemporal lobar degeneration. Hum Mol Genet. 2006;15(20):2988–3001.PubMedCrossRefGoogle Scholar
  24. Goldman JS, Farmer JM, Wood EM, Johnson JK, Boxer A, Neuhaus J, et al. Comparison of family histories in FTLD subtypes and related tauopathies. Neurology. 2005;65(11):1817–9.PubMedCrossRefGoogle Scholar
  25. Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76(11):1006–14. Epub 2011/02/18.PubMedCentralPubMedCrossRefGoogle Scholar
  26. Hodges JR, Patterson K, Oxbury S, Funnell E. Semantic dementia. Progressive fluent aphasia with temporal lobe atrophy. Brain. 1992;115(Pt 6):1783–806.PubMedCrossRefGoogle Scholar
  27. Hodges JR, Davies RR, Xuereb JH, Casey B, Broe M, Bak TH, et al. Clinicopathological correlates in frontotemporal dementia. Ann Neurol. 2004;56(3):399–406.PubMedCrossRefGoogle Scholar
  28. Hornberger M, Piguet O, Graham AJ, Nestor PJ, Hodges JR. How preserved is episodic memory in behavioral variant frontotemporal dementia? Neurology. 2010;74(6):472–9. Epub 2010/02/10.PubMedCentralPubMedCrossRefGoogle Scholar
  29. Houlden H, Baker M, Adamson J, Grover A, Waring S, Dickson D, et al. Frequency of tau mutations in three series of non-Alzheimer’s degenerative dementia. Annals of neurology. 1999;46(2):243–8.PubMedCrossRefGoogle Scholar
  30. Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H, et al. Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature. 1998;393(6686):702–5. Epub 1998/06/26.PubMedCrossRefGoogle Scholar
  31. Janssen JC, Warrington EK, Morris HR, Lantos P, Brown J, Revesz T, et al. Clinical features of frontotemporal dementia due to the intronic tau 10(+16) mutation. Neurology. 2002;58(8):1161–8. Epub 2002/04/24.PubMedCrossRefGoogle Scholar
  32. Josephs KA, Duffy JR, Strand EA, Machulda MM, Senjem ML, Master AV, et al. Characterizing a neurodegenerative syndrome: primary progressive apraxia of speech. Brain. 2012;135(5):1522–36.PubMedCentralPubMedCrossRefGoogle Scholar
  33. Joshi A, Roy EA, Black SE, Barbour K. Patterns of limb apraxia in primary progressive aphasia. Brain Cogn. 2003;53(2):403–7.PubMedCrossRefGoogle Scholar
  34. Karbe H, Kertesz A, Polk M. Profiles of language impairment in primary progressive aphasia. Arch Neurol. 1993;50(2):193.PubMedCrossRefGoogle Scholar
  35. Kertesz A, Hudson L, Mackenzie IR, Munoz DG. The pathology and nosology of primary progressive aphasia. Neurology. 1994;44(11):2065.PubMedCrossRefGoogle Scholar
  36. Kertesz A, McMonagle P, Blair M, Davidson W, Munoz DG. The evolution and pathology of frontotemporal dementia. Brain. 2005;128(Pt 9):1996–2005.PubMedCrossRefGoogle Scholar
  37. Kodama K, Okada S, Iseki E, Kowalska A, Tabira T, Hosoi N, et al. Familial frontotemporal dementia with a P301L tau mutation in Japan. J Neurol Sci. 2000;176(1):57–64. Epub 2000/06/24.PubMedCrossRefGoogle Scholar
  38. Le Ber I, Van Der Zee J, Hannequin D, Gijselinck I, Campion D, Puel M, et al. Progranulin null mutations in both sporadic and familial frontotemporal dementia. Hum Mutat. 2007;28(9):846–55.PubMedCrossRefGoogle Scholar
  39. Lendon CL, Lynch T, Norton J, McKeel Jr DW, Busfield F, Craddock N, et al. Hereditary dysphasic disinhibition dementia: a frontotemporal dementia linked to 17q21-22. Neurology. 1998;50(6):1546–55.PubMedCrossRefGoogle Scholar
  40. Lillo P, Hodges JR. Frontotemporal dementia and motor neurone disease: overlapping clinic-pathological disorders. J Clin Neurosci. 2009;16(9):1131–5.PubMedCrossRefGoogle Scholar
  41. Mann DM, South PW, Snowden JS, Neary D. Dementia of frontal lobe type: neuropathology and immunohistochemistry. J Neurol Neurosurg Psychiatry. 1993;56(6):605–14.PubMedCentralPubMedCrossRefGoogle Scholar
  42. Mathew R, Bak TH, Hodges JR. Diagnostic criteria for corticobasal syndrome: a comparative study. J Neurol Neurosurg Psychiatry. 2012;83(4):405–10.PubMedCrossRefGoogle Scholar
  43. Mioshi E, Bristow M, Cook R, Hodges JR. Factors underlying caregiver stress in frontotemporal dementia and Alzheimer's disease. Dement Geriatr Cogn Disord. 2009;27(1):76–81. Epub 2009/01/22.PubMedCrossRefGoogle Scholar
  44. Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology. 1998;51(6):1546–54.PubMedCrossRefGoogle Scholar
  45. Newsway V, Fish M, Rohrer JD, Majounie E, Williams N, Hack M, et al. Perry syndrome due to the DCTN1 G71R mutation: a distinctive levodopa responsive disorder with behavioral syndrome, vertical gaze palsy, and respiratory failure. Mov Disord. 2010;25(6):767–70.PubMedCrossRefGoogle Scholar
  46. Nuytemans K, Bademci G, Kohli MM, Beecham GW, Wang L, Young JI, et al. C9ORF72 intermediate repeat copies are a significant risk factor for Parkinson disease. Ann Hum Genet. 2013;77(5):351–63.Google Scholar
  47. Onari KSH. Anatomishe Beitrage zur Lehre von der Pickschen umschriebenen Grosshirnrinden-Atrophie (‘Picksche Krankheit’). Z Gesamte Neurol Psych. 1926;101:470–511.CrossRefGoogle Scholar
  48. Padovani A, Agosti C, Premi E, Bellelli G, Borroni B. Extrapyramidal symptoms in frontotemporal dementia: prevalence and clinical correlations. Neurosci Lett. 2007;422(1):39–42.PubMedCrossRefGoogle Scholar
  49. Pickering-Brown SM, Rollinson S, Du Plessis D, Morrison KE, Varma A, Richardson AM, et al. Frequency and clinical characteristics of progranulin mutation carriers in the Manchester frontotemporal lobar degeneration cohort: comparison with patients with MAPT and no known mutations. Brain. 2008;131(Pt 3):721–31.PubMedCrossRefGoogle Scholar
  50. Piggott MA, Perry EK, Marshall EF, McKeith IG, Johnson M, Melrose HL, et al. Nigrostriatal dopaminergic activities in dementia with Lewy bodies in relation to neuroleptic sensitivity: comparisons with Parkinson’s disease. Biol Psychiatry. 1998;44(8):765–74.PubMedCrossRefGoogle Scholar
  51. Piguet O, Brooks WS, Halliday GM, Schofield PR, Stanford PM, Kwok JB, et al. Similar early clinical presentations in familial and non-familial frontotemporal dementia. J Neurol Neurosurg Psychiatry. 2004;75(12):1743–5. Epub 2004/11/19.PubMedCentralPubMedCrossRefGoogle Scholar
  52. Pijnenburg Y, Sampson E, Harvey R, Fox N, Rossor M. Vulnerability to neuroleptic side effects in frontotemporal lobar degeneration. Int J Geriatr Psychiatry. 2003;18(1):67–72.PubMedCrossRefGoogle Scholar
  53. Poorkaj P, Grossman M, Steinbart E, Payami H, Sadovnick A, Nochlin D, et al. Frequency of tau gene mutations in familial and sporadic cases of non-Alzheimer dementia. Arch Neurol. 2001;58(3):383–7.PubMedCrossRefGoogle Scholar
  54. Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011;134(Pt 9):2456–77. Epub 2011/08/04.PubMedCentralPubMedCrossRefGoogle Scholar
  55. Ratnavalli E, Brayne C, Dawson K, Hodges JR. The prevalence of frontotemporal dementia. Neurology. 2002;58(11):1615–21. Epub 2002/06/12.PubMedCrossRefGoogle Scholar
  56. Reed LA, Wszolek ZK, Hutton M. Phenotypic correlations in FTDP-17. Neurobiol Aging. 2001;22(1):89–107. Epub 2001/02/13.PubMedCrossRefGoogle Scholar
  57. Renton AE, Majounie E, Waite A, Simon-Sanchez J, Rollinson S, Gibbs JR, et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron. 2011;72(2):257–68.PubMedCentralPubMedCrossRefGoogle Scholar
  58. Rinne JO, Laine M, Kaasinen V, Norvasuo-Heila MK, Nagren K, Helenius H. Striatal dopamine transporter and extrapyramidal symptoms in frontotemporal dementia. Neurology. 2002;58(10):1489–93.PubMedCrossRefGoogle Scholar
  59. Rohrer JD, Ridgway GR, Modat M, Ourselin S, Mead S, Fox NC, et al. Distinct profiles of brain atrophy in frontotemporal lobar degeneration caused by progranulin and tau mutations. Neuroimage. 2010a;53(3):1070–6.PubMedCentralPubMedCrossRefGoogle Scholar
  60. Rohrer JD, Rossor MN, Warren JD. Apraxia in progressive nonfluent aphasia. J Neurol. 2010b;257(4):569–74.PubMedCentralPubMedCrossRefGoogle Scholar
  61. Rosso SM, Donker Kaat L, Baks T, Joosse M, de Koning I, Pijnenburg Y, et al. Frontotemporal dementia in The Netherlands: patient characteristics and prevalence estimates from a population-based study. Brain. 2003;126(Pt 9):2016–22.PubMedCrossRefGoogle Scholar
  62. Saito Y, Geyer A, Sasaki R, Kuzuhara S, Nanba E, Miyasaka T, et al. Early-onset, rapidly progressive familial tauopathy with R406W mutation. Neurology. 2002;58(5):811–3.PubMedCrossRefGoogle Scholar
  63. Schroeter ML, Raczka K, Neumann J, von Cramon DY. Neural networks in frontotemporal dementia–a meta-analysis. Neurobiol Aging. 2008;29(3):418–26.PubMedCrossRefGoogle Scholar
  64. Seelaar H, Schelhaas HJ, Azmani A, Küsters B, Rosso S, Majoor-Krakauer D, et al. TDP-43 pathology in familial frontotemporal dementia and motor neuron disease without progranulin mutations. Brain. 2007;130(5):1375–85.PubMedCrossRefGoogle Scholar
  65. Sha S, Hou C, Viskontas IV, Miller BL. Are frontotemporal lobar degeneration, progressive supranuclear palsy and corticobasal degeneration distinct diseases? Nat Clin Pract Neurol. 2006;2(12):658–65. Epub 2006/11/23.PubMedCrossRefGoogle Scholar
  66. Sha SJ, Takada LT, Rankin KP, Yokoyama JS, Rutherford NJ, Fong JC, et al. Frontotemporal dementia due to C9ORF72 mutations: clinical and imaging features. Neurology. 2012;79(10):1002–11. Epub 2012/08/10.PubMedCentralPubMedCrossRefGoogle Scholar
  67. Snowden JS, Rollinson S, Thompson JC, Harris JM, Stopford CL, Richardson AM, et al. Distinct clinical and pathological characteristics of frontotemporal dementia associated with C9ORF72 mutations. Brain. 2012;135(Pt 3):693–708. Epub 2012/02/04.PubMedCentralPubMedCrossRefGoogle Scholar
  68. Soliveri P, Piacentini S, Girotti F. Limb apraxia in corticobasal degeneration and progressive supranuclear palsy. Neurology. 2005;64(3):448–53.PubMedCrossRefGoogle Scholar
  69. Spina S, Murrell JR, Yoshida H, Ghetti B, Bermingham N, Sweeney B, et al. The novel Tau mutation G335S: clinical, neuropathological and molecular characterization. Acta Neuropathol. 2007;113(4):461–70.PubMedCrossRefGoogle Scholar
  70. Stanford PM, Halliday GM, Brooks WS, Kwok JB, Storey CE, Creasey H, et al. Progressive supranuclear palsy pathology caused by a novel silent mutation in exon 10 of the tau gene: expansion of the disease phenotype caused by tau gene mutations. Brain. 2000;123(Pt 5):880–93. Epub 2000/04/25.PubMedCrossRefGoogle Scholar
  71. Stanford PM, Brooks WS, Teber ET, Hallupp M, McLean C, Halliday GM, et al. Frequency of tau mutations in familial and sporadic frontotemporal dementia and other tauopathies. J Neurol. 2004;251(9):1098–104.PubMedCrossRefGoogle Scholar
  72. Strong MJ. The syndromes of frontotemporal dysfunction in amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2008;9(6):323–38.PubMedCrossRefGoogle Scholar
  73. Tsuboi Y. Neuropathology of familial tauopathy. Neuropathology. 2006;26(5):471–4. Epub 2006/11/04.PubMedCrossRefGoogle Scholar
  74. Tsuboi Y, Baker M, Hutton ML, Uitti RJ, Rascol O, Delisle MB, et al. Clinical and genetic studies of families with the tau N279K mutation (FTDP-17). Neurology. 2002;59(11):1791–3. Epub 2002/12/11.PubMedCrossRefGoogle Scholar
  75. Van Swieten JC, Heutink P. Mutations in progranulin (<i>GRN</i>) within the spectrum of clinical and pathological phenotypes of frontotemporal dementia. Lancet Neurol. 2008;7(10):965–74.PubMedCrossRefGoogle Scholar
  76. Van Swieten J, Stevens M, Rosso S, Rizzu P, Joosse M, De Koning I, et al. Phenotypic variation in hereditary frontotemporal dementia with tau mutations. Ann Neurol. 1999;46(4):617–26.PubMedCrossRefGoogle Scholar
  77. Whitwell JL, Weigand SD, Boeve BF, Senjem ML, Gunter JL, DeJesus-Hernandez M, et al. Neuroimaging signatures of frontotemporal dementia genetics: C9ORF72, tau, progranulin and sporadics. Brain. 2012;135(Pt 3):794–806. Epub 2012/03/01.PubMedCentralPubMedCrossRefGoogle Scholar
  78. Wszolek ZK, Uitti RJ, Hutton M. A mutation in the microtubule-associated protein tau in pallido-nigro-luysian degeneration. Neurology. 2000;54(10):2028–30. Epub 2000/05/24.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  1. 1.FRONTIER - Frontotemporal Dementia Research Group at Neuroscience ResearchSydneyAustralia

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