CNS Drugs

, Volume 26, Issue 10, pp 841–870 | Cite as

Frontotemporal Lobar Degeneration

Epidemiology, Pathology, Diagnosis and Management
Review Article

Abstract

Frontotemporal lobar degeneration (FTLD) describes a spectrum of clinically, pathologically and genetically heterogeneous neurodegenerative disorders of unknown aetiology. FTLD spectrum disorders collectively represent a leading cause of early-onset dementia, with most cases presenting between 45 and 64 years of age.

FTLD is characterized by progressive changes in behaviour, executive dysfunction and/or language impairment and can be differentiated clinically into three frontotemporal dementia (FTD) syndromes as follows: (i) behavioural variant (bvFTD); (ii) semantic dementia (SD); and (iii) progressive nonfluent aphasia (PNFA). Additionally, there is a significant clinical, pathological and genetic overlap between FTD and motor neuron disease/amyotrophic lateral sclerosis (FTD-ALS) and the atypical parkinsonian syndromes, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). bvFTD is characterized by progressive behavioural impairment and a decline in executive function with frontal lobe-predominant atrophy, SD by a loss of object knowledge with prominent anomia and asymmetrical atrophy of the anterior temporal lobes and PNFA by expressive or motor speech deficits with predominantly left peri-sylvian atrophy.

Recent advances in molecular biology and immunohistochemical staining techniques have further classified the FTLD spectrum disorders based upon the predominant neuropathological protein into three main categories: (i) microtubule-associated protein tau (FTLD-TAU); (ii) TAR DNA-binding protein-43 (FTLD-TDP); and (iii) fused in sarcoma protein (FTLD-FUS). Up to 40% of FTD patients report a family history of neurodegenerative illness, and one-third to one-half of familial cases of FTD follow an autosomal dominant inheritance pattern. Mutations in MAPT, PGRN, TARDBP, VCP and CHMP2B have been described, along with a recently identified C9ORF72 hexanucleotide repeat expansion.

To date, there are no US FDA-approved treatments or disease-modifying therapies for FTD. Pharmacological strategies have focused on neurotransmitter replacement and modulation for the treatment of behavioural, motor and cognitive symptoms of FTD, and include selective serotonin reuptake inhibitors (SSRIs), atypical antipsychotics, acetylcholinesterase inhibitors and glutamate NMDA receptor antagonists. At present, adequate management of FTD symptoms involves a combination of pharmacological therapy with behavioural, physical and environmental modification techniques.

Notes

Acknowledgements

Special thanks to Drs Salvatore Spina and Bernardino Ghetti of the Indiana Alzheimer Disease Center for contributing the neuropathology figures to the manuscript. Dr Matthews is supported in part by the National Institute on Aging Indiana Alzheimer Disease Center NIA P30 AG010133. The authors have no conflicts of interest that are directly relevant to the content of this article.

References

  1. 1.
    Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998; 51(6): 1546–54PubMedCrossRefGoogle Scholar
  2. 2.
    Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 2011; 134(Pt 9): 2456–77PubMedCrossRefGoogle Scholar
  3. 3.
    Mesulam MM. Primary progressive aphasia. Ann Neurol 2001; 49(4): 425–32PubMedCrossRefGoogle Scholar
  4. 4.
    Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology 2011; 76(11): 1006–14PubMedCrossRefGoogle Scholar
  5. 5.
    Seelaar H, Rohrer JD, Pijnenburg YA, et al. Clinical, genetic and pathological heterogeneity of frontotemporal dementia: a review. J Neurol Neurosurg Psychiatr 2011; 82(5): 476–86PubMedCrossRefGoogle Scholar
  6. 6.
    Pick A. Über die Beziehungen der senilen Hirnatrophie zur Aphasie. Prager Med Wochenschr 1892; 17: 165–7Google Scholar
  7. 7.
    Alzheimer A. Über eigenartige Krankheitsfälle der späteren Alters. Z Gesamte Neurol Psychiatrie 1911; 4: 356–85CrossRefGoogle Scholar
  8. 8.
    Snowden JS, Neary D, Mann DM. Frontotemporal dementia. Br J Psychiatry 2002; 180: 140–3PubMedCrossRefGoogle Scholar
  9. 9.
    Knopman DS, Roberts RO. Estimating the number of persons with frontotemporal lobar degeneration in the US population. J Mol Neurosci 2011; 45(3): 330–5PubMedCrossRefGoogle Scholar
  10. 10.
    Diehl J, Kurz A. Frontotemporal dementia: patient characteristics, cognition, and behaviour. Int J Geriatr Psychiatry 2002; 17(10): 914–8PubMedCrossRefGoogle Scholar
  11. 11.
    Hodges JR, Davies R, Xuereb J, et al. Survival in frontotemporal dementia. Neurology 2003; 61(3): 349–54PubMedCrossRefGoogle Scholar
  12. 12.
    Arvanitakis Z. Update on frontotemporal dementia. Neurologist 2010; 16(1): 16–22PubMedCrossRefGoogle Scholar
  13. 13.
    Ratnavalli E, Brayne C, Dawson K, et al. The prevalence of frontotemporal dementia. Neurology 2002; 58(11): 1615–21PubMedCrossRefGoogle Scholar
  14. 14.
    Knopman DS, Petersen RC, Edland SD, et al. The incidence of frontotemporal lobar degeneration in Rochester, Minnesota, 1990 through 1994. Neurology 2004; 62(3): 506–8PubMedCrossRefGoogle Scholar
  15. 15.
    Borroni B, Alberici A, Archetti S, et al. New insights into biological markers of frontotemporal lobar degeneration spectrum. Curr Med Chem 2010; 17(10): 1002–9PubMedCrossRefGoogle Scholar
  16. 16.
    Russo SM. Frontotemporal dementia in The Netherlands: patient characteristics and prevalence estimates from a population-based study. Brain 2003; 126: 2016–22CrossRefGoogle Scholar
  17. 17.
    Roberson ED, Hesse JH, Rose KD, et al. Frontotemporal dementia progresses to death faster than Alzheimer disease. Neurology 2005; 65(5): 719–25PubMedCrossRefGoogle Scholar
  18. 18.
    Helzner EP, Scarmeas N, Cosentino S, et al. Survival in Alzheimer disease: a multiethnic, population-based study of incident cases. Neurology 2008; 71(19): 1489–95PubMedCrossRefGoogle Scholar
  19. 19.
    Hodges JR, Mitchell J, Dawson K, et al. Semantic dementia: demography, familial factors and survival in a consecutive series of 100 cases. Brain 2010; 133(Pt 1): 300–6PubMedCrossRefGoogle Scholar
  20. 20.
    Garcin B, Lillo P, Hornberger M, et al. Determinants of survival in behavioral variant frontotemporal dementia. Neurology 2009; 73(20): 1656–61PubMedCrossRefGoogle Scholar
  21. 21.
    Hornberger M, Piguet O, Kipps C, et al. Executive function in progressive and nonprogressive behavioral variant frontotemporal dementia. Neurology 2008; 71(19): 1481–8PubMedCrossRefGoogle Scholar
  22. 22.
    Davies RR, Kipps CM, Mitchell J, et al. Progression in frontotemporal dementia: identifying a benign behavioral variant by magnetic resonance imaging. Arch Neurol 2006; 63(11): 1627–31PubMedCrossRefGoogle Scholar
  23. 23.
    Stevens M, van Duijn CM, Kamphorst W, et al. Familial aggregation in frontotemporal dementia. Neurology 1998; 50(6): 1541–5PubMedCrossRefGoogle Scholar
  24. 24.
    Johnson JK, Diehl J, Mendez MF, et al. Frontotemporal lobar degeneration: demographic characteristics of 353 patients. Arch Neurol 2005; 62(6): 925–30PubMedCrossRefGoogle Scholar
  25. 25.
    Carthery-Goulart MT, Knibb JA, Patterson K, et al. Semantic dementia versus nonfluent progressive aphasia: neuropsychological characterization and differentiation. Alzheimer Dis Assoc Disord 2012; 26(1): 36–43PubMedCrossRefGoogle Scholar
  26. 26.
    Bathgate D, Snowden JS, Varma A, et al. Behaviour in frontotemporal dementia, Alzheimer’ss disease and vascular dementia. Acta Neurol Scand 2001; 103(6): 367–78PubMedCrossRefGoogle Scholar
  27. 27.
    McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’ss disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7(3): 263–9PubMedCrossRefGoogle Scholar
  28. 28.
    Hornberger M, Piguet O. Episodic memory in frontotemporal dementia: a critical review. Brain 2012; 135(Pt 3): 678–92PubMedCrossRefGoogle Scholar
  29. 29.
    Short RA, Broderick DF, Patton A, et al. Different patterns of magnetic resonance imaging atrophy for frontotemporal lobar degeneration syndromes. Arch Neurol 2005; 62(7): 1106–10PubMedCrossRefGoogle Scholar
  30. 30.
    Graff-Radford NR, Russell JW, Rezai K. Frontal degenerative dementia and neuroimaging. Adv Neurol 1995; 66: 37–47; discussion -50PubMedGoogle Scholar
  31. 31.
    Rosen HJ, Gorno-Tempini ML, Goldman WP, et al. Patterns of brain atrophy in frontotemporal dementia and semantic dementia. Neurology 2002; 58(2): 198–208PubMedCrossRefGoogle Scholar
  32. 32.
    Hughes LE, Nestor PJ, Hodges JR, et al. Magnetoencephalography of frontotemporal dementia: spatiotemporally localized changes during semantic decisions. Brain 2011; 134(Pt 9): 2513–22PubMedCrossRefGoogle Scholar
  33. 33.
    Rabinovici GD, Rosen HJ, Alkalay A, et al. Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD. Neurology 2011; 77(23): 2034–42PubMedCrossRefGoogle Scholar
  34. 34.
    Rosen HJ, Allison SC, Schauer GF, et al. Neuroanatomical correlates of behavioural disorders in dementia. Brain 2005; 128(Pt 11): 2612–25PubMedCrossRefGoogle Scholar
  35. 35.
    Zamboni G, Huey ED, Krueger F, et al. Apathy and disinhibition in frontotemporal dementia: insights into their neural correlates. Neurology 2008; 71(10): 736–42PubMedCrossRefGoogle Scholar
  36. 36.
    Rankin KP, Gorno-Tempini ML, Allison SC, et al. Structural anatomy of empathy in neurodegenerative disease. Brain 2006; 129(Pt 11): 2945–56PubMedCrossRefGoogle Scholar
  37. 37.
    Rosen HJ, Wilson MR, Schauer GF, et al. Neuroanatomical correlates of impaired recognition of emotion in dementia. Neuropsychologia 2006; 44(3): 365–73PubMedCrossRefGoogle Scholar
  38. 38.
    Piguet O, Petersen A, Yin Ka Lam B, et al. Eating and hypothalamus changes in behavioral-variant frontotemporal dementia. Ann Neurol 2011; 69(2): 312–9PubMedCrossRefGoogle Scholar
  39. 39.
    Woolley JD, Gorno-Tempini ML, Seeley WW, et al. Binge eating is associated with right orbitofrontal-insular-striatal atrophy in frontotemporal dementia. Neurology 2007; 69(14): 1424–33PubMedCrossRefGoogle Scholar
  40. 40.
    Rascovsky K. Cognitive profiles differ in autopsy-confirmed frontotemporal dementia and AD. Neurology 2005; 58(2): 1802–8Google Scholar
  41. 41.
    Josephs KA. Predicting functional decline in behavioural variant frontotemporal dementia. Brain 2011; 134: 432–48PubMedCrossRefGoogle Scholar
  42. 42.
    Wilson SM, Henry ML, Besbris M, et al. Connected speech production in three variants of primary progressive aphasia. Brain 2010; 133(Pt 7): 2069–88PubMedCrossRefGoogle Scholar
  43. 43.
    Cardarelli R, Kertesz A, Knebl JA. Frontotemporal dementia: a review for primary care physicians. Am Fam Physician 2010; 82(11): 1372–7PubMedGoogle Scholar
  44. 44.
    Gorno-Tempini ML, Dronkers NF, Rankin KP, et al. Cognition and anatomy in three variants of primary progressive aphasia. Ann Neurol 2004; 55(3): 335–46PubMedCrossRefGoogle Scholar
  45. 45.
    Mesulam MM. Slowly progressive aphasia without generalized dementia. Ann Neurol 1982; 11(6): 592–8PubMedCrossRefGoogle Scholar
  46. 46.
    Gorno-Tempini ML, Brambati SM, Ginex V, et al. The logopenic/phonological variant of primary progressive aphasia. Neurology 2008; 71(16): 1227–34PubMedCrossRefGoogle Scholar
  47. 47.
    Rabinovici GD, Seeley WW, Kim EJ, et al. Distinct MRI atrophy patterns in autopsy-proven Alzheimer’s disease and frontotemporal lobar degeneration. Am J Alzheimers Dis Other Demen 2007; 22(6): 474–88PubMedCrossRefGoogle Scholar
  48. 48.
    Rabinovici GD, Jagust WJ, Furst AJ, et al. Abeta amyloid and glucose metabolism in three variants of primary progressive aphasia. Ann Neurol 2008; 64(4): 388–401PubMedCrossRefGoogle Scholar
  49. 49.
    Grossman M, Payer F, Onishi K, et al. Language comprehension and regional cerebral defects in frontotemporal degeneration and Alzheimer’s disease. Neurology 1998; 50(1): 157–63PubMedCrossRefGoogle Scholar
  50. 50.
    Mesulam M, Wicklund A, Johnson N, et al. Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia. Ann Neurol 2008; 63(6): 709–19PubMedCrossRefGoogle Scholar
  51. 51.
    Alladi S, Xuereb J, Bak T, et al. Focal cortical presentations of Alzheimer’s disease. Brain 2007; 130(Pt 10): 2636–45PubMedCrossRefGoogle Scholar
  52. 52.
    Knibb JA, Xuereb JH, Patterson K, et al. Clinical and pathological characterization of progressive aphasia. Ann Neurol 2006; 59(1): 156–65PubMedCrossRefGoogle Scholar
  53. 53.
    Josephs KA, Duffy JR, Strand EA, et al. Characterizing a neurodegenerative syndrome: primary progressive apraxia of speech. Brain 2012; 135(Pt 5): 1522–36PubMedCrossRefGoogle Scholar
  54. 54.
    Josephs KA, Duffy JR, Strand EA, et al. Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech. Brain 2006; 129(Pt 6): 1385–98PubMedCrossRefGoogle Scholar
  55. 55.
    Duffy J. Apraxia of speech in degenerative neurologic disease. Aphasiology 2006; 20(6): 511–27CrossRefGoogle Scholar
  56. 56.
    Boeve B, Dickson D, Duffy J, et al. Progressive nonfluent aphasia and subsequent aphasic dementia associated with atypical progressive supranuclear palsy pathology. Eur Neurol 2003; 49(2): 72–8PubMedCrossRefGoogle Scholar
  57. 57.
    Josephs KA, Boeve BF, Duffy JR, et al. Atypical progressive supranuclear palsy underlying progressive apraxia of speech and nonfluent aphasia. Neurocase 2005; 11(4): 283–96PubMedCrossRefGoogle Scholar
  58. 58.
    Gorno-Tempini ML, Murray RC, Rankin KP, et al. Clinical, cognitive and anatomical evolution from nonfluent progressive aphasia to corticobasal syndrome: a case report. Neurocase 2004; 10(6): 426–36PubMedCrossRefGoogle Scholar
  59. 59.
    Lang AE. Cortical basal ganglionic degeneration presenting with “progressive loss of speech output and orofacial dyspraxia” [letter]. J Neurol Neurosurg Psychiatr 1992; 55(11): 1101PubMedCrossRefGoogle Scholar
  60. 60.
    Duffy JR, Peach RK, Strand EA. Progressive apraxia of speech as a sign of motor neuron disease. Am J Speech Lang Pathol 2007; 16(3): 198–208PubMedCrossRefGoogle Scholar
  61. 61.
    Deramecourt V, Lebert F, Debachy B, et al. Prediction of pathology in primary progressive language and speech disorders. Neurology 2010; 74(1): 42–9PubMedCrossRefGoogle Scholar
  62. 62.
    Didic M, Ceccaldi M, Poncet M. Progressive loss of speech: a neuropsychological profile of premotor dysfunction. Eur Neurol 1998; 39(2): 90–6PubMedCrossRefGoogle Scholar
  63. 63.
    Josephs KA, Duffy JR. Apraxia of speech and nonfluent aphasia: a new clinical marker for corticobasal degeneration and progressive supranuclear palsy. Curr Opin Neurol 2008; 21(6): 688–92PubMedCrossRefGoogle Scholar
  64. 64.
    Josephs KA, Duffy JR, Fossett TR, et al. Fluorodeoxyglucose F18 positron emission tomography in progressive apraxia of speech and primary progressive aphasia variants. Arch Neurol 2010; 67(5): 596–605PubMedCrossRefGoogle Scholar
  65. 65.
    Golbe LI, Davis PH, Schoenberg BS, et al. Prevalence and natural history of progressive supranuclear palsy. Neurology 1988; 38(7): 1031–4PubMedCrossRefGoogle Scholar
  66. 66.
    Nath U, Ben-Shlomo Y, Thomson RG, et al. The prevalence of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) in the UK. Brain 2001; 124(Pt 7): 1438–49PubMedCrossRefGoogle Scholar
  67. 67.
    Vanacore N, Bonifati V, Colosimo C, et al. Epidemiology of progressive supranuclear palsy: ESGAP Consortium. European Study Group on Atypical Parkinsonisms. Neurol Sci 2001; 22(1): 101–3PubMedCrossRefGoogle Scholar
  68. 68.
    Golbe LI. The epidemiology of PSP. J Neural Transm Suppl 1994; 42: 263–73PubMedCrossRefGoogle Scholar
  69. 69.
    Litvan I, Agid Y, Calne D, et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 1996; 47(1): 1–9PubMedCrossRefGoogle Scholar
  70. 70.
    Josephs KA. Neuropathological background of phenotypical variability in frontotemporal dementia. Acta Neuropathol 2011; 122: 137–53PubMedCrossRefGoogle Scholar
  71. 71.
    Hoglinger GU, Melhem NM, Dickson DW, et al. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat Genet 2011; 43(7): 699–705PubMedCrossRefGoogle Scholar
  72. 72.
    Boxer AL, Geschwind MD, Belfor N, et al. Patterns of brain atrophy that differentiate corticobasal degeneration syndrome from progressive supranuclear palsy. Arch Neurol 2006; 63(1): 81–6PubMedCrossRefGoogle Scholar
  73. 73.
    Boeve BF. The multiple phenotypes of corticobasal syndrome and corticobasal degeneration: implications for further study. J Mol Neurosci 2011; 45(3): 350–3PubMedCrossRefGoogle Scholar
  74. 74.
    Belfor NK, Kramer JH, Boxer A, et al. Patterns of neuropsychological impairment and brain atrophy support the similarities between corticobasal degeneration syndrome and frontotemporal dementia [abstract]. Neurology 2004; 62 (7 (Suppl. 5): A237Google Scholar
  75. 75.
    Cairns NJ, Bigio EH, Mackenzie IR, et al. Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol 2007; 114(1): 5–22PubMedCrossRefGoogle Scholar
  76. 76.
    Mackenzie IR, Neumann M, Bigio EH, et al. Nomenclature for neuropathologic subtypes of frontotemporal lobar degeneration: consensus recommendations. Acta Neuropathol 2009; 117(1): 15–8PubMedCrossRefGoogle Scholar
  77. 77.
    Kim EJ, Sidhu M, Gaus SE, et al. Selective frontoinsular von Economo neuron and fork cell loss in early behavioral variant frontotemporal dementia. Cereb Cortex 2012; 22(2): 251–9PubMedCrossRefGoogle Scholar
  78. 78.
    Seeley WW, Carlin DA, Allman JM, et al. Early frontotemporal dementia targets neurons unique to apes and humans. Ann Neurol 2006; 60(6): 660–7PubMedCrossRefGoogle Scholar
  79. 79.
    Holm IE, Isaacs AM, Mackenzie IR. Absence of FUS-immunoreactive pathology in frontotemporal dementia linked to chromosome 3 (FTD-3) caused by mutation in the CHMP2B gene. Acta Neuropathol 2009; 118(5): 719–20PubMedCrossRefGoogle Scholar
  80. 80.
    Goedert M, Spillantini MG. Tau mutations in frontotemporal dementia FTDP-17 and their relevance for Alzheimer’s disease. Biochim Biophys Acta 2000; 1502(1): 110–21PubMedCrossRefGoogle Scholar
  81. 81.
    Robert M, Mathuranath PS. Tau and tauopathies. Neurol India 2007; 55(1): 11–6PubMedCrossRefGoogle Scholar
  82. 82.
    Goedert M, Spillantini MG, Jakes R, et al. Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer’s disease. Neuron 1989; 3(4): 519–26PubMedCrossRefGoogle Scholar
  83. 83.
    Goedert M, Spillantini MG, Cairns NJ, et al. Tau proteins of Alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms. Neuron 1992; 8(1): 159–68PubMedCrossRefGoogle Scholar
  84. 84.
    Morris HR, Baker M, Yasojima K, et al. Analysis of tau haplotypes in Pick’s disease. Neurology 2002; 59(3): 443–5PubMedCrossRefGoogle Scholar
  85. 85.
    Dickson DW. Pick’s disease: a modern approach. Brain Pathol 1998; 8(2): 339–54PubMedCrossRefGoogle Scholar
  86. 86.
    Gozes I. Tau pathology and future therapeutics. Curr Alzheimer Res 2010; 7(8): 685–96PubMedCrossRefGoogle Scholar
  87. 87.
    Feany MB, Dickson DW. Widespread cytoskeletal pathology characterizes corticobasal degeneration. Am J Pathol 1995; 146(6): 1388–96PubMedGoogle Scholar
  88. 88.
    Komori T, Arai N, Oda M, et al. Astrocytic plaques and tufts of abnormal fibers do not coexist in corticobasal degeneration and progressive supranuclear palsy. Acta Neuropathol 1998; 96(4): 401–8PubMedCrossRefGoogle Scholar
  89. 89.
    Spina S, Farlow MR, Unverzagt FW, et al. The tauopathy associated with mutation +3 in intron 10 of Tau: characterization of the MSTD family. Brain 2008; 131(Pt 1): 72–89PubMedGoogle Scholar
  90. 90.
    Neumann M, Mackenzie IR, Cairns NJ, et al. TDP-43 in the ubiquitin pathology of frontotemporal dementia with VCP gene mutations. J Neuropathol Exp Neurol 2007; 66(2): 152–7PubMedCrossRefGoogle Scholar
  91. 91.
    Sreedharan J, Blair IP, Tripathi VB, et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 2008; 319(5870): 1668–72PubMedCrossRefGoogle Scholar
  92. 92.
    Kabashi E, Valdmanis PN, Dion P, et al. TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet 2008; 40(5): 572–4PubMedCrossRefGoogle Scholar
  93. 93.
    De Jesus-Hernandez M, Mackenzie IR, Boeve BF, et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 2011; 72(2): 245–56CrossRefGoogle Scholar
  94. 94.
    Arai T, Hasegawa M, Akiyama H, et al. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 2006; 351(3): 602–11PubMedCrossRefGoogle Scholar
  95. 95.
    Neumann M, Sampathu DM, Kwong LK, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006; 314(5796): 130–3PubMedCrossRefGoogle Scholar
  96. 96.
    Mackenzie IR, Neumann M, Baborie A, et al. A harmonized classification system for FTLD-TDP pathology. Acta Neuropathol 2011; 122(1): 111–3PubMedCrossRefGoogle Scholar
  97. 97.
    Kwiatkowski Jr TJ, Bosco DA, Leclerc AL, et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 2009; 323(5918): 1205–8PubMedCrossRefGoogle Scholar
  98. 98.
    Urwin H, Josephs KA, Rohrer JD, et al. FUS pathology defines the majority of tau- and TDP-43-negative frontotemporal lobar degeneration. Acta Neuropathol 2010; 120(1): 33–41PubMedCrossRefGoogle Scholar
  99. 99.
    Seelaar H, Klijnsma KY, de Koning I, et al. Frequency of ubiquitin and FUS-positive, TDP-43-negative frontotemporal lobar degeneration. J Neurol 2010; 257(5): 747–53PubMedCrossRefGoogle Scholar
  100. 100.
    Josephs KA. Caudate atrophy on MRI is a characteristic feature of FTLD-FUS. Eur J Neurol 2010; 17: 969–75PubMedCrossRefGoogle Scholar
  101. 101.
    Rohrer JD. Clinical and neuroanatomical signatures of tissue pathology in frontotemporal lobar degeneration. Brain 2011; 134:2565–81PubMedCrossRefGoogle Scholar
  102. 102.
    Rohrer JDAW, Jason D. Phenotypic signatures of genetic frontotemporal dementia. Curr Opin Neurol 2011; 24: 542–9PubMedCrossRefGoogle Scholar
  103. 103.
    Boeve BF, Boylan KB, Graff-Radford NR, et al. Characterization of frontotemporal dementia and/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72. Brain 2012; 135(Pt 3): 765–83PubMedCrossRefGoogle Scholar
  104. 104.
    Rohrer JD, Lashley T, Schott JM, et al. Clinical and neuroanatomical signatures of tissue pathology in frontotemporal lobar degeneration. Brain 2011; 134(Pt 9): 2565–81PubMedCrossRefGoogle Scholar
  105. 105.
    Whitwell JL, Weigand SD, Boeve BF, et al. Neuroimaging signatures of frontotemporal dementia genetics: C9ORF72, tau, progranulin and sporadics. Brain 2012; 135(Pt 3): 794–806PubMedCrossRefGoogle Scholar
  106. 106.
    Seelaar H, Kamphorst W, Rosso SM, et al. Distinct genetic forms of frontotemporal dementia. Neurology 2008; 71(16): 1220–6PubMedCrossRefGoogle Scholar
  107. 107.
    Yu CE, Bird TD, Bekris LM, et al. The spectrum of mutations in progranulin: a collaborative study screening 545 cases of neurodegeneration. Arch Neurol 2010; 67(2): 161–70PubMedCrossRefGoogle Scholar
  108. 108.
    Pickering-Brown SM, Rollinson S, Du Plessis D, 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): 721–31PubMedCrossRefGoogle Scholar
  109. 109.
    Chen-Plotkin AS, Martinez-Lage M, Sleiman PM, et al. Genetic and clinical features of progranulin-associated fronto temporal lobar degeneration. Arch Neurol 2011; 68(4): 488–97PubMedCrossRefGoogle Scholar
  110. 110.
    Schymick JC, Yang Y, Andersen PM, et al. Progranulin mutations and amyotrophic lateral sclerosis or amyotrophic lateral sclerosis-frontotemporal dementia phenotypes. J Neurol Neurosurg Psychiatr 2007; 78(7): 754–6PubMedCrossRefGoogle Scholar
  111. 111.
    Hutton M, Lendon CL, Rizzu P, et al. Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 1998; 393(6686): 702–5PubMedCrossRefGoogle Scholar
  112. 112.
    Poorkaj P, Bird TD, Wijsman E, et al. Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann Neurol 1998; 43(6): 815–25PubMedCrossRefGoogle Scholar
  113. 113.
    Rademakers R, Cruts M, van Broeckhoven C. The role of tau (MAPT) in frontotemporal dementia and related tauopathies. Hum Mutat 2004; 24(4): 277–95PubMedCrossRefGoogle Scholar
  114. 114.
    Houlden H, Baker M, Morris HR, et al. Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype. Neurology 2001; 56(12): 1702–6PubMedCrossRefGoogle Scholar
  115. 115.
    Alzheimer disease and frontotemporal dementia mutation database [online]. Available from URL: http://www.molgen.vib-ua.be/ADMutations/ [Accessed 2012 Aug 13]
  116. 116.
    Hasegawa MS, Michael J, Goedert M. Tau proteins with FTDP-17 mutations have a reduced ability to promote microtubule assembly. FEBS Lett 1998; 437(3): 207–10PubMedCrossRefGoogle Scholar
  117. 117.
    Bird TD, Nochlin D, Poorkaj P, et al. A clinical pathological comparison of three families with frontotemporal dementia and identical mutations in the tau gene (P301L). Brain 1999; 122(Pt 4): 741–56PubMedCrossRefGoogle Scholar
  118. 118.
    Geschwind DH, Robidoux J, Alarcon M, et al. Dementia and neurodevelopmental predisposition: cognitive dysfunction in presymptomatic subjects precedes dementia by decades in frontotemporal dementia. Ann Neurol 2001; 50(6): 741–6PubMedCrossRefGoogle Scholar
  119. 119.
    Baker M, Mackenzie IR, Pickering-Brown SM, et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 2006; 442(7105): 916–9PubMedCrossRefGoogle Scholar
  120. 120.
    Cruts M, Gijselinck I, van der Zee J, et al. Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 2006; 442(7105): 920–4PubMedCrossRefGoogle Scholar
  121. 121.
    Rohrer JD, Guerreiro R, Vandrovcova J, et al. The heritability and genetics of frontotemporal lobar degeneration. Neurology 2009; 73(18): 1451–6PubMedCrossRefGoogle Scholar
  122. 122.
    Gass J, Cannon A, Mackenzie IR, et al. Mutations in progranulin are a major cause of ubiquitin-positive frontotemporal lobar degeneration. Hum Mol Genet 2006; 15(20): 2988–3001PubMedCrossRefGoogle Scholar
  123. 123.
    Le Ber I, van der Zee J, Hannequin D, et al. Progranulin null mutations in both sporadic and familial frontotemporal dementia. Hum Mutat 2007; 28(9): 846–55PubMedCrossRefGoogle Scholar
  124. 124.
    Bateman A, Belcourt D, Bennett H, et al. Granulins, a novel class of peptide from leukocytes. Biochem Biophys Res Commun 1990; 173(3): 1161–8PubMedCrossRefGoogle Scholar
  125. 125.
    Suzuki M, Lee HC, Kayasuga Y, et al. Roles of progranulin in sexual differentiation of the developing brain and adult neurogenesis. J Reprod Dev 2009; 55(4): 351–5PubMedCrossRefGoogle Scholar
  126. 126.
    Zhou J, Gao G, Crabb JW, et al. Purification of an autocrine growth factor homologous with mouse epithelin precursor from a highly tumorigenic cell line. J Biol Chem 1993; 268(15): 10863–9PubMedGoogle Scholar
  127. 127.
    Ahmed Z, Sheng H, Xu YF, et al. Accelerated lipofuscinosis and ubiquitination in granulin knockout mice suggest a role for progranulin in successful aging. Am J Pathol 2010; 177(1): 311–24PubMedCrossRefGoogle Scholar
  128. 128.
    Zhu J, Nathan C, Jin W, et al. Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair. Cell 2002; 111(6): 867–78PubMedCrossRefGoogle Scholar
  129. 129.
    He Z, Bateman A. Progranulin (granulin-epithelin precursor, PC-cell-derived growth factor, acrogranin) mediates tissue repair and tumorigenesis. J Mol Med (Berl.) 2003; 81(10): 600–12CrossRefGoogle Scholar
  130. 130.
    He Z, Bateman A. Progranulin gene expression regulates epithelial cell growth and promotes tumor growth in vivo. Cancer Res 1999; 59(13): 3222–9PubMedGoogle Scholar
  131. 131.
    Lu R, Serrero G. Mediation of estrogen mitogenic effect in human breast cancer MCF-7 cells by PC-cell-derived growth factor (PCDGF/granulin precursor). Proc Natl Acad Sci U S A 2001; 98(1): 142–7PubMedCrossRefGoogle Scholar
  132. 132.
    Davidson B, Alejandro E, Florenes VA, et al. Granulinepithelin precursor is a novel prognostic marker in epithelial ovarian carcinoma. Cancer 2004; 100(10): 2139–47PubMedCrossRefGoogle Scholar
  133. 133.
    Finch N, Carrasquillo MM, Baker M, et al. TMEM106B regulates progranulin levels and the penetrance of FTLD in GRN mutation carriers. Neurology 2011; 76(5): 467–74PubMedCrossRefGoogle Scholar
  134. 134.
    Vance C, Al-Chalabi A, Ruddy D, et al. Familial amyotrophic lateral sclerosis with frontotemporal dementia is linked to a locus on chromosome 9p13.2–21.3. Brain 2006; 129(Pt 4): 868–76PubMedCrossRefGoogle Scholar
  135. 135.
    van Es MA, Veldink JH, Saris CG, et al. Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis. Nat Genet 2009; 41(10): 1083–7PubMedCrossRefGoogle Scholar
  136. 136.
    Renton AE, Majounie E, Waite A, et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 2011; 72(2): 257–68PubMedCrossRefGoogle Scholar
  137. 137.
    Gros-Louis F, Gaspar C, Rouleau GA. Genetics of familial and sporadic amyotrophic lateral sclerosis. Biochim Biophys Acta 2006; 1762(11–12): 956–72PubMedGoogle Scholar
  138. 138.
    Lomen-Hoerth C, Murphy J, Langmore S, et al. Are amyotrophic lateral sclerosis patients cognitively normal? Neurology 2003; 60(7): 1094–7PubMedCrossRefGoogle Scholar
  139. 139.
    Strong MJ, Lomen-Hoerth C, Caselli RJ, et al. Cognitive impairment, frontotemporal dementia, and the motor neuron diseases. Ann Neurol 2003; 54 Suppl. 5: S20–3PubMedCrossRefGoogle Scholar
  140. 140.
    Giordana MT, Ferrero P, Grifoni S, et al. Dementia and cognitive impairment in amyotrophic lateral sclerosis: a review. Neurol Sci 2011; 32(1): 9–16PubMedCrossRefGoogle Scholar
  141. 141.
    Phukan J, Pender NP, Hardiman O. Cognitive impairment in amyotrophic lateral sclerosis. Lancet Neurol 2007; 6(11): 994–1003PubMedCrossRefGoogle Scholar
  142. 142.
    Lillo P, Hodges JR. Frontotemporal dementia and motor neurone disease: overlapping clinic-pathological disorders. J Clin Neurosci 2009; 16(9): 1131–5PubMedCrossRefGoogle Scholar
  143. 143.
    Pearson JP, Williams NM, Majounie E, et al. Familial frontotemporal dementia with amyotrophic lateral sclerosis and a shared haplotype on chromosome 9p. J Neurol 2011; 258(4): 647–55PubMedCrossRefGoogle Scholar
  144. 144.
    Lomen-Hoerth C, Anderson T, Miller B. The overlap of amyotrophic lateral sclerosis and frontotemporal dementia. Neurology 2002; 59(7): 1077–9PubMedCrossRefGoogle Scholar
  145. 145.
    Coon EA, Sorenson EJ, Whitwell JL, et al. Predicting survival in frontotemporal dementia with motor neuron disease. Neurology 2011; 76(22): 1886–93PubMedCrossRefGoogle Scholar
  146. 146.
    Geser F, Lee VM, Trojanowski JQ. Amyotrophic lateral sclerosis and frontotemporal lobar degeneration: a spectrum of TDP-43 proteinopathies. Neuropathology 2010; 30(2): 103–12PubMedCrossRefGoogle Scholar
  147. 147.
    Morita M, Al-Chalabi A, Andersen PM, et al. A locus on chromosome 9p confers susceptibility to ALS and frontotemporal dementia. Neurology 2006; 66(6): 839–44PubMedCrossRefGoogle Scholar
  148. 148.
    Boxer AL, Mackenzie IR, Boeve BF, et al. Clinical, neuroimaging and neuropathological features of a new chromosome 9p-linked FTD-ALS family. J Neurol Neurosurg Psychiatr 2011; 82(2): 196–203PubMedCrossRefGoogle Scholar
  149. 149.
    Van Deerlin VM, Sleiman PM, Martinez-Lage M, et al. Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions. Nat Genet 2010; 42(3): 234–9PubMedCrossRefGoogle Scholar
  150. 150.
    Shatunov A, Mok K, Newhouse S, et al. Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome-wide association study. Lancet Neurol 2010; 9(10): 986–94PubMedCrossRefGoogle Scholar
  151. 151.
    Snowden JS, Thompson JC, Stopford CL, et al. The clinical diagnosis of early-onset dementias: diagnostic accuracy and clinicopathological relationships. Brain 2011; 134(Pt 9): 2478–92PubMedCrossRefGoogle Scholar
  152. 152.
    Woolley JD, Khan BK, Murthy NK, et al. The diagnostic challenge of psychiatric symptoms in neurodegenerative disease: rates of and risk factors for prior psychiatric diagnosis in patients with early neurodegenerative disease. J Clin Psychiatry 2011; 72(2): 126–33PubMedCrossRefGoogle Scholar
  153. 153.
    Vandenberghe R. Sense and sensitivity of novel criteria for frontotemporal dementia. Brain 2011; 134(Pt 9): 2450–3PubMedCrossRefGoogle Scholar
  154. 154.
    Grossman M. Biomarkers in frontotemporal lobar degeneration. Curr Opin Neurol 2010; 23(6): 643–8PubMedCrossRefGoogle Scholar
  155. 155.
    de Souza LC, Lamari F, Belliard S, et al. Cerebrospinal fluid biomarkers in the differential diagnosis of Alzheimer’s disease from other cortical dementias. J Neurol Neurosurg Psychiatr 2011; 82(3): 240–6PubMedCrossRefGoogle Scholar
  156. 156.
    Green AJ, Harvey RJ, Thompson EJ, et al. Increased tau in the cerebrospinal fluid of patients with frontotemporal dementia and Alzheimer’s disease. Neurosci Lett 1999; 259(2): 133–5PubMedCrossRefGoogle Scholar
  157. 157.
    Grossman M, Farmer J, Leight S, et al. Cerebrospinal fluid profile in frontotemporal dementia and Alzheimer’s disease. Ann Neurol 2005; 57(5): 721–9PubMedCrossRefGoogle Scholar
  158. 158.
    Mecocci P. Tau protein in cerebrospinal fluid: a new diagnostic and prognostic marker in Alzheimer’s disease? Alzheimer Dis Assoc Disord 1997; 12(3): 211–4CrossRefGoogle Scholar
  159. 159.
    Riemenschneider M, Wagenpfeil S, Diehl J, et al. Tau and Abeta42 protein in CSF of patients with frontotemporal degeneration. Neurology 2002; 58(11): 1622–8PubMedCrossRefGoogle Scholar
  160. 160.
    Arai H, Morikawa Y, Higuchi M, et al. Cerebrospinal fluid tau levels in neurodegenerative diseases with distinct taurelated pathology. Biochem Biophys Res Commun 1997; 236(2): 262–4PubMedCrossRefGoogle Scholar
  161. 161.
    Spies PE, Slats D, Sjogren JM, et al. The cerebrospinal fluid amyloid beta42/40 ratio in the differentiation of Alzheimer’s disease from non-Alzheimer’s dementia. Curr Alzheimer Res 2010; 7(5): 470–6PubMedCrossRefGoogle Scholar
  162. 162.
    Eriksen JL, Mackenzie IR. Progranulin: normal function and role in neurodegeneration. J Neurochem 2008; 104(2): 287–97PubMedGoogle Scholar
  163. 163.
    Ghidoni R, Benussi L, Glionna M, et al. Low plasma progranulin levels predict progranulin mutations in frontotemporal lobar degeneration. Neurology 2008; 71(16): 1235–9PubMedCrossRefGoogle Scholar
  164. 164.
    Sleegers K, Brouwers N, Van Damme P, et al. Serum biomarker for progranulin-associated frontotemporal lobar degeneration. Ann Neurol 2009; 65(5): 603–9PubMedCrossRefGoogle Scholar
  165. 165.
    Finch N, Baker M, Crook R, et al. Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members. Brain 2009; 132(Pt 3): 583–91PubMedCrossRefGoogle Scholar
  166. 166.
    Whitwell JL, Jack Jr CR, Boeve BF, et al. Atrophy patterns in IVS10+16, IVS10+3, N279K, S305N, P301L, and V337M MAPT mutations. Neurology 2009; 73(13): 1058–65PubMedCrossRefGoogle Scholar
  167. 167.
    Rabinovici GD, Furst AJ, O’Neil JP, et al. 11C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. Neurology 2007; 68(15): 1205–12PubMedCrossRefGoogle Scholar
  168. 168.
    Foster NL, Heidebrink JL, Clark CM, et al. FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer’s disease. Brain 2007; 130(Pt 10): 2616–35PubMedCrossRefGoogle Scholar
  169. 169.
    Minoshima S, Giordani B, Berent S, et al. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer’s disease. Ann Neurol 1997; 42(1): 85–94PubMedCrossRefGoogle Scholar
  170. 170.
    Ishii K, Sakamoto S, Sasaki M, et al. Cerebral glucose metabolism in patients with frontotemporal dementia. J Nucl Med 1998; 39(11): 1875–8PubMedGoogle Scholar
  171. 171.
    Womack KB, Diaz-Arrastia R, Aizenstein HJ, et al. Temporoparietal hypometabolism in frontotemporal lobar degeneration and associated imaging diagnostic errors. Arch Neurol 2011; 68(3): 329–37PubMedCrossRefGoogle Scholar
  172. 172.
    Klunk WE, Engler H, Nordberg A, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 2004; 55(3): 306–19PubMedCrossRefGoogle Scholar
  173. 173.
    Seeley WW, Crawford RK, Zhou J, et al. Neurodegenerative diseases target large-scale human brain networks. Neuron 2009; 62(1): 42–52PubMedCrossRefGoogle Scholar
  174. 174.
    Zhou J, Greicius MD, Gennatas ED, et al. Divergent network connectivity changes in behavioural variant frontotemporal dementia and Alzheimer’s disease. Brain 2010; 133(Pt 5): 1352–67PubMedCrossRefGoogle Scholar
  175. 175.
    Hu B. Off-label medication use in frontotemporal dementia. Am J Alzheimers Dis Other Demen 2010; 25(2): 128–33CrossRefGoogle Scholar
  176. 176.
    Swartz JR, Miller BL, Lesser IM, et al. Frontotemporal dementia: treatment response to serotonin selective reuptake inhibitors. J Clin Psychiatry 1997; 58(5): 212–6PubMedCrossRefGoogle Scholar
  177. 177.
    Moretti R, Torre P, Antonello RM, et al. Frontotemporal dementia: paroxetine as a possible treatment of behavior symptoms. A randomized, controlled, open 14-month study. Eur Neurol 2003; 49(1): 13–9PubMedCrossRefGoogle Scholar
  178. 178.
    Ikeda M, Shigenobu K, Fukuhara R, et al. Efficacy of fluvoxamine as a treatment for behavioral symptoms in frontotemporal lobar degeneration patients. Dement Geriatr Cogn Disord 2004; 17(3): 117–21PubMedCrossRefGoogle Scholar
  179. 179.
    Deakin JB, Rahman S, Nestor PJ, et al. Paroxetine does not improve symptoms and impairs cognition in frontotemporal dementia: a double-blind randomized controlled trial. Psychopharmacology (Berl) 2004; 172(4): 400–8CrossRefGoogle Scholar
  180. 180.
    Lebert F, Stekke W, Hasenbroekx C, et al. Frontotemporal dementia: a randomised, controlled trial with trazodone. Dement Geriatr Cogn Disord 2004; 17(4): 355–9PubMedCrossRefGoogle Scholar
  181. 181.
    Moretti R, Torre P, Antonello RM, et al. Rivastigmine in frontotemporal dementia: an open-label study. Drugs Aging 2004; 21(14): 931–7PubMedCrossRefGoogle Scholar
  182. 182.
    Kertesz A, Morlog D, Light M, et al. Galantamine in frontotemporal dementia and primary progressive aphasia. Dement Geriatr Cogn Disord 2008; 25(2): 178–85PubMedCrossRefGoogle Scholar
  183. 183.
    Mendez MF, Shapira JS, McMurtray A, et al. Preliminary findings: behavioral worsening on donepezil in patients with frontotemporal dementia. Am J Geriatr Psychiatry 2007; 15(1): 84–7PubMedCrossRefGoogle Scholar
  184. 184.
    Curtis RC, Resch DS. Case of pick’s central lobar atrophy with apparent stabilization of cognitive decline after treatment with risperidone. J Clin Psychopharmacol 2000; 20(3): 384–5PubMedCrossRefGoogle Scholar
  185. 185.
    Fellgiebel A, Muller MJ, Hiemke C, et al. Clinical improvement in a case of frontotemporal dementia under aripiprazole treatment corresponds to partial recovery of disturbed frontal glucose metabolism. World J Biol Psychiatry 2007; 8(2): 123–6PubMedCrossRefGoogle Scholar
  186. 186.
    Moretti R, Torre P, Antonello RM, et al. Olanzapine as a treatment of neuropsychiatric disorders of Alzheimer’s disease and other dementias: a 24-month follow-up of 68 patients. Am J Alzheimers Dis Other Demen 2003; 18(4): 205–14PubMedCrossRefGoogle Scholar
  187. 187.
    Swanberg MM. Memantine for behavioral disturbances in frontotemporal dementia: a case series. Alzheimer Dis Assoc Disord 2007; 21(2): 164–6PubMedCrossRefGoogle Scholar
  188. 188.
    Diehl-Schmid J, Forstl H, Perneczky R, et al. A 6-month, open-label study of memantine in patients with frontotemporal dementia. Int J Geriatr Psychiatry 2008; 23(7): 754–9PubMedCrossRefGoogle Scholar
  189. 189.
    Boxer AL, Lipton AM, Womack K, et al. An open-label study of memantine treatment in 3 subtypes of frontotemporal lobar degeneration. Alzheimer Dis Assoc Disord 2009; 23(3): 211–7PubMedCrossRefGoogle Scholar
  190. 190.
    Vercelletto M, Boutoleau-Bretonniere C, Volteau C, et al. Memantine in behavioral variant frontotemporal dementia: negative results. J Alzheimers Dis 2011; 23(4): 749–59PubMedGoogle Scholar
  191. 191.
    Knopman DS, Boeve BS, Caselli RJ, et al. Longitudinal tracking of FTLD: toward developing clinical trial methodology. Alzheimer Dis Assoc Disord 2007; 21(4): S58–63PubMedCrossRefGoogle Scholar
  192. 192.
    Sparks DL. Aging and Alzheimer’s disease: altered cortical serotonergic binding. Arch Neurol 1989; 46(2): 138–40PubMedCrossRefGoogle Scholar
  193. 193.
    Sparks DL, Markesbery WR. Altered serotonergic and cholinergic synaptic markers in Pick’s disease. Arch Neurol 1991; 48(8): 796–9PubMedCrossRefGoogle Scholar
  194. 194.
    Sparks DL, Danner FW, Davis DG, et al. Neurochemical and histopathologic alterations characteristic of Pick’s disease in a non-demented individual. J Neuropathol Exp Neurol 1994; 53(1): 37–42PubMedCrossRefGoogle Scholar
  195. 195.
    Yang Y, Schmitt HP. Frontotemporal dementia: evidence for impairment of ascending serotoninergic but not noradrenergic innervation. Immunocytochemical and quantitative study using a graph method. Acta Neuropathol 2001; 101(3): 256–70PubMedGoogle Scholar
  196. 196.
    Bowen DM, Procter AW, Mann DM, et al. Imbalance of a serotonergic system in frontotemporal dementia: implication for pharmacotherapy. Psychopharmacology (Berl) 2008; 196(4): 603–10CrossRefGoogle Scholar
  197. 197.
    Huey ED, Putnam KT, Grafman J. A systematic review of neurotransmitter deficits and treatments in frontotemporal dementia. Neurology 2006; 66(1): 17–22PubMedCrossRefGoogle Scholar
  198. 198.
    Lebert F. Behavioral benefits of trazodone are sustained for the long term in frontotemporal dementia. Therapy 2006; 3(1): 93–6CrossRefGoogle Scholar
  199. 199.
    Hirano S, Shinotoh H, Shimada H, et al. Cholinergic imaging in corticobasal syndrome, progressive supranuclear palsy and frontotemporal dementia. Brain 2010; 133(Pt 7): 2058–68PubMedCrossRefGoogle Scholar
  200. 200.
    Williams SM, Goldman-Rakic PS. Widespread origin of the primate mesofrontal dopamine system. Cereb Cortex 1998; 8(4): 321–45PubMedCrossRefGoogle Scholar
  201. 201.
    Rinne JO, Laine M, Kaasinen V, et al. Striatal dopamine transporter and extrapyramidal symptoms in frontotemporal dementia. Neurology 2002; 58(10): 1489–93PubMedCrossRefGoogle Scholar
  202. 202.
    Sperfeld AD, Collatz MB, Baier H, et al. FTDP-17: an early-onset phenotype with parkinsonism and epileptic seizures caused by a novel mutation. Ann Neurol 1999; 46(5): 708–15PubMedCrossRefGoogle Scholar
  203. 203.
    Kanazawa I, Kwak S, Sasaki H, et al. Studies on neurotransmitter markers of the basal ganglia in Pick’s disease, with special reference to dopamine reduction. J Neurol Sci 1988; 83(1): 63–74PubMedCrossRefGoogle Scholar
  204. 204.
    Kerssens CJ, Pijnenburg YA. Vulnerability to neuroleptic side effects in frontotemporal dementia. Eur J Neurol 2008; 15(2): 111–2PubMedCrossRefGoogle Scholar
  205. 205.
    US FDA. Public health advisory: deaths with antipsychotics in elderly patients with behavioural disturbances [online]. Available from URL: http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm053171.htm [Accessed 2012 Aug 13]
  206. 206.
    Chow TW, Graff-Guerrero A, Verhoeff NP, et al. Open-label study of the short-term effects of memantine on FDG-PET in frontotemporal dementia. Neuropsychiatr Dis Treat 2011; 7: 415–24PubMedCrossRefGoogle Scholar
  207. 207.
    Kosfeld M, Heinrichs M, Zak PJ, et al. Oxytocin increases trust in humans. Nature 2005; 435(7042): 673–6PubMedCrossRefGoogle Scholar
  208. 208.
    Baumgartner T, Heinrichs M, Vonlanthen A, et al. Oxytocin shapes the neural circuitry of trust and trust adaptation in humans. Neuron 2008; 58(4): 639–50PubMedCrossRefGoogle Scholar
  209. 209.
    Andari E, Duhamel JR, Zalla T, et al. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc Natl Acad Sci USA 2010; 107(9): 4389–94PubMedCrossRefGoogle Scholar
  210. 210.
    Lavenu I, Pasquier F, Lebert F, et al. Perception of emotion in frontotemporal dementia and Alzheimer disease. Alzheimer Dis Assoc Disord 1999; 13(2): 96–101PubMedCrossRefGoogle Scholar
  211. 211.
    Keane J, Calder AJ, Hodges JR, et al. Face and emotion processing in frontal variant frontotemporal dementia. Neuropsychologia 2002; 40(6): 655–65PubMedCrossRefGoogle Scholar
  212. 212.
    Fernandez-Duque D, Black SE. Impaired recognition of negative facial emotions in patients with frontotemporal dementia. Neuropsychologia 2005; 43(11): 1673–87PubMedCrossRefGoogle Scholar
  213. 213.
    Jesso S, Morlog D, Ross S, et al. The effects of oxytocin on social cognition and behaviour in frontotemporal dementia. Brain 2011; 134(Pt 9): 2493–501PubMedCrossRefGoogle Scholar
  214. 214.
    Cenik B, Sephton CF, Dewey CM, et al. Suberoylanilide hydroxamic acid (vorinostat) up-regulates progranulin transcription: rational therapeutic approach to frontotemporal dementia. J Biol Chem 2011; 286(18): 16101–8PubMedCrossRefGoogle Scholar
  215. 215.
    Bossu P, Salani F, Alberici A, et al. Loss of function mutations in the progranulin gene are related to proinflammatory cytokine dysregulation in frontotemporal lobar degeneration patients. J Neuroinflammation 2011; 8:65PubMedCrossRefGoogle Scholar
  216. 216.
    Kimura T, Hayashida H, Furukawa H, et al. Pilot study of pharmacological treatment for frontotemporal dementia: effect of Yokukansan on behavioral symptoms. Psychiatry Clin Neurosci 2010; 64(2): 207–10PubMedCrossRefGoogle Scholar
  217. 217.
    Kimura T, Hayashida H, Murata M, et al. Effect of ferulic acid and Angelica archangelica extract on behavioral and psychological symptoms of dementia in frontotemporal lobar degeneration and dementia with Lewy bodies. Geriatr Gerontol Int 2011; 11(3): 309–14PubMedCrossRefGoogle Scholar
  218. 218.
    Medina M, Garrido JJ, Wandosell FG. Modulation of GSK-3 as a therapeutic strategy on tau pathologies. Front Mol Neurosci 2011; 4: 24. Epub 2011/10/19PubMedCrossRefGoogle Scholar
  219. 219.
    Merrillees J. A model for management of behavioral symptoms in frontotemporal lobar degeneration. Alzheimer Dis Assoc Discord 2007; 21(4): S64–9CrossRefGoogle Scholar
  220. 220.
    Talerico KA, Evans LK. Responding to safety issues in frontotemporal dementias. Neurology 2001; 56 (11 Suppl. 4): S52–5PubMedCrossRefGoogle Scholar
  221. 221.
    Ahlskog JE, Geda YE, Graff-Radford NR, et al. Physical exercise as a preventive or disease-modifying treatment of dementia and brain aging. Mayo Clin Proc 2011; 86(9): 876–84PubMedCrossRefGoogle Scholar
  222. 222.
    Riedijk SR, De Vugt ME, Duivenvoorden HJ, et al. Caregiver burden, health-related quality of life and coping in dementia caregivers: a comparison of frontotemporal dementia and Alzheimer’s disease. Dement Geriatr Cogn Disord 2006; 22(5–6): 405–12PubMedCrossRefGoogle Scholar
  223. 223.
    Mioshi E, Bristow M, Cook R, et al. Factors underlying caregiver stress in frontotemporal dementia and Alzheimer’s disease. Dement Geriatr Cogn Disord 2009; 27(1): 76–81PubMedCrossRefGoogle Scholar
  224. 224.
    Boutoleau-Bretonniere C, Vercelletto M, Volteau C, et al. Zarit burden inventory and activities of daily living in the behavioral variant of frontotemporal dementia. Dement Geriatr Cogn Disord 2008; 25(3): 272–7PubMedCrossRefGoogle Scholar
  225. 225.
    Merrillees J, Ketelle R. Advanced practice nursing: meeting the caregiving challenges for families of persons with frontotemporal dementia. Clin Nurse Spec 2010; 24(5): 245–51Google Scholar

Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

  1. 1.Indiana University School of MedicineIndianapolisUSA

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