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Frontotemporal dementia: Clinical features and diagnosis

Authors
Suzee E Lee, MD
Bruce L Miller, MD
Section Editor
Steven T DeKosky, MD, FAAN, FACP, FANA
Deputy Editor
April F Eichler, MD, MPH

INTRODUCTION

Frontotemporal dementias (FTD) are a group of clinically and neuropathologically heterogeneous neurodegenerative disorders characterized by prominent changes in social behavior and personality or aphasia accompanied by degeneration of the frontal and/or temporal lobes. Some patients with FTD also develop a concomitant motor syndrome such as parkinsonism or motor neuron disease. FTD is one of the more common causes of early-onset dementia, with an average age of symptom onset in the sixth decade.

This topic will review the clinical features and diagnosis of the main clinical syndromes of FTD. The treatment of FTD and the genetics, pathology, and pathogenesis of FTD are discussed separately. (See "Frontotemporal dementia: Treatment" and "Frontotemporal dementia: Epidemiology, pathology, and pathogenesis".)

TERMINOLOGY

Terminology for frontotemporal dementia (FTD) has evolved over time. In 1892, Arnold Pick first described a patient with progressive aphasia and focal frontotemporal atrophy [1]. Alois Alzheimer later characterized the disorder as Pick disease, defined by distinctive round, silver-staining inclusions, called Pick bodies [2]. Subsequent clinicopathological studies determined that many patients diagnosed clinically with Pick disease did not have Pick neuropathology at autopsy, and thus Pick disease now designates a pathological diagnosis, rather than a clinical syndrome.

The term FTD has gained favor as an umbrella term for three clinical presentations: behavioral variant FTD (bvFTD) and two forms of primary progressive aphasia (PPA), the nonfluent and semantic variants. Historically, bvFTD has also been called “FTD” or “frontal variant FTD,” while semantic variant PPA has been called “temporal variant” FTD and semantic dementia. Nonfluent variant PPA is also referred to as agrammatic PPA. The third variant of PPA, the logopenic variant, is typically associated with Alzheimer pathology and is not included as one of the three clinical FTD syndromes.

The pathology underlying clinically-defined FTD is heterogeneous. The term frontotemporal lobar degeneration (FTLD) refers to this group of neuropathological diagnoses, further categorized by abnormal protein inclusions due to tau, TDP-43 (transactive response [Tar, abbreviated T] DNA binding protein 43 kDa), and other proteins. A clear distinction between clinical and neuropathological terminology is important in these disorders, since clinicopathological series have determined that clinical syndromes often fail to predict underlying pathology.

                        

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Literature review current through: Feb 2015. | This topic last updated: Mar 17, 2015.
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References
Top
  1. Pick A. Ueber die Beiehungen der senilen Hirnatrophie zur Aphasie. Prager Medicinische Wochenschrift 1892; 17:165.
  2. Alzheimer, A. Über eigenartige Krankheitsfälle des späteren Alters. . Z Gesamte Neurol Psychiatr. 1911; 4:356.
  3. Johnson JK, Diehl J, Mendez MF, et al. Frontotemporal lobar degeneration: demographic characteristics of 353 patients. Arch Neurol 2005; 62:925.
  4. Ratnavalli E, Brayne C, Dawson K, Hodges JR. The prevalence of frontotemporal dementia. Neurology 2002; 58:1615.
  5. Rosen HJ, Allison SC, Schauer GF, et al. Neuroanatomical correlates of behavioural disorders in dementia. Brain 2005; 128:2612.
  6. Rankin KP, Gorno-Tempini ML, Allison SC, et al. Structural anatomy of empathy in neurodegenerative disease. Brain 2006; 129:2945.
  7. Woolley JD, Gorno-Tempini ML, Seeley WW, et al. Binge eating is associated with right orbitofrontal-insular-striatal atrophy in frontotemporal dementia. Neurology 2007; 69:1424.
  8. Whitwell JL, Sampson EL, Loy CT, et al. VBM signatures of abnormal eating behaviours in frontotemporal lobar degeneration. Neuroimage 2007; 35:207.
  9. Piguet, O, Petersen, A, Yin Ka Lam, B, et al. Eating and hypothalamus changes in behavioral-variant frontotemporal dementia. Ann Neurol 2012; 69:312.
  10. Williamson, C, Alcantar, O, Rothlind, J, et al. Standardised measurement of self-awareness deficits in FTD and AD. J Neurol Neurosurg Psychiatry; 81:140.
  11. Warren JD, Rohrer JD, Rossor MN. Clinical review. Frontotemporal dementia. BMJ 2013; 347:f4827.
  12. Rankin KP, Salazar A, Gorno-Tempini ML, et al. Detecting sarcasm from paralinguistic cues: anatomic and cognitive correlates in neurodegenerative disease. Neuroimage 2009; 47:2005.
  13. Shany-Ur T, Poorzand P, Grossman SN, et al. Comprehension of insincere communication in neurodegenerative disease: lies, sarcasm, and theory of mind. Cortex 2012; 48:1329.
  14. Hornberger M, Piguet O, Graham AJ, et al. How preserved is episodic memory in behavioral variant frontotemporal dementia? Neurology 2010; 74:472.
  15. Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 2011; 134:2456.
  16. Rascovsky K, Hodges JR, Kipps CM, et al. Diagnostic criteria for the behavioral variant of frontotemporal dementia (bvFTD): current limitations and future directions. Alzheimer Dis Assoc Disord 2007; 21:S14.
  17. Piguet O, Hornberger M, Mioshi E, Hodges JR. Behavioural-variant frontotemporal dementia: diagnosis, clinical staging, and management. Lancet Neurol 2011; 10:162.
  18. Perry RJ, Graham A, Williams G, et al. Patterns of frontal lobe atrophy in frontotemporal dementia: a volumetric MRI study. Dement Geriatr Cogn Disord 2006; 22:278.
  19. Knopman DS, Boeve BF, Parisi JE, et al. Antemortem diagnosis of frontotemporal lobar degeneration. Ann Neurol 2005; 57:480.
  20. Mendez MF, Shapira JS, McMurtray A, et al. Accuracy of the clinical evaluation for frontotemporal dementia. Arch Neurol 2007; 64:830.
  21. Pijnenburg YA, Mulder JL, van Swieten JC, et al. Diagnostic accuracy of consensus diagnostic criteria for frontotemporal dementia in a memory clinic population. Dement Geriatr Cogn Disord 2008; 25:157.
  22. Rosen HJ, Hartikainen KM, Jagust W, et al. Utility of clinical criteria in differentiating frontotemporal lobar degeneration (FTLD) from AD. Neurology 2002; 58:1608.
  23. Broe M, Hodges JR, Schofield E, et al. Staging disease severity in pathologically confirmed cases of frontotemporal dementia. Neurology 2003; 60:1005.
  24. Boccardi M, Sabattoli F, Laakso MP, et al. Frontotemporal dementia as a neural system disease. Neurobiol Aging 2005; 26:37.
  25. Seeley WW, Crawford R, Rascovsky K, et al. Frontal paralimbic network atrophy in very mild behavioral variant frontotemporal dementia. Arch Neurol 2008; 65:249.
  26. Rosen HJ, Wilson MR, Schauer GF, et al. Neuroanatomical correlates of impaired recognition of emotion in dementia. Neuropsychologia 2006; 44:365.
  27. Rosso SM, Roks G, Stevens M, et al. Complex compulsive behaviour in the temporal variant of frontotemporal dementia. J Neurol 2001; 248:965.
  28. Ames D, Cummings JL, Wirshing WC, et al. Repetitive and compulsive behavior in frontal lobe degenerations. J Neuropsychiatry Clin Neurosci 1994; 6:100.
  29. Whitwell JL, Jack CR Jr, Senjem ML, Josephs KA. Patterns of atrophy in pathologically confirmed FTLD with and without motor neuron degeneration. Neurology 2006; 66:102.
  30. Baborie A, Griffiths TD, Jaros E, et al. Pathological correlates of frontotemporal lobar degeneration in the elderly. Acta Neuropathol 2011; 121:365.
  31. Rabinovici GD, Rosen HJ, Alkalay A, et al. Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD. Neurology 2011; 77:2034.
  32. Whitwell JL, Avula R, Senjem ML, et al. Gray and white matter water diffusion in the syndromic variants of frontotemporal dementia. Neurology 2010; 74:1279.
  33. Blennerhassett R, Lillo P, Halliday GM, et al. Distribution of pathology in frontal variant Alzheimer's disease. J Alzheimers Dis 2014; 39:63.
  34. Barber R, Snowden JS, Craufurd D. Frontotemporal dementia and Alzheimer's disease: retrospective differentiation using information from informants. J Neurol Neurosurg Psychiatry 1995; 59:61.
  35. Clinical and neuropathological criteria for frontotemporal dementia. The Lund and Manchester Groups. J Neurol Neurosurg Psychiatry 1994; 57:416.
  36. Levy ML, Miller BL, Cummings JL, et al. Alzheimer disease and frontotemporal dementias. Behavioral distinctions. Arch Neurol 1996; 53:687.
  37. Perri R, Koch G, Carlesimo GA, et al. Alzheimer's disease and frontal variant of frontotemporal dementia-- a very brief battery for cognitive and behavioural distinction. J Neurol 2005; 252:1238.
  38. Kertesz A, Blair M, McMonagle P, Munoz DG. The diagnosis and course of frontotemporal dementia. Alzheimer Dis Assoc Disord 2007; 21:155.
  39. Bathgate D, Snowden JS, Varma A, et al. Behaviour in frontotemporal dementia, Alzheimer's disease and vascular dementia. Acta Neurol Scand 2001; 103:367.
  40. Bozeat S, Gregory CA, Ralph MA, Hodges JR. Which neuropsychiatric and behavioural features distinguish frontal and temporal variants of frontotemporal dementia from Alzheimer's disease? J Neurol Neurosurg Psychiatry 2000; 69:178.
  41. Miller BL, Ikonte C, Ponton M, et al. A study of the Lund-Manchester research criteria for frontotemporal dementia: clinical and single-photon emission CT correlations. Neurology 1997; 48:937.
  42. Mendez MF, Shapira JS, Woods RJ, et al. Psychotic symptoms in frontotemporal dementia: prevalence and review. Dement Geriatr Cogn Disord 2008; 25:206.
  43. Snowden JS, Rollinson S, Thompson JC, et al. Distinct clinical and pathological characteristics of frontotemporal dementia associated with C9ORF72 mutations. Brain 2012; 135:693.
  44. 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; 135:765.
  45. 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; 22:474.
  46. Mesulam MM. Primary progressive aphasia. Ann Neurol 2001; 49:425.
  47. Mesulam MM. Primary progressive aphasia and the language network: the 2013 H. Houston Merritt Lecture. Neurology 2013; 81:456.
  48. Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology 2011; 76:1006.
  49. Knibb JA, Xuereb JH, Patterson K, Hodges JR. Clinical and pathological characterization of progressive aphasia. Ann Neurol 2006; 59:156.
  50. Hodges JR. Frontotemporal dementia (Pick's disease): clinical features and assessment. Neurology 2001; 56:S6.
  51. Boxer AL, Miller BL. Clinical features of frontotemporal dementia. Alzheimer Dis Assoc Disord 2005; 19 Suppl 1:S3.
  52. Mesulam MM, Grossman M, Hillis A, et al. The core and halo of primary progressive aphasia and semantic dementia. Ann Neurol 2003; 54 Suppl 5:S11.
  53. Eslinger PJ, Dennis K, Moore P, et al. Metacognitive deficits in frontotemporal dementia. J Neurol Neurosurg Psychiatry 2005; 76:1630.
  54. Le Rhun E, Richard F, Pasquier F. Natural history of primary progressive aphasia. Neurology 2005; 65:887.
  55. Josephs KA, Duffy JR, Strand EA, et al. Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech. Brain 2006; 129:1385.
  56. Rosen HJ, Allison SC, Ogar JM, et al. Behavioral features in semantic dementia vs other forms of progressive aphasias. Neurology 2006; 67:1752.
  57. Neary D, Snowden JS, Mann DM. Familial progressive aphasia: its relationship to other forms of lobar atrophy. J Neurol Neurosurg Psychiatry 1993; 56:1122.
  58. Snowden JS, Thompson JC, Neary D. Knowledge of famous faces and names in semantic dementia. Brain 2004; 127:860.
  59. Hodges JR, Patterson K, Ward R, et al. The differentiation of semantic dementia and frontal lobe dementia (temporal and frontal variants of frontotemporal dementia) from early Alzheimer's disease: a comparative neuropsychological study. Neuropsychology 1999; 13:31.
  60. Gorno-Tempini ML, Dronkers NF, Rankin KP, et al. Cognition and anatomy in three variants of primary progressive aphasia. Ann Neurol 2004; 55:335.
  61. Rabinovici GD, Jagust WJ, Furst AJ, et al. Abeta amyloid and glucose metabolism in three variants of primary progressive aphasia. Ann Neurol 2008; 64:388.
  62. Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998; 51:1546.
  63. Mesulam M, Wicklund A, Johnson N, et al. Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia. Ann Neurol 2008; 63:709.
  64. Josephs KA, Whitwell JL, Duffy JR, et al. Progressive aphasia secondary to Alzheimer disease vs FTLD pathology. Neurology 2008; 70:25.
  65. Deramecourt V, Lebert F, Debachy B, et al. Prediction of pathology in primary progressive language and speech disorders. Neurology 2010; 74:42.
  66. Grossman M. The non-fluent/agrammatic variant of primary progressive aphasia. Lancet Neurol 2012; 11:545.
  67. Gefen T, Gasho K, Rademaker A, et al. Clinically concordant variations of Alzheimer pathology in aphasic versus amnestic dementia. Brain 2012; 135:1554.
  68. Mesulam MM, Weintraub S, Rogalski EJ, et al. Asymmetry and heterogeneity of Alzheimer's and frontotemporal pathology in primary progressive aphasia. Brain 2014; 137:1176.
  69. Strong MJ. The syndromes of frontotemporal dysfunction in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 2008; 9:323.
  70. Lomen-Hoerth C, Anderson T, Miller B. The overlap of amyotrophic lateral sclerosis and frontotemporal dementia. Neurology 2002; 59:1077.
  71. Josephs KA. Frontotemporal lobar degeneration. Neurol Clin 2007; 25:683.
  72. Mitsuyama Y. Dementia with motor neuron disease. Neuropathology 2000; 20 Suppl:S79.
  73. Neary D, Snowden JS, Mann DM. Cognitive change in motor neurone disease/amyotrophic lateral sclerosis (MND/ALS). J Neurol Sci 2000; 180:15.
  74. Ikeda M, Ishikawa T, Tanabe H. Epidemiology of frontotemporal lobar degeneration. Dement Geriatr Cogn Disord 2004; 17:265.
  75. Neary D, Snowden JS, Mann DM, et al. Frontal lobe dementia and motor neuron disease. J Neurol Neurosurg Psychiatry 1990; 53:23.
  76. Murphy JM, Henry RG, Langmore S, et al. Continuum of frontal lobe impairment in amyotrophic lateral sclerosis. Arch Neurol 2007; 64:530.
  77. Lomen-Hoerth C, Murphy J, Langmore S, et al. Are amyotrophic lateral sclerosis patients cognitively normal? Neurology 2003; 60:1094.
  78. Chang JL, Lomen-Hoerth C, Murphy J, et al. A voxel-based morphometry study of patterns of brain atrophy in ALS and ALS/FTLD. Neurology 2005; 65:75.
  79. Lillo, P, Garcin, B, Hornberger, M, et al. Neurobehavioral features in frontotemporal dementia with amyotrophic lateral sclerosis. Arch Neurol; 67:826.
  80. Rohrer JD, Isaacs AM, Mizielinska S, et al. C9orf72 expansions in frontotemporal dementia and amyotrophic lateral sclerosis. Lancet Neurol 2015; 14:291.
  81. Caselli RJ, Windebank AJ, Petersen RC, et al. Rapidly progressive aphasic dementia and motor neuron disease. Ann Neurol 1993; 33:200.
  82. Mitsuyama Y. Presenile dementia with motor neuron disease in Japan: clinico-pathological review of 26 cases. J Neurol Neurosurg Psychiatry 1984; 47:953.
  83. Olney RK, Murphy J, Forshew D, et al. The effects of executive and behavioral dysfunction on the course of ALS. Neurology 2005; 65:1774.
  84. Gibb WR, Luthert PJ, Marsden CD. Corticobasal degeneration. Brain 1989; 112 ( Pt 5):1171.
  85. Riley DE, Lang AE, Lewis A, et al. Cortical-basal ganglionic degeneration. Neurology 1990; 40:1203.
  86. Rebeiz JJ, Kolodny EH, Richardson EP Jr. Corticodentatonigral degeneration with neuronal achromasia. Arch Neurol 1968; 18:20.
  87. Boeve BF, Lang AE, Litvan I. Corticobasal degeneration and its relationship to progressive supranuclear palsy and frontotemporal dementia. Ann Neurol 2003; 54 Suppl 5:S15.
  88. Lee SE, Rabinovici GD, Mayo MC, et al. Correlates of Alzheimer’s Disease Pathology in Corticobasal Syndrome. Ann Neurol 2011.
  89. Whitwell JL, Jack CR Jr, Boeve BF, et al. Imaging correlates of pathology in corticobasal syndrome. Neurology 2010; 75:1879.
  90. Vanvoorst WA, Greenaway MC, Boeve BF, et al. Neuropsychological findings in clinically atypical autopsy confirmed corticobasal degeneration and progressive supranuclear palsy. Parkinsonism Relat Disord 2008; 14:376.
  91. Grimes DA, Lang AE, Bergeron CB. Dementia as the most common presentation of cortical-basal ganglionic degeneration. Neurology 1999; 53:1969.
  92. Kertesz A, McMonagle P, Blair M, et al. The evolution and pathology of frontotemporal dementia. Brain 2005; 128:1996.
  93. Murray R, Neumann M, Forman MS, et al. Cognitive and motor assessment in autopsy-proven corticobasal degeneration. Neurology 2007; 68:1274.
  94. Geda YE, Boeve BF, Negash S, et al. Neuropsychiatric features in 36 pathologically confirmed cases of corticobasal degeneration. J Neuropsychiatry Clin Neurosci 2007; 19:77.
  95. Graham NL, Bak TH, Hodges JR. Corticobasal degeneration as a cognitive disorder. Mov Disord 2003; 18:1224.
  96. Pillon B, Blin J, Vidailhet M, et al. The neuropsychological pattern of corticobasal degeneration: comparison with progressive supranuclear palsy and Alzheimer's disease. Neurology 1995; 45:1477.
  97. Belfor N, Amici S, Boxer AL, et al. Clinical and neuropsychological features of corticobasal degeneration. Mech Ageing Dev 2006; 127:203.
  98. Kertesz A, Martinez-Lage P, Davidson W, Munoz DG. The corticobasal degeneration syndrome overlaps progressive aphasia and frontotemporal dementia. Neurology 2000; 55:1368.
  99. Kertesz A, Davidson W, McCabe P, et al. Primary progressive aphasia: diagnosis, varieties, evolution. J Int Neuropsychol Soc 2003; 9:710.
  100. STEELE JC, RICHARDSON JC, OLSZEWSKI J. PROGRESSIVE SUPRANUCLEAR PALSY. A HETEROGENEOUS DEGENERATION INVOLVING THE BRAIN STEM, BASAL GANGLIA AND CEREBELLUM WITH VERTICAL GAZE AND PSEUDOBULBAR PALSY, NUCHAL DYSTONIA AND DEMENTIA. Arch Neurol 1964; 10:333.
  101. Litvan I, Hauw JJ, Bartko JJ, et al. Validity and reliability of the preliminary NINDS neuropathologic criteria for progressive supranuclear palsy and related disorders. J Neuropathol Exp Neurol 1996; 55:97.
  102. Nath U, Ben-Shlomo Y, Thomson RG, et al. Clinical features and natural history of progressive supranuclear palsy: a clinical cohort study. Neurology 2003; 60:910.
  103. Donker Kaat L, Boon AJ, Kamphorst W, et al. Frontal presentation in progressive supranuclear palsy. Neurology 2007; 69:723.
  104. Kertesz A, McMonagle P. Behavior and cognition in corticobasal degeneration and progressive supranuclear palsy. J Neurol Sci 2010; 289:138.
  105. 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.
  106. Osaki Y, Ben-Shlomo Y, Lees AJ, et al. Accuracy of clinical diagnosis of progressive supranuclear palsy. Mov Disord 2004; 19:181.
  107. Bak TH, Caine D, Hearn VC, Hodges JR. Visuospatial functions in atypical parkinsonian syndromes. J Neurol Neurosurg Psychiatry 2006; 77:454.
  108. Rosso SM, Donker Kaat L, Baks T, et al. Frontotemporal dementia in The Netherlands: patient characteristics and prevalence estimates from a population-based study. Brain 2003; 126:2016.
  109. Hodges JR, Davies RR, Xuereb JH, et al. Clinicopathological correlates in frontotemporal dementia. Ann Neurol 2004; 56:399.
  110. Hodges JR, Davies R, Xuereb J, et al. Survival in frontotemporal dementia. Neurology 2003; 61:349.
  111. Le Ber I, Guedj E, Gabelle A, et al. Demographic, neurological and behavioural characteristics and brain perfusion SPECT in frontal variant of frontotemporal dementia. Brain 2006; 129:3051.
  112. Goldman JS, Farmer JM, Wood EM, et al. Comparison of family histories in FTLD subtypes and related tauopathies. Neurology 2005; 65:1817.
  113. Goldman JS, Rademakers R, Huey ED, et al. An algorithm for genetic testing of frontotemporal lobar degeneration. Neurology 2011; 76:475.