Skip to main content
SpringerLink
Log in

Frontotemporal Lobar Degeneration

  • Chapter
  • First Online:
Imaging Dementia

  • 555 Accesses

Abstract

Main imaging findings:

  • Patterns of atrophy (CT/MRI) or functional alterations (PET/SPECT) supporting clinical diagnosis of FTLD variants:

    • bvFTD: bilateral, often asymmetrical involvement of frontal and anterior temporal structures;

    • nfvPPA: left posterior fronto-insular damage;

    • svPPA: anterior temporal lobe involvement, usually left greater than right.

  • Neuroimaging markers which may suggest, even in presymptomatic stages, specific genetic and pathological substrates of FTLD:

    • gray matter atrophy (CT/structural MRI);

    • white matter microstructural damage (DT MRI);

    • functional alterations (FDG-PET/SPECT, fMRI).

  • Molecular imaging with PET tracers:

    • amyloid: easier distinction of FTLD from AD in atypical cases;

    • tau: potentially useful to distinguish in vivo different FTLD subtypes, although current tracers lack sufficient specificity.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 54.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 69.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology. 1998;51:1546–54.

    Article  CAS  PubMed  Google Scholar 

  2. Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011;134:2456–77.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Josephs KA, Duffy JR, Strand EA, et al. Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech. Brain. 2006;129:1385–98.

    Article  PubMed  Google Scholar 

  4. Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76:1006–14.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Gorno-Tempini ML, Dronkers NF, Rankin KP, et al. Cognition and anatomy in three variants of primary progressive aphasia. Ann Neurol. 2004;55:335–46.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Rohrer JD, Warren JD, Modat M, et al. Patterns of cortical thinning in the language variants of frontotemporal lobar degeneration. Neurology. 2009;72:1562–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hodges JR, Patterson K. Semantic dementia: a unique clinicopathological syndrome. Lancet Neurol. 2007;6:1004–14.

    Article  CAS  PubMed  Google Scholar 

  8. Seelaar H, Rohrer JD, Pijnenburg YA, Fox NC, van Swieten JC. Clinical, genetic and pathological heterogeneity of frontotemporal dementia: a review. J Neurol Neurosurg Psychiatry. 2011;82:476–86.

    Article  PubMed  Google Scholar 

  9. Wilhelmsen KC. Frontotemporal dementia is on the MAPtau. Ann Neurol. 1997;41:139–40.

    Article  CAS  PubMed  Google Scholar 

  10. Hutton M, Lewis J, Dickson D, Yen SH, McGowan E. Analysis of tauopathies with transgenic mice. Trends Mol Med. 2001;7:467–70.

    Article  CAS  PubMed  Google Scholar 

  11. Neumann M, Sampathu DM, Kwong LK, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science. 2006;314:130–3.

    Article  CAS  PubMed  Google Scholar 

  12. Baker M, Mackenzie IR, Pickering-Brown SM, et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature. 2006;442:916–9.

    Article  CAS  PubMed  Google Scholar 

  13. Rohrer JD, Isaacs AM, Mizielinska S, et al. C9orf72 expansions in frontotemporal dementia and amyotrophic lateral sclerosis. Lancet Neurol. 2015;14:291–301.

    Google Scholar 

  14. Neumann M, Rademakers R, Roeber S, et al. A new subtype of frontotemporal lobar degeneration with FUS pathology. Brain. 2009;132:2922–31.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Rosen HJ, Gorno-Tempini ML, Goldman WP, et al. Patterns of brain atrophy in frontotemporal dementia and semantic dementia. Neurology. 2002;58:198–208.

    Article  CAS  PubMed  Google Scholar 

  16. Boccardi M, Sabattoli F, Laakso MP, et al. Frontotemporal dementia as a neural system disease. Neurobiol Aging. 2005;26:37–44.

    Article  PubMed  Google Scholar 

  17. 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;22:278–87.

    Article  PubMed  Google Scholar 

  18. Du AT, Schuff N, Kramer JH, et al. Different regional patterns of cortical thinning in Alzheimer’s disease and frontotemporal dementia. Brain. 2007;130:1159–66.

    Article  PubMed  Google Scholar 

  19. Seeley WW, Crawford R, Rascovsky K, et al. Frontal paralimbic network atrophy in very mild behavioral variant frontotemporal dementia. Arch Neurol. 2008;65:249–55.

    Article  PubMed  PubMed Central  Google Scholar 

  20. 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 Dement. 2007;22:474–88.

    Article  CAS  Google Scholar 

  21. Borroni B, Brambati SM, Agosti C, et al. Evidence of white matter changes on diffusion tensor imaging in frontotemporal dementia. Arch Neurol. 2007;64:246–51.

    Article  PubMed  Google Scholar 

  22. Cardenas VA, Boxer AL, Chao LL, et al. Deformation-based morphometry reveals brain atrophy in frontotemporal dementia. Arch Neurol. 2007;64:873–7.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Chao LL, Schuff N, Clevenger EM, et al. Patterns of white matter atrophy in frontotemporal lobar degeneration. Arch Neurol. 2007;64:1619–24.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Schroeter ML, Raczka K, Neumann J, Yves von Cramon D. Towards a nosology for frontotemporal lobar degenerations-a meta-analysis involving 267 subjects. NeuroImage. 2007;36:497–510.

    Article  PubMed  Google Scholar 

  25. Harris JM, Gall C, Thompson JC, et al. Sensitivity and specificity of FTDC criteria for behavioral variant frontotemporal dementia. Neurology. 2013;80:1881–7.

    Article  PubMed  Google Scholar 

  26. Schroeter ML, Laird AR, Chwiesko C, et al. Conceptualizing neuropsychiatric diseases with multimodal data-driven meta-analyses—the case of behavioral variant frontotemporal dementia. Cortex. 2014;57:22–37.

    Article  PubMed  Google Scholar 

  27. Whitwell JL, Przybelski SA, Weigand SD, et al. Distinct anatomical subtypes of the behavioural variant of frontotemporal dementia: a cluster analysis study. Brain. 2009;132:2932–46.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Shimizu H, Hokoishi K, Fukuhara R, Komori K, Ikeda M. Two cases of frontotemporal dementia with predominant temporal lobe atrophy. Psychogeriatrics. 2009;9:204–7.

    Article  CAS  PubMed  Google Scholar 

  29. Murray ME, Kouri N, Lin WL, et al. Clinicopathologic assessment and imaging of tauopathies in neurodegenerative dementias. Alzheimers Res Ther. 2014;6:1.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Rankin KP, Mayo MC, Seeley WW, et al. Behavioral variant frontotemporal dementia with corticobasal degeneration pathology: phenotypic comparison to bvFTD with Pick’s disease. J Mol Neurosci. 2011;45:594–608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Josephs KA, Whitwell JL, Dickson DW, et al. Voxel-based morphometry in autopsy proven PSP and CBD. Neurobiol Aging. 2008;29:280–9.

    Article  PubMed  Google Scholar 

  32. Boxer AL, Geschwind MD, Belfor N, et al. Patterns of brain atrophy that differentiate corticobasal degeneration syndrome from progressive supranuclear palsy. Arch Neurol. 2006;63:81–6.

    Article  PubMed  Google Scholar 

  33. Whitwell JL, Jack CR Jr, Boeve BF, et al. Voxel-based morphometry patterns of atrophy in FTLD with mutations in MAPT or PGRN. Neurology. 2009;72:813–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Rohrer JD, Ridgway GR, Modat M, et al. Distinct profiles of brain atrophy in frontotemporal lobar degeneration caused by progranulin and tau mutations. NeuroImage. 2010;53:1070–6.

    Article  CAS  PubMed  Google Scholar 

  35. Perry DC, Brown JA, Possin KL, et al. Clinicopathological correlations in behavioural variant frontotemporal dementia. Brain. 2017;140:3329–45.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Bocchetta M, Cardoso MJ, Cash DM, et al. Patterns of regional cerebellar atrophy in genetic frontotemporal dementia. Neuroimage Clin. 2016;11:287–90.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Whitwell JL, Boeve BF, Weigand SD, et al. Brain atrophy over time in genetic and sporadic frontotemporal dementia: a study of 198 serial magnetic resonance images. Eur J Neurol. 2015;22:745–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Rohrer JD, Rosen HJ. Neuroimaging in frontotemporal dementia. Int Rev Psychiatry. 2013;25:221–9.

    Article  PubMed  Google Scholar 

  39. Murray ME, DeJesus-Hernandez M, Rutherford NJ, et al. Clinical and neuropathologic heterogeneity of c9FTD/ALS associated with hexanucleotide repeat expansion in C9ORF72. Acta Neuropathol. 2011;122:673–90.

    Google Scholar 

  40. Snowden JS, Rollinson S, Thompson JC, et al. Distinct clinical and pathological characteristics of frontotemporal dementia associated with C9ORF72 mutations. Brain. 2012;135:693–708.

    Google Scholar 

  41. Mackenzie IR, Neumann M. Subcortical TDP-43 pathology patterns validate cortical FTLD-TDP subtypes and demonstrate unique aspects of C9orf72 mutation cases. Acta Neuropathol. 2020;139:83–98.

    Google Scholar 

  42. Mahoney CJ, Beck J, Rohrer JD, et al. Frontotemporal dementia with the C9ORF72 hexanucleotide repeat expansion: clinical, neuroanatomical and neuropathological features. Brain. 2012;135:736–50.

    Google Scholar 

  43. Whitwell JL, Weigand SD, Boeve BF, et al. Neuroimaging signatures of frontotemporal dementia genetics: C9ORF72, tau, progranulin and sporadics. Brain. 2012;135:794–806.

    Google Scholar 

  44. 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 Psychiatry. 2011;82:196–203.

    Article  PubMed  Google Scholar 

  45. Agosta F, Ferraro PM, Riva N, et al. Structural and functional brain signatures of C9orf72 in motor neuron disease. Neurobiol Aging. 2017;57:206–19.

    Article  CAS  PubMed  Google Scholar 

  46. Bede P, Omer T, Finegan E, et al. Connectivity-based characterisation of subcortical grey matter pathology in frontotemporal dementia and ALS: a multimodal neuroimaging study. Brain Imaging Behav. 2018;12:1696–707.

    Article  PubMed  Google Scholar 

  47. Bocchetta M, Iglesias JE, Neason M, et al. Thalamic nuclei in frontotemporal dementia: Mediodorsal nucleus involvement is universal but pulvinar atrophy is unique to C9orf72. Hum Brain Mapp. 2020;41:1006–16.

    Article  PubMed  Google Scholar 

  48. Karageorgiou E, Miller BL. Frontotemporal lobar degeneration: a clinical approach. Semin Neurol. 2014;34:189–201.

    Article  PubMed  Google Scholar 

  49. Lee SE, Seeley WW, Poorzand P, et al. Clinical characterization of bvFTD due to FUS neuropathology. Neurocase. 2012;18:305–17.

    Article  PubMed  Google Scholar 

  50. Josephs KA, Whitwell JL, Parisi JE, et al. Caudate atrophy on MRI is a characteristic feature of FTLD-FUS. Eur J Neurol. 2010;17:969–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Snowden JS, Hu Q, Rollinson S, et al. The most common type of FTLD-FUS (aFTLD-U) is associated with a distinct clinical form of frontotemporal dementia but is not related to mutations in the FUS gene. Acta Neuropathol. 2011;122:99–110.

    Article  CAS  PubMed  Google Scholar 

  52. Agosta F, Canu E, Sarro L, Comi G, Filippi M. Neuroimaging findings in frontotemporal lobar degeneration spectrum of disorders. Cortex. 2012;48:389–413.

    Article  PubMed  Google Scholar 

  53. Varma AR, Adams W, Lloyd JJ, et al. Diagnostic patterns of regional atrophy on MRI and regional cerebral blood flow change on SPECT in young onset patients with Alzheimer’s disease, frontotemporal dementia and vascular dementia. Acta Neurol Scand. 2002;105:261–9.

    Article  CAS  PubMed  Google Scholar 

  54. Likeman M, Anderson VM, Stevens JM, et al. Visual assessment of atrophy on magnetic resonance imaging in the diagnosis of pathologically confirmed young-onset dementias. Arch Neurol. 2005;62:1410–5.

    Article  PubMed  Google Scholar 

  55. Lehmann M, Rohrer JD, Clarkson MJ, et al. Reduced cortical thickness in the posterior cingulate gyrus is characteristic of both typical and atypical Alzheimer’s disease. J Alzheimers Dis. 2010;20:587–98.

    Article  PubMed  Google Scholar 

  56. Whitwell JL, Jack CR Jr, Przybelski SA, et al. Temporoparietal atrophy: a marker of AD pathology independent of clinical diagnosis. Neurobiol Aging. 2011;32:1531–41.

    Article  PubMed  Google Scholar 

  57. Canu E, Agosta F, Mandic-Stojmenovic G, et al. Multiparametric MRI to distinguish early onset Alzheimer’s disease and behavioural variant of frontotemporal dementia. Neuroimage Clin. 2017;15:428–38.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Davies RR, Kipps CM, Mitchell J, et al. Progression in frontotemporal dementia: identifying a benign behavioral variant by magnetic resonance imaging. Arch Neurol. 2006;63:1627–31.

    Article  PubMed  Google Scholar 

  59. Kipps CM, Davies RR, Mitchell J, et al. Clinical significance of lobar atrophy in frontotemporal dementia: application of an MRI visual rating scale. Dement Geriatr Cogn Disord. 2007;23:334–42.

    Article  PubMed  Google Scholar 

  60. Josephs KA, Whitwell JL, Jack CR, Parisi JE, Dickson DW. Frontotemporal lobar degeneration without lobar atrophy. Arch Neurol. 2006;63:1632–8.

    Article  PubMed  Google Scholar 

  61. Rogalski E, Cobia D, Harrison TM, et al. Progression of language decline and cortical atrophy in subtypes of primary progressive aphasia. Neurology. 2011;76:1804–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Garibotto V, Borroni B, Agosti C, et al. Subcortical and deep cortical atrophy in frontotemporal lobar degeneration. Neurobiol Aging. 2011;32:875–84.

    Article  PubMed  Google Scholar 

  63. van de Pol LA, Hensel A, van der Flier WM, et al. Hippocampal atrophy on MRI in frontotemporal lobar degeneration and Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2006;77:439–42.

    Article  PubMed  Google Scholar 

  64. Mummery CJ, Patterson K, Price CJ, et al. A voxel-based morphometry study of semantic dementia: relationship between temporal lobe atrophy and semantic memory. Ann Neurol. 2000;47:36–45.

    Article  CAS  PubMed  Google Scholar 

  65. Galton CJ, Patterson K, Graham K, et al. Differing patterns of temporal atrophy in Alzheimer’s disease and semantic dementia. Neurology. 2001;57:216–25.

    Article  CAS  PubMed  Google Scholar 

  66. Chan D, Fox NC, Scahill RI, et al. Patterns of temporal lobe atrophy in semantic dementia and Alzheimer’s disease. Ann Neurol. 2001;49:433–42.

    Article  CAS  PubMed  Google Scholar 

  67. Boxer AL, Miller BL. Clinical features of frontotemporal dementia. Alzheimer Dis Assoc Disord. 2005;19(Suppl 1):S3–6.

    Article  PubMed  Google Scholar 

  68. Collins JA, Montal V, Hochberg D, et al. Focal temporal pole atrophy and network degeneration in semantic variant primary progressive aphasia. Brain. 2017;140:457–71.

    Article  PubMed  Google Scholar 

  69. Josephs KA, Whitwell JL, Knopman DS, et al. Two distinct subtypes of right temporal variant frontotemporal dementia. Neurology. 2009;73:1443–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Brambati SM, Rankin KP, Narvid J, et al. Atrophy progression in semantic dementia with asymmetric temporal involvement: a tensor-based morphometry study. Neurobiol Aging. 2009;30:103–11.

    Article  CAS  PubMed  Google Scholar 

  71. Chare L, Hodges JR, Leyton CE, et al. New criteria for frontotemporal dementia syndromes: clinical and pathological diagnostic implications. J Neurol Neurosurg Psychiatry. 2014;85:865–70.

    Article  PubMed  Google Scholar 

  72. Grossman M. Primary progressive aphasia: clinicopathological correlations. Nat Rev Neurol. 2010;6:88–97.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Spinelli EG, Mandelli ML, Miller ZA, et al. Typical and atypical pathology in primary progressive aphasia variants. Ann Neurol. 2017;81:430–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Rohrer JD, Lashley T, Schott JM, et al. Clinical and neuroanatomical signatures of tissue pathology in frontotemporal lobar degeneration. Brain. 2011;134:2565–81.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Hodges JR, Mitchell J, Dawson K, et al. Semantic dementia: demography, familial factors and survival in a consecutive series of 100 cases. Brain. 2010;133:300–6.

    Article  PubMed  Google Scholar 

  76. Mesulam M, Wicklund A, Johnson N, et al. Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia. Ann Neurol. 2008;63:709–19.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Josephs KA, Whitwell JL, Duffy JR, et al. Progressive aphasia secondary to Alzheimer disease vs FTLD pathology. Neurology. 2008;70:25–34.

    Article  CAS  PubMed  Google Scholar 

  78. Canu E, Agosta F, Imperiale F, et al. Added value of multimodal MRI to the clinical diagnosis of primary progressive aphasia variants. Cortex. 2019;113:58–66.

    Article  PubMed  Google Scholar 

  79. Rohrer JD, Rossor MN, Warren JD. Alzheimer’s pathology in primary progressive aphasia. Neurobiol Aging. 2012;33:744–52.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Agosta F, Ferraro PM, Canu E, et al. Differentiation between subtypes of primary progressive aphasia by using cortical thickness and diffusion-tensor MR imaging measures. Radiology. 2015;276:219–27.

    Article  PubMed  Google Scholar 

  81. Jeong Y, Cho SS, Park JM, et al. 18F-FDG PET findings in frontotemporal dementia: an SPM analysis of 29 patients. J Nucl Med. 2005;46:233–9.

    PubMed  Google Scholar 

  82. Grimmer T, Diehl J, Drzezga A, Forstl H, Kurz A. Region-specific decline of cerebral glucose metabolism in patients with frontotemporal dementia: a prospective 18F-FDG-PET study. Dement Geriatr Cogn Disord. 2004;18:32–6.

    Article  CAS  PubMed  Google Scholar 

  83. Ishii K, Sakamoto S, Sasaki M, et al. Cerebral glucose metabolism in patients with frontotemporal dementia. J Nucl Med. 1998;39:1875–8.

    CAS  PubMed  Google Scholar 

  84. Mendez MF, Shapira JS, McMurtray A, Licht E, Miller BL. Accuracy of the clinical evaluation for frontotemporal dementia. Arch Neurol. 2007;64:830–5.

    Article  PubMed  Google Scholar 

  85. Morbelli S, Ferrara M, Fiz F, et al. Mapping brain morphological and functional conversion patterns in predementia late-onset bvFTD. Eur J Nucl Med Mol Imaging. 2016;43:1337–47.

    Article  PubMed  Google Scholar 

  86. Diehl-Schmid J, Grimmer T, Drzezga A, et al. Decline of cerebral glucose metabolism in frontotemporal dementia: a longitudinal 18F-FDG-PET-study. Neurobiol Aging. 2007;28:42–50.

    Article  CAS  PubMed  Google Scholar 

  87. Sjogren M, Gustafson L, Wikkelso C, Wallin A. Frontotemporal dementia can be distinguished from Alzheimer’s disease and subcortical white matter dementia by an anterior-to-posterior rCBF-SPET ratio. Dement Geriatr Cogn Disord. 2000;11:275–85.

    Article  CAS  PubMed  Google Scholar 

  88. Ibach B, Poljansky S, Marienhagen J, et al. Contrasting metabolic impairment in frontotemporal degeneration and early onset Alzheimer’s disease. NeuroImage. 2004;23:739–43.

    Article  CAS  PubMed  Google Scholar 

  89. Charpentier P, Lavenu I, Defebvre L, et al. Alzheimer’s disease and frontotemporal dementia are differentiated by discriminant analysis applied to (99m)Tc HmPAO SPECT data. J Neurol Neurosurg Psychiatry. 2000;69:661–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Kanda T, Ishii K, Uemura T, et al. Comparison of grey matter and metabolic reductions in frontotemporal dementia using FDG-PET and voxel-based morphometric MR studies. Eur J Nucl Med Mol Imaging. 2008;35:2227–34.

    Article  PubMed  Google Scholar 

  91. McNeill R, Sare GM, Manoharan M, et al. Accuracy of single-photon emission computed tomography in differentiating frontotemporal dementia from Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2007;78:350–5.

    Article  CAS  PubMed  Google Scholar 

  92. Womack KB, Diaz-Arrastia R, Aizenstein HJ, et al. Temporoparietal hypometabolism in frontotemporal lobar degeneration and associated imaging diagnostic errors. Arch Neurol. 2011;68:329–37.

    Article  PubMed  Google Scholar 

  93. Tosun D, Schuff N, Rabinovici GD, et al. Diagnostic utility of ASL-MRI and FDG-PET in the behavioral variant of FTD and AD. Ann Clin Transl Neurol. 2016;3:740–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Vijverberg EG, Wattjes MP, Dols A, et al. Diagnostic accuracy of MRI and additional [18F]FDG-PET for behavioral variant frontotemporal dementia in patients with late onset behavioral changes. J Alzheimers Dis. 2016;53:1287–97.

    Article  PubMed  Google Scholar 

  95. Buhour MS, Doidy F, Laisney M, et al. Pathophysiology of the behavioral variant of frontotemporal lobar degeneration: a study combining MRI and FDG-PET. Brain Imaging Behav. 2017;11:240–52.

    Article  PubMed  Google Scholar 

  96. Rabinovici GD, Jagust WJ, Furst AJ, et al. Abeta amyloid and glucose metabolism in three variants of primary progressive aphasia. Ann Neurol. 2008;64:388–401.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Nestor PJ, Graham NL, Fryer TD, et al. Progressive non-fluent aphasia is associated with hypometabolism centred on the left anterior insula. Brain. 2003;126:2406–18.

    Article  PubMed  Google Scholar 

  98. Zahn R, Buechert M, Overmans J, et al. Mapping of temporal and parietal cortex in progressive nonfluent aphasia and Alzheimer’s disease using chemical shift imaging, voxel-based morphometry and positron emission tomography. Psychiatry Res. 2005;140:115–31.

    Article  PubMed  Google Scholar 

  99. Perneczky R, Diehl-Schmid J, Pohl C, Drzezga A, Kurz A. Non-fluent progressive aphasia: cerebral metabolic patterns and brain reserve. Brain Res. 2007;1133:178–85.

    Article  CAS  PubMed  Google Scholar 

  100. Nestor PJ, Balan K, Cheow HK, et al. Nuclear imaging can predict pathologic diagnosis in progressive nonfluent aphasia. Neurology. 2007;68:238–9.

    Article  CAS  PubMed  Google Scholar 

  101. Nestor PJ, Fryer TD, Hodges JR. Declarative memory impairments in Alzheimer’s disease and semantic dementia. NeuroImage. 2006;30:1010–20.

    Article  PubMed  Google Scholar 

  102. Drzezga A, Grimmer T, Henriksen G, et al. Imaging of amyloid plaques and cerebral glucose metabolism in semantic dementia and Alzheimer’s disease. NeuroImage. 2008;39:619–33.

    Article  PubMed  Google Scholar 

  103. Jacova C, Hsiung GY, Tawankanjanachot I, et al. Anterior brain glucose hypometabolism predates dementia in progranulin mutation carriers. Neurology. 2013;81:1322–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Caroppo P, Habert MO, Durrleman S, et al. Lateral temporal lobe: an early imaging marker of the presymptomatic GRN disease? J Alzheimers Dis. 2015;47:751–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Cistaro A, Pagani M, Montuschi A, et al. The metabolic signature of C9ORF72-related ALS: FDG PET comparison with nonmutated patients. Eur J Nucl Med Mol Imaging. 2014;41:844–52.

    Google Scholar 

  106. Deters KD, Risacher SL, Farlow MR, et al. Cerebral hypometabolism and grey matter density in MAPT intron 10 +3 mutation carriers. Am J Neurodegener Dis. 2014;3:103–14.

    PubMed  PubMed Central  Google Scholar 

  107. Chételat G, Arbizu J, Barthel H, et al. Amyloid-PET and 18F-FDG-PET in the diagnostic investigation of Alzheimer’s disease and other dementias. Lancet Neurol. 2020;19:951–62.

    Article  PubMed  Google Scholar 

  108. Rowe CC, Ng S, Ackermann U, et al. Imaging beta-amyloid burden in aging and dementia. Neurology. 2007;68:1718–25.

    Article  CAS  PubMed  Google Scholar 

  109. Rabinovici GD, Furst AJ, O’Neil JP, et al. 11C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. Neurology. 2007;68:1205–12.

    Article  CAS  PubMed  Google Scholar 

  110. Engler H, Santillo AF, Wang SX, et al. In vivo amyloid imaging with PET in frontotemporal dementia. Eur J Nucl Med Mol Imaging. 2008;35:100–6.

    Article  PubMed  Google Scholar 

  111. Leyton CE, Villemagne VL, Savage S, et al. Subtypes of progressive aphasia: application of the International Consensus Criteria and validation using beta-amyloid imaging. Brain. 2011;134:3030–43.

    Article  PubMed  Google Scholar 

  112. Rabinovici GD, Rosen HJ, Alkalay A, et al. Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD. Neurology. 2011;77:2034–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Rowe CC, Ackerman U, Browne W, et al. Imaging of amyloid beta in Alzheimer’s disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism. Lancet Neurol. 2008;7:129–35.

    Article  CAS  PubMed  Google Scholar 

  114. Villemagne VL, Ong K, Mulligan RS, et al. Amyloid imaging with (18)F-florbetaben in Alzheimer disease and other dementias. J Nucl Med. 2011;52:1210–7.

    Article  PubMed  Google Scholar 

  115. Mesulam MM, Weintraub S, Rogalski EJ, et al. Asymmetry and heterogeneity of Alzheimer’s and frontotemporal pathology in primary progressive aphasia. Brain. 2014;137:1176–92.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Bergeron D, Gorno-Tempini ML, Rabinovici GD, et al. Prevalence of amyloid-beta pathology in distinct variants of primary progressive aphasia. Ann Neurol. 2018;84:729–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Ossenkoppele R, Jansen WJ, Rabinovici GD, et al. Prevalence of amyloid PET positivity in dementia syndromes: a meta-analysis. JAMA. 2015;313:1939–49.

    Article  PubMed  PubMed Central  Google Scholar 

  118. Jansen WJ, Ossenkoppele R, Knol DL, et al. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA. 2015;313:1924–38.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Leuzy A, Chiotis K, Lemoine L, et al. Tau PET imaging in neurodegenerative tauopathies-still a challenge. Mol Psychiatry. 2019;24:1112–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Kikuchi A, Okamura N, Hasegawa T, et al. In vivo visualization of tau deposits in corticobasal syndrome by 18F-THK5351 PET. Neurology. 2016;87:2309–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Smith R, Scholl M, Widner H, et al. In vivo retention of (18)F-AV-1451 in corticobasal syndrome. Neurology. 2017;89:845–53.

    Article  PubMed  PubMed Central  Google Scholar 

  122. Whitwell JL, Lowe VJ, Tosakulwong N, et al. [(18) F]AV-1451 tau positron emission tomography in progressive supranuclear palsy. Mov Disord. 2017;32:124–33.

    Article  CAS  PubMed  Google Scholar 

  123. Schonhaut DR, McMillan CT, Spina S, et al. (18) F-flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: a multicenter study. Ann Neurol. 2017;82:622–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Passamonti L, Vazquez Rodriguez P, Hong YT, et al. 18F-AV-1451 positron emission tomography in Alzheimer’s disease and progressive supranuclear palsy. Brain. 2017;140:781–91.

    PubMed  PubMed Central  Google Scholar 

  125. Smith R, Schain M, Nilsson C, et al. Increased basal ganglia binding of (18) F-AV-1451 in patients with progressive supranuclear palsy. Mov Disord. 2017;32:108–14.

    Article  CAS  PubMed  Google Scholar 

  126. Bevan-Jones WR, Cope TE, Jones PS, et al. [(18)F]AV-1451 binding in vivo mirrors the expected distribution of TDP-43 pathology in the semantic variant of primary progressive aphasia. J Neurol Neurosurg Psychiatry. 2018;89:1032–7.

    Article  CAS  PubMed  Google Scholar 

  127. Josephs KA, Martin PR, Botha H, et al. [(18) F]AV-1451 tau-PET and primary progressive aphasia. Ann Neurol. 2018;83:599–611.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Neumann M, Kwong LK, Truax AC, et al. TDP-43-positive white matter pathology in frontotemporal lobar degeneration with ubiquitin-positive inclusions. J Neuropathol Exp Neurol. 2007;66:177–83.

    Article  CAS  PubMed  Google Scholar 

  129. Mackenzie IR, Neumann M. Molecular neuropathology of frontotemporal dementia: insights into disease mechanisms from postmortem studies. J Neurochem. 2016;138(Suppl 1):54–70.

    Article  CAS  PubMed  Google Scholar 

  130. Caroppo P, Le Ber I, Camuzat A, et al. Extensive white matter involvement in patients with frontotemporal lobar degeneration: think progranulin. JAMA Neurol. 2014;71:1562–6.

    Article  PubMed  Google Scholar 

  131. Sudre CH, Bocchetta M, Cash D, et al. White matter hyperintensities are seen only in GRN mutation carriers in the GENFI cohort. Neuroimage Clin. 2017;15:171–80.

    Article  PubMed  PubMed Central  Google Scholar 

  132. Woollacott IOC, Bocchetta M, Sudre CH, et al. Pathological correlates of white matter hyperintensities in a case of progranulin mutation associated frontotemporal dementia. Neurocase. 2018;24:166–74.

    Article  PubMed  PubMed Central  Google Scholar 

  133. Agosta F, Scola E, Canu E, et al. White matter damage in frontotemporal lobar degeneration spectrum. Cereb Cortex. 2012;22:2705–14.

    Article  CAS  PubMed  Google Scholar 

  134. Whitwell JL, Avula R, Senjem ML, et al. Gray and white matter water diffusion in the syndromic variants of frontotemporal dementia. Neurology. 2010;74:1279–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Zhang Y, Schuff N, Du AT, et al. White matter damage in frontotemporal dementia and Alzheimer’s disease measured by diffusion MRI. Brain. 2009;132:2579–92.

    Article  PubMed  PubMed Central  Google Scholar 

  136. Zhang Y, Tartaglia MC, Schuff N, et al. MRI signatures of brain macrostructural atrophy and microstructural degradation in frontotemporal lobar degeneration subtypes. J Alzheimers Dis. 2013;33:431–44.

    Article  PubMed  Google Scholar 

  137. Mahoney CJ, Ridgway GR, Malone IB, et al. Profiles of white matter tract pathology in frontotemporal dementia. Hum Brain Mapp. 2014;35:4163–79.

    Article  PubMed  PubMed Central  Google Scholar 

  138. McMillan CT, Irwin DJ, Avants BB, et al. White matter imaging helps dissociate tau from TDP-43 in frontotemporal lobar degeneration. J Neurol Neurosurg Psychiatry. 2013;84:949–55.

    Article  PubMed  Google Scholar 

  139. Agosta F, Galantucci S, Magnani G, et al. MRI signatures of the frontotemporal lobar degeneration continuum. Hum Brain Mapp. 2015;36:2602–14.

    Article  PubMed  PubMed Central  Google Scholar 

  140. Avants BB, Cook PA, Ungar L, Gee JC, Grossman M. Dementia induces correlated reductions in white matter integrity and cortical thickness: a multivariate neuroimaging study with sparse canonical correlation analysis. NeuroImage. 2010;50:1004–16.

    Article  PubMed  Google Scholar 

  141. Galantucci S, Tartaglia MC, Wilson SM, et al. White matter damage in primary progressive aphasias: a diffusion tensor tractography study. Brain. 2011;134:3011–29.

    Article  PubMed  PubMed Central  Google Scholar 

  142. Schwindt GC, Graham NL, Rochon E, et al. Whole-brain white matter disruption in semantic and nonfluent variants of primary progressive aphasia. Hum Brain Mapp. 2013;34:973–84.

    Article  PubMed  Google Scholar 

  143. Mahoney CJ, Malone IB, Ridgway GR, et al. White matter tract signatures of the progressive aphasias. Neurobiol Aging. 2013;34:1687–99.

    Article  PubMed  PubMed Central  Google Scholar 

  144. Mandelli ML, Caverzasi E, Binney RJ, et al. Frontal white matter tracts sustaining speech production in primary progressive aphasia. J Neurosci. 2014;34:9754–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Catani M, Mesulam MM, Jakobsen E, et al. A novel frontal pathway underlies verbal fluency in primary progressive aphasia. Brain. 2013;136:2619–28.

    Article  PubMed  PubMed Central  Google Scholar 

  146. Acosta-Cabronero J, Patterson K, Fryer TD, et al. Atrophy, hypometabolism and white matter abnormalities in semantic dementia tell a coherent story. Brain. 2011;134:2025–35.

    Article  PubMed  Google Scholar 

  147. Agosta F, Galantucci S, Canu E, et al. Disruption of structural connectivity along the dorsal and ventral language pathways in patients with nonfluent and semantic variant primary progressive aphasia: a DT MRI study and a literature review. Brain Lang. 2013;127:157–66.

    Article  PubMed  Google Scholar 

  148. Agosta F, Henry RG, Migliaccio R, et al. Language networks in semantic dementia. Brain. 2010;133:286–99.

    Article  PubMed  Google Scholar 

  149. Zhou J, Greicius MD, Gennatas ED, et al. Divergent network connectivity changes in behavioural variant frontotemporal dementia and Alzheimer’s disease. Brain. 2010;133:1352–67.

    Article  PubMed  PubMed Central  Google Scholar 

  150. Farb NA, Grady CL, Strother S, et al. Abnormal network connectivity in frontotemporal dementia: evidence for prefrontal isolation. Cortex. 2013;49:1856–73.

    Article  PubMed  Google Scholar 

  151. Filippi M, Agosta F, Scola E, et al. Functional network connectivity in the behavioral variant of frontotemporal dementia. Cortex. 2013;49:2389–401.

    Article  PubMed  Google Scholar 

  152. Whitwell JL, Josephs KA, Avula R, et al. Altered functional connectivity in asymptomatic MAPT subjects: a comparison to bvFTD. Neurology. 2011;77:866–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Seeley WW, Menon V, Schatzberg AF, et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci. 2007;27:2349–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Agosta F, Sala S, Valsasina P, et al. Brain network connectivity assessed using graph theory in frontotemporal dementia. Neurology. 2013;81:134–43.

    Article  PubMed  Google Scholar 

  155. Seeley WW, Crawford RK, Zhou J, Miller BL, Greicius MD. Neurodegenerative diseases target large-scale human brain networks. Neuron. 2009;62:42–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Bonakdarpour B, Rogalski EJ, Wang A, et al. Functional connectivity is reduced in early-stage primary progressive aphasia when atrophy is not prominent. Alzheimer Dis Assoc Disord. 2017;31:101–6.

    Article  PubMed  PubMed Central  Google Scholar 

  157. Guo CC, Gorno-Tempini ML, Gesierich B, et al. Anterior temporal lobe degeneration produces widespread network-driven dysfunction. Brain. 2013;136:2979–91.

    Article  PubMed  PubMed Central  Google Scholar 

  158. Agosta F, Galantucci S, Valsasina P, et al. Disrupted brain connectome in semantic variant of primary progressive aphasia. Neurobiol Aging. 2014;35:2646–55.

    Article  PubMed  Google Scholar 

  159. Ferrari R, Manzoni C, Hardy J. Genetics and molecular mechanisms of frontotemporal lobar degeneration: an update and future avenues. Neurobiol Aging. 2019;78:98–110.

    Article  PubMed  CAS  Google Scholar 

  160. Janssen JC, Schott JM, Cipolotti L, et al. Mapping the onset and progression of atrophy in familial frontotemporal lobar degeneration. J Neurol Neurosurg Psychiatry. 2005;76:162–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Rohrer JD, Warren JD, Barnes J, et al. Mapping the progression of progranulin-associated frontotemporal lobar degeneration. Nat Clin Pract Neurol. 2008;4:455–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. 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;131:72–89.

    Article  PubMed  Google Scholar 

  163. Borroni B, Alberici A, Cercignani M, et al. Granulin mutation drives brain damage and reorganization from preclinical to symptomatic FTLD. Neurobiol Aging. 2012;33:2506–20.

    Article  CAS  PubMed  Google Scholar 

  164. Dopper EG, Rombouts SA, Jiskoot LC, et al. Structural and functional brain connectivity in presymptomatic familial frontotemporal dementia. Neurology. 2014;83:e19–26.

    Article  PubMed  Google Scholar 

  165. Panman JL, Jiskoot LC, Bouts M, et al. Gray and white matter changes in presymptomatic genetic frontotemporal dementia: a longitudinal MRI study. Neurobiol Aging. 2019;76:115–24.

    Article  PubMed  Google Scholar 

  166. Rohrer JD, Nicholas JM, Cash DM, et al. Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the genetic frontotemporal dementia initiative (GENFI) study: a cross-sectional analysis. Lancet Neurol. 2015;14:253–62.

    Article  PubMed  PubMed Central  Google Scholar 

  167. Borroni B, Alberici A, Premi E, et al. Brain magnetic resonance imaging structural changes in a pedigree of asymptomatic progranulin mutation carriers. Rejuvenation Res. 2008;11:585–95.

    Article  CAS  PubMed  Google Scholar 

  168. Jiskoot LC, Bocchetta M, Nicholas JM, et al. Presymptomatic white matter integrity loss in familial frontotemporal dementia in the GENFI cohort: a cross-sectional diffusion tensor imaging study. Ann Clin Transl Neurol. 2018;5:1025–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Lee SE, Sias AC, Mandelli ML, et al. Network degeneration and dysfunction in presymptomatic C9ORF72 expansion carriers. Neuroimage Clin. 2017;14:286–97.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neuroimaging Research Unit, Division of Neuroscience, Neurology Unit, Neurorehabilitation Unit, Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Massimo Filippi

  2. Vita-Salute San Raffaele University, Milan, Italy

    Massimo Filippi & Federica Agosta

  3. Neuroimaging Research Unit, Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Federica Agosta

Authors
  1. Massimo Filippi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Federica Agosta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Massimo Filippi .

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Filippi, M., Agosta, F. (2021). Frontotemporal Lobar Degeneration. In: Imaging Dementia. Springer, Cham. https://doi.org/10.1007/978-3-030-66773-3_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-66773-3_3

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-66772-6

  • Online ISBN: 978-3-030-66773-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation