Current Neurology and Neuroscience Reports

, Volume 10, Issue 6, pp 484–490 | Cite as

The New Classification of Primary Progressive Aphasia into Semantic, Logopenic, or Nonfluent/Agrammatic Variants

Article

Abstract

Primary progressive aphasia (PPA), typically resulting from a neurodegenerative disease such as frontotemporal lobar degeneration or Alzheimer’s disease, is characterized by a progressive loss of specific language functions with relative sparing of other cognitive domains. Three variants of PPA are now recognized: semantic variant, logopenic variant, and nonfluent/agrammatic variant. We discuss recent work characterizing the neurolinguistic, neuropsychological, imaging and pathologic profiles associated with these variants. Improved reliability of diagnoses will be increasingly important as trials for etiology-specific treatments become available. We also discuss the implications of these syndromes for theories of language function.

Keywords

Primary progressive aphasia (PPA) Semantic variant PPA (svPPA) Semantic dementia (SD) Semantic PPA (PPA-S) Logopenic variant PPA (lvPPA) Logopenic progressive aphasia (LPA) Logopenic PPA (PPA-L) Nonfluent/agrammatic variant PPA (navPPA) Progressive nonfluent aphasia (PNFA) Agrammatic PPA (PPA-G) Frontotemporal dementia (FTD, FTLD) Alzheimer’s disease (AD) 

Notes

Acknowledgments

Michael F. Bonner has received grant support from the US National Institutes of Health (NIH). Sharon Ash has received grants from NIH (AG15116, AG17586, NS44266, and NS53488). Murray Grossman has received grants from NIH (NS054575, AG15116, AG17586, NS44266, NS53488, and AG32953).

Disclosure

Murray Grossman is a member and a medical advisor for the board of the Association for Frontotemporal Dementias; he has been a consultant for Pfizer, Forest, and Allon; he has received honoraria for Ground Rounds, Penn State; and has received expenses for travel/accommodations for Grand Rounds, UCSF, and McGill. Sharon Ash has received royalties from Mouton de Gruyter for The Atlas of North American English: Phonetics, Phonology and Sound Change, published in 2006.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Mesulam MM: Primary progressive aphasia. Ann Neurol 2001, 49:425–432.CrossRefPubMedGoogle Scholar
  2. 2.
    Mesulam MM: Primary progressive aphasia--a language-based dementia. N Engl J Med 2003, 349:1535–1542.CrossRefPubMedGoogle Scholar
  3. 3.
    Gorno-Tempini ML, Dronkers NF, Rankin KP, et al.: Cognition and anatomy in three variants of primary progressive aphasia. Ann Neurol 2004, 55:335–346.CrossRefPubMedGoogle Scholar
  4. 4.
    • Grossman M: Primary progressive aphasia: clinicopathological correlations. Nat Rev Neurol 2010, 6:88–97. This paper summarizes the autopsy-confirmed pathology results from 145 PPA patients across seven institutions. The current findings for neuropsychological, neuroimaging, genetic, and cerebrospinal fluid biomarkers of the PPA variants are reviewed.CrossRefPubMedGoogle Scholar
  5. 5.
    Mesulam M, Wieneke C, Rogalski E, et al.: Quantitative template for subtyping primary progressive aphasia. Arch Neurol 2009, 66:1545–1551.CrossRefPubMedGoogle Scholar
  6. 6.
    Hu WT, McMillan C, Libon D, et al.: Multi-modal predictors for Alzheimer’s disease in non-fluent primary progressive aphasia. Neurology 2010, 75:595–602.CrossRefPubMedGoogle Scholar
  7. 7.
    • Hodges JR, Patterson K: Semantic dementia: a unique clinicopathological syndrome. Lancet Neurol 2007, 6:1004–1014. This paper provides an overview of SD. Clinical and pathologic features are summarized. The authors discuss neuropsychological findings and considerations in choosing testing methods for these patients.CrossRefPubMedGoogle Scholar
  8. 8.
    Meteyard L, Patterson K: The relation between content and structure in language production: an analysis of speech errors in semantic dementia. Brain Lang 2009, 110:121–134.CrossRefPubMedGoogle Scholar
  9. 9.
    Kertesz A, Jesso S, Harciarek M, et al.: What is semantic dementia?: a cohort study of diagnostic features and clinical boundaries. Arch Neurol 2010, 67:483–489.CrossRefPubMedGoogle Scholar
  10. 10.
    Halpern C, Glosser G, Clark R, et al.: Dissociation of numbers and objects in corticobasal degeneration and semantic dementia. Neurology 2004, 62:1163–1169.PubMedGoogle Scholar
  11. 11.
    Mesulam M, Rogalski E, Wieneke C, et al.: Neurology of anomia in the semantic variant of primary progressive aphasia. Brain 2009, 132(Pt 9):2553–2565.CrossRefPubMedGoogle Scholar
  12. 12.
    Adlam AL, Patterson K, Rogers TT, et al.: Semantic dementia and fluent primary progressive aphasia: two sides of the same coin? Brain 2006, 129(Pt 11):3066–3080.CrossRefPubMedGoogle Scholar
  13. 13.
    Knibb JA, Xuereb JH, Patterson K, et al.: Clinical and pathological characterization of progressive aphasia. Ann Neurol 2006, 59:156–165.CrossRefPubMedGoogle Scholar
  14. 14.
    Patterson K, Nestor PJ, Rogers TT: Where do you know what you know? The representation of semantic knowledge in the human brain. Nat Rev Neurosci 2007, 8:976–987.CrossRefPubMedGoogle Scholar
  15. 15.
    Weinstein J, Koenig P, Gunawardena D, et al.: Preserved musical semantic memory in semantic dementia. Arch Neurol 2010 (in press).Google Scholar
  16. 16.
    Hailstone JC, Omar R, Warren JD: Relatively preserved knowledge of music in semantic dementia. J Neurol Neurosurg Psychiatry 2009, 80:808–809.CrossRefPubMedGoogle Scholar
  17. 17.
    Yi HA, Moore P, Grossman M: Reversal of the concreteness effect for verbs in semantic dementia. Neuropsychology 2007, 21:9–19.CrossRefPubMedGoogle Scholar
  18. 18.
    • Bonner MF, Vesely L, Price C, et al.: Reversal of the concreteness effect in semantic dementia. Cogn Neuropsychol 2009, 26:568–579. This paper examines the proposed deficit in visual semantic features in SD. The authors find that atrophy in ventral temporal cortex correlates with a deficit in concrete word knowledge.CrossRefPubMedGoogle Scholar
  19. 19.
    Martin A: The representation of object concepts in the brain. Annu Rev Psychol 2007, 58:25–45.CrossRefPubMedGoogle Scholar
  20. 20.
    Jefferies E, Patterson K, Jones RW, et al.: Comprehension of concrete and abstract words in semantic dementia. Neuropsychology 2009, 23:492–499.CrossRefPubMedGoogle Scholar
  21. 21.
    Rohrer JD, Warren JD, Modat M, et al.: Patterns of cortical thinning in the language variants of frontotemporal lobar degeneration. Neurology 2009, 72:1562–1569.CrossRefPubMedGoogle Scholar
  22. 22.
    Avants B, Anderson C, Grossman M, et al.: Spatiotemporal normalization for longitudinal analysis of gray matter atrophy in frontotemporal dementia. Med Image Comput Comput Assist Interv 2007, 10(Pt 2):303–310.PubMedGoogle Scholar
  23. 23.
    Rohrer JD, McNaught E, Foster J, et al.: Tracking progression in frontotemporal lobar degeneration: serial MRI in semantic dementia. Neurology 2008, 71:1445–1451.CrossRefPubMedGoogle Scholar
  24. 24.
    Duda JT, Avants BB, Asmuth JC, et al.: A fiber tractography based examination of neurodegeneration on language-network neuroanatomy. Med Image Comput Comput Assist Interv 2008, 12:191–198.Google Scholar
  25. 25.
    Agosta F, Henry RG, Migliaccio R, et al.: Language networks in semantic dementia. Brain 2010, 133:286–299.CrossRefPubMedGoogle Scholar
  26. 26.
    Josephs KA, Whitwell JL, Duffy JR, et al.: Progressive aphasia secondary to Alzheimer disease vs FTLD pathology. Neurology 2008, 70:25–34.CrossRefPubMedGoogle Scholar
  27. 27.
    Grossman M, Libon DJ, Forman MS, et al.: Distinct antemortem profiles in patients with pathologically defined frontotemporal dementia. Arch Neurol 2007, 64:1601–1609.CrossRefPubMedGoogle Scholar
  28. 28.
    •• Gorno-Tempini ML, Brambati SM, Ginex V, et al.: The logopenic/phonological variant of primary progressive aphasia. Neurology 2008, 71:1227–1234. This paper characterizes the language impairments and neuroimaging data in six lvPPA patients. This is one of only a handful of studies characterizing this patient group. The results are discussed in light of the proposed phonological-loop deficit for lvPPA.CrossRefPubMedGoogle Scholar
  29. 29.
    Kertesz A, Davidson W, McCabe P: Primary progressive aphasia: diagnosis, varieties, evolution. J Int Neuropsychol Soc 2003, 9:710–719.CrossRefPubMedGoogle Scholar
  30. 30.
    Sonty SP, Mesulam M, Thompson CK, et al.: Primary progressive aphasia: PPA and the language network. Ann Neurol 2003, 53:35–49.CrossRefPubMedGoogle Scholar
  31. 31.
    Galton CJ, Patterson K, Xuereb JH, et al.: Atypical and typical presentations of Alzheimer’s disease: a clinical, neuropsychological, neuroimaging and pathological study of 13 cases. Brain 2000, 123:484–498.CrossRefPubMedGoogle Scholar
  32. 32.
    Mendez MF, Clark DG, Shapira JS, et al.: Speech and language in progressive nonfluent aphasia compared with early Alzheimer’s disease. Neurology 2003, 61:1108–1113.PubMedGoogle Scholar
  33. 33.
    Rohrer JD, Ridgway GR, Crutch SJ, et al.: Progressive logopenic/phonological aphasia: erosion of the language network. Neuroimage 2010, 49:984–993.CrossRefPubMedGoogle Scholar
  34. 34.
    Baldo JV, Dronkers NF: The role of inferior parietal and inferior frontal cortex in working memory. Neuropsychology 2006, 20:529–538.CrossRefPubMedGoogle Scholar
  35. 35.
    Grossman M, Mega M, Cummings J, et al.: The aphasias and related disturbances. In Clinical Neurology. Edited by Baker AB, Joynt RJ. Philadelphia: Lippincott Williams and Wilkins; 2004:1–83.Google Scholar
  36. 36.
    Grossman M, Ash S: Primary progressive aphasia: a review. Neurocase 2004, 10:3–18.CrossRefPubMedGoogle Scholar
  37. 37.
    Knibb JA, Woollams AM, Hodges JR, et al.: Making sense of progressive non-fluent aphasia: an analysis of conversational speech. Brain 2009, 132(Pt 10):2734–2746.CrossRefPubMedGoogle Scholar
  38. 38.
    •• Ash S, McMillan C, Gunawardena D, et al.: Speech errors in progressive non-fluent aphasia. Brain Lang 2010, 113:13–20. This paper provides a detailed, quantitative study of speech sound errors in the connected speech of navPPA patients, with linguistic, neuropsychological, and neural correlates. It is argued that speech errors in navPPA mainly arise within the language system and are not caused by a motor impairment.CrossRefPubMedGoogle Scholar
  39. 39.
    Ash S, Moore P, Vesely L, et al.: Non-fluent speech in frontotemporal lobar degeneration. J Neurolinguistics 2009, 22:370–383.CrossRefGoogle Scholar
  40. 40.
    Josephs KA, Duffy JR, Strand EA, et al.: Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech. Brain 2006, 129(Pt 6):1385–1398.CrossRefPubMedGoogle Scholar
  41. 41.
    Ogar JM, Dronkers NF, Brambati SM, et al.: Progressive nonfluent aphasia and its characteristic motor speech deficits. Alzheimer Dis Assoc Disord 2007, 21:S23–S30.CrossRefPubMedGoogle Scholar
  42. 42.
    Peelle JE, Troiani V, Gee J, et al.: Sentence comprehension and voxel-based morphometry in progressive nonfluent aphasia, semantic dementia, and nonaphasic frontotemporal dementia. J Neurolinguistics 2008, 21:418–432.CrossRefPubMedGoogle Scholar
  43. 43.
    Peelle JE, Cooke A, Moore P, et al.: Syntactic and thematic components of sentence processing in progressive nonfluent aphasia and nonaphasic frontotemporal dementia. J Neurolinguistics 2007, 20:482–494.CrossRefPubMedGoogle Scholar
  44. 44.
    Weintraub S, Rubin NP, Mesulam MM: Primary progressive aphasia: longitudinal course, neuropsychological profile, and language features. Arch Neurol 1990, 47:1329–1335.PubMedGoogle Scholar
  45. 45.
    Libon DJ, Xie SX, Moore P, et al.: Patterns of neuropsychological impairment in frontotemporal dementia. Neurology 2007, 68:369–375.CrossRefPubMedGoogle Scholar
  46. 46.
    Patterson K, Graham NL, Ralph MA, et al.: Progressive non-fluent aphasia is not a progressive form of non-fluent (post-stroke) aphasia. Aphasiology 2006, 20:1018–1034.CrossRefGoogle Scholar
  47. 47.
    Gunawardena D, Ash S, McMillan CT, et al.: Why are progressive non-fluent aphasics non-fluent? Neurology 2010, 75:588–594.CrossRefPubMedGoogle Scholar
  48. 48.
    Dronkers NF: A new brain region for coordinating speech articulation. Nature 1996, 384:159–161.CrossRefPubMedGoogle Scholar
  49. 49.
    Hillis AE, Work M, Barker PB, et al.: Re-examining the brain regions crucial for orchestrating speech articulation. Brain 2004, 127(Pt 7):1479–1487.CrossRefPubMedGoogle Scholar
  50. 50.
    Nestor PJ: Nuclear imaging can predict pathologic diagnosis in progressive nonfluent aphasia. Neurology 2007, 68:238–239.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Michael F. Bonner
    • 1
  • Sharon Ash
    • 1
    • 2
  • Murray Grossman
    • 1
  1. 1.Department of Neurology, 2 GibsonHospital of the University of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of Neurology, 3 West GatesHospital of the University of PennsylvaniaPhiladelphiaUSA

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