Current Neurology and Neuroscience Reports

, Volume 12, Issue 6, pp 709–714 | Cite as

Primary Progressive Aphasia and Alzheimer’s Disease: Brief History, Recent Evidence

Behavior (HS Kirshner, Section Editor)

Abstract

Primary progressive aphasia (PPA) has been recognized as a syndrome distinct from the usual pattern of language deterioration in Alzheimer’s disease and typically more related to the pathology of frontotemporal dementia (FTD). In recent years, however, the syndromes of primary progressive aphasia have become more complex, divided into the three subtypes of progressive nonfluent aphasia (PNFA), semantic dementia (SD), and logopenic/phonological progressive aphasia (LPA). These syndromes have not only made the linguistic analysis more complex, but the associated pathologies have also become more variable. In particular, PNFA is usually, but not always, associated with FTD pathology and often evidence of a tau mutation, but rarely AD; SD is usually associated with FTD of the ubiquitin staining or progranulin (TAR-DNA) mutation type, but, again, occasionally AD; LPA is typically associated with AD pathology. Patterns of atrophy on magnetic resonance imaging (MRI) generally conform to these subtypes, with PNFA associated with left frontal and insular atophy, SD associated with bilateral temporal atrophy, and LPA associated with L superior-posterior temporal and parietal atrophy. These patterns can also be seen on positron emission (PET) scanning with fluorodeoxyglucose. The newer amyloid binding ligand PET technologies are less useful for detecting regional atrophy patterns but more useful for indication of the underlying pathology. We can thus speak of syndromes of PPA or underlying pathological bases of PPA.

Keywords

Aphasia Primary progressive aphasia (PPA) Frontotemporal dementia (FTD) Frontotemporal lobar degeneration (FTLD) Progressive nonfluent aphasia (PNFA) Semantic dementia (SD) Logopenic progressive aphasia (LPA) Alzheimer’s disease (AD) 

References

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

  1. 1.
    Alzheimer A. Uber eine eigenartige Erkrankung der Hirnrinde, Allgemeine Zeitschrift fur Psychiatrie und Psychisch-Gerichtliche Medizin 1907;64:146–8. Translated in Rottenberg DA, Hochberg FH. Neurological classics in modern translation. New York: Hafner Press; 1977: pp 41–3.Google Scholar
  2. 2.
    Sim M, Sussman I. Alzheimer's disease: its natural history and differential diagnosis. J Nerv Ment Dis. 1962;135:489–99.PubMedCrossRefGoogle Scholar
  3. 3.
    Ferm L. Behavioral activities in demented geriatric patients. Gerontol Clin. 1974;16:185–94.CrossRefGoogle Scholar
  4. 4.
    Sjogren T, Sjogren H, Lindgren AGH. Morbus Alzheimer and morbus Pick: a genetic, clinical, and pathoanatomic study. Acta Psychiatr Neurol Scand. 1974;82(Suppl):185–94.Google Scholar
  5. 5.
    Kirshner HS, Webb WG, Kelly MP. The naming disorder of dementia. Neuropsychologia. 1984;22:23–30.PubMedCrossRefGoogle Scholar
  6. 6.
    Robinson KM, Grossman M, White-Devine T, D’Esposito M. Category-specific difficulty naming with verbs in Alzheimer’s disease. Neurology. 1996;47:178–82.PubMedCrossRefGoogle Scholar
  7. 7.
    Goodglass H, Kaplan E. The assessment of aphasia and related disorders. Philadelphia: Lea & Febiger; 1972.Google Scholar
  8. 8.
    Appell J, Kertesz A, Fisman M. A study of language functioning in Alzheimer patients. Brain Lang. 1982;17:73–91.PubMedCrossRefGoogle Scholar
  9. 9.
    Critchley M. And all the daughters of musick shall be brought low. Language function in the elderly. Arch Neurol. 1984;41:1135–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Cummings JL, Benson DF, Hill MA, Read S. Aphasia in dementia of the Alzheimer type. Neurology. 1985;35:394–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Murdoch BE, Chenery HJ, Wilks V, Boyle RS. Language disorders in Dementia of the Alzheimer type. Brain Lang. 1987;31:122–37.PubMedCrossRefGoogle Scholar
  12. 12.
    Faber-Langendoen K, Morris JC, Knesevich JW, et al. Aphasia in senile dementia of the Alzheimer type. Ann Neurol. 1988;23:365–70.PubMedCrossRefGoogle Scholar
  13. 13.
    Albert ML. Language in normal and dementing elderly. In: Obler LK, Albert ML, editors. Language and communication in the elderly: clinical, therapeutic, and experimental issues. Lexington: DC Heath; 1980. p. 145–50.Google Scholar
  14. 14.
    Cummings JL, Houlihan JP, Hill MA. The pattern of reading deterioration in dementia of the Alzheimer type: observations and implication. Brain Lang. 1986;29:315–23.PubMedCrossRefGoogle Scholar
  15. 15.
    Kirshner HS, Bakar M. Syndromes of language dissolution in aging and dementia. Comp Therapy. 1995;21:519–23.Google Scholar
  16. 16.
    Schwartz MF, Marin OSM, Saffran EM. Dissociations of language in dementia: a case study. Brain Lang. 1977;277–306.Google Scholar
  17. 17.
    Bayles KA, Tomoeda CK, Cruz RF, Mahendra N. Communication abilities of individuals with late-stage Alzheimer disease. Alzheimer Dis Assoc Disord. 2000;14:176–81.PubMedCrossRefGoogle Scholar
  18. 18.
    Pick A. On the relation between aphasia and senile atrophy of the brain. In: DA Rottenberg, FH Hochberg (eds). Neurological classics in modern translation. New York, Hafner; 1977: pp 35–40 [originally published in 1892].Google Scholar
  19. 19.
    •• Mesulam MM. Slowly progressive aphasia without generalized dementia. Ann Neurol. 1982;11:592–8. This is the initial article describing PPA. PubMedCrossRefGoogle Scholar
  20. 20.
    Kirshner HS, Webb WG, Kelly MP, et al. Language disturbance. An initial symptom of cortical degenerations and dementia. Arch Neurol. 1984;41:491–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Green J, Morris JC, Sandson J, et al. Progressive aphasia: a precursor of global dementia? Neurology. 1990;40:423–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Weintraub S, Rubin NP, Mesulam MM. Primary progressive aphasia. Longitudinal course, neuropsychological profile, and language features. Arch Neurol. 1990;47:1329–35.PubMedCrossRefGoogle Scholar
  23. 23.
    Miller BL, Cummings J, Mishkin F, et al. Emergence of artistic talent in frontotemporal dementia. Neurology. 1998;51:978–82.PubMedCrossRefGoogle Scholar
  24. 24.
    Miller BL, Hou CE. Portraits of artists: emergence of visual creativity in dementia. Arch Neurol. 2004;61:842–4.PubMedCrossRefGoogle Scholar
  25. 25.
    Kirshner HS, Tanridag O, Thurman L, et al. Progressive aphasia without dementia: two cases with focal spongiform degeneration. Ann Neurol. 1987;22:527–32.PubMedCrossRefGoogle Scholar
  26. 26.
    Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology. 1998;51:1546–54.PubMedCrossRefGoogle Scholar
  27. 27.
    • 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. The most recent criteria for bvFTD.PubMedCrossRefGoogle Scholar
  28. 28.
    •• 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. This article was the first to clarify the three separate syndromes of PPA. PubMedCrossRefGoogle Scholar
  29. 29.
    Gorno-Tempini ML, Brambati SM, Ginex V, et al. The logopenic/phonological variant of primary progressive aphasia. Neurology. 2008;71:1227–34.PubMedCrossRefGoogle Scholar
  30. 30.
    Heutink P, Stevens M, Rizzu P, et al. Hereditary frontotemporal dementia is linked to chromosome 17q21-q22: a genetic and clinicopathological study of three Dutch families. Ann Neurol. 1997;41:150–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Hutton M, Lendon CL, Rizzu P, et al. Association of missense an d5’-splice-site mutations in tau with the inherited dementia FTDP-17. Nature. 1998;393:702–5.PubMedCrossRefGoogle Scholar
  32. 32.
    Poorkaj P, Bird TD, Wijsman E, et al. Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann Neurol. 1998;43:815–25.PubMedCrossRefGoogle Scholar
  33. 33.
    Snowden JS, Goulding PS, Neary D. Semantic dementia: a form of circumscribed cerebral atrophy. Behav Neurol. 1989;2:167–82.Google Scholar
  34. 34.
    Hodges JR, Patterson K, Oxbury S, et al. Semantic dementia. Progressive fluent aphasia with temporal lobe atrophy. Brain. 1992;115:1783–806.PubMedCrossRefGoogle Scholar
  35. 35.
    Hodges JR, Patterson K. Semantic dementia: a unique clinicopathological syndrome. Lancet Neurol. 2007;6:1004–14.PubMedCrossRefGoogle Scholar
  36. 36.
    Forman MS, Farmer J, Johnson JK, et al. Frontotemporal dementia: clinicopathological correlations. Ann Neurol. 2006;59:952–62.PubMedCrossRefGoogle Scholar
  37. 37.
    Forman MS, Mackenzie IR, Cairns NJ, et al. Novel ubiquitin neuropathology in frontotemporal dementia with valosin-containing protein gene mutations. J Neuropathol Exp Neurol. 2006;65:571–81.PubMedCrossRefGoogle Scholar
  38. 38.
    Baker M, Mackenzie IR, Pickering-Brown SM, Gass J, Rademakers R, Lindholm C. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature. 2006;442:916–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Cruts M, Gijselinck I, van den Zee J, et al. Null mutations in progranulin cause ubiquitin positive frontotemporal dementia linked to chromosome 17q21. Nature. 2006;442:920–24.PubMedCrossRefGoogle Scholar
  40. 40.
    Rohrer JD, Rossor MN, Warren JD. Alzheimer’s pathology in primary progressive aphasia. Neurobiol Aging. 2012;33:744–52.PubMedCrossRefGoogle Scholar
  41. 41.
    Josephs KA, Whitwell JL, Duffy JR, et al. Progressive aphasia secondary to Alzheimer disease vs FTLD pathology. Neurology. 2008;70:25–34.PubMedCrossRefGoogle Scholar
  42. 42.
    Mesulam MM. Primary progressive aphasia. Ann Neurol. 2001;49:425–32.PubMedCrossRefGoogle Scholar
  43. 43.
    Mesulam MM. Primary progressive aphasia—a language-based dementia. N Engl J Med. 2003;349:1535–42.PubMedCrossRefGoogle Scholar
  44. 44.
    Kirshner HS. Frontotemporal dementia and primary progressive aphasia: an update. Curr Neurol Neurosci Rep. 2010;10:504–11.PubMedCrossRefGoogle Scholar
  45. 45.
    Alladi S, Xuereb J, Bak T, et al. Focal cortical presentations of Alzheimer’s disease. Brain. 2007;130:2636–45.PubMedCrossRefGoogle Scholar
  46. 46.
    • Xiong L, Xuereb JH, Spillantini MG, et al. Clinical comparison of progressive aphasia associated with Alzheimer versus FTD-spectrum pathology. J Neurol Neurosurg Psychiatry. 2011;82:254–60. This is a useful article for exploring differences between AD and FTD cases. PubMedCrossRefGoogle Scholar
  47. 47.
    Hu WT, McMillan C, Libon D, et al. Multimodal predictors for Alzheimer disease in nonfluent primary progressive aphasia. Neurology. 2010;75:595–602.PubMedCrossRefGoogle Scholar
  48. 48.
    • Rohrer JD, Rossor MN, Warren JD. Syndromes of nonfluent primary progressive aphasia: a clinical and neurolinguistic analysis. Neurology. 2010;75:603–10. This article sets out specific language findings indicative of pathological substrates of progressive nonfluent aphasia. PubMedCrossRefGoogle Scholar
  49. 49.
    Grossman M. Primary progressive aphasia: clinicopathological correlations. Nat Rev Neurol. 2010;6:88–97.PubMedCrossRefGoogle Scholar
  50. 50.
    Giannakopoulos P, Hof PR, Bouras C. Alzheimer’s disease with asymmetric atrophy of the cerebral hemispheres: morphometric analysis of four cases. Acta Neuropathol. 1994;88:440–7.PubMedCrossRefGoogle Scholar
  51. 51.
    Gefen T, Gasho K, Rademaker A, et al. Clinically concordant variations of Alzheimer pathology in aphasic versus amnestic dementia. Brain. 2012;135:1554–65.PubMedCrossRefGoogle Scholar
  52. 52.
    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.PubMedCrossRefGoogle Scholar
  53. 53.
    Deramecourt V, Lebert F, Debachy B, et al. Prediction of pathology in primary progressive language and speech disorders. Neurology. 2010;74:42–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Tyrrell PJ, Warrington EK, Frackowiak RS, et al. Heterogeneity in progressive aphasia due to focal cortical atrophy. A clinical and PET study Brain. 1990;113:1321–36.Google Scholar
  55. 55.
    Sojkova J, Zhou Y, An Y, et al. Longitudinal patterns of B-amyloid deposition in nondemented older adults. Arch Neurol. 2011;68:644–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Small GW, Kepe V, Ercoli LM, et al. PET of brain amyloid and tau in mild cognitive impairment. N Engl J Med. 2006;355:2652–63.PubMedCrossRefGoogle Scholar
  57. 57.
    Clark CM, Schneider JA, Bedell BJ, et al. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA. 2011;305:275–83.PubMedCrossRefGoogle Scholar
  58. 58.
    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.PubMedCrossRefGoogle Scholar
  59. 59.
    Pereira JM, Williams GB, Acosta-Cabronero J, et al. Atrophy patterns in histologic vs clinical groupings of frontotemporal lobar degeneration. Neurology. 2009;72:1653–60.PubMedCrossRefGoogle Scholar
  60. 60.
    Knibb JA, Xuereb JH, Patterson K, Hodges JR. Clinical and pathological characterization of progressive aphasia. Ann Neurol. 2006;59:156–65.PubMedCrossRefGoogle Scholar
  61. 61.
    Kertesz A, McMonagle P, Blair M, et al. The evolution and pathology of frontotemporal dementia. Brain. 2005;128:1996–2005.PubMedCrossRefGoogle Scholar
  62. 62.
    Migliaccio R, Agosta F, Rascovsky K, Karydas A, et al. Clinical syndromes associated with posterior atrophy: early age at onset AD spectrum. Neurology. 2009;73:1571–8.PubMedCrossRefGoogle Scholar
  63. 63.
    Mesulam M, Wicklund A, Johnson N, et al. Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia. Ann Neurol. 2008;63:709–19.PubMedCrossRefGoogle Scholar
  64. 64.
    Wolk DA, Price JC, Madeira C, et al. Amyloid imaging in dementias with atypical presentation. Alzheimers Dement 2012;1–10.Google Scholar
  65. 65.
    Leyton CE, Villemagne VL, Savage S, et al. Subtypes of progressive aphasia: application of the international consensus criteria and validation using B-amyloid imaging. Brain. 2011;134:3030–43.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of NeurologyVanderbilt University Medical CenterNashvilleUSA

Personalised recommendations