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Towards a Clearer Definition of Logopenic Progressive Aphasia

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Abstract

Logopenic progressive aphasia is the most recently described clinical variant of primary progressive aphasia (PPA), defined by impairment of lexical retrieval and sentence repetition. Unlike other PPA variants, the logopenic variant of PPA (lv-PPA) is commonly associated with Alzheimer’s disease (AD), a fact that is relevant to the selection of patients for clinical trials and disease-modifying therapies. Despite the straightforward definition and coherent pathological association, the existence of lv-PPA has been challenged, as its distinction from AD or other PPA variants can be difficult. Despite these issues, lv-PPA patients display characteristic linguistic deficits, a pattern of brain atrophy, and possibly genetic susceptibility, which warrant considering this variant as a discrete AD endophenotype. More specific clinical and anatomical markers can strengthen the consistency of this syndrome.

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References

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

  1. Gorno-Tempini ML, Dronkers NF, Rankin KP, Ogar JM, Phengrasamy L, Rosen HJ, et al. Cognition and anatomy in three variants of primary progressive aphasia. Ann Neurol. 2004;55:335–46.

    Article  PubMed  Google Scholar 

  2. Gorno-Tempini ML, Brambati SM, Ginex V, Ogar J, Dronkers NF, Marcone A, et al. The logopenic/phonological variant of primary progressive aphasia. Neurology. 2008;71:1227–34.

    Article  PubMed  CAS  Google Scholar 

  3. •• Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76:1006–14. This international consensus provides a common framework and operational definitions for each clinical variant of primary aphasia.

    Article  PubMed  Google Scholar 

  4. Knibb JA, Xuereb JH, Patterson K, Hodges JR. Clinical and pathological characterization of progressive aphasia. Ann Neurol. 2006;59:156–65.

    Article  PubMed  Google Scholar 

  5. Forman MS, Farmer J, Johnson JK, Clark CM, Arnold SE, Coslett HB, et al. Frontotemporal dementia: clinicopathological correlations. Ann Neurol. 2006;59:952–62.

    Article  PubMed  Google Scholar 

  6. • Sajjadi SA, Patterson K, Arnold RJ, Watson PC, Nestor PJ. Primary progressive aphasia: a tale of two syndromes and the rest. Neurology. 2012;78:1670–7. This report offers an alternative view to the current tripartite PPA classification and challenges the existence of lv-PPA as a discrete PPA variant.

    Article  PubMed  CAS  Google Scholar 

  7. Croot K, Ballard K, Leyton CE, Hodges JR. Apraxia of speech and phonological errors in the diagnosis of nonfluent/agrammatic and logopenic variants of primary progressive aphasia. J Speech Lang Hear Res. 2012;55:S1562–72.

    Article  PubMed  Google Scholar 

  8. Mesulam MM, Wieneke C, Thompson C, Rogalski E, Weintraub S. Quantitative classification of primary progressive aphasia at early and mild impairment stages. Brain. 2012;135:1537–53.

    Article  PubMed  Google Scholar 

  9. Etcheverry L, Seidel B, Grande M, Schulte S, Pieperhoff P, Sudmeyer M, et al. The time course of neurolinguistic and neuropsychological symptoms in three cases of logopenic primary progressive aphasia. Neuropsychologia. 2012;50:1708–18.

    Article  PubMed  Google Scholar 

  10. • Leyton CE, Hsieh S, Mioshi E, Hodges JR. Cognitive decline in logopenic aphasia: more than losing words. Neurology. 2013;80:897–903. This longitudinal study demonstrates the rapid cognitive deterioration of lv-PPA and suggests that most lv-PPA patients become demented after the first year of follow-up.

    Article  PubMed  Google Scholar 

  11. Leyton CE, Villemagne VL, Savage S, Pike KE, Ballard KJ, Piguet O, 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 

  12. • Wilson SM, Henry ML, Besbris M, Ogar JM, Dronkers NF, Jarrold W, et al. Connected speech production in three variants of primary progressive aphasia. Brain. 2010;133:2069–88. This was one of the first studies that offer a comprehensive description of linguistic findings and their neural correlates across PPA variants.

    Article  PubMed  Google Scholar 

  13. Rohrer JD, Ridgway GR, Crutch SJ, Hailstone J, Goll JC, Clarkson MJ, et al. Progressive logopenic/phonological aphasia: erosion of the language network. Neuroimage. 2009;49:984–93.

    Article  PubMed  Google Scholar 

  14. Magnin E, Chopard G, Ferreira S, Sylvestre G, Dariel E, Ryff I, et al. Initial neuropsychological profile of a series of 20 patients with logopenic variant of primary progressive aphasia. J Alzheimers Dis. 2013;36:799–808.

    PubMed  Google Scholar 

  15. Ash S, Evans E, O'Shea J, Powers J, Boller A, Weinberg D, et al. Differentiating primary progressive aphasias in a brief sample of connected speech. Neurology. 2013;81:329–36.

    Article  PubMed  Google Scholar 

  16. Savage S, Hsieh S, Leslie F, Foxe D, Piguet O, Hodges JR. Distinguishing subtypes in primary progressive aphasia: application of the Sydney language battery. Dement Geriatr Cogn Disord. 2013;35:208–18.

    Article  PubMed  Google Scholar 

  17. Leyton CE, Piguet O, Savage S, Burrell J, Hodges JR. The neural basis of logopenic progressive aphasia. J Alzheimers Dis. 2012;32:1051–9.

    PubMed  CAS  Google Scholar 

  18. Brambati SM, Ogar J, Neuhaus J, Miller BL, Gorno-Tempini ML. Reading disorders in primary progressive aphasia: a behavioral and neuroimaging study. Neuropsychologia. 2009;47:1893–900.

    Article  PubMed  CAS  Google Scholar 

  19. Crutch SJ, Lehmann M, Warren JD, Rohrer JD. The language profile of posterior cortical atrophy. J Neurol Neurosurg Psychiatry. 2013;84:460–6.

    Article  PubMed  Google Scholar 

  20. Magnin E, Sylvestre G, Lenoir F, Dariel E, Bonnet L, Chopard G, et al. Logopenic syndrome in posterior cortical atrophy. J Neurol. 2013;260:528–33.

    Article  PubMed  Google Scholar 

  21. Foxe DG, Irish M, Hodges JR, Piguet O. Verbal and visuospatial span in logopenic progressive aphasia and Alzheimer's disease. J Int Neuropsychol Soc. 2013;19:247–53.

    Article  PubMed  Google Scholar 

  22. • Lehmann M, Ghosh PM, Madison C, Laforce Jr R, Corbetta-Rastelli C, Weiner MW, et al. Diverging patterns of amyloid deposition and hypometabolism in clinical variants of probable Alzheimer's disease. Brain. 2013;136:844–58. This study, by means of a multimodal imaging analysis, demonstrates that atypical presentations of AD are associated with degeneration of specific functional networks.

    Article  PubMed  Google Scholar 

  23. Sapolsky D, Bakkour A, Negreira A, Nalipinski P, Weintraub S, Mesulam MM, et al. Cortical neuroanatomic correlates of symptom severity in primary progressive aphasia. Neurology. 2010;75:358–66.

    Article  PubMed  CAS  Google Scholar 

  24. Mesulam M, Wieneke C, Rogalski E, Cobia D, Thompson C, Weintraub S. Quantitative template for subtyping primary progressive aphasia. Arch Neurol. 2009;66:1545–51.

    Article  PubMed  Google Scholar 

  25. Josephs KA, Dickson DW, Murray ME, Senjem ML, Parisi JE, Petersen RC, et al. Quantitative neurofibrillary tangle density and brain volumetric MRI analyses in Alzheimer's disease presenting as logopenic progressive aphasia. Brain Lang. 2013. doi:10.1016/j.bandl.2013.02.003.

    Google Scholar 

  26. Hsieh S, Hodges JR, Leyton CE, Mioshi E. Longitudinal changes in primary progressive aphasias: differences in cognitive and dementia staging measures. Dement Geriatr Cogn Disord. 2012;34:135–41.

    Article  PubMed  CAS  Google Scholar 

  27. Harasty JA, Halliday GM, Kril JJ, Code C. Specific temporoparietal gyral atrophy reflects the pattern of language dissolution in Alzheimer's disease. Brain. 1999;122(4):675–86.

    Article  PubMed  Google Scholar 

  28. Ahn HJ, Seo SW, Chin J, Suh MK, Lee BH, Kim ST, et al. The cortical neuroanatomy of neuropsychological deficits in mild cognitive impairment and Alzheimer's disease: a surface-based morphometric analysis. Neuropsychologia. 2011;49:3931–45.

    Article  PubMed  Google Scholar 

  29. Teipel SJ, Willoch F, Ishii K, Burger K, Drzezga A, Engel R, et al. Resting state glucose utilization and the CERAD cognitive battery in patients with Alzheimer's disease. Neurobiol Aging. 2006;27:681–90.

    Article  PubMed  CAS  Google Scholar 

  30. Apostolova LG, Lu P, Rogers S, Dutton RA, Hayashi KM, Toga AW, et al. 3D mapping of language networks in clinical and pre-clinical Alzheimer's disease. Brain Lang. 2008;104:33–41.

    Article  PubMed  Google Scholar 

  31. Croot K, Hodges JR, Xuereb J, Patterson K. Phonological and articulatory impairment in Alzheimer's disease: a case series. Brain Lang. 2000;75:277–309.

    Article  PubMed  CAS  Google Scholar 

  32. Becker JT, Huff FJ, Nebes RD, Holland A, Boller F. Neuropsychological function in Alzheimer's disease. Pattern of impairment and rates of progression. Arch Neurol. 1988;45:263–8.

    Article  PubMed  CAS  Google Scholar 

  33. Hodges JR, Salmon DP, Butters N. Semantic memory impairment in Alzheimer's disease: failure of access or degraded knowledge? Neuropsychologia. 1992;30:301–14.

    Article  PubMed  CAS  Google Scholar 

  34. Hodges JR, Patterson K. Is semantic memory consistently impaired early in the course of Alzheimer's disease? Neuroanatomical and diagnostic implications. Neuropsychologia. 1995;33:441–59.

    Article  PubMed  CAS  Google Scholar 

  35. Peters F, Collette F, Degueldre C, Sterpenich V, Majerus S, Salmon E. The neural correlates of verbal short-term memory in Alzheimer's disease: an fMRI study. Brain. 2009;132:1833–46.

    Article  PubMed  Google Scholar 

  36. Huntley JD, Howard RJ. Working memory in early Alzheimer's disease: a neuropsychological review. Int J Geriatr Psychiatry. 2009;25:121–32.

    Article  Google Scholar 

  37. Leff AP, Schofield TM, Crinion JT, Seghier ML, Grogan A, Green DW, et al. The left superior temporal gyrus is a shared substrate for auditory short-term memory and speech comprehension: evidence from 210 patients with stroke. Brain. 2009;132:3401–10.

    Article  PubMed  Google Scholar 

  38. Richardson FM, Ramsden S, Ellis C, Burnett S, Megnin O, Catmur C, et al. Auditory short-term memory capacity correlates with gray matter density in the left posterior STS in cognitively normal and dyslexic adults. J Cogn Neurosci. 2011;23:3746–56.

    Article  PubMed  Google Scholar 

  39. Acheson DJ, Hamidi M, Binder JR, Postle BR. A common neural substrate for language production and verbal working memory. J Cogn Neurosci. 2011;23:1358–67.

    Article  PubMed  Google Scholar 

  40. Baldo JV, Katseff S, Dronkers NF. Brain regions underlying repetition and auditory-verbal short-term memory deficits in aphasia: evidence from voxel-based lesion symptom mapping. Aphasiology. 2012;26:338–54.

    Article  Google Scholar 

  41. Amici S, Ogar J, Brambati SM, Miller BL, Neuhaus J, Dronkers NL, et al. Performance in specific language tasks correlates with regional volume changes in progressive aphasia. Cogn Behav Neurol. 2007;20:203–11.

    Article  PubMed  Google Scholar 

  42. Page MPA, Madge A, Cumming N, Norris DG. Speech errors and the phonological similarity effect in short-term memory: evidence suggesting a common locus. J Mem Lang. 2007;56:49–64.

    Article  Google Scholar 

  43. Corina DP, Loudermilk BC, Detwiler L, Martin RF, Brinkley JF, Ojemann G. Analysis of naming errors during cortical stimulation mapping: implications for models of language representation. Brain Lang. 2010;115:101–12.

    Article  PubMed  Google Scholar 

  44. Appell J, Kertesz A, Fisman M. A study of language functioning in Alzheimer patients. Brain Lang. 1982;17:73–91.

    Article  PubMed  CAS  Google Scholar 

  45. Cummings JL, Benson F, Hill MA, Read S. Aphasia in dementia of the Alzheimer type. Neurology. 1985;35:394–7.

    Article  PubMed  CAS  Google Scholar 

  46. Ahmed S, de Jager CA, Haigh AM, Garrard P. Logopenic aphasia in Alzheimer's disease: clinical variant or clinical feature? J Neurol Neurosurg Psychiatry. 2012;83:1056–62.

    Article  PubMed  Google Scholar 

  47. Caffarra P, Gardini S, Cappa S, Dieci F, Concari L, Ghetti C, et al. Degenerative jargon aphasia: unusual progression of logopenic/phonological progressive aphasia? Behav Neurol. 2012;26:89–93.

    Google Scholar 

  48. Rohrer JD, Rossor MN, Warren JD. Neologistic jargon aphasia and agraphia in primary progressive aphasia. J Neurol Sci. 2009;277:155–9.

    Article  PubMed  Google Scholar 

  49. • Deramecourt V, Lebert F, Debachy B, Mackowiak-Cordoliani MA, Bombois S, Kerdraon O, et al. Prediction of pathology in primary progressive language and speech disorders. Neurology. 2010;74:42–9. This clincopathology series defines clinical subtypes of PPA associated with specific disorders.

    Article  PubMed  CAS  Google Scholar 

  50. Madhavan A, Whitwell JL, Weigand SD, Duffy JR, Strand EA, Machulda MM, et al. FDG PET and MRI in logopenic primary progressive aphasia versus dementia of the Alzheimer's type. PLoS One. 2013;8:e62471.

    Article  PubMed  CAS  Google Scholar 

  51. Johnson DY, Dunkelberger DL, Henry M, Haman A, Greicius MD, Wong K, et al. Sporadic Jakob-Creutzfeldt disease presenting as primary progressive aphasia. JAMA Neurol. 2013;70:254–7.

    Article  PubMed  Google Scholar 

  52. Martory MD, Roth S, Lovblad KO, Neumann M, Lobrinus JA, Assal F. Creutzfeldt-Jakob disease revealed by a logopenic variant of primary progressive aphasia. Eur Neurol. 2012;67:360–2.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  55. Rabinovici GD, Jagust WJ, Furst AJ, Ogar JM, Racine CA, Mormino EC, et al. Aβ amyloid and glucose metabolism in three variants of primary progressive aphasia. Ann Neurol. 2008;64:388–401.

    Article  PubMed  Google Scholar 

  56. Gil-Navarro S, Llado A, Rami L, Castellvi M, Bosch B, Bargallo N, et al. Neuroimaging and biochemical markers in the three variants of primary progressive aphasia. Dement Geriatr Cogn Disord. 2013;35:106–17.

    Article  PubMed  CAS  Google Scholar 

  57. Kas A, Uspenskaya O, Lamari F, de Souza LC, Habert MO, Dubois B, et al. Distinct brain perfusion pattern associated with CSF biomarkers profile in primary progressive aphasia. J Neurol Neurosurg Psychiatry. 2012;83:695–8.

    Article  PubMed  Google Scholar 

  58. • Gefen T, Gasho K, Rademaker A, Lalehzari M, Weintraub S, Rogalski E, et al. Clinically concordant variations of Alzheimer pathology in aphasic versus amnestic dementia. Brain. 2012;135:1554–65. This quantitative clinicopathology study demonstrates that lv-PPA patients have a cortical distribution of neurofibrillary changes that differs from that of typical AD cases.

    Article  PubMed  Google Scholar 

  59. Atchison TB, Bradshaw M, Massman PJ. Investigation of profile difference between Alzheimer's disease patients declining at different rates: examination of baseline neuropsychological data. Arch Clin Neuropsychol. 2004;19:1007–15.

    Article  PubMed  Google Scholar 

  60. Nagahama Y, Nabatame H, Okina T, Yamauchi H, Narita M, Fujimoto N, et al. Cerebral correlates of the progression rate of the cognitive decline in probable Alzheimer's disease. Eur Neurol. 2003;50:1–9.

    Article  PubMed  Google Scholar 

  61. Rogalski EJ, Rademaker A, Harrison TM, Helenowski I, Johnson N, Bigio E, et al. ApoE E4 is a susceptibility factor in amnestic but not aphasic dementias. Alzheimer Dis Assoc Disord. 2011;25:159–63.

    Article  PubMed  CAS  Google Scholar 

  62. Wolk DA, Dickerson BC. Apolipoprotein E (APOE) genotype has dissociable effects on memory and attentional-executive network function in Alzheimer's disease. Proc Natl Acad Sci U S A. 2010;107:10256–61.

    Article  PubMed  CAS  Google Scholar 

  63. Machulda MM, Whitwell JL, Duffy JR, Strand EA, Dean PM, Senjem ML, et al. Identification of an atypical variant of logopenic progressive aphasia. Brain Lang. 2013. doi:10.1016/j.bandl.2013.02.007.

    Google Scholar 

  64. Migliaccio R, Agosta F, Rascovsky K, Karydas A, Bonasera S, Rabinovici GD, et al. Clinical syndromes associated with posterior atrophy: early age at onset AD spectrum. Neurology. 2009;73:1571–8.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

John R. Hodges has received grant support from the National Health and Medical Research Council of Australia.

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Conflict of Interest

Cristian E. Leytona declares that he has no conflict of interest.

John R. Hodges is a Senior Principal Research Fellow for Neuroscience Research Australia, and an ARC Federation Fellow and Professor of Cognitive Neurology at the University of New South Wales. He receives editor royalties and speaker royalties for Henry Stewart Talks.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Neuroscience Research Australia, Barker Street, PO Box 1165, Randwick, NSW, 2031, Australia

    Cristian E. Leyton & John R. Hodges

  2. ARC Centre of Excellence in Cognition and Its Disorders, Sydney, NSW, Australia

    Cristian E. Leyton & John R. Hodges

  3. School of Medical Sciences, The University of New South Wales, Sydney, NSW, Australia

    John R. Hodges

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Correspondence to Cristian E. Leyton.

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Leyton, C.E., Hodges, J.R. Towards a Clearer Definition of Logopenic Progressive Aphasia. Curr Neurol Neurosci Rep 13, 396 (2013). https://doi.org/10.1007/s11910-013-0396-6

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