Skip to main content

Advertisement

SpringerLink
Log in

Amyloid pet in primary progressive aphasia: case series and systematic review of the literature

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Primary progressive aphasia (PPA) is considered a heterogeneous syndrome, with different clinical subtypes and neuropathological causes. Novel PET biomarkers may help to predict the underlying neuropathology, but many aspects remain unclear. We studied the relationship between amyloid PET and PPA variant in a clinical series of PPA patients. A systematic review of the literature was performed. Patients with PPA were assessed over a 2-year period and classified based on language testing and the International Consensus Criteria as non-fluent/agrammatic (nfvPPA), semantic (svPPA), logopenic variant (lvPPA) or as unclassifiable (ucPPA). All patients underwent a Florbetapir (18-F) PET scan and images were analysed by two nuclear medicine physicians, using a previously validated reading method. Relevant studies published between January 2004 and January 2016 were identified by searching Medline and Web of Science databases. Twenty-four PPA patients were included (13 women, mean age 68.8, SD 8.3 years; range 54–83). Overall, 13/24 were amyloid positive: 0/2 (0%) nfvPPA, 0/4 (0%) svPPA, 10/14 (71.4%) lvPPA and 3/4 (75%) ucPPA (p = 0.028). The systematic review identified seven relevant studies, six including all PPA variants and one only lvPPA. Pooling all studies together, amyloid PET positivity was 122/224 (54.5%) for PPA, 14/52 (26.9%) for nfvPPA, 6/47 (12.8%) for svPPA, 101/119 for lvPPA (84.9%) and 12/22 (54.5%) for ucPPA. Amyloid PET may help to identify the underlying neuropathology in PPA. It could be especially useful in ucPPA, because in these cases it is more difficult to predict pathology. ucPPA is frequently associated with amyloid pathology.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Mesulam MM (1982) Slowly progressive aphasia without generalized dementia. Ann Neurol 11:592–598

    Article  CAS  PubMed  Google Scholar 

  2. Mesulam MM (2001) Primary progressive aphasia. Ann Neurol 49:425–432

    Article  CAS  PubMed  Google Scholar 

  3. Gorno-Tempini ML, Hillis AE, Weintraub S et al (2011) Classification of primary progressive aphasia and its variants. Neurology 76:1006–1014

    Article  PubMed  PubMed Central  Google Scholar 

  4. Gorno-Tempini ML, Dronkers NF, Rankin KP et al (2004) Cognition and anatomy in three variants of primary progressive aphasia. Ann Neurol 55:335–346

    Article  PubMed  PubMed Central  Google Scholar 

  5. Nestor PJ, Graham NL, Fryer TD, Williams GB, Patterson K, Hodges JR (2003) Progressive non-fluent aphasia is associated with hypometabolism centered on the left anterior insula. Brain 126:2406–2418

    Article  PubMed  Google Scholar 

  6. Mummery CJ, Patterson K, Price CJ, Ashburner J, Frackowiak RS, Hodges JR (2000) A voxel-based morphometry study of semantic dementia: relationship between temporal lobe atrophy and semantic memory. Ann Neurol 47:36–45

    Article  CAS  PubMed  Google Scholar 

  7. Josephs KA, Duffy JR, Strand EA, Whitwell JL, Layton KF, Parisi JE, Hauser MF, Witte RJ, Boeve BF, Knopman DS, Dickson DW, Jack CR Jr, Petersen RC (2006) Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech. Brain 129:1385–1398

    Article  PubMed  PubMed Central  Google Scholar 

  8. Knibb JA, Xuereb JH, Patterson K, Hodges JR (2006) Clinical and pathological characterization of progressive aphasia. Ann Neurol 59:156–165

    Article  PubMed  Google Scholar 

  9. Mesulam M, Wicklund A, Johnson N, Rogalski E, Léger GC, Rademaker A, Weintraub S, Bigio EH (2008) Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia. Ann Neurol 63:709–719

    Article  PubMed  PubMed Central  Google Scholar 

  10. Grossman M, Wood EM, Moore P, Neumann M, Kwong L, Forman MS, Clark CM, McCluskey LF, Miller BL, Lee VM, Trojanowski JQ (2007) TDP-43 pathologic lesions and clinical phenotype in frontotemporal lobar degeneration with ubiquitin-positive inclusions. Arch Neurol 64:1449–1454

    Article  PubMed  Google Scholar 

  11. Chare L, Hodges JR, Leyton CE, McGinley C, Tan RH, Kril JJ, Halliday GM (2014) New criteria for frontotemporal dementia syndromes: clinical and pathological diagnostic implications. J Neurol Neurosurg Psychiatry 85:866–871

    Article  Google Scholar 

  12. McKhann GM, Knopman DS, Chertkow H et al (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:263–269

    Article  PubMed  PubMed Central  Google Scholar 

  13. Dubois B, Feldman HH, Jacova C et al (2014) Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol 13:614–629

    Article  PubMed  Google Scholar 

  14. Rabinovici GD, Jagust WJ, Furst AJ, Ogar JM, Racine CA, Mormino EC, O’Neil JP, Lal RA, Dronkers NF, Miller BL, Gorno-Tempini ML (2008) Abeta amyloid and glucose metabolism in three variants of primary progressive aphasia. Ann Neurol 64:388–401

    Article  PubMed  PubMed Central  Google Scholar 

  15. Leyton CE, Villemagne VL, Savage S, Pike KE, Ballard KJ, Piguet O, Burrell JR, Rowe CC, Hodges JR (2011) Subtypes of progressive aphasia: application of the International Consensus Criteria and validation using β-amyloid imaging. Brain 134:3030–3043

    Article  PubMed  Google Scholar 

  16. Ikeda M, Tashiro Y, Takai E et al (2014) CSF levels of Aβ1-38/Aβ1-40/Aβ1-42 and (11)C PiB-PET studies in three clinical variants of primary progressive aphasia and Alzheimer’s disease. Amyloid 21:238–245

    Article  CAS  PubMed  Google Scholar 

  17. Josephs KA, Duffy JR, Strand EA, Machulda MM, Senjem ML, Lowe VJ, Jack CR Jr, Whitwell JL (2014) APOE ε4 influences β-amyloid deposition in primary progressive aphasia and speech apraxia. Alzheimers Dement 10:630–636

    Article  PubMed  PubMed Central  Google Scholar 

  18. Matías-Guiu JA, Cabrera-Martín MN, Moreno-Ramos T, Valles-Salgado M, Fernandez-Matarrubia M, Carreras JL, Matías-Guiu J (2015) Amyloid and FDG-PET study of logopenic primary progressive aphasia: evidence for the existence of two subtypes. J Neurol 262:1463–1472

    Article  PubMed  Google Scholar 

  19. Martersteck A, Murphy C, Rademaker A, Wieneke C, Weintraub S, Chen K, Mesulam MM, Rogalski E, Initiative Alzheimer’s Disease Neuroimaging (2016) Alzheimer’s disease neuroimaging initiative. Is in vivo amyloid distribution asymmetric in primary progressive aphasia? Ann Neurol 79:496–501

    Article  CAS  PubMed  Google Scholar 

  20. Clark CM, Pontecorvo MJ, Beach TG, for the AV-45-A16 Study Group et al (2012) Cerebral PET with Florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study. Lancet Neurol 11:669–678

    Article  CAS  PubMed  Google Scholar 

  21. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097

    Article  PubMed  PubMed Central  Google Scholar 

  22. Josephs KA, Duffy JR, Strand EA, Machulda MM, Vemuri P, Senjem ML, Perkerson RB, Baker MC, Lowe V, Jack CR Jr, Rademakers R, Whitwell JL (2014) Progranulin-associated PiB-negative logopenic primary progressive aphasia. J Neurol 261:604–614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Botha H, Duffy JR, Whitwell JL, Strand EA, Machulda MM, Schwarz CG, Reid RI, Spychalla AJ, Senjem ML, Jones DT, Lowe V, Jack CR, Josephs KA (2015) Classification and clinicoradiologic features of primary progressive aphasia (PPA) and apraxia of speech. Cortex 69:220–236

    Article  PubMed  PubMed Central  Google Scholar 

  24. Whitwell JL, Duffy JR, Strand EA, Machulda MM, Senjem ML, Schwarz CG, Reid R, Baker MC, Perkerson RB, Lowe VJ, Rademakers R, Jack CR Jr, Josephs KA (2015) Clinical and neuroimaging biomarkers of amyloid-negative logopenic primary progressive aphasia. Brain Lang 142:45–53

    Article  PubMed  PubMed Central  Google Scholar 

  25. Whitwell JL, Weigand SD, Duffy JR, Strand EA, Machulda MM, Senjem ML, Gunter JL, Lowe VJ, Jack CR Jr, Josephs KA (2016) Clinical and MRI models predicting amyloid deposition in progressive aphasia and apraxia of speech. Neuroimage Clin 11:90–98

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ballard KJ, Savage S, Leyton CE, Vogel AP, Hornberger M, Hodges JR (2014) Logopenic and nonfluent variants of primary progressive aphasia are differentiated by acoustic measures of speech production. PLoS One 9(2):e89864

    Article  PubMed  PubMed Central  Google Scholar 

  27. Leyton CE, Hodges JR, McLean CA, Kril JJ, Piguet O, Ballard KJ (2015) Is the logopenic-variant of primary progressive aphasia a unitary disorder? Cortex 67:122–133

    Article  PubMed  Google Scholar 

  28. Lehmann M, Ghosh PM, Madison C, Laforce R Jr, Corbetta-Rastelli C, Weiner MW, Greicius MD, Seeley WW, Gorno-Tempini ML, Rosen HJ, Miller BL, Jagust WJ, Rabinovici GD (2013) Diverging patterns of amyloid deposition and hypometabolism in clinical variants of probable Alzheimer’s disease. Brain 136:844–858

    Article  PubMed  PubMed Central  Google Scholar 

  29. Whitwell JL, Lowe VJ, Duffy JR, Strand EA, Machulda MM, Kantarci K, Wille SM, Senjem ML, Murphy MC, Gunter JL, Jr Jack CR, Josephs KA (2013) Elevated occipital β-amyloid deposition is associated with widespread cognitive impairment in logopenic progressive aphasia. J Neurol Neurosurg Psychiatry 84:1357–1364

    Article  PubMed  PubMed Central  Google Scholar 

  30. Jung Y, Whitwell JL, Duffy JR, Strand EA, Machulda MM, Senjem ML, Lowe V, Jack CR Jr, Josephs KA (2014) Amyloid burden correlates with cognitive decline in Alzheimer’s disease presenting with aphasia. Eur J Neurol 21:1040–1043

    Article  CAS  PubMed  Google Scholar 

  31. Jung Y, Whitwell JL, Duffy JR, Strand EA, Machulda MM, Senjem ML, Jack CR, Lowe VJ, Josephs KA (2016) Regional β-amyloid burden does not correlate with cognitive or language deficits in Alzheimer’s disease presenting as aphasia. Eur J Neurol 23:313–319

    Article  CAS  PubMed  Google Scholar 

  32. Laforce R Jr, Tosun D, Ghosh P, Lehmann M, Madison CM, Weiner MW, Miller BL, Jagust WJ, Rabinovici GD (2014) Parallel ICA of FDG-PET and PiB-PET in three conditions with underlying Alzheimer’s pathology. Neuroimage Clin 4:508–516

    Article  PubMed  PubMed Central  Google Scholar 

  33. Mendez MF, Sabodash V (2015) Clinical amyloid imaging in logopenic progressive aphasia. Alzheimer Dis Assoc Disord 29:94–96

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Teichmann M, Kas A, Boutet C, Ferrieux S, Nogues M, Samri D, Rogan C, Dormont D, Dubois B, Migliaccio R (2013) Deciphering logopenic primary progressive aphasia: a clinical, imaging and biomarker investigation. Brain 136:3474–3488

    Article  PubMed  Google Scholar 

  35. Patricio CM, Gabriela C, Julieta RM et al (2015) Concordance between 11C-PIB-PET and clinical diagnosis in a memory clinic. Am J Alzheimers Dis Other Demen 30:599–606

    Article  PubMed  Google Scholar 

  36. Sajjadi SA, Patterson K, Arnold RJ, Watson PC, Nestor PJ (2012) Primary progressive aphasia: a tale of two syndromes and the rest. Neurology 78:1670–1677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Sajjadi SA, Patterson K, Nestor PJ (2014) Logopenic, mixed, or Alzheimer-related aphasia? Neurology 82:1127–1131

    Article  PubMed  Google Scholar 

  38. Harris JM, Gall C, Thompson JC, Richardson AM, Neary D, du Plessis D, Pal P, Mann DM, Snowden JS, Jones M (2013) Classification and pathology of primary progressive aphasia. Neurology 81:1832–1839

    Article  PubMed  Google Scholar 

  39. Hodges JR (2016) Pathological diagnosis during life in patients with primary progressive aphasia: seeking the holy grail. JAMA Neurol 73:788–789

    Article  PubMed  Google Scholar 

  40. Mesulam MM (2013) Primary progressive aphasia and the language network: the 2013 H. Houston Merritt Lecture. Neurology 81:456–462

    Article  PubMed  Google Scholar 

  41. Hodges JR, Mitchell J, Dawson K, Spillantini MG, Xuereb JH, McMonagle P, Nestor PJ, Patterson K (2010) Semantic dementia: demography, familial factors and survival in a consecutive series of 100 cases. Brain 133:300–306

    Article  PubMed  Google Scholar 

  42. Hu WT, McMillan C, Libon D, Leight S, Forman M, Lee VM, Trojanowski JQ, Grossman M (2010) Multimodal predictors for Alzheimer disease in nonfluent primary progressive aphasia. Neurology 75:595–602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Rohrer JD, Ridgway GR, Crutch SJ, Hailstone J, Goll JC, Clarkson MJ, Mead S, Beck J, Mummery C, Ourselin S, Warrington EK, Rossor MN, Warren JD (2010) Progressive logopenic/phonological aphasia: erosion of the language network. Neuroimage 49:984–993

    Article  PubMed  PubMed Central  Google Scholar 

  44. Kas A, Uspenskaya O, Lamari F, de Souza LC, Habert MO, Dubois B, Teichmann M, Sarazin M (2012) Distinct brain perfusion pattern associated with CSF biomarkers profile in primary progressive aphasia. J Neurol Neurosurg Psychiatry 83:695–698

    Article  PubMed  Google Scholar 

  45. Gil-Navarro S, Lladó A, Rami L, Castellví M, Bosch B, Bargalló N, Lomeña F, Reñé R, Montagut N, Antonell A, Molinuevo JL, Sánchez-Valle R (2013) Neuroimaging and biochemical markers in the three variants of primary progressive aphasia. Dement Geriatr Cogn Disord 35:106–117

    Article  CAS  PubMed  Google Scholar 

  46. Santangelo R, Coppi E, Ferrari L, Bernasconi MP, Pinto P, Passerini G, Comi G, Magnani G (2015) Cerebrospinal fluid biomarkers can play a pivotal role in the diagnostic work up of primary progressive aphasia. J Alzheimers Dis 43:1429–1440

    CAS  PubMed  Google Scholar 

  47. Jansen WJ, Ossenkoppele R, Knol DL et al (2015) Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA 313:1924–1938

    Article  PubMed  PubMed Central  Google Scholar 

  48. Ossenkoppele R, Jansen WJ, Rabinovici G et al (2015) Prevalence of amyloid PET positivity in dementia syndromes. A Meta-analysis. JAMA 313:1939–1949

    Article  PubMed  PubMed Central  Google Scholar 

  49. Gefen T, Gasho K, Rademaker A, Lalehzari M, Weintraub S, Rogalski E, Wieneke C, Bigio E, Geula C, Mesulam MM (2012) Clinically concordant variations of Alzheimer pathology in aphasic versus amnestic dementia. Brain 135:1554–1565

    Article  PubMed  PubMed Central  Google Scholar 

  50. Mesulam MM, Weintraub S, Rogalski EJ, Wieneke C, Geula C, Bigio EH (2014) Asymmetry and heterogeneity of Alzheimer’s and frontotemporal pathology in primary progressive aphasia. Brain 137:1176–1192

    Article  PubMed  PubMed Central  Google Scholar 

  51. Ossenkoppele R, Schonhaut DR, Schöll M et al (2016) Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease. Brain 139:1551–1567

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Hospital Universitario Doce de Octubre, C/Andalucía, Km 5,4, E-28041, Madrid, Spain

    Alberto Villarejo-Galende, Sara Llamas-Velasco, Verónica Puertas-Martín, Marta González-Sánchez, Rocío Trincado, David A. Pérez-Martínez & Alejandro Herrero-San Martín

  2. Department of Nuclear Medicine, Hospital Universitario Doce de Octubre, Madrid, Spain

    Adolfo Gómez-Grande, Pilar Sarandeses, Patrick Pilkington & Sebastián Ruiz-Solis

  3. Department of Basic Psychology, Psychobiology and Methodology of Behavioral Science, University of Salamanca, Salamanca, Spain

    Israel Contador

  4. Imas12. CIBERNED, Madrid, Spain

    Alberto Villarejo-Galende, Sara Llamas-Velasco, Verónica Puertas-Martín, Marta González-Sánchez, Rocío Trincado, David A. Pérez-Martínez & Alejandro Herrero-San Martín

  5. Universidad Complutense de Madrid, Madrid, Spain

    Alberto Villarejo-Galende & David A. Pérez-Martínez

Authors
  1. Alberto Villarejo-Galende
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sara Llamas-Velasco
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adolfo Gómez-Grande
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Verónica Puertas-Martín
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Israel Contador
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pilar Sarandeses
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marta González-Sánchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rocío Trincado
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Patrick Pilkington
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sebastián Ruiz-Solis
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. David A. Pérez-Martínez
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Alejandro Herrero-San Martín
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alberto Villarejo-Galende.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical standard

The Ethics Committee for medical research of Hospital Universitario Doce de Octubre has approved this study.

Funding

Drs. Llamas-Velasco (CM13/00079) and González-Sánchez (CM15/00222) have been supported by a Rio Hortega grant for clinical research (Instituto de Salud Carlos III, Spain).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Villarejo-Galende, A., Llamas-Velasco, S., Gómez-Grande, A. et al. Amyloid pet in primary progressive aphasia: case series and systematic review of the literature. J Neurol 264, 121–130 (2017). https://doi.org/10.1007/s00415-016-8324-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-016-8324-8

Keywords

Search

Navigation