Difficulties of clinical diagnosis in primary progressive aphasia. Clinical observation

Cover Page

Cite item

Full Text


Primary progressive aphasia is a syndrome characterized by progressive speech dysfunction. There are three types of this condition. The first — agrammatic — type of primary progressive aphasia is typical for frontotemporal dementia and characterized by progressive worsening of speech during several years without other neurological symptoms. For this type, alexia is typical (can be present before the onset of other clinical symptoms) along with agraphia and oral apraxia.

Second type of primary progressive aphasia, semantic aphasia, may also be present in frontotemporal dementia.

The third type of primary progressive aphasia is a logopenic variant which is a manifestation of the atypical variant of Alzheimer’s disease. In this type, the speech disorders are prevailing over the mnestic manifestations. Differential diagnosis in that case is difficult given lack of specific markers in patients with Alzheimer’s disease.

As a clinical illustration, we present a case of a 50-year-old patient. She has been considering herself ill from the age of 45 years, when her speech impairment emerged and started to progress; she also started to experience difficulties in recalling and correct pronunciation of the words. No significant pathologies in internal organs were identified. Her neurological examination showed pyramidal insufficiency more on the right, slight muscle rigidity in the limbs, acheirokinesis, and mild ataxia. Examination of patient’s higher cerebral functions showed mixed aphasia (amnestic and motor), frequent agrammatisms, paraphasias, anomias, apraxia more in the left arm, simultaneous agnosia, partial hemispatial neglect of the left side, alexia, agraphia, acalculia, and finger agnosia. Frontal Assessment Battery test score was 8 and Mini Mental State Examination score was 16. Vascular, infectious, metabolic, autoimmune, tumorous, and iatrogenic causes of dementia have been ruled out. Speech disturbances were typical for agrammatic variant of primary progressive aphasia, but didn’t contradict with logopenic type of Alzheimer’s disease. The PET scan showed no hemispheric asymmetry. We suggested that the most probable diagnosis could be primary progressive aphasia, which can be a manifestation of both frontotemporal dementia and Alzheimer’s disease. Moreover, the differential diagnosis based on clinical manifestations only, without specific PET investigation or specific CSF study is rather difficult.

About the authors

Yevgeniy P. Barantsevich

Academician I.P. Pavlov First St. Petersburg State Medical University

Email: ejvcons@mail.ru
Russian Federation, Saint Petersburg

Yuri P. Koval’chuk

Academician I.P. Pavlov First St. Petersburg State Medical University

Email: ejvcons@mail.ru
Russian Federation, Saint Petersburg

Yekaterina V. Mel’nik

Academician I.P. Pavlov First St. Petersburg State Medical University

Email: ejvcons@mail.ru
Russian Federation, Saint Petersburg

Vladimir S. Emanuel’

Academician I.P. Pavlov First St. Petersburg State Medical University

Author for correspondence.
Email: ejvcons@mail.ru
Russian Federation, Saint Petersburg

Yulia V. Emanuel’

Academician I.P. Pavlov First St. Petersburg State Medical University

Email: ejvcons@mail.ru
Russian Federation, Saint Petersburg


  1. Smolentseva I.G., Sozinova E.V., Vasenina E.E., Levin O.S. [Characteristics of cognitive and behavioral disturbances in patients with semantic dementia with a prevalent atrophy of the right or left hemisphere]. Zhurnal nevrologii i psikhiatrii 2012; (10): 25–32. (In Russ.)
  2. Mesulam M.M., Wieneke C., Thompson C. et al. Quantitative classification of primary progressive aphasia at early and mild impairment stages. Brain 2012; 135 (Pt 5): 1537–1553. doi: 10.1093/brain/aws080. PMID: 22525158.
  3. Stepkina D.A., Zakharov V.V., Yakhno N.N. [Primary progressive aphasia syndrome]. Nevrologicheskiy zhurnal 2014; (5): 22–28. (In Russ.)
  4. Rohrer J.D., Rossor M.N., Warren J.D. Alzheimer's pathology in primary progressive aphasia. Neurobiol Ageing 2012; 33: 744–752. doi: 10.1016/j.neurobiolaging.2010.05.020. PMID: 20580129.
  5. Rogalski E.J., Mesulam M.M. Clinical trajectories and biological features of primary progressive aphasia (PPA). Curr Alzheimer Res 2009; 6: 331–336. doi: 10.2174/156720509788929264. PMID: 19689231.
  6. Snowden J., Neary D., Mann D. Frontotemporal lobar degeneration: clinical and pathological relationships. Acta Neuropathol 2007; 114: 31–38. doi: 10.1007/s00401-007-0236-3. PMID: 17569065.
  7. Gefen T., Gasho K., Rademaker A. et al. Clinically concordant variations of Alzheimer pathology in aphasic versus amnestic dementia. Brain 2012; 135(Pt 5): 1554–1565. doi: 10.1093/brain/aws076. PMID: 22522938.
  8. Yakhno N.N., Zakharov V.V., Lokshina A.B., et al. [Dementia: a guide for practioners]. Moscow: MEDpress-inform, 2011. (In Russ.)
  9. Zakharov V.V. [Differential diagnosis of cognitive impairment]. Effektivnaya farmakoterapiya. Nevrologiya i psikhiatriya 2016; 3: 8–17. (In Russ.)
  10. O'Brien J.T., Thomas A. Vascular dementia. Lancet 2015; 386:1698–1706. doi: 10.1016/S0140-6736(15)00463-8. PMID: 26595643.
  11. URL: https://www.fiercebiotech.com/research/big-data-analysis-links-herpes-virus-to-alzheimer-s-development (data of access 26.07.2018). (In Russ.)
  12. McKeon A. Autoimmune еncephalopathies and dementias. Continuum (Minneap Minn) 2016 (2 Dementia): 538–558. doi: 10.1212/CON.0000000000000299. PMID: 27042907.
  13. Rosenbaum A.I., Maxfield F.R. Niemann–Pick type C disease: molecular mechanisms and potential therapeutic approaches. J Neurochem 2011; 116: 789–795. doi: 10.1111/j.1471-4159.2010.06976.x. PMID: 20807315.
  14. Klyushnikov S.A. [Algorithm for diagnosing Niemann–Pick disease, type C]. Nervnye bolezni 2012; (4): 16–20. (In Russ.)
  15. Huang J.Y., Peng S.F., Yang C.C. et al. Neuroimaging findings in a brain with Niemann–Pick type C disease. J Formos Med Assoc 2011; 110: 537–542. doi: 10.1016/s0929-6646(11)60080-6. PMID: 21783023.
  16. Neary D., Snowden J.S., Gustafson L. et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998; 51: 1546–1554. doi: 10.1212/wnl.51.6.1546. PMID: 9855500.
  17. Vasenina E.E., Levin O.S. [Primary progressive aphasias]. Zhurnal nevrologii i psikhiatrii 2014; (2): 3–12. (In Russ.)
  18. Ling H., O'Sullivan S.S., Holton J.L. et al. Does corticobasal degeneration exist? A clinicopathological re-evaluation. Brain 2010; 133(Pt 7): 2045–57. doi: 10.1093/brain/awq123. PMID: 20584946.
  19. Oeckl P., Steinacker P., Feneberg E., Otto M. Neurochemical biomarkers in the diagnosis of frontotemporal lobar degeneration: an update. J Neurochem 2016; 138 (Suppl 1): 184–192. doi: 10.1111/jnc.13669. PMID: 27186717.
  20. Gorno-Tempini M.L., Brambati S.M., Ginex V. et al. The logopenic/phonological variant of primary progressive aphasia. Neurology 2008; 71: 1227–1234. doi: 10.1212/01.wnl.0000320506.79811.da. PMID: 18633132.
  21. Gorno-Tempini M.L., Hillis A.E., Weintraub S. et al. Classification of primary progressive aphasia and its variants. Neurology 2011; 76: 1006–1014. doi: 10.1212/WNL.0b013e31821103e6. PMID: 21325651.
  22. Bonner M.F., Ash S., Grossman M. The new classification of primary progressive aphasia into semantic, logopenic, or nonfluent/agrammatic variants. Curr Neurol Neurosci Rep 2010; 10: 484–490. doi: 10.1007/s11910-010-0140-4. PMID: 20809401.
  23. Liepelt I., Gaenslen A., Godau J. et al. Rivastigmine for the treatment of dementia in patients with progressive supranuclear palsy: Clinical observations as a basis for power calculations and safety analysis. Alzheimers Dement 2010; 6: 70–74. doi: 10.1016/j.jalz.2009.04.1231. PMID: 20129321.
  24. Kertesz A., Morlog D., Light M. et al. Galantamine in frontotemporal dementia and primary progressive aphasia. Dement Geriatr Cogn Disord 2008; 25: 178–185. doi: 10.1159/000113034. PMID: 18196898.
  25. Chen R., Chan P.T., Chu H. et al. Treatment effects between monotherapy of donepezil versus combination with memantine for Alzheimer disease: A meta-analysis. PLoS One 2017; 12: e0183586. doi: 10.1371/journal.pone.0183586. PMID: 28827830.
  26. Kishi T., Matsunaga S., Iwata N. The effects of memantine on behavioral disturbances in patients with Alzheimer's disease: a meta-analysis. Neuropsychiatr Dis Treat 2017; 13: 1909–1928. doi: 10.2147/NDT.S142839. PMID: 28790827.
  27. Swanberg M.M. Memantine for behavioral disturbances in frontotemporal dementia: a case series. Alzheimer Dis Assoc Disord 2007; 21: 164–166. doi: 10.1097/WAD.0b013e318047df5d. PMID: 17545743.
  28. Boxer A.L., Lipton A.M., Womack K. et al. An open-label study of memantine treatment in 3 subtypes of frontotemporal lobar degeneration. Alzheimer Dis Assoc Disord 2009; 23: 211–217. doi: 10.1097/WAD.0b013e318197852f. PMID: 19812461.
  29. Johnson N.A., Rademaker A., Weintraub S. et al. Pilot trial of memantine in primary progressive aphasia. Alzheimer Dis Assoc Disord 2010; 24: 308. doi: 10.1097/WAD.0b013e3181cf468d. PMID: 20798612.
  30. Feldman D., Krishnan A.V., Swami S. et al. The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer 2014; 14: 342–357. doi: 10.1038/nrc3691. PMID: 24705652.
  31. Manson J.E., Bassuk S.S., Lee I.M. et al. The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemp Clin Trials 2012; 33: 159–171. doi: 10.1016/j.cct.2011.09.009. PMID: 21986389.
  32. Dankers W., Colin E.M., van Hamburg J.P., Lubberts E. Vitamin D in autoimmunity: molecular mechanisms and therapeutic potential. Front Immunol 2017; 7: 697. doi: 10.3389/fimmu.2016.00697. PMID: 28163705.
  33. Littlejohns T.J., Henley W.E., Lang I.A. et al. Vitamin D and the risk of dementia and Alzheimer disease. Neurology 2014; 83: 920–928. doi: 10.1212/WNL.0000000000000755. PMID: 25098535.

Supplementary files

Supplementary Files

Copyright (c) 2019 Barantsevich Y.P., Koval’chuk Y.P., Mel’nik Y.V., Emanuel’ V.S., Emanuel’ Y.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77-83204 от 12.05.2022.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies