Current Treatment Options in Neurology

, Volume 14, Issue 2, pp 126–136 | Cite as

Treatment Options for Tauopathies

  • Tarik KarakayaEmail author
  • Fabian Fußer
  • David Prvulovic
  • Harald Hampel
Cognitive Disorders (M Geschwind, Section Editor)

Opinion statement

To date, there are no approved and established pharmacologic treatment options for tauopathies, a very heterogenous group of neuropsychiatric diseases often leading to dementia and clinically diagnosed as atypical Parkinson syndromes. Among these so-called Parkinson plus syndromes are progressive supranuclear palsy (PSP), also referred to as Steele-Richardson-Olszewski syndrome; frontotemporal dementia (FTD); and corticobasal degeneration (CBD). Available treatment strategies are based mainly on small clinical trials, miscellaneous case reports, or small case-controlled studies. The results of these studies and conclusions about the efficacy of the medication used are often contradictory. Approved therapeutic agents for Alzheimer´s dementia, such as acetylcholinesterase inhibitors and memantine, have been used off-label to treat cognitive and behavioral symptoms in tauopathies, but the outcome has not been consistent. Therapeutic agents for the symptomatic treatment of Parkinson’s disease (levodopa or dopamine agonists) are used for motor symptoms in tauopathies. For behavioral or psychopathological symptoms, treatment with antidepressants—especially selective serotonin reuptake inhibitors—could be helpful. Antipsychotics are often not well tolerated because of their adverse effects, which are pronounced in tauopathies; these drugs should be given very carefully because of an increased risk of cerebrovascular events. In addition to pharmacologic options, physical, occupational, or speech therapy can be applied to improve functional abilities. Each pharmacologic or nonpharmacologic intervention should be fitted to the specific symptoms of the individual patient, and decisions about the type and duration of treatment should be based on its efficacy for the individual and the patient’s tolerance. Currently, no effective treatment is available that targets the cause of these diseases. Current research focuses on targeting tau protein pathology, including pathologic aggregation or phosphorylation; these approaches seem to be very promising.


Tauopathies Tau proteins Neurodegenerative diseases PSP Progressive supranuclear palsy FTD Frontotemporal dementia CBD Corticobasal degeneration Treatment Dementia Parkinson plus syndromes SSRIs Acetylcholinesterase inhibitors Antipsychotics Trazodone Memantine Levodopa 



No potential conflicts of interest relevant to this article were reported.

References and Recommended Reading

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

  1. 1.
    Wakabayashi K, Mori F, Tanji K, et al. Involvement of the peripheral nervous system in synucleinopathies, tauopathies and other neurodegenerative proteinopathies of the brain. Acta Neuropathol. 2010;120:1–12.PubMedCrossRefGoogle Scholar
  2. 2.
    Sha S, Hou C, Viskontas IV, Miller BL. Are frontotemporal lobar degeneration, progressive supranuclear palsy and corticobasal degeneration distinct diseases? Nat Clin Pract Neurol. 2006;2:658–65.PubMedCrossRefGoogle Scholar
  3. 3.•
    Espay AJ, Litvan I. Parkinsonism and frontotemporal dementia: the clinical overlap. J Mol Neurosci. 2011;45(3):343–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Rabinovici GD, Miller BL. Frontotemporal lobar degeneration: epidemiology, pathophysiology, diagnosis and management. CNS Drugs. 2010;24:375–98.PubMedCrossRefGoogle Scholar
  5. 5.
    Schneider A, Mandelkow E. Tau-based treatment strategies in neurodegenerative diseases. Neurotherapeutics. 2008;3:443–57.CrossRefGoogle Scholar
  6. 6.
    Rankin KP, Mayo MC, Seeley WW, et al. Behavioral variant frontotemporal dementia with corticobasal degeneration pathology: phenotypic comparison to bvFTD with Pick’s disease. J Mol Neurosci. 2011;45(3):594–608.PubMedCrossRefGoogle Scholar
  7. 7.
    Hu WT, Trojanowski JQ, Shaw LM. Biomarkers in frontotemporal lobar degenerations–progress and challenges. Prog Neurobiol. 2011;95(4):636–48.PubMedCrossRefGoogle Scholar
  8. 8.
    Huey ED, Putnam KT, Grafman J. A systematic review of neurotransmitter deficits and treatments in frontotemporal dementia. Neurology. 2006;66:17–22.PubMedCrossRefGoogle Scholar
  9. 9.
    Piguet O, Hornberger M, Mioshi E, Hodges JR. Behavioural-variant frontotemporal dementia: diagnosis, clinical staging, and management. Lancet Neurol. 2011;10:162–72.PubMedCrossRefGoogle Scholar
  10. 10.
    Herrmann N, Black SE, Chow T, et al. Serotonergic function and treatment of behavioral and psychological symptoms of frontotemporal dementia. Am J Geriatr Psychiatry. 2011 Nov 4 (Epub ahead of print).Google Scholar
  11. 11.
    Mendez MF. Frontotemporal dementia: therapeutic interventions. Front Neurol Neurosci. 2009;24:168–78.PubMedCrossRefGoogle Scholar
  12. 12.
    Kuszczyk M, Słomka M, Antkiewicz-Michaluk L, et al. 1-Methyl-1,2,3,4-tetrahydroisoquinoline and established uncompetitive NMDA receptor antagonists induce tolerance to excitotoxicity. Pharmacol Rep. 2010;62:1041–50.PubMedGoogle Scholar
  13. 13.
    Chow TW, Graff-Guerrero A, Verhoeff NP, et al. Open-label study of the short-term effects of memantine on FDG-PET in frontotemporal dementia. Neuropsychiatr Dis Treat. 2011;7:415–24.PubMedCrossRefGoogle Scholar
  14. 14.
    Fellgiebel A, Müller MJ, Hiemke C, et al. Clinical improvement in a case of frontotemporal dementia under aripiprazole treatment corresponds to partial recovery of disturbed frontal glucose metabolism. World J Biol Psychiatry. 2007;8:123–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Hickey C, Chisholm T, Passmore MJ, et al. Differentiating the dementias. revisiting synucleinopathies and tauopathies. Curr Alzheimer Res. 2008;5:52–60.PubMedCrossRefGoogle Scholar
  16. 16.
    Wenning GK, Krismer F, Poewe W. New insights into atypical parkinsonism. Curr Opin Neurol. 2011;24:331–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Geser F, Wenning GK. Klinik und Therapie der Multisystematrophie und progressiven supranukleären Paralyse. Psychopharmakotherapie. 2005;12:40–50. GermanGoogle Scholar
  18. 18.
    Barsottini OG, Felício AC, Aquino CC, Pedroso JL. Progressive supranuclear palsy: new concepts. Arq Neuropsiquiatr. 2010;68:938–46.PubMedCrossRefGoogle Scholar
  19. 19.
    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;6:70–4.PubMedCrossRefGoogle Scholar
  20. 20.•
    Ludolph AC, Kassubek J, Landwehrmeyer BG, et al. Tauopathies with parkinsonism: clinical spectrum, neuropathologic basis, biological markers, and treatment options. Eur J Neurol. 2009;16:297–309.PubMedCrossRefGoogle Scholar
  21. 21.••
    Wenning GK, Litvan I, Tolosa E. Milestones in atypical and secondary Parkinsonisms. Mov Disord. 2011;26:1083–95.PubMedCrossRefGoogle Scholar
  22. 22.
    Liepelt I, Maetzler W, Blaicher HP, et al. Treatment of dementia in parkinsonian syndromes with cholinesterase inhibitors. Dement Geriatr Cogn Disord. 2007;23:351–67.PubMedCrossRefGoogle Scholar
  23. 23.
    Chaturvedi RK, Beal MF. Mitochondrial approaches for neuroprotection. Ann N Y Acad Sci. 2008;1147:395–412.PubMedCrossRefGoogle Scholar
  24. 24.
    Mendez MF, Shapira JS, Miller BL. Stereotypical movements and frontotemporal dementia. Mov Disord. 2005;20:742–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Hargrave R, Rafal R. Depression in corticobasal degeneration. Psychosomatics. 1998;39:481–2.PubMedCrossRefGoogle Scholar
  26. 26.
    Moretti R, Torre P, Antonello RM, et al. Frontotemporal dementia: paroxetine as a possible treatment of behavior symptoms. A randomized, controlled, open 14-month study. Eur Neurol. 2003;49:13–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Deakin JB, Rahman S, Nestor PJ, et al. Paroxetine does not improve symptoms and impairs cognition in frontotemporal dementia: a double-blind randomized controlled trial. Psychopharmacology. 2004;172:400–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Friess E, Kuempfel T, Modell S, et al. Paroxetine treatment improves motor symptoms in patients with multiple system atrophy. Parkinsonism Relat Disord. 2006;12:432–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Ceravolo R, Nuti A, Piccinni A, et al. Paroxetine in Parkinson’s disease: effects on motor and depressive symptoms. Neurology. 2000;55:1216–8.PubMedGoogle Scholar
  30. 30.
    Ikeda M, Shigenobu K, Fukuhara R, et al. Efficacy of fluvoxamine as a treatment for behavioral symptoms in frontotemporal lobar degeneration patients. Dement Geriatr Cogn Disord. 2004;17:117–21.PubMedCrossRefGoogle Scholar
  31. 31.
    Lebert F, Stekke W, Hasenbroekx C, Pasquier F. Frontotemporal dementia: a randomised, controlled trial with trazodone. Dement Geriatr Cogn Disord. 2004;17:355–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Mendez MF, Shapira JS, McMurtray A, et al. Preliminary findings: behavioral worsening on donepezil in patients with frontotemporal dementia. Am J Geriatr Psychiatry. 2007;15:84–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Miyasaki JM, Shannon K, Voon V, et al. Practice parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review) – Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006;66:966–1002.CrossRefGoogle Scholar
  34. 34.
    Litvan I, Phipps M, Pharr VL, et al. Randomized placebo-controlled trial of donepezil in patients with progressive supranuclear palsy. Neurology. 2001;57:467–73.PubMedGoogle Scholar
  35. 35.
    Moretti R, Torre P, Antonello RM, et al. Rivastigmine in frontotemporal dementia: an open-label study. Drugs Aging. 2004;21:931–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Emre M, Aarsland D, Albanese A, et al. Rivastigmine for dementia associated with Parkinson’s disease. N Engl J Med. 2004;351:2509–18.PubMedCrossRefGoogle Scholar
  37. 37.
    McKeith I, Del Ser T, Spano P, et al. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet. 2000;356:2031–6.PubMedCrossRefGoogle Scholar
  38. 38.
    Kertesz A, Morlog D, Light M, et al. Galantamine in frontotemporal dementia and primary progressive aphasia. Dement Geriatr Cogn Disord. 2008;25:178–85.PubMedCrossRefGoogle Scholar
  39. 39.
    Diehl-Schmid J, Förstl H, Perneczky R, et al. A 6-month, open-label study of memantine in patients with frontotemporal dementia. Int J Geriatr Psychiatry. 2008;23:754–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Vercelletto M, Boutoleau-Bretonnière C, Volteau C, et al. Memantine in behavioral variant frontotemporal dementia: negative results. J Alzheimers Dis. 2011;23:749–59.PubMedGoogle Scholar
  41. 41.
    Aarsland D, Ballard C, Walker Z, et al. Memantine in patients with Parkinson’s disease dementia or dementia with Lewy bodies: a double-blind, placebo-controlled, multicentre trial. Lancet Neurol. 2009;8:613–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Boxer AL, Lipton AM, Womack K, et al. An open-label study of memantine treatment in 3 subtypes of frontotemporal lobar degeneration. Alzheimer Dis Assoc Disord. 2009;23:211–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Weintraub D, Chen P, Ignacio RV, et al. Patterns and trends in antipsychotic prescribing for Parkinson disease psychosis. Arch Neurol. 2011;68:899–904.PubMedCrossRefGoogle Scholar
  44. 44.
    Trojanowski JQ, Duff K, Fillit H, et al. New directions for frontotemporal dementia drug discovery. Alzheimers Dement. 2008;4:89–93.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Tarik Karakaya
    • 1
    Email author
  • Fabian Fußer
    • 1
  • David Prvulovic
    • 1
  • Harald Hampel
    • 1
  1. 1.Department of PsychiatryJ.W. Goethe-UniversityFrankfurtGermany

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