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Treatment Options for Tauopathies

  • Cognitive Disorders (M Geschwind, Section Editor)
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Current Treatment Options in Neurology Aims and scope Submit manuscript

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.

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References and Recommended Reading

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

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  3. Espay AJ, Litvan I. Parkinsonism and frontotemporal dementia: the clinical overlap. J Mol Neurosci. 2011;45(3):343–9.

    Article  PubMed  CAS  Google Scholar 

  4. Rabinovici GD, Miller BL. Frontotemporal lobar degeneration: epidemiology, pathophysiology, diagnosis and management. CNS Drugs. 2010;24:375–98.

    Article  PubMed  CAS  Google Scholar 

  5. Schneider A, Mandelkow E. Tau-based treatment strategies in neurodegenerative diseases. Neurotherapeutics. 2008;3:443–57.

    Article  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  7. Hu WT, Trojanowski JQ, Shaw LM. Biomarkers in frontotemporal lobar degenerations–progress and challenges. Prog Neurobiol. 2011;95(4):636–48.

    Article  PubMed  CAS  Google Scholar 

  8. Huey ED, Putnam KT, Grafman J. A systematic review of neurotransmitter deficits and treatments in frontotemporal dementia. Neurology. 2006;66:17–22.

    Article  PubMed  CAS  Google Scholar 

  9. Piguet O, Hornberger M, Mioshi E, Hodges JR. Behavioural-variant frontotemporal dementia: diagnosis, clinical staging, and management. Lancet Neurol. 2011;10:162–72.

    Article  PubMed  Google Scholar 

  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).

  11. Mendez MF. Frontotemporal dementia: therapeutic interventions. Front Neurol Neurosci. 2009;24:168–78.

    Article  PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  15. Hickey C, Chisholm T, Passmore MJ, et al. Differentiating the dementias. revisiting synucleinopathies and tauopathies. Curr Alzheimer Res. 2008;5:52–60.

    Article  PubMed  CAS  Google Scholar 

  16. Wenning GK, Krismer F, Poewe W. New insights into atypical parkinsonism. Curr Opin Neurol. 2011;24:331–8.

    Article  PubMed  CAS  Google Scholar 

  17. Geser F, Wenning GK. Klinik und Therapie der Multisystematrophie und progressiven supranukleären Paralyse. Psychopharmakotherapie. 2005;12:40–50. German

    Google Scholar 

  18. Barsottini OG, Felício AC, Aquino CC, Pedroso JL. Progressive supranuclear palsy: new concepts. Arq Neuropsiquiatr. 2010;68:938–46.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  21. Wenning GK, Litvan I, Tolosa E. Milestones in atypical and secondary Parkinsonisms. Mov Disord. 2011;26:1083–95.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  23. Chaturvedi RK, Beal MF. Mitochondrial approaches for neuroprotection. Ann N Y Acad Sci. 2008;1147:395–412.

    Article  PubMed  CAS  Google Scholar 

  24. Mendez MF, Shapira JS, Miller BL. Stereotypical movements and frontotemporal dementia. Mov Disord. 2005;20:742–5.

    Article  PubMed  Google Scholar 

  25. Hargrave R, Rafal R. Depression in corticobasal degeneration. Psychosomatics. 1998;39:481–2.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  35. Moretti R, Torre P, Antonello RM, et al. Rivastigmine in frontotemporal dementia: an open-label study. Drugs Aging. 2004;21:931–7.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  44. Trojanowski JQ, Duff K, Fillit H, et al. New directions for frontotemporal dementia drug discovery. Alzheimers Dement. 2008;4:89–93.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Tarik Karakaya MD, PhD.

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Karakaya, T., Fußer, F., Prvulovic, D. et al. Treatment Options for Tauopathies. Curr Treat Options Neurol 14, 126–136 (2012). https://doi.org/10.1007/s11940-012-0168-7

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