Skip to main content
Log in

Verlaufsmodifizierende Therapien der Alzheimer-Demenz

Course modifying therapy of Alzheimer’s dementia

  • Leitthema
  • Published:
Der Nervenarzt Aims and scope Submit manuscript

Zusammenfassung

Die Behandlung der Alzheimer-Demenz stützt sich aktuell auf symptomatische Therapieansätze. Medikamente, die den Verlauf der Krankheit positiv beeinflussen, befinden sich in verschiedenen Stadien der Entwicklung und klinischen Prüfung. Aufgrund der teilweise ungeklärten Pathogenese sind Rückschläge in der Entwicklung solcher Neuansätze vorprogrammiert. Klinisch-epidemiologische Beobachtungen, die einen neuroprotektiven Effekt von Statinen und nichtsteroidalen Antirheumatika nahelegen, müssen hinsichtlich ihrer molekularen Zusammenhänge weiter aufgeklärt werden. Verlaufsmodifizierende Therapien wirken möglicherweise nur Jahre bis Jahrzehnte vor Beginn der klinischen Apparenz. Daher stellt die Behandlung internistischer Risikofaktoren wie Fettleibigkeit und Hypertonie im mittleren Lebensabschnitt sowie die Ernährung mit mediterraner Diät derzeit eine sinnvolle präventive Maßnahme mit hohem Potenzial zur Verlaufsmodifikation dar.

Summary

The current therapy of Alzheimer’s disease is primarily symptomatic. Drugs which aim to modify the course of the disease are currently being developed and tested in clinical trials. Given the complex and partly unknown pathogenesis of the disease, failure of such forms of therapy has to be taken into account. Clinical epidemiology suggests a possible neuroprotective effect of statins and non-steroidal anti-inflammatory drugs, however, the molecular basis of these effects has to be further unraveled. Therapies that modify the course of Alzheimer’s disease are only likely to be effective years if not decades before the disease becomes clinically apparent. Thus, the therapy of risk factors including arterial hypertension and obesity in midlife as well as a Mediterranean diet currently provides the highest chance of modifying the course of the disease.

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

Access this article

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

Instant access to the full article PDF.

Abb. 1

Literatur

  1. Statistisches Bundesamt, Robert-Koch-Institut (2005) Altersdemenz Heft 28

  2. IQWiG (2008) Nutzenbewertung von Cholinesterasehemmern, ginkgohaltigen Präparaten und Memantin bei Patienten mit Demenz, auch im Vergleich untereinander, Vorbericht A05–A19

  3. Pirtillä T et al (2004) Long-term efficacy and safety of galantamine in patients with mild to moderate Alzheimer‚s disease: A multicenter trial. Eur J Neurol 11:734–741

    Article  Google Scholar 

  4. Heneka MT, O’Banion MK (2007) Inflammatory processes in Alzheimer‚s disease. J Neuroimmunol 184:69–91

    Article  CAS  PubMed  Google Scholar 

  5. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science 297:353–356

    Article  CAS  PubMed  Google Scholar 

  6. Wolfe MS (2008) Gamma-secretase inhibition and modulation for Alzheimer’s disease. Curr Alzheimer Res 5:158–164

    Article  CAS  PubMed  Google Scholar 

  7. Green RC et al (2001) Safety and efficacy of tarenflurbil in subjects with mild Alzheimer’s desease: results from an 18-month multi-center phase 3 trial. Alzheimers Demen 4(Suppl 1):165

    Article  Google Scholar 

  8. Aisen PS (2005) The development of anti-amyloid therapy for Alzheimer’s disease: From secretase modulators to polymerisation inhibitors. CNS Drugs 19:989–996

    Article  CAS  PubMed  Google Scholar 

  9. Gauthier S et al (2009) Effect of tramiprosate in patients with mild-to moderate Alzheimer‚s disease: Exploratory analyses of the MRI subgroup of the Alphase study. J Nutr Health Aging 13:550–557

    Article  CAS  PubMed  Google Scholar 

  10. Saumier D et al (2009) Domain-specific cognitive effects of tramiprosate in patients with mild to moderate Alzheimer‚s disease: ADAS-cog subscale results from the Alphase study. J Nutr Health Aging 13:808–812

    Article  CAS  PubMed  Google Scholar 

  11. Schenk D (2002) Amyloid-beta immunotherapy for Alzheimer’s disease: the end of the beginning. Nat Rev Neurosci 3:824–828

    Article  CAS  PubMed  Google Scholar 

  12. Brody DL, Holtzman DM (2008) Active and passive immunotherapy for neurodegenerative disorders. Annu Rev Neurosci 31:175–193

    Article  CAS  PubMed  Google Scholar 

  13. Holmes C et al (2008) Long-term effects of Abeta42 immunisation in Alzheimer’s disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet 372:216–223

    Article  CAS  PubMed  Google Scholar 

  14. Boche D et al (2008) Consequence of Abeta immunization on the vasculature of human Alzheimer’s disease brain. Brain 131:3299–3310

    Article  CAS  PubMed  Google Scholar 

  15. Szabo P et al (2008) Natural human antibodies to amyloid beta peptide. Autoimmun Rev 7:415–420

    Article  CAS  PubMed  Google Scholar 

  16. Salloway S et al (2009) A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer’s disease. Neurology 73:2061–2070

    Article  CAS  PubMed  Google Scholar 

  17. Ballatore C et al (2007) Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat Rev Neurosci 8:663–672

    Article  CAS  PubMed  Google Scholar 

  18. Sigurdsson EM (2008) Immunotherapy targeting pathological tau protein in Alzheimer’s disease and related tauopathies. J Alzheimers Dis 15:157–168

    CAS  PubMed  Google Scholar 

  19. Heneka MT et al (2007) Drug insight: Effects mediated by peroxisome proliferator-activated receptor-gamma in CNS disorders. Nat Clin Pract Neurol 3:496–504

    Article  CAS  PubMed  Google Scholar 

  20. Risner ME et al (2006) Rosiglitazone in Alzheimer’s Disease Study Group. Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer’s disease. Pharmacogenomics J 6:246–254

    CAS  PubMed  Google Scholar 

  21. Höglund K, Blennow K (2007) Effect of HMG-CoA reductase inhibitors on beta amyloid peptide levels: Implications for Alzheimer‚s disease. CNS Drugs 21:449–462

    Article  PubMed  Google Scholar 

  22. Haag MD et al (2009) Statins are associated with a reduced risk of Alzheimer’s disease regardless of lipophilicity. The Rotterdam Study. J Neurol Neurosurg Psychiatry 80:13–17

    Article  CAS  PubMed  Google Scholar 

  23. Luchsinger JA et al (2005) Aggregation of vascular risk factors and risk of incident Alzheimer’s disease. Neurology 65:545–551

    Article  CAS  PubMed  Google Scholar 

  24. Kivipelto M et al (2005) Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer‚s disease. Arch Neurol 62:1556–1560

    Article  PubMed  Google Scholar 

  25. Whitmer RA et al (2008) Central obesity and increased risk of dementia more than three decades later. Neurology 71:1057–1064

    Article  CAS  PubMed  Google Scholar 

  26. Stranahan AM et al (2008) Diet induced insulin resistance impairs hippocampal synaptic plasticity and cognition in middle-aged rats. Hippocampus 18:1085–1088

    Article  PubMed  Google Scholar 

  27. Cao D et al (2007) Intake of sucrose sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer’s disease. J Biol Chem 282:36275–36282

    Article  CAS  PubMed  Google Scholar 

  28. Schröder H et al (2004) Adherence to the traditional mediterranean diet is inversively associated with body mass index and obesity in a spanish population. J Nutr 134:3355–3361

    PubMed  Google Scholar 

  29. Scarmeas N et al (2009) Mediterranean diet and mild cognitive impairment. Arch Neurol 66:216–225

    Article  PubMed  Google Scholar 

  30. Rozzini L et al (2005) Effects of cholinesterase inhibitors appear greater in patients on established antihypertensive therapy. Int J Geriatr Psychiatry 20:547–551

    Article  PubMed  Google Scholar 

  31. Doody RS et al (2008) Effect of dimebon on cognition, activities of daily living, behaviour, and globalfunction in patients with mild-to-moderate Alzheimer’s disease: A randomised, double-blind, placebo-controlled study. Lancet 372:207–215

    Article  CAS  PubMed  Google Scholar 

  32. Moreira PI et al (2008) Alzheimer’s disease and the role of free radicals in the pathogenesis of the disease. CNS Neurol Disord Drug Targets 7:3–10

    Article  CAS  PubMed  Google Scholar 

  33. IQWiG (2008) Nichtmedikamentöse Behandlung der Alzheimer Demenz, Vorbericht A05–19D

  34. Karsten SL, Geschwind DH (2005) Exercise your amyloid. Cell 120:572–574

    Article  CAS  PubMed  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M.T. Heneka.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Heneka, M. Verlaufsmodifizierende Therapien der Alzheimer-Demenz. Nervenarzt 81, 807–814 (2010). https://doi.org/10.1007/s00115-010-3000-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00115-010-3000-1

Schlüsselwörter

Keywords

Navigation