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Fortschr Neurol Psychiatr 2002; 70(2): 78-83
DOI: 10.1055/s-2002-19920
Originalarbeit
Georg Thieme Verlag Stuttgart · New York

Einfluss der Therapie mit Azetyl-Cholinesterase-Inhibitoren (AChEI) auf psychopathologische Symptome bei der Alzheimer-Krankheit

Influence of Treatment with Acetyl-Cholinesterase Inhibitors on Psychopathological Symptoms in Alzheimer's DiseaseM.  Rösler1 , U.  Frey2
  • 1Arbeitsgruppe Gerontopsychiatrie (Prof. Dr. K. Wanke/Prof. Dr. M. Rösler) Universitätskliniken des Saarlandes, Homburg
  • 2Arbeitsgruppe Gerontopsychiatrie (Prof. Dr. K. Wanke/Prof. Dr. M. Rösler) Universitätsnervenklinik Homburg, Klinik für Psychiatrie und Psychotherapie (Prof. Dr. K. Wanke), Universitätskliniken des Saarlandes, Homburg
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Publication History

Publication Date:
01 February 2002 (online)

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Zusammenfassung

Nachdem zunächst die therapeutische Beeinflussung der kognitiven Defizite bei Patienten mit einer Demenz vom Alzheimer Typ (DAT) ganz im Vordergrund stand, wird in letzter Zeit zunehmend den psychopathologischen Symptomen und Verhaltensstörungen (Behavioral and Psychological Symptoms of Dementia, BPSD) Beachtung geschenkt. Häufig sind nämlich gerade diese für die Betroffenen und für die sie versorgenden Personen erheblich belastend. Die Therapiemöglichkeiten sind mit der Zulassung von Azetyl-Cholinesterase-Inhibitoren (AChEI) der zweiten Generation in den letzten Jahren erweitert worden. Bei der klinischen Evaluation dieser Medikamente wurden zunächst deren Effekte auf die kognitiven Funktionen und Alltagsfertigkeiten bei DAT-Patienten untersucht. Zwischenzeitlich mehren sich Berichte, nach denen eine cholinerge Therapie auch BPSD bei DAT-Patienten günstig beeinflussen kann. Dadurch kann eine deutliche Entlastung der Patienten und Verminderung des Pflegebedarfs erreicht werden. Die Datenlage bezüglich der drei am Markt eingeführten AChEI spricht eindeutig für einen günstigen Einfluss im Sinne der Symptomreduktion oder der Symptomstabilisierung auf die BPSD in ihrer Gesamtheit. Es liegen zunehmend Hinweise dafür vor, dass es spezifische Symptomgruppen gibt, die besonders positiv auf die AChEI-Therapie ansprechen. Halluzinationen, depressive Symptome, Aggressivität und Reizbarkeit zeigen deutliche Symptomreduktionen unter einer Behandlung mit AChEI.

Abstract

The treatment of the cognitive deficits has been the major focus in patients with Alzheimer's disease (DAT) so far. Recently there is increasing interest in Behavioral and Psychological Symptoms of Dementia (BPSD), which can place much burden on DAT patients and their caregivers. With the introduction of Acetylcholinesterase Inhibitors (AChEI) of the second generation the therapeutic armament has been extended. The clinical evaluation of AChEI has found growing evidence that these compounds do not only improve cognitive abilities and activities of daily living (ADL), but also BPSD. The given data regarding the three AChEI available on the market allow the conclusion that there is a general improvement in BPSD. Beside these particularly positive effects on hallucinations, mood symptoms, aggressiveness, and agitation seem possible but need further clarification.

Literatur

  • 1 Burns A, Jacoby R, Levy R. Psychiatric phenomena in Alzheimer's disease. IV: Disorders of behaviour.  Br J Psychiatry. 1990;  157 86-94
    PubMedGoogle Scholar
  • 2 Mega M S, Cummings J L, Fiorello T, Gornbein J. The spectrum of behavioural changes in Alzheimer's disease.  Neurology. 1996;  46 130-135
    CrossrefPubMedGoogle Scholar
  • 3 Cummings J L, Masterman D L. Assessment of treatment-associated changes in behavior and cholinergic therapy of neuropsychiatric symptoms in Alzheimer's disease.  J Clin Psychiatry. 1998;  59 (suppl 13) 23-30
    PubMedGoogle Scholar
  • 4 Rabins P V, Mace N L, Lucas M J. The impact of dementia on the family.  JAMA. 1982;  248 333-335
    CrossrefPubMedGoogle Scholar
  • 5 Pruchno R A, Resch N L. Aberrant behaviors and Alzheimer's disease: mental health effect on spouse caregivers.  J Gerontol. 1989;  44 177-182
    PubMedGoogle Scholar
  • 6 Ballard C, Lowery K, Powell I, O'Brien J, James I. Impact of behavioural and psychological symptoms of dementia on caregivers.  Int Psychogeriatr. 2000;  12 93-105
    CrossrefPubMedGoogle Scholar
  • 7 Stoppe G, Staedt J. Psychopharmakotherapie von Verhaltensstörungen bei Demenzkranken.  Z Gerontol Geriatr. 1999;  32 153-158
    CrossrefPubMedGoogle Scholar
  • 8 Rösler M, Retz W, Retz-Junginger P, Dennler H J. Effects of two-year treatment with the cholinesterase inhibitor rivastigmine on behavioural symptoms in Alzheimer's disease.  Behav Neurol. 1998/1999;  11 211-216
    PubMedGoogle Scholar
  • 9 Arendt T. Das Syndrom der partiellen cholinergen Deafferentierung des kortikalen Mantels - ein Konzept zur Beschreibung des brain-behaviour-relationships bei dementiellen Erkrankungen.  Fortschr Neurol Psychiat. 1991;  59 81-91
    PubMedGoogle Scholar
  • 10 Whitehouse P J, Price D L, Clark A W, Coyle J T, DeLong M R. Alzheimer's disease: evidence for selective loss of cholinergic neurons in the nucleus basalis.  Ann Neurol. 1981;  10 122-126
    CrossrefPubMedGoogle Scholar
  • 11 Gsell W, Strein I, Riederer P. The neurochemistry of Alzheimer type, vascular type and mixed type dementias compared.  J Neural Transm Suppl. 1996;  47 73-101
    PubMedGoogle Scholar
  • 12 Kaufer D I, Cummings J L, Christine D. Effect of tacrine on behavioral symptoms in Alzheimer's disease: an open-label study.  J Geriatr Psychiatry Neurol. 1996;  9 1-6
    PubMedGoogle Scholar
  • 13 Perry E, Ballard C, Spurden D, Cheng A, Johnson M, McKeith I, Piggott M, Perry R. Cholinergic systems in the human brain: psychopharmacology and psychosis.  Alz Dis Rev. 1998;  3 117-124
    PubMedGoogle Scholar
  • 14 Ballard C, Lowery K, Harrison R, McKeith I G. Noncognitive symptoms in Lewy body dementia. In: Perry R (Hrsg.). Dementia with Lewy Bodies Cambridge: Cambridge University Press 1996: 67-84
    Google Scholar
  • 15 Perry E K, Haroutunian V, Davis K L, Levy R, Lantos P, Eagger S, Honavar M, Dean A, Griffiths M, McKeith I G, Perry R H. Neocortical cholinergic activities differentiate Lewy body dementia from classical Alzheimer's disease.  Neuroreport. 1994;  55 1454-1456
    PubMedGoogle Scholar
  • 16 Cummings J L, Back C. The cholinergic hypothesis of neuropsychiatric symptoms in Alzheimer's disease.  Am J Geriatr Psychiatry. 1998;  6 64-78
    PubMedGoogle Scholar
  • 17 Janowsky D S, Risch S C, Gillin J C. Adrenergic-cholinergic balance and the treatment of affective disorders.  Prog Neuropsychopharmacol Biol Psychiatry. 1983;  7 297-307
    CrossrefPubMedGoogle Scholar
  • 18 Schmidt B H, Hinz V C, Blokland A. Preclinical pharmacology of metrifonate: a promise for Alzheimer therapy. In: Becker R, Giacobini E (Hrsg.). Alzheimer Disease: from molecular Biology to Therapy Boston: Birkhäuser 1996: 217-221
    Google Scholar
  • 19 Becker R E, Colliver J A, Markwell S J, Moriearty P L, Unni L K, Vicari S. Double-blind, placebo-controlled study of metrifonate, an acetylcholinesterase inhibitor, for Alzheimer's disease.  Alzheimer Dis Assoc Disord. 1996;  10 124-131
    PubMedGoogle Scholar
  • 20 Becker R E, Colliver J A, Markwell S J, Moriearty P L, Unni L K, Vicari S. Effects of metrifonate on cognitive decline in Alzheimer's disease: a double-blind, placebo-controlled, 6-month study.  Alzheimer Dis Assoc Disord. 1998;  12 54-57
    PubMedGoogle Scholar
  • 21 Cummings J I, Cyrus P A, Bieber F, Mas J, Orazem J, Gulanski B. Metrifonate treatment of the cognitive deficits of Alzheimer's disease.  Neurology. 1998;  50 1214-1221
    PubMedGoogle Scholar
  • 22 Morris J C, Cyrus P A, Orazam J, Mas J, Bieber F, Ruzicka B B, Gulanski B. Metrifonate benefits cognitive, behavioral and global function in patients with Alzheimer's disease.  Neurology. 1998;  50 1222-1230
    PubMedGoogle Scholar
  • 23 Ringmann J M, Cummings J L. Metrifonate: Update on a new antidementia agent.  J Clin Psychiatry. 1999;  60 776-782
    PubMedGoogle Scholar
  • 24 Cummings J L, Mega M, Gray K, Rosenberg-Thompson S, Carusi D A, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia.  Neurology. 1994;  44 2308-2314
    CrossrefPubMedGoogle Scholar
  • 25 Rosen W G, Mohs R C, Davis K L. A new rating scale for Alzheimer's disease.  Am J Psychiatry. 1984;  141 1356-1364
    CrossrefPubMedGoogle Scholar
  • 26 Raskind M A, Cyrus P A, Ruzicka B B, Gulanski B I. The effects of metrifonate on the cognitive, behavioural, and functional performance of Alzheimer's disease patients.  J Clin Psychiatry. 1999;  60 318-325
    PubMedGoogle Scholar
  • 27 Cummings J L, Cyrus P A, Ruzicka B B. The efficacy of metrifonate in improving the behavioural disturbance of Alzheimer's disease patients.  Neurology. 1998;  50 (suppl 4) A251
    PubMedGoogle Scholar
  • 28 Gelinas I, Gauthier S, Cyrus P A. The efficacy of metrifonate in enhancing the ability of Alzheimer's disease patients to perform basic and instrumental activities of daily living.  Neurology. 1998;  50 (suppl 4) A90-A91
    PubMedGoogle Scholar
  • 29 Shikiar R, Shakespeare A, Sagnier P P, Wilkinson D, McKeith I, Dartigues J F, Dubois B. The impact of metrifonate therapy on caregivers of patients with Alzheimer's disease: results from the MALT clinical trial.  JAGS. 2000;  48 268-274
    PubMedGoogle Scholar
  • 30 Möller H J. Beispiele klinischer Prüfmodelle für den Wirksamkeitsnachweis von Nootropika. In: Lungershausen E (Hrsg.). Demenz: Herausforderung für Forschung, Medizin und Gesellschaft Berlin, Heidelberg, New York, Tokyo: Springer 1992: 147-157
    Google Scholar
  • 31 Farlow M, Gracon S I, Hershey L A, Lewis K W, Sadowsky C H, Dolan-Ureno J. A controlled trial of tacrine in Alzheimer's disease.  JAMA. 1992;  268 2523-2529
    CrossrefPubMedGoogle Scholar
  • 32 Knapp M J, Knopman D S, Solomon P R. A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease.  JAMA. 1994;  271 985-991
    CrossrefPubMedGoogle Scholar
  • 33 Kaufer D, Cummings J L, Christine D. Differential neuropsychiatric symptom responses to tacrine in Alzheimer's disease: relationship to dementia severity.  Neuropsychiatry Clin Neurosci. 1998;  10 55-63
    PubMedGoogle Scholar
  • 34 Rogers S L, Doody R S, Mohs R C, Friedhoff L T. Donezepil HCL (E2020) improves cognitive and global function in patients with mild to moderately severe Alzheimer's disease: results of a 15-week phase III study.  Poster, 35th Anual Meeting of the ACNP. 1996;  9-13
    PubMedGoogle Scholar
  • 35 Rogers S L, Farlow M R, Doody R S, Mohs R C, Friedhoff L T. A 24-week, doubleblind placebocontrolled trial of Donezepil in patients with Alzheimer's disease.  Neurology. 1998;  50 136-145
    CrossrefPubMedGoogle Scholar
  • 36 Burns A, Rossor M, Hecker J, Gauthier S, Petit H, Möller H J, Rogers S L, Friedhoff L T. The effects of donezepil in Alzheimer's disease - results from a multinational trial.  Dement Geriatr Cogn Disord. 1999;  10 237-244
    CrossrefPubMedGoogle Scholar
  • 37 Tariot P N, Mack J L, Patterson M B, Edland S D, Weiner M F, Fillenbaum G, Blazina L, Teri L, Rubin E, Mortimer J A, Stern Y. The behavioral rating scale for dementia of the Consortium to Establish a Registry for Alzheimer's disease.  Am J Psychiatry. 1995;  152 1349-1357
    CrossrefPubMedGoogle Scholar
  • 38 Weiner M F, Martin-Cock K, Foster B M, Saine K, Fontaine C S, Svetlik D A. Effects of Donepezil on emotional/behavioral symptoms in Alzheimer's disease patients.  J Clin Psychiatry. 2000;  61 487-492
    PubMedGoogle Scholar
  • 39 Mega M S, Masterman D M, O'Connor S M, Barclay T R, Cummings J L. The spectrum of behavioural responses to cholinesterase inhibitor therapy in Alzheimer's disease.  Arch Neurol. 1999;  56 1388-1393
    CrossrefPubMedGoogle Scholar
  • 40 Feldman H, Gauthier S, Hecker J, Vellas B, Subbiah P, Whalen E. A 24-week, randomised double-blind study of donepezil in moderate to severe Alzheimer's disease.  Neurology. 2001;  57 613-620
    CrossrefPubMedGoogle Scholar
  • 41 Winblad B, Engedal K, Soininen H, Verhey F, Waldemar G, Wimo A, Wetterholm A L, Zhang R, Haglund A, Subbiah P. A 1-year, randomised, placebo-controlled study of donezepil in patients with mild to moderate AD.  Neurology. 2001;  57 489-495
    PubMedGoogle Scholar
  • 42 Rösler M, Anand R, Cicin-Sain A, Gauthier S, Agid Y, Dal-Bianco P, Stählin H B, Hartman R, Gharabawi M. Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial.  BMJ. 1999;  318 633-640
    PubMedGoogle Scholar
  • 43 Corey-Bloom J, Anand R, Veach J. A randomized trial evaluating the efficacy and safety of ENA 713 (rivastigmine tartrate), a new acetyl cholinesterase inhibitor, in patients with mild to mederatey severe Alzheimer's disease.  Int J Geriatr Psychopharmacol. 1998;  1 55-65
    PubMedGoogle Scholar
  • 44 Reisberg B, Borenstein J, Salob S P, Ferris S H, Franssen E, Georgotas A. Behavioral symptoms in Alzheimer's disease: phenomenology and treatment.  J Clin Psychiatry. 1987;  48 Suppl 9-15
    PubMedGoogle Scholar
  • 45 Cummings J, Anand R, Koumaras B, Hartman R. Rivastigmine provides behavioural benefits to Alzheimer's disease patients residing in a nursing home: findings from a 26-week trial.  Neurology. 2000;  54 (Suppl 3) A468
    PubMedGoogle Scholar
  • 46 McKeith I G, Grace J B, Walker Z, Byrne E J, Wilkinson D, Stevens T, Perry E K. Rivastigmine in the treatment of dementia with Lewy bodies: preliminary findings from an open trial.  Int J Geriat Psychiatry. 2000;  15 387-392
    PubMedGoogle Scholar
  • 47 Proskurnina N F, Yakovleva A P. Alkaloids of Galanthus woronowi. II. Isolation of a new alkaloid.  Zh Obshch Khim (J Gen Chem). 1952;  22 1899-1902
    PubMedGoogle Scholar
  • 48 Thomsen T, Kewitz H. Galanthamine treatment in senile dementia of Alzheimer's type: a case report. In: Kewitz H, Thomsen T, Bickel U (Hrsg.). Pharmacological Interventions on central cholinergic Mechanisms in senile Dementia (Alzheimer's Disease) München: W. Zuckschwerdt 1989: 238-241
    Google Scholar
  • 49 Snorrason E, Steffansson J. Galanthamine hydrobromide in mania.  Lancet. 1991;  337 557
    PubMedGoogle Scholar
  • 50 Vovin R, Fakturovich A, Golenkov A, Lukin V. Correction of apathetic-abulic manifestations of schizophrenia with cholinotropic drugs.  Zh Nevropatol Psikhiatr Im SS Korsakova. 1991;  91 111-115
    PubMedGoogle Scholar
  • 51 Tariot P N, Solomon P R, Morris J C, Kershaw P, Lilienfeld S, Ding C. A 5-month, randomised, placebo-controlled trial of galantamine in AD.  Neurology. 2000;  54 2269-2276
    PubMedGoogle Scholar
  • 52 Wilcock G K, Lilienfeld S, Gaens E. Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: multicentre randomised controlled trial.  BMJ. 2000;  321 1-7
    CrossrefPubMedGoogle Scholar
  • 53 Imbimbo B P, Troetel W M, Martelli P, Lucchelli F. and the Eptastigmine Study Group . A 6-month, double-blind, placebo-controlled trial of eptastigmine in Alzheimer's disease.  Dement Geriatr Cogn Disord. 2000;  11(1) 17-24
    CrossrefPubMedGoogle Scholar
  • 54 Canal N, Imbimbo B P. for the Eptastigmine Study Group . Relationship between pharmacodynamic activity and cognitive effects of eptastigmine in patients with Alzheimer's disease.  Clin Pharmacol Ther. 1996;  60 218-228
    CrossrefPubMedGoogle Scholar
  • 55 Imbimbo B P, Martelli P, Troetel W M, Lucchelli F, Lucca U, Thal L J. Efficacy and safety of eptastigmine for the treatment of patients with Alzheimer's disease.  Neurology. 1999;  52 700-708
    PubMedGoogle Scholar
  • 56 Imbimbo B, Verdelli G, Martelli P, Marchesini D. and the Eptastigmine Study Group . Two-year treatment of Alzheimer's disease with eptastigmine.  Dement Geriatr Cogn Disord. 1999;  10 139-147
    CrossrefPubMedGoogle Scholar
  • 57 Frey U, Retz W, Riederer P, Rösler M. Neue Aspekte in der antidementiven Pharmakotherapie der Alzheimer-Erkrankung.  Akt Neurol. 2000;  27 305-317
    PubMedGoogle Scholar
  • 58 Anand R, Gharabawi G, Enz A. Efficacy and safety results of the early phase studies with Exelon (ENA 713) in Alzheimer's disease: an overview.  J Drug Dev Clin Pract. 1996;  8 109-116
    PubMedGoogle Scholar
  • 59 Greig N H, Utsuki T, Yu Q , Zhu X, Holloway H, Perry T A, Lee B, Ingram D, Lahiri D B. A new therapeutic target in Alzheimer's disease: attention to butyrylcholinesterase.  Cur Med Res Opinion. 2001;  17 1-7
    PubMedGoogle Scholar
  • 60 Maelicke A, Schröder H, Schrattenholz A. Modulatory control by non-competitive agonists of nicotinic cholinergic neurotransmission in the central nervous system.  Semin Neurosci. 1995;  7 103-114
    CrossrefPubMedGoogle Scholar
  • 61 Maelicke A, Schrattenholz A, Samochocki M, Radina M, Albuquerque E X. Allosterically potentiating ligands of nicotinic receptors as a treatment strategy for Alzheimer's disease.  Behav Brain Res. 2000;  113 199-206
    CrossrefPubMedGoogle Scholar

Prof. Dr. M. Rösler

Universitätsnervenklinik · Universitätskliniken des Saarlandes

66421 Homburg

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