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Fortschr Neurol Psychiatr 2003; 71(4): 199-204
DOI: 10.1055/s-2003-38509
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Ausprägung, Stabilität und Muster kognitiver und nicht kognitiver Symptome bei Patienten mit Alzheimer-Demenz

Verlaufsbeobachtungen über zwei Jahre unter konstanten Behandlungsbedingungen mit RivastigminPresentation and Stability of Cognitive and Noncognitive Symptom Patterns in Patients with Alzheimer's Disease Disease Course Over a Two-Year Period Under Constant Treatment Conditions with Rivastigmine T.  Wobrock1 , P.  Retz-Junginger2 , W.  Retz2 , T.  Supprian1 , M.  Rösler2
  • 1Arbeitsgruppe Gerontopsychiatrie, Universitäts-Nervenklinik und Poliklinik - Psychiatrie und Psychotherapie, Universitätskliniken des Saarlandes, Homburg/Saar
  • 2Arbeitsgruppe Gerontopsychiatrie, Institut für gerichtliche Psychiatrie und Psychologie, Universitätskliniken des Saarlandes, Homburg/Saar
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Publication History

Publication Date:
04 April 2003 (online)

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Zusammenfassung

Die vorliegende Arbeit beschreibt den Verlauf von kognitiven und nicht kognitiven Symptomen bei Patienten mit Alzheimer-Demenz unter konstanten Behandlungsbedingungen mit einem Azetylcholinesterase-Inhibitor (Rivastigmin) und untersucht Zusammenhänge zwischen kognitiver Beeinträchtigung und nicht kognitiven Symptomen der Erkrankung. Von ursprünglich 91 Patienten konnten bei 44 Patienten mit leicht bis mäßig ausgeprägter Alzheimer-Demenz über den gesamten 2-Jahres-Zeitraum die globale funktionelle Beeinträchtigung (GDS), der kognitive Status (MMSE, ADAS-kog) und Verhaltensauffälligkeiten sowie psychopathologische Symptome (Behave-AD) erhoben werden. Dabei kam es unter der Therapie nach einer Stabilisierung der kognitiven Symptome über den Zeitraum von einem Jahr zu einer langsam voranschreitenden kognitiven Verschlechterung, während die psychopathologischen Phänomene auch nach 2 Jahren noch eine tendenzielle Besserung erkennen ließen und die wahnhafte Symptomatik sogar signifikant abnahm. In der durchgeführten Faktorenanalyse stellten kognitive Störungen als Kernsymptom der Alzheimer-Demenz über den gesamten Krankheitsverlauf einen konstanten Faktor dar und korrelierten mit der globalen Funktionsbeeinträchtigung. Psychopathologische Phänomene zeigten während der Erkrankung eine höhere Variabilität, wobei sich sowohl affektive Störungen in Kombination mit aggressivem Verhalten als auch halluzinatorische Phänomene im Verlauf als annähernd eigenständige Faktoren präsentierten. Damit konnte ergänzend zu anderen Verlaufsuntersuchungen erstmalig auch an Alzheimer-Patienten, die konstant mit einem Azetylcholinesterase-Inhibitor (Rivastigmin) behandelt wurden, gezeigt werden, dass bestimmte psychopathologische Phänomene eigenständige Faktoren im Krankheitsverlauf darstellen können.

Abstract

The course of behavioural and psychotic features of patients with Alzheimer's disease treated with an inhibitor of the acetylcholinesterase (rivastigmine), and their association to cognitive impairment is presented in the study. Standardized examination of global functional deterioration (GDS), cognitive impairment (MMSE) and behavioural or psychotic symptoms (Behave-AD) were performed over two years. We could analyse the complete data from 44 of initially 91 patients with mild to moderate Alzheimer's disease. The cognitive component (measured by MMSE, ADAS-cog) and the functional assessment (GDS) showed a continuous decline after a one year period of stabilization, in contrast with behavioural and psychotic symptoms, especially delusions, which still improved after treatment of two years. While cognitive items in correlation with functional aspects formed a homogenous factor over the two-year period, psychotic features displayed more variability over time evaluated by factor analysis. Nevertheless mood and anxiety disorder in combination with aggressive behaviour as well as hallucinations formed an independent factor in the course of Alzheimer's disease. In addition to other studies of the course of Alzheimer's disease we could demonstrate that distinct behavioural and psychotic symptoms may also present as independent factors in Alzheimer patients under constant treatment conditions with an inhibitor of the acetylcholinesterase (rivastigmine).

Literatur

  • 1 Guo Z, Fratiglioni L, Zhu L, Fastbom J, Winblad B, Viitanen M. Occurrence and Progression of Dementia in a Community Population Aged 75 Years and Older.  Arch Neurol. 1999;  56 991-996
    CrossrefPubMedSearch in Google Scholar
  • 2 Wernicke T F, Reischies F M. Prevalence of dementia in old age: Clinical diagnosis in subjects aged 95 years and older.  Neurology. 1994;  44 250-253
    PubMedSearch in Google Scholar
  • 3 Mega M S, Cummings J L, Fiorello T, Gornbein J. The spectrum of behavioral changes in Alzheimer's disease.  Neurology. 1996;  46 130-135
    CrossrefPubMedSearch in Google Scholar
  • 4 Drevets W C, Rubin E H. Psychotic symptoms and the longitudinal course of senile dementia of the Alzheimer type.  Biol Psychiatry. 1989;  25 39-48
    CrossrefPubMedSearch in Google Scholar
  • 5 Rosen J, Zubenko G S. Emergence of psychosis and depression in the longitudinal evaluation of Alzheimer's disease.  Biol Psychiatry. 1991;  29 224-232
    CrossrefPubMedSearch in Google Scholar
  • 6 Haupt M, Romero B, Kurz A. Delusions and hallucinations in Alzheimer's disease: results from a two-year longitudinal study.  Int J Geriatr Psychiat. 1996;  11 965-972
    CrossrefPubMedSearch in Google Scholar
  • 7 Devanand D P, Jacobs D M, Tang M X, Del Castillo-Castaneda C, Sano M, Marder K, Bell K, Bylsma F W, Brandt J, Albert M, Stern Y. The course of psychopathologic features in mild to moderate Alzheimer disease.  Arch Gen Psychiatry. 1997;  54 257-263
    PubMedSearch in Google Scholar
  • 8 Haupt M, Jänner M, Ebeling S, Stierstorfer A, Kretschmar C. Presentation and stability of noncognitive symptom patterns in patients with Alzheimer's disease.  Alz Dis Ass Dis. 1998;  12 323-329
    PubMedSearch in Google Scholar
  • 9 Steele C, Rovner B, Chase G A, Folstein M. Psychiatric symptoms and nursing home placement of patients with Alzheimer's disease.  Am J Psychiatry. 1990;  147 1049-1051
    PubMedSearch in Google Scholar
  • 10 Haupt M, Kurz A. Predictors of nursing home placement in patients with Alzheimer's disease.  Int J Geriatr Psychiat. 1993;  8 741-746
    CrossrefPubMedSearch in Google Scholar
  • 11 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
    CrossrefPubMedSearch in Google Scholar
  • 12 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
    CrossrefPubMedSearch in Google Scholar
  • 13 Rösler M, Anand R, Cicin-Sain A, Gauthier S, Agid Y, Dal-Bianco P, Stähelin H B, Hartman R, Gharabawi M. Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial.  BMJ. 1999;  318 633-638
    PubMedSearch in Google Scholar
  • 14 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
    CrossrefPubMedSearch in Google Scholar
  • 15 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
    PubMedSearch in Google Scholar
  • 16 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 Neurology. 1998/1999;  11 211-216
    PubMedSearch in Google Scholar
  • 17 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
    PubMedSearch in Google Scholar
  • 18 Mc Khann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan E M. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease.  Neurology. 1984;  34 936-944
    PubMedSearch in Google Scholar
  • 19 Folstein M F, Folstein S E, McHugh P R. “Mini Mental State”. A practical method for grading the cognitive state of patients for the clinician.  J Psychiatric Res. 1975;  12 1-22
    CrossrefPubMedSearch in Google Scholar
  • 20 Mohs R C, Rosen W G, Davis K L. Defining treatment efficacy in patient with Alzheimer's disease: A report of progress in research. Edited by Corkin S, Davis KL, Growdon JH et al. New York: Raven Press 1982
    Search in Google Scholar
  • 21 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. 5) 9-15
    PubMedSearch in Google Scholar
  • 22 Reisberg B, Ferris S, de Leon M, Crook T. Global Deterioration Scale (GDS).  Psychopharmacol Bull. 1988;  24 661-663
    PubMedSearch in Google Scholar
  • 23 Birkett D P. The psychiatric differentation of senility and arteriosclerosis.  Br J Psychiatry. 1972;  120 321-325
    PubMedSearch in Google Scholar
  • 24 Leuchter A F, Spar J E. The late onset psychoses.  J Nerv Ment Disord. 1985;  173 488-494
    PubMedSearch in Google Scholar
  • 25 Ballard C, Oyebode F. Psychotic symptoms in patients with dementia.  Int J Geriatr Psychiat. 1995;  10 743-752
    CrossrefPubMedSearch in Google Scholar
  • 26 Cummings J L, Miller B, Hill M A, Neshres R. Neuropsychiatric aspects of multi-infarct dementia and dementia of the Alzheimer-type.  Arch Neurol. 1987;  44 389-393
    PubMedSearch in Google Scholar
  • 27 Rabins P V, Mace N L, Lucas M J. The impact of dementia on the family.  J Am Med Assoc. 1982;  248 333-335
    CrossrefPubMedSearch in Google Scholar
  • 28 Wragg R, Jeste D. Overview of depression and psychosis in Alzheimer's disease.  Am J Psychiatry. 1988;  146 577-587
    PubMedSearch in Google Scholar
  • 29 Gormley N, Rizwan M R, Lovestone S. Clinical predictors of aggressive behaviour in Alzheimer's disease.  Int J Geriatr Psychiat. 1998;  13 109-115
    CrossrefPubMedSearch in Google Scholar
  • 30 Keene J, Hope T, Fairburn C G, Jacoby R, Gedling K, Ware C JG. Natural history of aggressive behaviour in dementia.  Int J Geriat Psychiatry. 1999;  14 541-548
    CrossrefPubMedSearch in Google Scholar
  • 31 Borson S, Raskind M A. Clinical features and pharmacologic treatment of behavioral symptoms of Alzheimer's disease.  Neurology. 1997;  48 (Suppl. 6) S17-S24
    PubMedSearch in Google Scholar
  • 32 Farlow M, Anand R, Messina Jr J, Hartmann R, Veach J. A 52-week study of the efficacy of rivastigmine in patients with mild to moderately severe Alzheimer's disease.  Eur Neurol. 2000;  44 236-241
    CrossrefPubMedSearch in Google Scholar
  • 33 Rogers S L, Friedhoff L T. Long-term efficacy and safety of donepezil in the treatment of Alzheimer's disease: an interim analysis of the result of a US multicentre open label extension study.  Eur Neuropsychopharmacol. 1998;  8 67-75
    CrossrefPubMedSearch in Google Scholar
  • 34 Weiner M F, Martin-Cock K, Forster 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
    PubMedSearch in Google Scholar
  • 35 Rösler M. The efficacy of cholinesterase inhibitors in treating the behavioural symptoms of dementia.  Int J Clin Pract. 2002;  Supplement 127 20-36
    PubMedSearch in Google Scholar
  • 36 Migliorelli E, Teson A, Sabe L, Petracchi M, Leiguarda R, Starkstein S E. Prevalence and correlates of dysthymia and major depression among patients with Alzheimer's disease.  Am J Psychiatry. 1995;  152 37-44
    PubMedSearch in Google Scholar
  • 37 Haupt M, Kurz A, Jänner M. A 2-year follow-up of behavioural and psychological symptoms in Alzheimer's disease.  Dement Geriatr Cogn Disord. 2000;  11 147-152
    CrossrefPubMedSearch in Google Scholar
  • 38 Hope T, Keene J, Fairburn C G, Jacoby R, McShane R. Natural history of behavioural changes and psychiatric symptoms in Alzheimer's disease.  Br J Psychiatry. 1999;  174 39-44
    PubMedSearch in Google Scholar
  • 39 Burns A, Jacoby R, Levy R. Psychiatric phenomena in Alzheimer's disease. II: Disorders of perception.  Br J Psychiatry. 1990;  157 76-81
    PubMedSearch in Google Scholar
  • 40 Förstl H, Besthorn C, Geiger-Kabisch C, Sattel H, Schreiter-Gasser U. Psychotic features and the course of Alzheimer's disease: relationship to cognitive, electroencephalographic and computerized tomography findings.  Acta Psychiatr Scand. 1993;  87 395-399
    CrossrefPubMedSearch in Google Scholar
  • 41 Patel V, Hope T. Aggessive behaviour in elderly people with dementia: a review.  Int J Geriatr Psychiatry. 1993;  8 457-472
    PubMedSearch in Google Scholar
  • 42 Burns A, Jacoby R, Levy R. Psychiatric phenomena in Alzheimer's disease. IV: Disorders of behaviour.  Br J Psychiatry. 1990;  157 86-94
    PubMedSearch in Google Scholar

Dr. med. T. Wobrock

Universitäts-Nervenklinik und Poliklinik · Psychiatrie und Psychotherapie

66421 Homburg/Saar

Email: thomas.wobrock@uniklinik-saarland.de