CNS Drugs

, Volume 24, Issue 2, pp 163–176 | Cite as

Effects of Donepezil,Galantamine and Rivastigmine in 938 Italian Patients with Alzheimer’s Disease

A Prospective,Observational Study
  • Aurelia Santoro
  • Paola Siviero
  • Nadia Minicuci
  • Elena Bellavista
  • Michele Mishto
  • Fabiola Olivieri
  • Francesca Marchegiani
  • Andrea Maria Chiamenti
  • Luisa Benussi
  • Roberta Ghidoni
  • Benedetta Nacmias
  • Silvia Bagnoli
  • Andrea Ginestroni
  • Osvaldo Scarpino
  • Emidio Feraco
  • Walter Gianni
  • Guido Cruciani
  • Roberto Paganelli
  • Angelo Di Iorio
  • Mario Scognamiglio
  • Luigi Maria Edoardo Grimaldi
  • Carlo Gabelli
  • Sandro Sorbi
  • Giuliano Binetti
  • Gaetano Crepaldi
  • Claudio Franceschi
Original Research Article

Abstract

Background: Acetylcholinesterase inhibitors (AChEIs) have been used to improve cognitive status and disability in patients with mild to moderate Alzheimer’s disease (AD). However, while the efficacy of AChEIs (i.e. how they act in randomized controlled trials) in this setting is widely accepted, their effectiveness (i.e. how they behave in the real world) remains controversial.

Objective: To compare the effects of three AChEIs, donepezil (Aricept®), galantamine (Reminyl®) and rivastigmine (Exelon®), in an Italian national, prospective, observational study representative of the ‘real world’ clinical practice of AChEI treatment for AD.

Methods: 938 patients with mild to moderate AD collected within the framework of the Italian National Cronos Project (CP), involving several UVAs (AD Evaluation Units) spread over the entire national territory, who were receiving donepezil, galantamine or rivastigmine were followed for 36 weeks by measuring: (i) function, as determined by the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) scales; (ii) cognition, as measured by the Mini-Mental State Examination (MMSE) and the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) [primary outcome measures]; and (iii) behaviour, as measured on the Neuropsychiatric Inventory (NPI) and Clinical Dementia Rating (CDR) scale. Moreover, all patients were genotyped for apolipoprotein E (apoE) genetic variants.

Results: No statistically significant improvement in the primary outcome measures (MMSE and ADAS-Cog) was observed with drug therapy at 36 weeks, at which point all groups had lost, on average, 1 point on the MMSE and gained 2–3 points on the ADAS-Cog scale compared with baseline. On the secondary outcome measures at week 36, all treatment groups showed a significant worsening on the ADL and IADL scales compared with baseline, while on the NPI scale there were no significant differences from baseline except for the galantamine-treated group which worsened significantly. Moreover, patients receiving galantamine worsened significantly compared with the donepezil-treated group on the IADL scale. ApoE ε4 allele did not influence the effect of drug therapy.

Conclusion: Over a 36-week follow-up period, no significant difference in the effects of donepezil, galantamine and rivastigmine on a variety of functional and cognitive parameters was observed in a large number of apoE-genotyped patients with mild to moderate AD recruited within the framework of a national project representative of the scenario usually encountered in actual clinical practice in Italy. The limitations (possibility of administration of lower drug doses than are used in clinical trials, relatively short follow-up period and the lack of randomization) and strengths (large number of patients, concomitant observation of the three drugs and the number of parameters assessed, including apoE genotype) of the present study are acknowledged. Our type of naturalistic study should complement clinical trials because ‘real world’ practice operates in the face of the numerous variables (e.g. health status and co-morbidities) associated with a complex disease such as AD in elderly people.

Notes

Acknowledgements

This work was supported by: the PRRIITT (Programme for Industrial Research, Innovation and Technology Transfer) programme of the Emilia-Romagna Region (and Fondi Strutturali Obiettivo 2); the Italian Ministry of Health Grant ‘Progetto Finalizzato Studio delle differenze uomo-donna nei meccanismi patogenetici delle malattie cardiovascolari’; the Italian Ministry of Health Grant ex art 56 533F/B 1; the Italian Ministry of University and Research (MiUR) PRIN 2006 Project (♯2006061707); the Italian Ministry of Health Grant “An integrated approach to identify functional, biochemical and genetic markers in centenarians and Alzheimer’s disease patients”; the University of Bologna Grant ‘Ricerca Fondamentale Orientata (RFO ex 60%) 2005’; and Roberto and Cornelia Pallotti Legacy for Cancer Research Grants to Claudio Franceschi. The authors have no conflicts of interest that are directly relevant to the content of this study.

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Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Aurelia Santoro
    • 1
    • 2
  • Paola Siviero
    • 3
  • Nadia Minicuci
    • 3
  • Elena Bellavista
    • 1
    • 2
  • Michele Mishto
    • 1
    • 2
    • 4
  • Fabiola Olivieri
    • 5
    • 6
  • Francesca Marchegiani
    • 7
  • Andrea Maria Chiamenti
    • 8
  • Luisa Benussi
    • 9
  • Roberta Ghidoni
    • 9
    • 10
  • Benedetta Nacmias
    • 11
  • Silvia Bagnoli
    • 11
  • Andrea Ginestroni
    • 11
  • Osvaldo Scarpino
    • 12
  • Emidio Feraco
    • 13
  • Walter Gianni
    • 14
  • Guido Cruciani
    • 15
  • Roberto Paganelli
    • 16
  • Angelo Di Iorio
    • 16
  • Mario Scognamiglio
    • 17
  • Luigi Maria Edoardo Grimaldi
    • 18
  • Carlo Gabelli
    • 8
  • Sandro Sorbi
    • 10
  • Giuliano Binetti
    • 8
  • Gaetano Crepaldi
    • 3
  • Claudio Franceschi
    • 1
    • 2
  1. 1.Department of Experimental PathologyUniversity of BolognaBolognaItaly
  2. 2.Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity ‘L. Galvani’ (CIG)University of BolognaBolognaItaly
  3. 3.National Council ResearchInstitute of NeurosciencePadovaItaly
  4. 4.Institute of BiochemistryMedical Faculty CharitéBerlinGermany
  5. 5.Department of Molecular Pathology and Innovative TherapyPolytechnic University of AnconaAnconaItaly
  6. 6.Center of CytologyItalian National Research Center on Ageing (INRCA)AnconaItaly
  7. 7.Center of Genetics and Molecular BiologyItalian National Research Center on Ageing (INRCA)AnconaItaly
  8. 8.Research Consortium Luigi Amaducci (CRIC)Arcugnano, VicenzaItaly
  9. 9.NeuroBioGen Lab-Memory ClinicIstituto di Ricovero e Cura a Carattere Scientifico (IRCCS) ‘Centro S. Giovanni di Dio-FBF’BresciaItaly
  10. 10.Proteomics UnitIstituto di Ricovero e Cura a Carattere Scientifico (IRCCS) ‘Centro S. Giovanni di Dio-FBF’BresciaItaly
  11. 11.Department of Neurological and Psychiatric SciencesUniversity of FlorenceFlorenceItaly
  12. 12.Neurology UnitGeriatric Hospital, Italian National Research Center on Ageing (INRCA)AnconaItaly
  13. 13.Italian National Research Center on Ageing (INRCA)CosenzaItaly
  14. 14.Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)Italian National Research Center on Ageing (INRCA)RomeItaly
  15. 15.Italian National Research Center on Ageing (INRCA)FermoItaly
  16. 16.Department of Medicine and Sciences of Aging, Laboratory of Clinical EpidemiologyUniversity G. D’AnnunzioChietiItaly
  17. 17.Department of Elderly AssistanceNaplesItaly
  18. 18.Department of NeurologyFondazione Istituto San Raffaele ‘G. Giglio’ di CefalùCefalùItaly

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