Influence of Rivastigmine transdermal on butyrylcholinesterase levels in patients with Alzheimer's disease

Santos, Gustavo Alves Andrade dos; Canineu, Paulo Renato; Gonçalves, Ivair Donizette; Pardi, Paulo Celso

doi:10.1590/S1980-57642011DN05040012

Abstract

Cholinesterase inhibitors (ChE-Is) are among the main drugs approved for the treatment of Alzheimer's disease (AD). Rivastigmine in the form of a transdermal patch is an alternative delivery method, and can give greater treatment compliance.

Objectives:

To conduct a preliminary assessment of the neurocognitive and biological effects of oral and transdermal Rivastigmine in patients with AD and to identify a potential biological marker and demonstrate a possible relationship between esterase levels and behavioral scores of AD patients.

Methods:

Forty patients with AD were treated with cholinesterase inhibitors (ChE-Is), evaluated using the MMSE and NPI, and simultaneously sampled to determine their serum levels of AChE and BuChE for 180 days.

Results:

The differences obtained between oral and transdermal forms, as assessed by the MMSE and NPI scores of the AD patients, were not significant at the three time points examined (0, 90, and 180 days). However, serum BuChE levels of the transdermal group differed significantly (p<0.0004) compared with those of the oral group at 90 days.

Conclusion:

Use of a transdermal ChE-I, rivastigmine tartrate significantly reduced BuChE levels in the AD patients studied.

Key words:
Alzheimer's disease; rivastigmine; acetylcholine; Mini Mental State Examination; Neuropsychiatric Inventory; esterases.

Resumo

Os inibidores das colinesterases estão entre as principais drogas aprovadas para tratamento da doença de Alzheimer (DA). Rivastigmina na forma de adesivo transdérmico é um método alternativo de liberação e pode fornecer uma maior aderância ao tratamento.

Objetivos:

Conduzir uma abordagem preliminar dos efeitos neurocognitivos e biológicos da rivastigmina oral e transdérmica em pacientes com DA e identificar um potencial marcador biológico e demonstrar uma possível relação entre níveis de esterases e escores de comportamento de pacientes com DA.

Métodos:

Quarenta pacientes com DA com inibidores de colinesterases foram avaliados usando o MEEM e o INP e colhidas amostras para determinar seus níveis séricos de AChE e BuChE por 180 dias.

Resultados:

As diferenças obtidas entre as formas oral e transdérmica, avaliadas pelo MEEM e INP não diferiram em três ocasiões (0, 90 e 180 dias). Todavia, os níveis de BuChE no grupo transdérmico diferiu significativamente (p<0.0004) comparados ao grupo de administração oral em 90 dias.

Conclusão:

O uso do tartarato de rivastigmina, forma transdérmica reduziu significativamente os níveis de BuChE nos pacientes estudados com DA.

Palavras-chave:
doença de Alzheimer; rivastigmina; acetilcolina; Mini Exame do Estado Mental; Inventário Neuropsiquiátrico; esterases.

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References

Assal F, Cummings JL. Neuropsychiatric symptoms in the dementias. Curr Opin Neurol 2002;15:445-450.
Canineu, PR, Canineu RFB, Canineu PRB, Silva MC. Terapia Multidisciplinar: uma proposta de tratamento global do idoso. Mundo Saude 2005;29:662-665.
Forlenza OV. Tratamento farmacológico da doença de Alzheimer. Rev Psiq Clín 2005;32:137-148.
Grossberg GT. Cholinesterase inhibitors for the treatment of Alzheimer's disease: getting on and staying on. Curr Ther Res 2003;64:216-235.
Minett TSC, Bertolucci PHF. Terapia colinérgica na doença de Alzheimer. Rev Neurociências 2000;8:11-14.
Trinh NH, Hoblyn J, Mohanty S, Yaffe K. Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta-analysis. JAMA 2003;289:210-216.
Cummings JL. Use of cholinesterase inhibitors in clinical practice. Am J Geriatr Psychiatry 2003;11:131-145.
Danysz W, Parsons CG, Möbius HJ, A Stoffler, G Quack. Neuroprotective and symptomatological action of memantine relevant for Alzheimer's disease - a unified hypothesis on the mechanism of action. Neurotox Res 2000;2:85-98.
Rosler M, Anand R, Cicin-Sain A, et al. Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomized controlled trial. BMJ 1999;318:633-640.
Winblad B, Kawata AK, Beusterien KM et al. Caregiver preference for rivastigmine patch relative to capsules for treatment of probable Alzheimer's disease. Int J Geriatr Psychiatry 2007;22:485-491.
Ellis JM. Cholinesterase inhibitors in the treatment of dementia. JAOA 2005;105:145-158.
"Neuropsychiatric Inventory". Available at Available at http://www.hipocampo.org/npi.asp Accessed 03/12/2010.
» http://www.hipocampo.org/npi.asp
Winblad B, Grossberg G, Frolich L, et al. IDEAL: a 6-month, double-blind, placebo-controlled study of the first skin patch for Alzheimer disease. Neurology 2007;69:14-22.
Almeida OP, Crocco EI. Percepção dos déficits cognitivos e alterações do comportamento em pacientes com doença de Alzheimer. Arq Neuropsiquiatr 2000;58:292-299.
Laks J, Batista EMR, Guilherme ERL, et al. O Mini exame do estado mental em idosos de uma comunidade - dados parciais de Santo Antônio de Pádua, Rio de Janeiro. Arq Neuropsiquiatr 2003;61:782-785.
Ishizaki J, Meguro K, Ambo H, et al. A normative, community-based study of mini-mental state in elderly adults: the effect of age and educational level. J Gerontol B Psychol Sci Soc Sci 1998;53:359-363.
Quesada JJ, Ferrucci L, Calvani D, Valente C, Salani B, Bavazzano A. Formal education as an effect modifier of the relationship between Mini-Mental State Examination Score and IADLs disability in the older population. Aging (Milano) 1997;9:175-179.
Almeida O. Mini exame do estado mental e o diagnóstico de demência no Brasil. Arq Neuropsiquiatr 1998;56:605-612.
Brucki SMD, Nitrini R, Caramelli P, Bertolucci PHF, Okamoto IH. Sugestões para o uso do Mini-Exame do Estado Mental no Brasil. Arq Neuropsipquiatr 2003;61:777-781.
Das UM. Acetylcholinesterase and butyrylcholinesterase as possible markers of low-grade systemic inflammation. Med Sci Monit 2007;13:RA214-221.
Gauthier S, Juby A, Rehel B, Schecter R. EXACT: rivastigmine improves the high prevalence of attention deficits and mood and behaviour symptoms in Alzheimer's disease. Int J Clin Pract 2007;61:886-895.
Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308-2314.
Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology 1997; 48(Suppl 6):S10-16.
Kaplay SS. Acetylcholinesterase and butyrylcholinesterase of developing human brain. Biol Neonate 1976;28:65-73.
Jope RS, Walter-Ryan WG, Alarcon RD, Lally KM. Cholinergic processes in blood samples from patients with major psychiatric disorders. Biol Psychiatry 1985;20:1258-1266.
Giacobini E, Spiegel R, Enz A, Veroff AE, Cutler NR. Inhibition of acetyl-and butyryl-cholinesterase in the cerebrospinal fluid of patients with Alzheimer's disease by rivastigmine: correlation with cognitive benefit. J Neural Transm 2002;109:1053-1065.
Giacobini E. Cholinesterases: new roles in brain function and in Alzheimer's disease. Neurochem Res 2003;28:515-522.
Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L. Association between CSF biomarkers and incipient Alzheimers disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol 2006;5:228-234.

Publication Dates

Publication in this collection
Oct-Dec 2011

History

Received
06 Sept 2011
Accepted
08 Nov 2011

This is an open-access article distributed under the terms of the Creative Commons Attribution License

[1] Assal F, Cummings JL. Neuropsychiatric symptoms in the dementias. Curr Opin Neurol 2002;15:445-450.

[2] Canineu, PR, Canineu RFB, Canineu PRB, Silva MC. Terapia Multidisciplinar: uma proposta de tratamento global do idoso. Mundo Saude 2005;29:662-665.

[3] Forlenza OV. Tratamento farmacológico da doença de Alzheimer. Rev Psiq Clín 2005;32:137-148.

[4] Grossberg GT. Cholinesterase inhibitors for the treatment of Alzheimer's disease: getting on and staying on. Curr Ther Res 2003;64:216-235.

[5] Minett TSC, Bertolucci PHF. Terapia colinérgica na doença de Alzheimer. Rev Neurociências 2000;8:11-14.

[6] Trinh NH, Hoblyn J, Mohanty S, Yaffe K. Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta-analysis. JAMA 2003;289:210-216.

[7] Cummings JL. Use of cholinesterase inhibitors in clinical practice. Am J Geriatr Psychiatry 2003;11:131-145.

[8] Danysz W, Parsons CG, Möbius HJ, A Stoffler, G Quack. Neuroprotective and symptomatological action of memantine relevant for Alzheimer's disease - a unified hypothesis on the mechanism of action. Neurotox Res 2000;2:85-98.

[9] Rosler M, Anand R, Cicin-Sain A, et al. Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomized controlled trial. BMJ 1999;318:633-640.

[10] Winblad B, Kawata AK, Beusterien KM et al. Caregiver preference for rivastigmine patch relative to capsules for treatment of probable Alzheimer's disease. Int J Geriatr Psychiatry 2007;22:485-491.

[11] Ellis JM. Cholinesterase inhibitors in the treatment of dementia. JAOA 2005;105:145-158.

[12] "Neuropsychiatric Inventory". Available at Available at http://www.hipocampo.org/npi.asp Accessed 03/12/2010.
» http://www.hipocampo.org/npi.asp

[13] Winblad B, Grossberg G, Frolich L, et al. IDEAL: a 6-month, double-blind, placebo-controlled study of the first skin patch for Alzheimer disease. Neurology 2007;69:14-22.

[14] Almeida OP, Crocco EI. Percepção dos déficits cognitivos e alterações do comportamento em pacientes com doença de Alzheimer. Arq Neuropsiquiatr 2000;58:292-299.

[15] Laks J, Batista EMR, Guilherme ERL, et al. O Mini exame do estado mental em idosos de uma comunidade - dados parciais de Santo Antônio de Pádua, Rio de Janeiro. Arq Neuropsiquiatr 2003;61:782-785.

[16] Ishizaki J, Meguro K, Ambo H, et al. A normative, community-based study of mini-mental state in elderly adults: the effect of age and educational level. J Gerontol B Psychol Sci Soc Sci 1998;53:359-363.

[17] Quesada JJ, Ferrucci L, Calvani D, Valente C, Salani B, Bavazzano A. Formal education as an effect modifier of the relationship between Mini-Mental State Examination Score and IADLs disability in the older population. Aging (Milano) 1997;9:175-179.

[18] Almeida O. Mini exame do estado mental e o diagnóstico de demência no Brasil. Arq Neuropsiquiatr 1998;56:605-612.

[19] Brucki SMD, Nitrini R, Caramelli P, Bertolucci PHF, Okamoto IH. Sugestões para o uso do Mini-Exame do Estado Mental no Brasil. Arq Neuropsipquiatr 2003;61:777-781.

[20] Das UM. Acetylcholinesterase and butyrylcholinesterase as possible markers of low-grade systemic inflammation. Med Sci Monit 2007;13:RA214-221.

[21] Gauthier S, Juby A, Rehel B, Schecter R. EXACT: rivastigmine improves the high prevalence of attention deficits and mood and behaviour symptoms in Alzheimer's disease. Int J Clin Pract 2007;61:886-895.

[22] Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308-2314.

[23] Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology 1997; 48(Suppl 6):S10-16.

[24] Kaplay SS. Acetylcholinesterase and butyrylcholinesterase of developing human brain. Biol Neonate 1976;28:65-73.

[25] Jope RS, Walter-Ryan WG, Alarcon RD, Lally KM. Cholinergic processes in blood samples from patients with major psychiatric disorders. Biol Psychiatry 1985;20:1258-1266.

[26] Giacobini E, Spiegel R, Enz A, Veroff AE, Cutler NR. Inhibition of acetyl-and butyryl-cholinesterase in the cerebrospinal fluid of patients with Alzheimer's disease by rivastigmine: correlation with cognitive benefit. J Neural Transm 2002;109:1053-1065.

[27] Giacobini E. Cholinesterases: new roles in brain function and in Alzheimer's disease. Neurochem Res 2003;28:515-522.

[28] Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L. Association between CSF biomarkers and incipient Alzheimers disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol 2006;5:228-234.

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