Vitamin D3 Attenuates Type 3 Diabetic-Associated Cognitive Deficits in Rats through Regulating Neurotrophins and Enhancing Cholinergic Transmission Pathway

Objective: To examine the protective effect of Vitamin D3 against Type 3 diabetes-induced cognitive dysfunction in rats. Materials and Methods: Type 3 diabetes was induced by a high-fat diet plus streptozotocin in rats. Rats were divided into seven groups: negative control, positive control, Vitamin D3 groups (100, 500 and 1000 IU/kg/day), Vitamin D3 plus rivastigmine, and rivastigmine monotherapy. A radial arm maze test was used to assess cognitive function. Levels of acetylcholinesterase (AChE), dopamine (DA), nerve growth factor, neurotrophin-3 (NT-3), and glial cell line-derived neurotrophic factor (GDNF) in the hippocampus were estimated by the enzyme-linked immunosorbent assay kits. Results: Chronic treatment with Vitamin D3 significantly (P < 0.05) and dose dependently alleviated cognitive deficits, with enhancing cholinergic transmission pathway activity through attenuated hippocampal AChE and increased DA level (P < 0.001). Moreover, Vitamin D3 significantly increased (P < 0.001) neurotrophin levels as an underlying mechanism for the resulted improvement. Conclusion: Vitamin D3 plus rivastigmine (combined group) is better than Vitamin D (100 and 500 mg/kg/day) for improvement of AChE, DA, NT-3, and GDNF levels. Vitamin D (500 and 1000 IU/kg/day) was effective as a combined group in terms of the behavioral test.

Toxicidad cardiovascular por parches transdérmicos de rivastigmina. A propósito de dos casos clínicos / Cardiovascular toxicity by rivastigmine transdermal patches. Two case report / Toxicidade cardiovascular por adesivos transdérmicos de rivastigmina. Relato de dois casos

Resumen: La rivastigmina, fármaco anticolinesterásico, mejora la neurotransmisión colinérgica y es utilizado en el tratamiento de las enfermedades de Alzheimer y de Parkinson. En el Centro de Información y Asesoramiento Toxicológico se han registrado casos de intoxicación por el uso de parches transdérmicos de rivastigmina, los cuales han aumentado en número en el último tiempo. Presentamos dos casos clínicos de intoxicación aguda por parches transdérmicos de rivastigmina en los que se constataron arritmias cardíacas graves, asociando un descenso de colinesterasa plasmática. Se destacan los riesgos del uso de esta medicación con el fin de estar atentos a los primeros síntomas de intoxicación, poder actuar en forma oportuna y prevenir nuevos eventos.

Summary: Rivastigmine, an anticholinesterase drug, improves cholinergic neurotransmission and is used in the treatment of Alzheimer's and Parkinson's diseases. In the Center for Information and Toxicological Advice there have been cases of intoxication due to the use of transdermal rivastigmine patches, which have increased in recent times. We present two clinical cases of acute intoxication by transdermal patches of rivastigmine in which serious cardiac arrhythmias were found, associating a decrease in plasma cholinesterase. The risks of the use of this medication are highlighted in order to be attentive to the first symptoms of intoxication, to be able to act timely and to prevent new events.

Resumo: A rivastigmina, um anticolinesterásico, melhora a neurotransmissão colinérgica e é usada no tratamento das doenças de Alzheimer e Parkinson. No Centro de Informação e Conselhos Toxicológicos, houve casos de intoxicação devido ao uso de adesivos transdérmicos de rivastigmina, que aumentaram nos últimos tempos. Se apresentam dois relatos de caso de intoxicação aguda por adesivos transdérmicos de rivastigmina. Em ambos os casos, foram encontradas arritmias cardíacas graves, associando uma diminuição na colinesterase plasmática. Os riscos do uso desse medicamento são destacados para estar atento aos primeiros sintomas de intoxicação, para poder atuar de forma oportuna e prevenir novos eventos.

Effect of compound Haishe capsule combined with rivastigmine on serum thyroid hormone, inflammatory factor and coagulation function in patients with Alzheimer's disease / 中国基层医药

Objective@#To investigate the effects of compound Haishe capsule combined with rivastigmine capsule on serum thyroid hormone, inflammatory factors and coagulation function in patients with Alzheimer's disease(AD).@*Methods@#From January 2016 to January 2018, 74 patients with AD in the Seventh People's Hospital of Hangzhou were randomly divided into control group and observation group according to the digital table, with 37 cases in each group.The control group was treated with rivastigmine capsule, while the observation group was treated with compound Haishe capsule on the basis of the control group.The two groups were treated for 6 months.The therapeutic effects of the two groups were compared.The changes of BEHAVE-AD and ADAS-Cog scores, thyroid hormones, inflammatory factors and coagulation function were compared before and after treatment.@*Results@#The total effective rate of the observation group was 94.59%(35/37), which was higher than 72.97%(27/37) of the control group(u=6.366, P<0.05). After treatment, the scores of BEHAVE-AD and ADAS-Cog in the observation group were (4.87±0.64)points, (14.28±1.82)points, respectively, which were lower than those in the control group[(8.91±1.07)points, (18.93±1.25)points](t=19.710, 12.811, all P<0.05). After treatment, the level of FT4 in the observation group was (13.09±0.71)pmol/L, which was higher than (12.30±0.52)pmol/L in the control group (t=5.460, P<0.05). After treatment, the levels of CRP and IL-6 in the observation group were (2.13±0.38)mg/L, (31.32±5.64)ng/L, respectively, which were lower than those in the control group[(3.47±0.61)mg/L, (58.93±12.15)ng/L](t=11.342, 12.538, all P<0.05). After treatment, the levels of D-dimer and Fib in the observation group were (519.82±10.29)μg/L, (3.21±0.32)ng/L, respectively, which were lower than those in the control group[(552.31±8.31)μg/L, (4.12±0.49)ng/L](t=14.942, 9.458, all P<0.05).@*Conclusion@#Compound Haishe capsule combined with rivastigmine capsule is effective in the treatment of AD, and can improve thyroid hormone and coagulation function, and reduce the level of inflammatory factors.

Effect of compound Haishe capsule combined with rivastigmine on serum thyroid hormone, inflammatory factor and coagulation function in patients with Alzheimer＇s disease / 中国基层医药

Objective To investigate the effects of compound Haishe capsule combined with rivastigmine capsule on serum thyroid hormone ,inflammatory factors and coagulation function in patients with Alzheimer＇s disease (AD).Methods From January 2016 to January 2018,74 patients with AD in the Seventh People＇s Hospital of Hangzhou were randomly divided into control group and observation group according to the digital table ,with 37 cases in each group.The control group was treated with rivastigmine capsule ,while the observation group was treated with compound Haishe capsule on the basis of the control group.The two groups were treated for 6 months.The therapeutic effects of the two groups were compared.The changes of BEHAVE-AD and ADAS-Cog scores,thyroid hormones,inflammatory factors and coagulation function were compared before and after treatment.Results The total effective rate of the observation group was 94.59%(35／37),which was higher than 72.97%(27／37) of the control group(u＝6.366,P＜0.05).After treatment, the scores of BEHAVE -AD and ADAS -Cog in the observation group were (4.87 ± 0.64)points,(14.28 ±1.82 ) points, respectively, which were lower than those in the control group [( 8.91 ± 1.07)points,(18.93 ±1.25)points] ( t＝19.710,12.811,all P＜0.05).After treatment,the level of FT4 in the observation group was (13.09 ±0.71) pmol／L,which was higher than (12.30 ±0.52) pmol／L in the control group (t＝5.460,P＜0.05).After treatment,the levels of CRP and IL-6 in the observation group were (2.13 ±0.38)mg／L, (31.32 ±5.64)ng／L,respectively,which were lower than those in the control group [(3.47 ±0.61) mg／L,(58.93 ± 12.15)ng／L](t＝11.342,12.538,all P＜0.05).After treatment,the levels of D-dimer and Fib in the observation group were (519.82 ±10.29) μg／L,(3.21 ±0.32) ng／L,respectively,which were lower than those in the control group[(552.31 ±8.31) μg／L,(4.12 ±0.49) ng／L] ( t＝14.942,9.458,all P＜0.05).Conclusion Compound Haishe capsule combined with rivastigmine capsule is effective in the treatment of AD , and can improve thyroid hormone and coagulation function ,and reduce the level of inflammatory factors.

Rivastigmine prevents injury induced by ischemia and reperfusion in rat liver

Abstract Purpose: To evaluate whether pre-treatment with rivastigmine is able to attenuate the I/R induced lesions in rat liver. Methods: SHAM animals or those submitted to I/R, non-treated or pre-treated with rivastigminine (2mg/kg) either 50 or 15 minutes before ischemia, were used. After I/R protocol, these animals were killed and their livers were harvested to measurement of the mitochondrial swelling as well as the malondialdehyde (MDA), nitrite and nitrate tissue concentration. Blood was also harvested for serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) determinations. Results: I/R promoted a significant increase of mitochondrial swelling in the studied animals. This increase of mitochondrial swelling was partially prevented by rivastigmine, but only if administered 50 minutes before ischemia. No significant modification of MDA, nitrite or nitrate tissue concentrations was observed in consequence of I/R, followed or not by rivastigmine treatments. In addition, I/R elevated both AST and ALT. These elevations of serum enzymes were not reversed by the different rivastigmine treatments. Conclusions: Rivastigmine administered 50 minutes before ischemia attenuates I/R-induced mitochondrial swelling, that indicates liver injury. This protective effect may be related to a greater stimulation of α7nAChR present in the Kupffer cells by the non-methabolized ACh, leading to an attenuation of I/R-induced inflammation.

Determination of Donepezil and Rivastigmine in Human Serum by High-performance Liquid Chromatogra-phy Combined with Mass Spectrum / 中国药师

Objective: To develop an LC-MS/MS method for the determination of donepezil and rivastigmine in human serum. Methods: After protein precipitation with 600μl acetonitrile, the serum samples were analyzed by LC-MS/MS. Using loratadine as the internal standard, a Waters Xselect CSH C18(150 mm×3 mm, 2. 5 μm) column was used with the mobile phase consisting of water (containing 10 mmol·L-1ammonium acetate)-acetonitrile(20 ∶ 80)at a flow rate of 0. 4 ml·min-1with the column temperature at 40 ℃. The ion transitions were performed in a positive electrospray ionization multiple reaction-monitoring mode regarding [M+H] +as the molecular ion peak of donepezil and rivastigmine monitored with m/z 380. 1→m/z 91. 1 and m/z 251→m/z 206. 5, respectively. The internal standard was monitored with m/z 383. 1→m/z 337. 1. Results: The linear range of donepezil and rivastigmine was 0. 5-400 ng·ml-1(r>0. 99) and the lowest quantification limit was 0. 5 ng·ml-1. For donepezil, the intra-day and inter-day RSD was 2. 06% to 12. 51% , the relative error was -6. 60% to 4. 20% , and the relative recovery was ranged from 80. 76% to 96. 17% (RSD<15% ). For rivastigmine, the intra-day and inter-day RSD was 1. 69% to 9. 31% , the relative error was -5. 58% to 5. 20% , and the mean relative recovery was ranged from 96. 69% to 100. 15% (RSD<15% ). For the two compounds, the serum samples were stable at -40℃ for 75 d and kept stable after three repeated freeze-thaw cycles. The prepared samples were stable in the automatic sample injector (4℃) for 5 h (RSD<15% ). Conclusion: The developed assay method can be applied in the therapeutic monitoring and pharmacokinetic study of donepezil and rivastigmine in human serum.

Evaluation of Acute and Chronic Effects of D-Galactose on Memory and Learning in Wistar Rats

OBJECTIVE: D-galactose has been commonly used in rodent models to induce accelerated effects of aging, including those on learning, memory, and muscular tone and coordination. This is normally seen on chronic administration of D-galactose. However, there is minimal suggestive evidence on the short-term effects of the same. The aim of the study was to study the acute and chronic effects of D-galactose on learning and memory in Wistar rats. METHODS: Twenty four male Wistar rats were randomly assigned to the control, standard (rivastigmine), oral D-galactose (200 mg/kg/day) and subcutaneous D-galactose (200 mg/kg/day) for a total duration of 8 weeks. Effects on learning and memory were assessed at 2 weeks, 4 weeks and 8 weeks by Morris water maze model and passive avoidance testing. RESULTS: Both oral and subcutaneous D-galactose showed positive effects on learning and memory on acute dosing, whereas this beneficial effect was lost during chronic dosing. CONCLUSION: Short-term administration of D-galactose showed positive effects, while long-term administration nullified these effects.

Therapeutic Progress of Mental Diseases ( Fourth):Alzheimer's Disease / 医药导报

Alzheimer's disease ( AD) is the most common type of dementia. Currently, there is a lack of drugs that could effectively slow and halt the progression of AD. The present review describes the advancements in the treatment of AD, mainly including drugs for symptomatic control, drugs that control the behavioral and psychological symptoms of dementia, and some other drugs for AD and the non-pharmaceutical treatments. It is hoped that early diagnosis, early intervention and comprehensive therapy could relieve the symptoms and slow the progression of AD.

Therapeutic Progress of Mental Diseases ( Fourth):Alzheimer's Disease / 医药导报

Alzheimer's disease ( AD) is the most common type of dementia. Currently, there is a lack of drugs that could effectively slow and halt the progression of AD. The present review describes the advancements in the treatment of AD, mainly including drugs for symptomatic control, drugs that control the behavioral and psychological symptoms of dementia, and some other drugs for AD and the non-pharmaceutical treatments. It is hoped that early diagnosis, early intervention and comprehensive therapy could relieve the symptoms and slow the progression of AD.

Clinical efficacy and adverse effects of nimodipine combined with rivastigmine in the treatment of senile vascular dementia / 中国基层医药

Objective To learn the clinical efficacy and adverse effects of nimodipine combined with riva stigmine in the treatment of senile vascular dementia,and to provide effective treatment for the disease.Methods 151 elderly patients with senile vascular dementia were randomly divided into observation group (78 cases) and control group (73 cases) by using the random number table method.The control group was given nimodipine,and the observation group was given nimodipine combined with rivastigmine.The cognitive function was assessed by mini mental state examination(MMSE) scale,clinical dementia rating (CDR) scale was used to evaluate the degree of dementia,and activity of daily living (ADL) scale was used to evaluate the ability of daily activities.P300 test was performed before and after treatment for 12 weeks,and latency period (P300-PL) and amplitude (P300-A) of P300 were determined.The adverse drug reactions of the two groups were observed during the treatment period.Results After 12 weeks of treatment,the MMSE scores of the two groups were higher than before treatment,the CDR,ADL scores of the two groups were significantly lower than before treatment (t =8.353,18.289,6.627,2.463,10.681,5.201,all P ＜ 0.05).After 12 weeks of treatment,the MMSE score of the observation group [(23.17 ±3.95) points] was significantly higher than that of the control group [(19.88 ± 4.43) points],the ADL,CDR scores of the observation group were (1.47 ± 0.26) points and (39.87 ± 7.43) points,which were significantly lower than (1.80 ± 0.34) points,(41.16 ± 6.40) points of the control group (t =4.823,6.725,5.278,all P ＜ 0.05).After 12 weeks of treatment,the P300-PL of the two groups were lower than those before treatment,the P300-A of the two groups were significantly higher than those before treatment (t =12.051,6.429,2.477,2.104,all P ＜ 0.05).After 12 weeks of treatment,P300-PL of the observation group [(321 ± 39)ms] was significantly lower than that of control group [(356 ± 44) ms] (t =5.180,P ＜ 0.05).In the course of treatment,the incidence rate of adverse reaction of the control group was 9.59％,that of the observation group was 11.54％,there was no statistically significant difference (x2 =0.151,P ＞ 0.05).Conclusion Nimodipine combined with rivastigrnine can effectively treat senile vascular dementia,improve cognitive function,degree of dementia and daily activity ability of patients,the incidence rate of adverse drug reaction is low,and the therapeutic method is well tolerated with good clinical application value.

Intranasal absorption of rivastigmine hydrogen tartrate and brain targeting evaluation / 药学学报

To investigate factors influencing the intranasal absorption of rivastigmine hydrogen tartrate (RHT), we studied the pharmacokinetics of RHT after intranasal administration and evaluated its brain targeting behavior. In situ rat nasal perfusion model was used in the study and pH impact was examined on the intranasal absorption of RHT. High performance liquid chromatography (HPLC) method was established to measure RHT concentration in the plasma and brain tissue after intranasal and intravenous administration. The pharmacokinetic parameters, drug targeting index (DTI), and nose-to-brain direct transport percentage (DTP) were calculated. It was demonstrated that the intranasal absorption mechanism of RHT was passive diffusion. The absorption rate was highest at pH 6.0. The absolute bioavailability of intranasally administrated RHT was 73.58%. Compared with that of intravenous administration, RHT absorption into the brain was faster and more efficient after intranasal delivery, and the DTI value was 195.27% of intravenous injection. Moreover, 48.79% of the drug can be absorbed directly from the nose into the brain without systematic circulation. Meanwhile, drug elimination half-time in the brain was prolonged by 1.4 fold compared to that of intravenous injection. In conclusion, intranasal administration of RHT not only improves drug absorption into the system, but also enhances drug absorption rate and content in the brain remarkably, which is an advantage in the treatment of central nervous system-related diseases.

The Effect of Rivastigmine Transdermal Patch on Sleep Apnea in Patients with Probable Alzheimer's Disease

BACKGROUND AND PURPOSE: This study was designed to evaluate the effect on sleep of rivastigmine transdermal patch in patients with probable Alzheimer's disease (AD). METHODS: Patients with probable AD underwent a sleep questionnaire, overnight polysomnography and neuropsychological tests before and after rivastigmine transdermal patch treatment. We analyzed the data from enrolled patients with AD. RESULTS: Fourteen patients with probable AD were finally enrolled in this study. The respiratory disturbance index after the rivastigmine patch treatment was improved in patients with probable AD and sleep breathing disorder, compared with that of before treatment (p<0.05). CONCLUSIONS: Rivastigmine transdermal patch application are expected to improve the symptoms of sleep disordered breathing in patients with probable AD. Further placebo controlled studies are needed to confirm these results.

An improved preparing process for rivastigmine / 中国药科大学学报

@#An improved manufacturing process for rivastigmine(1)was developed by performing the condensation reaction of m-hydroxyacetophenone(4)with N-ethyl-N-methyl carbamoyl chloride, then Corey-Bakshi-Shibata(CBS)chiral reduction to(R)-3-(1-hydroxyethyl)phenyl ethyl(methyl)carbamate(2)and then mesylation with methanesulfonyl chloride and nucleophilic substitution with dimethylamine, respectively. To be successful, a crucial reductive process in the conversion of ketone(3)to chiralalcohol(2)had to be correctly understood and optimized via orthogonal experiment. The whole improved process was convenient for operation and purification, with completion of the synthesis of rivastigmine and an overall yield of 88%.

Design, synthesis and evaluation of genistein-polyamine conjugates as multi-functional anti-Alzheimer agents

A series of genistein-polyamine conjugates (4a-4h) were designed, synthesized and evaluated as multi-functional anti-Alzheimer agents. The results showed that these compounds had significant cholinesterases (ChEs) inhibitory activity. Compound 4b exhibited the strongest inhibition to acetylcholinesterase (AChE) with an IC50 value of 2.75 μmol/L, which was better than that of rivastigmine (5.60 μmol/L). Lineweaver-Burk plot and molecular modeling study showed that compound 4b targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, compound 4b showed potent metal-chelating ability. In addition, it was found that 4a-4h did not affect HepG-2 cell viability at the concentration of 10 μmol/L.

Factors Influencing Skin Tolerability to the Rivastigmine Patch in Patients with Alzheimer's Disease

BACKGROUND AND PURPOSE: The one-day rivastigmine patch is reportedly well tolerated and has minimal side effects. However, Asian patients show more side effects than those in Western countries. We evaluated tolerability of the rivastigmine patch in South Korean patients with Alzheimer's disease (AD) and the specific factors affecting adverse events of the skin. METHODS: A 6-month, open labeled, multi-centered, observational study was carried out in 440 patients with probable AD from July 2009 to September 2010 (NCT01312363). RESULTS: A total of 25.9% of the patients experienced adverse skin events at the rivastigmine patch application site and 17.0% discontinued treatment due to adverse events at the skin application site. The most common adverse events were itching and erythema. Patients with an allergic history and users of electric heating appliances reported skin discomfort. Older age was associated with discontinuing treatment. CONCLUSION: These results suggest that the rivastigmine patch induced some adverse skin events and may contribute to understanding and improving skin tolerability to the rivastigmine patch.

Estudo de bioequivalência entre duas formulações de rivastigmina cápsulas de 6 mg, em voluntários sadios após administração de dose única / Study of bioequivalence between two formulations of rivastigmine 6 mg capsules, in healthy volunteers after a single dose administration

O estudo foi realizado para comparar a biodisponibilidade/bioequivalência de duas formulações de rivastigmina 6 mg cápsulas (Aché Laboratórios Farmacêuticos S/A, formulação teste, e Exelon® por Novartis Biociências S/A - formulação referência, Brasil) em 56 voluntários de ambos os sexos. O estudo foi realizado através de um desenho aberto, randomizado, cruzado em dois períodos com tempo de washout de 7 dias. As amostras de plasma de 46 dos 56 voluntários inicialmente incluídos foram obtidas ao longo de um intervalo de 12 horas. As concentrações de rivastigmina foram determinadas através de um equipamento LC-MS-MS, utilizando zolpidem como padrão interno. A partir dos dados obtidos calcularam-se os seguintes parâmetros farmacocinéticos: ASC0-t , ASC0-¥ e Cmax. A razão das médias geométricas de Rivastigmina/Exelon® 6 mg foi de 100,97% para ASC0-t, 101,38% para ASC0-¥ e 89,01% para Cmax; os intervalos de confiança de 90% foram de 93,20% - 109,39%, 93,65% - 109,75% e 81,10% - 97,70%, respectivamente. Uma vez que os intervalos de confiança de 90% para Cmax e ASC0-t estiveram dentro da faixa de 80% - 125% proposta pelo FDA e pela ANVISA (Agência Nacional de Vigilância Sanitária do Brasil), conclui-se que a cápsula de rivastigmina 6 mg foi bioequivalente ao comprimido de Exelon® de 6 mg e, dessa forma, o produto teste pode ser considerado intercambiável na prática médica.

Quantitative determination of rivastigmine in rat plasma and tissues by HPLC-MS/MS method / 中国药学杂志

OBJECTIVE: To establish a highly accurate, sensitive and credible high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of rivastigmine in rat plasma and tissues. METHODS: All biological samples were extracted with ethyl acetate. Chromatographic separation was performed on an Agilent C18 column (4.6 mm × 100 mm, 3.5 μm) using water-methanol (20:80) as mobile phase at a flow rate of 0.3 mL · min-1. The MS analysis was performed by multiple reaction monitoring (MRM) with electronic spray ionization source (ESI+) for quantitative response of rivastigmine (251.3 → 206) and the internal standard, antipyrine (189.1 → 106.1) respectively. RESULTS: The calibration curves of rivastigmine in plasma and tissues showed satisfactory linearity, and the relative extraction recovery of three concentrations in plasma and all tissues were over 60% except some individuals and all RSDs met the requirements. The limit of quantification of rivastigmine in plasma and tissues were 0.1 and 0.2 ng · mL-1 respectively. CONCLUSION: The method is rapid, accurate, highly selective and sensitive, and is suitable for the quantitative analysis of rivastigmine in biological sample of rats. Copyright 2012 by the Chinese Pharmaceutical Association.

Efficacy and Safety of Switching from Oral Cholinesterase Inhibitors to the Rivastigmine Transdermal Patch in Patients with Probable Alzheimer's Disease

BACKGROUND AND PURPOSE: The goal of this study was to estimate the efficacy and safety of the rivastigmine transdermal patch in patients with probable Alzheimer's disease (AD) who cannot tolerate or do not respond to oral cholinesterase inhibitors (ChEIs). METHODS: A 24-week, prospective, open-label, single-arm, multicenter study was conducted from June 2009 to June 2010 in patients with probable AD. The enrolled patients had either a poor response or a decline in global function after treatment with oral ChEIs, or they were not able to tolerate treatment with oral ChEIs due to adverse events such as nausea or vomiting. A poor response was defined as a decrease of at least 2 points on the Korean version of the Mini-Mental State Examination (K-MMSE) within the previous 6 months (the decline in global function was determined by the investigator or caregiver). The efficacy of treatment was assessed using a follow-up Clinical Global Impression of Change (CGIC) assessment and K-MMSE conducted after 24 weeks, and safety was measured by the occurrence of adverse events and patient disposition. RESULTS: In total, 164 patients aged 74.7+/-7.52 years (mean+/-SD) and with 5.12+/-3.64 years of education were included. The study was completed by 70% of the patients (n=116), with 12.2% discontinuing due to adverse events. The most frequently reported adverse events (11%) were skin lesions, such as erythema or itching, followed by gastrointestinal problems (1.2%). Either an improvement or no decline in CGIC scores was reported for 82% of the patients. CONCLUSIONS: The immediate switching of patients from an oral ChEI to the rivastigmine transdermal patch without a washout period was safe and well tolerated by the probable-AD patients in this study.

A prospective study on the use of rivastigmine transdermal patch in Alzheimersdementia in a routine clinical setting

There is not much published literature on the use of rivastigmine patch in a "routine" clinical setting. Objectives: In this naturalistic longitudinal observational study we sought to evaluate the safety, tolerability and efficacy of the rivastigmine patch in patients with early and late onset moderate Alzheimer's disease in a routine clinical setting. Methods: Out of all routine clinical referrals, the first 30 patients with diagnosis of moderate Alzheimer's dementia who were started on rivastigmine patch were included in the study. Rivastigmine patch dose was titrated from 4.6 to 9.5 mg/ 24 hours as appropriate. The primary outcome measure was safety and tolerability, measured by the incidence of adverse events and discontinuation due to any reason. The secondary outcome measure was to examine improvement on global, functional and behavioral domains as demonstrated by the MMSE (Mini Mental State Examination) score, BADLS (Bristol Activities of Daily Living Skills) score, patient and carer feedback and clinical judgment. Results: Adverse events were reported in 20% of patients and 10% of total patients needed discontinuation of treatment. Improvement on global, functional and behavioral domains was observed in two thirds of patients whereas one third showed a relative decline. The most common side effect was skin irritation or erythema. Conclusions: The rivastigmine transdermal patch may provide a treatment option for those patients who require a change in their current oral cholinesterase inhibitor therapy due to safety or tolerability concerns.

Não há muita publicação na literatura sobre o uso do adesivo de rivastigmina na prática clínica. Objetivos: Em um estudo observacional longitudinal naturalístico nós tentamos avaliar a segurança, tolerabilidade e eficácia do adesivo transdérmico de rivastigmina em pacientes com doença de Alzheimer moderada de início precoce e tardio. Métodos: Os primeiros 30 pacientes ambulatoriais com DA moderada de clínicas de referência que iniciaram o uso de adesivo de rivastigmina foram incluídos no estudo. A dose foi escalonada de 4,6 a 9,5 mg/24 hs quando apropriado. As medidas de desfecho primário foram a segurança e tolerabilidade medidas pela incidência de eventos adversos e descontinuação por alguma razão. A medida de desfecho secundário foi a melhora global, funcional e comportamental, demonstrada pelos escores do Mini-Exame do Estado Mental (MEEM), escores na escala de Atividade de Vida Diária de Bristol, retorno do paciente e cuidador e julgamento clínico. Resultados: Eventos adversos foram reportados em 20% dos pacientes e 10% deles descontinuaram o tratamento. Melhora em domínios global, funcional e comportamental foi observada em dois terços dos pacientes, enquanto que, no terço restante um declínio relativo foi observado. O efeito colateral mais comum foi irritação ou eritema de pele. Conclusões: O adesivo transdérmico de rivastigmina pode ser uma opção terapêutica para aqueles pacientes que requeiram mudança na sua terapia oral com inibidor da colinesterase devido à sua segurança e tolerabilidade.

El papel de la rivastigmina en la demencia de origen vascular / The definition of its role in vascular dementia

Vascular dementia represents the second most common type of dementia. The classification of vascular dementia broadly follows three clinico-pathological processes: multi-infarct dementia, single strategic infarct dementia and subcortical dementia. Currently, no established standard treatment for vascular cognitive impairment exists. Reductions in acetylcholine and acetyltransferase activity are common to both Alzheimer's disease and vascular cognitive impairment raising the possibility that cholinesterase inhibitors may also be beneficial for the latter. This review has been conducted to assess the efficacy of rivastigmine in the treatment of people with vascular cognitive impairment. From existing trial data there is some evidence of benefit of rivastigmine in vascular cognitive impairment. However, this conclusion is based on studies which had small numbers of patients, which sought to compare rivastigmine to treatments other than placebo or which used data extrapolated post hoc from large studies involving patients with Alzheimer's disease and vascular risk factors of unclear significance. From these perspectives, one can conclude that large placebocontrolled, double blind and adequately randomised trials are needed before firm conclusions can and should be drawn. The methodology of such trials should acknowledge the biological and clinical features unique to vascular cognitive impairment and its subtypes

La demencia vascular representa el segundo tipo más frecuente de demencia. La clasificación de la demencia vascular sigue tres procesos clínico-patológicos generales: demencia multiinfarto, demencia por infarto único ubicado en una zona estratégica y demencia subcortical. Actualmente no existen tratamientos estandarizados establecidos para los trastornos cognitivos de causa vascular. La disminución de la actividad de la acetilcolinesterasa es una estrategia habitualmente utilizada tanto para el tratamiento de los pacientes que presentan enfermedad de Alzheimer como para aquellos con trastornos cognitivos de causa vascular. En consecuencia, es posible que los inhibidores de la colinesterasa sean una opción conveniente. La presente revisión se llevó a cabo con el propósito de evaluar la eficacia de la rivastigmina para el tratamiento de los individuos que presentan trastornos cognitivos de origen vascular. De acuerdo con los datos provenientes de diferentes estudios, la rivastigmina sería útil para tratar pacientes con deterioro cognitivo de origen vascular. No obstante, esta conclusión se efectuó sobre la base de estudios en los cuales se incluyó un número reducido de pacientes, se buscó comparar la rivastigmina con agentes diferentes del placebo o se extrapolaron datos a partir de estudios de gran magnitud efectuados con pacientes que presentaban enfermedad de Alzheimer y factores de riesgo vasculares de relevancia poco clara. Desde ese punto de vista, se puede concluir que es necesario realizar estudios de gran tamaño, controlados con placebo a doble ciego y adecuadamente aleatorizados antes de poder alcanzar conclusiones sólidas. La metodología empleada en dichos estudios debería responder a las características biológicas y clínicas particulares del deterioro cognitivo vascular y sus subtipos