Design, synthesis and evaluation of 5-aminobenzimidazolone derivatives as acetylcholinesterase inhibitors / 药学学报

The target compounds were prepared from 5-aminobenzimidazolone by two steps reaction, and their AChE inhibitory activities were measured by Ellman method in vitro. The AChE inhibitory activity of compound 4d is the best of them, and its IC50 value is equal to 7.2 μmol·L(-1), which is better than that of rivastigmine; moreover the 4d had no inhibitory activities to BuChE. Therefore, the inhibitory activities of 5-aminobenzimidazolone derivatives to acetylcholinesterase are worth further researching.

Vascular O-GlcNAcylation augments reactivity to constrictor stimuli by prolonging phosphorylated levels of the myosin light chain

O-GlcNAcylation is a modification that alters the function of numerous proteins. We hypothesized that augmented O-GlcNAcylation levels enhance myosin light chain kinase (MLCK) and reduce myosin light chain phosphatase (MLCP) activity, leading to increased vascular contractile responsiveness. The vascular responses were measured by isometric force displacement. Thoracic aorta and vascular smooth muscle cells (VSMCs) from rats were incubated with vehicle or with PugNAc, which increases O-GlcNAcylation. In addition, we determined whether proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation. PugNAc enhanced phenylephrine (PE) responses in rat aortas (maximal effect, 14.2±2 vs 7.9±1 mN for vehicle, n=7). Treatment with an MLCP inhibitor (calyculin A) augmented vascular responses to PE (13.4±2 mN) and abolished the differences in PE-response between the groups. The effect of PugNAc was not observed when vessels were preincubated with ML-9, an MLCK inhibitor (7.3±2 vs 7.5±2 mN for vehicle, n=5). Furthermore, our data showed that differences in the PE-induced contractile response between the groups were abolished by the activator of AMP-activated protein kinase (AICAR; 6.1±2 vs 7.4±2 mN for vehicle, n=5). PugNAc increased phosphorylation of myosin phosphatase target subunit 1 (MYPT-1) and protein kinase C-potentiated inhibitor protein of 17 kDa (CPI-17), which are involved in RhoA/Rho-kinase-mediated inhibition of myosin phosphatase activity. PugNAc incubation produced a time-dependent increase in vascular phosphorylation of myosin light chain and decreased phosphorylation levels of AMP-activated protein kinase, which decreased the affinity of MLCK for Ca2+/calmodulin. Our data suggest that proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation, favoring vascular contraction.

Determinación de la sensibilidad a insecticidas organofosforados, carbamato y piretroides en poblaciones de Aedes aegypti Linneaus, 1762 ( Díptera: Culicidae ) de Panamá / Determining the status of susceptibility to organophosphate, carbamate and pyrethroids insecticides in populations of Aedes aegypti Linneaus, 1762 ( Diptera: Culicidae ) in Panamá

Introducción. Se llevó a cabo un estudio para determinar la sensibilidad de Aedes aegypti provenientes de regiones de alto riesgo de transmisión de dengue en Panamá, a insecticidas organofosforados, carbamatos y piretroides. Objetivo. Evaluar la sensibilidad a insecticidas piretroides, organofosforados y carbamatos en poblaciones de Ae. aegypti provenientes de ocho sitios pertenecientes a siete municipios de Panamá. Materiales y métodos. Se recolectaron poblaciones de Ae. aegypti en diferentes tipos de criaderos localizados en áreas urbanas y se criaron en condiciones controladas de laboratorio. Con la generación F 1 de cada una de las cepas se hicieron bioensayos de sensibilidad siguiendo la metodología estandarizada por la Organización Mundial de la Salud para larvas y adultos. Resultados. Las ocho cepas de Ae. aegypti resultaron sensibles a los insecticidas piretroides deltametrina, lambdacihalotrina y ciflutrina, el organofosforado fenitrotión y los carbamato propoxur y bendiocarb. Solo la cepa CHITRE resultó con resistencia moderada al insecticida deltametrina en larvas (FR 50 =5x). Sin embargo, en adultos resultó sensible. Conclusiones. Es necesaria la vigilancia periódica de la sensibilidad de las poblaciones de Ae. aegypti de los municipios evaluados, con el propósito de conservar en las poblaciones el carácter sensible a estos insecticidas. Los insecticidas aplicados para el control de Ae. aegypti pueden seguir siendo utilizados en los municipios evaluados, pero depende de la sensibilidad de los mosquitos en el área específica.

Introduction: We studied the susceptibility to organophosphate, carbamate and pyrethroid insecticides of Aedes aegypti from different regions of high transmission risk for dengue in Panama. Objective: To evaluate the susceptibility to organophosphate, carbamate and pyrethroid insecticides in Ae. aegypti from eight sites belonging to seven municipalities in Panamá. Materials and methods: We collected Ae. aegypti larval populations in different types of breeding sites located in urban areas. Insects were reared in laboratory control conditions. With the F 1 generation of each strain we performed susceptibility bioassays using WHO standardized methodology for larvae and adults. Results: The eight Ae. Aegypti strains were susceptible to the pyrethroid insecticides: deltamethrin, lambdacyhalothrin and cifluthrin, to the organophosphate fenitrothrion, and to the carbamates propoxur and bendiocarb. Only the CHITRE strain exhibited a moderate resistance to the insecticide deltamethrin in larvae (FR 50 =5x). However, adults were susceptible. Conclusions: It is necessary to perform periodic surveillance to evaluate the susceptibility of Ae. aegypti populations in the studied municipalities with the purpose of preserving their susceptible. The insecticides applied for Ae. aegypti control can still be used in the evaluated municipalities; however it will depend on the susceptibility of the mosquitoes in the specific area.

Medicamentos utilizados para trastornos cognitivos: Análisis de un millón y medio de prescripciones en la Argentina / Drugs used for cognitive impairment: Analysis of 1.5 million prescriptions in Argentina

Los costos originados por trastornos cognitivos y demencias son significativos para los sistemas de salud. Según guías nacionales e internacionales, los fármacos recomendados para su tratamiento son inhibidores de colinesterasa (donepecilo, galantamina y rivastigmina) y memantina. En la Argentina también son utilizados otros nootrópicos, galantamina, rivastigmina, vasodilatadores, vitaminas y antioxidantes. El objetivo del presente estudio es describir y comparar el patrón de prescripción de drogas para el tratamiento de trastornos cognitivos y demencias en las distintas regiones del país. Se realizó un estudio observacional retrospectivo a partir de las prescripciones (1 814 108 envases) realizadas en la práctica clínica habitual durante el segundo semestre del 2008 y el primer y segundo semestre del 2009. El trabajo fue realizado sobre la población total del Instituto Nacional de Servicios Sociales para Jubilados y Pensionados. Se analizaron variables demográficas, cantidad y tasa de prescripciones, presentaciones y dosis utilizadas por regiones. Considerando todo el país, memantina fue la droga más prescripta en esos períodos, con un total de 570 893 envases. Memantina, donepecilo, rivastigmina e idebenona presentaron un incremento en las tasas de prescripción 2008-2009. Analizando los cambios regionales en tasas de prescripción, la memantina aumentó en el Noroeste y Noreste argentino, la idebenona en el Noroeste y la Patagonia y el donepecilo en el Noreste. Grupos de fármacos no recomendados fueron altamente prescriptos en todas las regiones del país. Algunos fueron indicados en adultos jóvenes o de mediana edad.

Cognitive impairment and dementia treatment costs are significant for health systems. According to national and international guidelines, recommended drugs for treatment of dementias are cholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine. Despite these guidelines recommendations, other nootropics, vasodilators and antioxidants are often used in Argentina. The purpose of this study was to describe and compare the prescription pattern of commonly used drugs for the treatment of cognitive disorders and dementia in different regions of Argentina. An observational, retrospective study of 1 814 108 recipes prescribed to National Institute of Social Services for Retired and Pensioners outpatients during the during the second half of 2008 and the first and second half of 2009 was performed, taking in count the whole country and also different Argentina´s regions. Demographic variables, quantity and rate of prescriptions, dosage forms and strengths were analyzed. Considering the entire country, memantine was the most prescribed drug in these periods (570 893 packages). An increase in the memantine, donepezil, rivastigmine and idebenone rates of prescription was observed. Prescription rate of memantine increased in the North-West and North-East regions, that of idebenone in the North-East region and Patagonia and donepezil in the North-East region. Non recommended drugs were highly prescribed in all the analyzed regions. Some of them were indicated to young and middle-aged patients.

[Comparison of PBO and DEF effects on creating bendiocarb and carbaryl insecticide resistance in German cockroach]

German cockroach [Blattella germanica, Blattodea:Blattellidae] is considered one of the common pests in hospitals, hotels, households and dormitories which can transfer different pathogenic fungi, viruses and bacteria. The aim of this study was to determine the resistance mechanisms to bendiocarb and carbaryl in German cockroache, in vivo. In this study, German cockroach strains were collected from several hospitals and dormitories in Tehran and transferred to insectarium. The strains were reared under the same laboratory conditions. At first the discriminative doses of bendiocarb and carbaryl were determined by surface contact method. Then the susceptibility level and types of resistance mechanisms to bendiocarb and carbaryl, in the strains were studied by using PBO and DEF as synergists. Simultaneous use of DEF as synergist, with bendiocarb and carbaryl led to the breakdown of resistance in all strains. But use of PBO instead of DEF did not overcome the resistance in the strains collected from Mofid, Alvand and Vali Asr hospitals and Shariati dormitory. In general, the effect of DEF in breaking the resistance was more than that of PBO. Complete breakdown of resistance after simultaneous use of DEF with bendiocarb and carbaryl insecticides, indicated the essential role of esterase enzymes in producing resistance to bendiocarb and carbaryl in the strains. But PBO did not break the resistance completely in most wild strains, which may be due to other possible mechanisms of resistance such as reduction of cuticle penetration or insensitivity to acetyl cholinesterase enzyme

Field studies on dominant rodents and the efficacy of certain insecticides to their fleas in Dakahlia governorate, Egypt

A preliminary survey of domestic rodent and the efficacy of bendiocarb, diazi-non and pirimiphos-methyl insecticides to their fleas were carried out in Dakahlia Governorates [Aga, Meet-Ghamr, El-Senbellawen, Temi El-Amded, Eeni-Abed, Dekernes, Nabarow, Talkha, Menia El-Nasr and El-Kordy]. Rodent index [number of rodent /trap] and percentage frequency of drodent species were recorded from October 2010 to May 2011. The main rodent species found were the Norway rat, Rattus norvegicus, the grey-bellied rat, R, rattus alex-andrinus, the white-bellied rat, R. r. frugivorus and the house mouse, Mus muscu-lus. The rodent index at Beni-Abed, Nabarow, Meet-Ghamr, Dekernes and El-Kordy centers showed 0.46, 0.39, 0.34, 0.33 and 0.33, respectively, while Menia El-Nasr center showed the lowest [0.08]. Aga, Talkha, El-Senbellawen, and Temi El-Amded centers showed moderate [0.25, 0.21, 0.2 and 0.16, respectively]. The com-monest flea species was the oriental rat flea, Xenopsylla cheopis, the mouse flea, Leptopsylla segnis, the dog flea, Ctenocephalides canis and the sticktight flea Echidnophaga gallinacea. The highest number of fleas was on R. norvegicus [Flea index=10.9] while lowest number was on Mus musculus [Flea index=0.1]. X. cheopis was the highest frequency distributed for all domestic rodent species [60.9%], while, C. canis was the lowest [1.6%]. The results showed tfiat bendiocarb was effective [Lc5o=0.389%] than diazinon [Lc5o=1.039%] and pirimiphos-methyl [Lc5o -2.056%]

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.

Preparation of rivastigmine liposome and its pharmacokinetics in rats after intranasal administration / 药学学报

To prepare rivastigmine liposome, rivastigmine was loaded into liposome via ammonium sulfate gradient method. Its pharmacokinetic profile in rats was evaluated after intranasal administration. The size, zeta potential, entrapped efficiency and release of rivastigmine from the liposome in vitro were determined. Plasma concentration of rivastigmine was determined by high performance liquid chromatography-tandem mass spectrometry (HPLC/MS) using antipyrine as internal standard. The pharmacokinetic parameters were calculated by DAS 2.0. The entrapped efficiency of rivastigmine liposome was (33.41 +/- 6.58) %, with the mean diameter of 154-236 nm and zeta potential of (-10.47 +/- 2.41) mV. The release behavior of rivastigmine was fitting the first order equation in vitro. The pharmacokinetic studies indicated that the C(max), T(max) and AUC(0-infinity), of rivastigmine liposome were (1.50 +/- 0.15) mg x L(-1), 15 min and (89.06 +/- 8.30) mg x L(-') x min, respectively. Rivastimine liposome was absorbed rapidly, and could reach a certain concentration in rat plasma after intranasal delivery.

Dietary Risk Assessment for Pesticide Residues of Vegetables in Seoul, Korea

This paper specifically discusses the risk assessment on the pesticide residues in vegetables collected from traditional markets, big marts and departments in the southern part of Seoul. Vegetable samples were 6,583 cases from January to December in 2009. Monte-Carlo simulation was used to calculate the uncertainty for the risk index using pesticide residues, average dietary intake for vegetables and acceptable daily intake. Deterministic risk indexes were 7.33% of diethofencarb, 5.13% of indoxacarb, 3.96% of EPN, 3.92% of diniconazole and 3.09% of chlorothalonil, respectively. And other pesticides were below 3%. Distributions of risk indexes obtained by the Monte-Carlo simulations were similar to the deterministic values, even though the confidence intervals for 95% were very wide. We confirmed that health risks caused by eating vegetables exceeded maximum residue limits of pesticide are very low and the population is generally safe, judging from the risk indexes located between 0.07 to 9.49%.

Pharmacological Treatment for Delirium in Cancer Patients / 신경정신의학

OBJECTIVES: Despite the fact that delirium is a frequent neuropsychiatric disorder in cancer patients, there are, in Korea, no guidelines for the pharmacological treatment of such delirium. This systematic review evaluated the efficacy and safety of some pharmacological interventions and summarized the results. METHODS: We searched PubMed, Embase, CINAHL, the Cochrane Library, and the KMbase, targeting from January 1990 to October 2008, using key words. Moreover, we included systematic reviews, meta-analyses, and randomized controlled trial literature in the search. Then, we stratified the trials based on their evidence levels. RESULTS AND CONCLUSION: We identified 13 randomized, controlled studies and 2 case-control studies that met our inclusion criteria. These showed that haloperidol was the medication of choice to treat delirium. In addition, they revealed that atypical antipsychotics have not shown clear superiority with regard to effectiveness as compared to haloperidol. Neither donepezil nor rivastigmine were shown to be effective in preventing or treating delirium.

New Antiepileptic Drugs in Childhood Epilepsy

Many new antiepileptic drugs (AEDs) have been developed in the last two decades, contributing to the optimal treatment for childhood epilepsy. The goal of the treatment is to achieve seizure-free without any side effects, that deteriorates the quality of life by causing negative consequences. The new AEDs have not shown better efficacy, but generally seem to be better tolerated, having fewer systemic reactions and better pharmacokinetics than the established AEDs. The new AEDs have a broad spectrum of activities, which offer new opportunities to patients who have not shown any favorable responses to the established ones. There are more choices when trying to select AEDs for epileptic seizures and syndromes. Majority of the new AEDs have more than one action mechanism. AEDs acting selectively through the GABAergic system are tiagabine and vigabatrin; acting by inhibition of voltagedependent Na+ and Ca2+ channels are lamotirigine, oxcabarbazepine and topiramate; and acting by inhibition of glutamate-mediated excitation are felbamate, topiramate. The pharmacokinetic parameters of the new AEDs compared to the established AEDs, new AEDs have improved in terms of longer half-lives, permitting less frequent daily dosing, reduced potential for drug interactions. Considerations in selecting an AEDs are not only dependent on seizure types or syndromes, side effect profile, action mechanism, drug interaction, pharmacokinetic profile, facility of drug initiation, but also on age and sex of patients. Patients with worsened seizurefrequency or development of new types of seizure after the introduction of AEDs, should be questioned on the previously diagnosed seizure types or syndromes.

Alcohol and Cognitive Disorder / 대한정신약물학회지

Despite epidemiological studies reporting no negative effects of mild to moderate alcohol drinking on cognitive functioning, a recent well-controlled study showed that chronic mild drinking diminished the volume of the brain and was associated with cognitive decline that worsened as a function of the amount of alcohol consumed. Animal studies have demonstrated that neural cell damage follows chronic alcohol intake and withdrawal. In addition, acute excessive alcohol intake has been shown to result in temporary impairment of memory, and chronic alcohol drinking is often related to neuronal damage and cognitive disorders. Even though a diverse spectrum of cognitive disorders can develop after sustained alcohol drinking, no definite diagnostic criteria existed before those proposed by Oslin; the availability of these criteria will provide more structured clinical and academic approaches to alcohol-related cognitive decline, including dementia. In general, diminished cognitive functioning has been related to excessive alcohol consumption, with cognitive functioning gradually recovering over time. With the exception of the administration of thiamine in Wernicke-Korsakoff syndrome, only supportive pharmacotherapies have been provided for patients with alcohol-related cognitive disorders. However, experimental trials with rivastigmine or donepezil have been conducted for special populations with persistent cognitive impairments, and these studies reported favorable outcomes. We administered memantine for alcohol-related dementia and observed improvements in verbal memory and scores on the mini-mental status exam. We anticipate that novel and appropriate therapeutic agents for various conditions in this domain will be developed based on systematic diagnostic criteria and the accumulation of neurobiological evidence about alcohol-related cognitive decline.

Nonpharmacological Interventions for Alzheimer's Disease

Although acetylcholinesterase inhibitors (e.g., tacrine, donepezil, rivastigmine, and galantamine) and NMDA receptor antagonists (e.g., memantin) have demonstrated efficacy in the temporal symptomatic control of cognitive decline and daily function in Alzheimer's disease (AD) patients, their effect is not good enough to restore premorbid function, nor is it maintained in the later stages. Therefore, nonpharmacological interventions are being increasingly advocated in order to optimize the cognition, affect and global functioning of AD patients. We reviewed the current nonpharmacological interventions for AD. Nonpharmacological interventions can be divided into two groups. One is cognitive interventions (e.g., Memory rehabilitations, Reality orientation, Reminiscence therapy and so on) and the other is behavioral interventions (e.g., unmet needs interventions, learning and behavioral interventions, environmental vulnerability and reduced stress-threshold interventions). Cognitive interventions are aimed to slow and compensate cognitive decline of AD patients. On the other hand, behavioral interventions are aimed to reduce neuropsychiatric symptoms (depression, anxiety, agitation, wandering, aggression and so on) of AD patients. Although many of the nonpharmacological interventions have proven beneficial for AD patients, their efficacy was still ambiguous. Randomized and controlled study with a larger sample size is needed to confirm efficacy of nonpharmacological interventions.

Effects of 6 months of treatment with donepezil and rivastigmine on results of neuropsychological tests of MMSE, NPI, clock and bender in patients with Alzheimer's disease

Alzheimer's disease is the most common degenerative disease of brain. Nowadays, acetyl cholinesterase inhibitors, including donepezil, rivastigmine and galantamine, are standard treatments to slow down disease progression. Purpose of our study was to show effects of treatment with donepezil and rivastigmine and to compare these effects between two drugs. Samples selected from patients who had Alzheimer disease with DSM IV criteria and were candidate of receiving donepezil or rivastigmine for the first time. We used four neuropsychological tests including MMSE, NPI, Clock and Bender to assess patient's cognitive and behavioral changes during treatment with two drugs. Patients divided to two groups [each group 35 cases], one group taking donepezil and the other rivastigmine. The four tests were completed once before starting treatment and then, 1 month, 3 months and 6 months after treatment with Donepezil and Rivastigmine. MMSE, 6 months after treatment with Donepezil, improved from 20.63 before treatment to 21.83, which was statistically significant. Also, MMSE, 6 months after treatment with Rivastigmine, improved from 20.03 before treatment to 22.71, which was statistically significant. About Clock test, there was a significant improvement from 5.74 before treatment to 6.4 after 6 months of treatment with Rivastigmine; while this significant improvement was not seen in patients receiving Donepezil. In two other tests, no significant differences were seen before and after treatment. Also, No significant difference was detected between two groups and so no different effects on these tests between Donepezil and Rivastigmine in 6 months period of treatment

Pharmacological Treatment in Alcohol-induced Cognitive Disorder

Alcohol-induced cognitive disorder is a very severe problem in problem alcohol drinker and alcohol itself seems to be one of the main causalities in the development of senile dementia. However, the spectrum of alcohol induced cognitive disorder is quite broad, for example, it covered from alcohol-induced persistent amnestic disorder to Wernicke-Korsakoff syndrome and alcohol-induced persistent dementia. By that reason, broad spectrum of cognitive impairment by excessive alcohol drinking is regarded as alcohol related dementia. The pharmacological treatment is not well established yet in alcohol related dementia, except Wernicke-Korsakoff syndrome which is definitely related to thiamine deficiency. Therefore we introduced that some reports about the clinical efficacies by rivastigmine or donepezil trial and recent outcomes of memantine trial by authors in this review.

Synthesis of S-(+)-rivastigmine hydrogentartrate / 南方医科大学学报

<p><b>OBJECTIVE</b>To optimize the synthetic procedure of S-(+)-rivastigmine hydrogentartrate which was known as an agent for the treatment of Alzheimer disease.</p><p><b>METHODS</b>S-(+)-rivastigmine hydrogentartrate was synthesized by using 1-(3-hydroxyphenyl)ethanone as the starting material via oximation, reduction and N-methylation to produce the key intermediate 3-1-dimethylaminoethylphenol, which finally reacted with N-ethyl-N-methylcarbamoyl chloride. The enantiomers were resolved with di-(+)-p-toluoyl-D-tartaric acid, and the title compound was prepared by mixing S-rivastigmine base with L-(+)-tartrate.</p><p><b>RESULTS</b>The total yield of S-(+)-rivastigmine hydrogentartrate was 4.17%.</p><p><b>CONCLUSION</b>The materials in this procedure are all commercially available. The reaction conditions are mild and total yield is high.</p>

Efficacy of rivastigmine on activities of daily living in Sri Lankan patients with Alzheimer disease and on improving caregiver burden: a prospective study.

OBJECTIVE: This open label, parallel group, prospective cohort study investigated the efficacy of rivastigmine treatment on activities of daily living (ADL) in patients with mild to moderate Alzheimer's disease (AD) and the possible benefits of this therapy on caregiver stress levels. METHODS: Thirty eight consecutive patients with mild to moderate AD were recruited; 22 received rivastigmine 3-6 mg twice daily (treatment group) for 20 weeks. Sixteen patients who did not receive rivastigmine served as the control group. The 17-item ADL Index was used to assess ADL and to determine the presence of functional deterioration. Caregivers were evaluated with the Caregiver Stress Scale (CSS). Each patient was required to have a committed caregiver and all caregivers were interviewed and administered the ADL Index and the Caregiver Stress Scale (CSS) at the start of treatment (week 0) and at the end of 20 weeks of treatment (week 20). RESULTS: Patients in the control group showed a significant decline in ADL Index score at 20 weeks compared to rivastigmine-treated patients (difference in mean ADL Index score = 8.5; p < 0.001). At week 20, mean change from baseline scores for CSS total and individual domain scores were better for caregivers in the treatment group than those in the control group (CSS total mean difference = 19.2). CONCLUSION: We conclude that treatment of AD patients with rivastigmine for 20 weeks produces a significant improvement in patient ADL functioning, and lower levels of caregiver stress.