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There is frequently a degree of variability among different types of dementia specialists in clinical practice in both the clinical diagnosis and the management of patients with Alzheimer's disease and cerebrovascular disease (CVD). This variability may have an adverse effect on the use of medical resources as well as on patients' well-being. The main objective of this study was to describe the current diagnosis and management of patients with Alzheimer's disease and CVD in Spain. Other objectives were to determine whether there were significant differences in the diagnosis and management of these patients depending on physician characteristics and/or patient profile.
One Swiss University Hospital.
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To evaluate the change in cognition (at week 26 vs baseline) observed in patients from 3 large clinical trials of AD who prematurely discontinued treatment with placebo or rivastigmine.
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In untreated patients with Alzheimer disease (AD) the functional ability is gradually lost. What happens to the patients after continuous long-term cholinesterase inhibitor (ChEI) treatment is less investigated. The objective of this study was to describe the longitudinal functional outcome and analyze factors affecting the outcome in ChEI-treated patients. In an open, 3-year, nonrandomized, prospective, multicenter study in a routine clinical setting, 790 patients were treated with either donepezil, rivastigmine, or galantamine. At baseline and every 6 months, they were assessed with several rating scales including Instrumental Activities of Daily Living (IADL), Physical Self-Maintenance Scale (PSMS), and Mini-Mental State Examination (MMSE). A faster functional decline was associated with lower cognitive ability at baseline, older age, and the interaction of higher education and longer time in the study. The patients residing with a spouse or relative showed slower deterioration in IADL score. A higher mean dose of ChEI, regardless of drug agent, was also related to slower instrumental ADL decline. Prediction models for longitudinal functional outcome were provided. AD severity at baseline is a key factor in obtaining reliable clinical prognoses of the long-term ADL ability. The dosage of ChEI treatment could possibly lead to a different functional outcome.
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Cerebrovascular disease (CVD) and ischemic brain injury secondary to cardiovascular disease are common causes of dementia and cognitive decline in the elderly. CVD also contributes to cognitive loss in Alzheimer disease (AD).
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To evaluate the prevalence of cholinesterase inhibitor (ChI) treatment in subjects with dementia in European countries.
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Eighteen-month observational, prospective, multi-center, open-label study conducted on AD patients with Standardized Mini-Mental State Examination (SMMSE) score of 10-26 and Global Deterioration Scale (GDS) score of 4-6. Patients were treated with the rivastigmine transdermal patch (Exelon patch*) 5 cm² (4.6 mg/24 hours) or 10 cm² (9.5 mg/24 hours), once daily.
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We reviewed animal studies and human clinical studies to address whether sex can predict and influence the response to ChEI treatment based on differences in neuroanatomy, pharmacokinetics, and prevalence of dementia.
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To date, acetylcholinesterase (AChE) inhibitors have been clinically effective drugs for the palliative treatment of Alzheimer's disease, but their clinical efficacy is limited, mainly due to their adverse effects on peripheral organs. Since patients of Alzheimer's disease often exhibit depression as well as memory impairment, dual inhibitors of AChE and serotonin transporter (SERT) would be a better therapeutic method. Anti-depressive effects based on SERT inhibition would reduce the dose-related side effects of AChE inhibitors. Such dual inhibitors were designed by the hybridization of rivastigmine and fluoxetine based on a hypothetical model of the AChE active site. Various derivatives were synthesized and evaluated for their in vitro inhibition, and then (S)-5j (RS-1259), which possessed balanced inhibitory activities of AChE (IC(50)=101 nM) and SERT (IC(50)=42 nM), was successfully obtained. An ex vivo experiment in mice indicated that (S)-5j (RS-1259) simultaneously inhibited AChE and SERT in the brain following an oral administration. The simultaneous elevation of extracellular levels of acetylcholine and serotonin in the rat hippocampus was actually confirmed by microdialysis.
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A randomized open label study in 84 ambulant Alzheimer's patients with at least 6 months follow-up and treated either with oral galantamine (group G) or rivastigmine transdermal patch (group R). Data collection included patients' demographic and disease variables. Adverse events were collected and, in case of interruption of the primary treatment, the alternative treatment was registered.
Incremental cost-effectiveness ratio (ICER) expressed as cost per unit decrease in the Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) subscale.
The results point to a 'normalization' of the EEG power spectrum due to medication, and the intracortical localization of these effects showed an increase of cortical activity in frontal, parietal, and temporal regions that are well-known to be affected in Alzheimer's disease. The topographic convergence of the present results with the memory network proposed by Vincent et al. (J. Neurophysiol. 96:3517-3531, 2006) leads to the speculation that in our group of patients, rivastigmine specifically activates brain regions that are involved in memory functions, notably a key symptom in this degenerative disease.
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The current clinical view on pharmacological treatment and the Croatian reality regarding approved antidementia drugs is presented. Dementia is a syndrome of high incidence and Alzheimer's disease is the most common cause of dementia. New data show that dementia prevalence will nearly double every 20 years, and we believe that current estimated number of persons with dementia (PWD) for Croatia is more than 80,000. The standard treatment with antidementia drugs is unavailable in Croatia, for the majority of PWD, because antidementia drugs are not on the reimbursement list, although Croatian algorithm for psychopharmacological treatment and Alzheimer Disease Societies Croatia recommend early and adequate treatment. Alzheimer's dementia is becoming a world's health priority in 21st century, so we strongly believe that antidementia drugs should be reimbursed in Croatia.
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The purpose of this explanatory study was to determine whether medication prescribing for Alzheimer's disease (AD) differs by racial and ethnic group membership. The following research question was examined in this study: Are there prescribing pattern differences for AD among racial and ethnic groups? Additional beneficiary characteristic variables examined included: diabetes, memory loss, psychological disorder, age category, and gender.
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In this pilot study, the revaluation in accordance with the recommendations of the Haute autorité de santé (HAS) led to the discontinuation of two third of anti-dementia drugs. Safety of sudden discontinuation of MSD remains to be studied.
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Higher doses of ChEI might reduce the use of HHS, possibly reducing the costs of community-based care. Female spouses provide more informal care than do male spouses, so the likelihood of using HHS is greater among women with AD. The "silent group" of more cognitively impaired and frail elderly AD patients receives less HHS, which might precipitate institutionalization.
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The cholinesterase inhibitors (ChEIs) donepezil, rivastigmine and galantamine are the current mainstays in the drug treatment of Alzheimer's disease (AD). There is convincing evidence that these agents provide at least modest cognitive, behavioural and functional benefit for 6-12 months at all stages of the disease. Longer term benefits cannot be directly examined by placebo-controlled trials. Nevertheless, the results of virtually all open-label extensions of the pivotal trials, studies of patients with AD at different levels of severity and clinical trials using other designs favour treatment over no treatment for periods of up to 5 years. There are plausible biological reasons why ChEIs might be expected to work over a prolonged period of time although, to date, studies using various markers to chart the effects of medication on long-term disease progression have yielded mixed results. The most contentious issue regarding long-term treatment is economic, but the majority of available economic analyses suggest net savings over the long term if patients with AD receive persistent treatment with ChEIs.
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We conducted a computer-based search using PubMed (up to February 15, 2006) and ISI Web of Science (conference proceeding abstracts from January 2003 to December 2005) databases. We used the search terms "schizophrenia," "cognition or memory" and "tacrine or donepezil or rivastigmine or galantamine." Studies included were critically analyzed for allocation, blindness, duration and study design, demographic data, and clinical and neuropsychological outcome assessments. We excluded studies that involved patients with psychiatric disorders other than schizophrenia-spectrum or if they involved animals or molecular investigations. We also excluded conference proceeding abstracts with no explicit neuropsychological battery and/or results.
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A total of 46 patients with a diagnosis of schizophrenia entered into a 12-week, double-blind, clinical trial for random assignment to rivastigmine or placebo, as adjuvant to their current antipsychotic medication. Positive and Negative Symptom Scale (PANSS) and Mini Mental State Examination (MMSE) had been used as the primary outcome measures. Clinical Global Impressions- Improvement (CGI-I) Scale and Extrapyramidal Symptom Rating Scale (ESRS) had been used as the secondary measures. Treatment efficacy was evaluated by a Student's t test and repeated-measures analysis of variance (ANOVA). Statistical significance was defined as a two-sided p value ⩽ 0.05. Cohen's standard (d) and correlation measures of effect size (r) had been calculated for comparing baseline to endpoint changes.
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Rivastigmine transdermal patch has shown higher caregiver satisfaction and greater preference than oral formulation in patients with Alzheimer's disease. However, there is limited literature available related to caregiver preference or treatment compliance in real-world clinical settings. To date, no such data are available from Asia and the Middle East, which account for a sizeable proportion of patients with Alzheimer's disease. The objective of this study was to evaluate treatment preference and compliance with oral and transdermal medications in daily clinical practice in an ethnically diverse patient population from Asia and the Middle East with mild-to-moderate Alzheimer's disease.
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Recently advances in understanding the molecular basis of Alzheimer's disease have led to the consideration of the relationship between cholinergic inhibitors and amyloid deposition as a new hypothesis for the future rational design of effective anti-Alzheimer drugs. In the present review, the non-cholinergic functions of acetylcholinesterase (AChE) and the therapeutic potential of peripheral and dual binding site AChE inhibitors in delaying the neurodegenerative process will be discussed.