Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new exelon research articles will be listed here shortly after becoming available to us.
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Medical research on exelon
Treatment of dementia associated with Parkinson's disease.
Parkinsonism Relat Disord. 2007; 13 Suppl 3: S457-61
Emre M
Dementia affects approximately one-third of all patients with Parkinson's disease. Currently there is no treatment to halt or reverse the disease progression. Symptomatic treatment approaches are based on substituting neurotransmitter deficits or ameliorating associated behavioral symptoms. The most prominent deficits are cholinergic, and treatment with cholinesterase inhibitors (ChE-I) has been shown to provide some benefits in cognitive and behavioral symptoms without undue worsening in motor symptoms. Based on a large, randomized, placebo controlled trial, the ChE-I rivastigmine has been approved for the treatment of dementia associated with PD.
Mov Disord. 2008 Nov 12;
Lane R, He Y, Morris C, Leverenz JB, Emre M, Ballard C
Apolipoprotein E (APOE) epsilon4 and butyrylcholinesterase-K (BuChE-K) are associated with an increased risk for Alzheimer's disease. The primary objective was to evaluate frequencies of these alleles in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). A secondary objective was to evaluate influences on rate of cognitive decline. This analysis used data from participants consenting to pharmacogenetic testing in placebo-controlled rivastigmine studies. Allele frequencies in DLB and PDD were compared using logistic regression. Within the PDD placebo sample, associations with cognitive decline were evaluated (the DLB sample was too small for these evaluations). Fifty-seven DLB and 323 PDD subjects provided APOE and BuChE data. Allelic frequencies were higher in DLB, relative to PDD subjects, for BuChE-K (P = 0.06), APOE epsilon4 (P < 0.001), or both alleles together (P < 0.001). More rapid cognitive decline was seen in PDD patients carrying both alleles, compared with other genotypes. Subjects with hyperhomocysteinemia were associated with more rapid decline in the presence of BuChE-K, with or without APOE epsilon4. These results suggest that genetic and biochemical risk factors for AD and PDD pathology may be important in dementia onset and progression in these Lewy body disorders. (c) 2008 Movement Disorder Society.
Psychopharmacology (Berl). 2008 Nov 14;
Deiana S, Harrington CR, Wischik CM, Riedel G
RATIONALE: The cholinergic system is involved in cognition as well as in age-related cognitive decline and Alzheimer disease (AD). Cholinergic enhancers ameliorate AD symptoms and represent the main current therapy for AD. MTC (Methylthioninium chloride), an antioxidant with metabolism-enhancing properties may be a novel candidate with pro-cognitive capacities. OBJECTIVES: This study was performed: (1) to assess the pro-cognitive efficacy of MTC and establish its dose-response; (2) to compare the efficacy of MTC with rivastigmine and (3) to determine the potential for combination therapy by co-administration of MTC and rivastigmine. METHODS: Spatial cognition of female NMRI mice was tested in a reference memory water maze task. Subjects received intra-peritoneal injections of scopolamine (0.5 mg/kg) followed by vehicle, and/or MTC and/or rivastigmine (0.15-4 mg/kg MTC; 0.1-0.5 mg/kg rivastigmine) in mono or combination treatment. RESULTS: Scopolamine treatment prevented spatial learning in NMRI female mice and the deficit was reversed by both rivastigmine and MTC in a dose-dependent manner. Mono-therapy with high doses of rivastigmine (>0.5 mg/kg) caused severe side effects but MTC was safe up to 4 mg/kg. Co-administration of sub-effective doses of both drugs acted synergistically in reversing learning deficits and scopolamine-induced memory impairments. CONCLUSIONS: In our model, MTC reversed the spatial learning impairment. When combined with the ChEI rivastigmine, the effect of MTC appeared to be amplified indicating that combination therapy could potentially improve not only symptoms but also contribute beneficially to neuronal metabolism by minimising side effects at lower doses.
The therapeutical potential of alpha-synuclein antiaggregatory agents for dementia with Lewy bodies.
Curr Med Chem. 2008; 15(26): 2748-59
Beyer K, Ariza A
Dementia with Lewy bodies (DLB), the second most frequent cause of dementia after Alzheimer disease (AD), is characterized by the widespread distribution of Lewy bodies in virtually every brain area. Clinically, DLB is distinguished from AD by fluctuating cognition, prominent visual hallucinations and parkinsonism, and from Parkinson disease, by the appearance of parkinsonism within one year of cognitive or behavioral decline. The main component of Lewy bodies is alpha-synuclein. Accumulating evidence suggests that its aggregation constitutes one of the first steps preceding Lewy body formation, so that antiaggregation strategies would be very useful to prevent alpha-synuclein fibril formation. Main therapies nevertheless applied up to the present remain symptomatological. In this context, cholinesterase inhibitors such as rivastigmine, galantamine and donepezil, are used for the treatment of delusions and other psychotic symptoms. This review focuses on the recent discovery of possible alpha-synuclein anti-aggregation factors, where four main classes can be defined. First, beta-synuclein as well as alpha-synuclein derived peptides in addition to antibodies present a group of proteins and peptides that directly interact with alpha-synuclein and so inhibit its aggregation. Second, small molecules interfere with alpha-synuclein aggregation by their covalent binding, although not all of them are suitable for an appropriate inhibition of alpha-synuclein aggregation. Third, to inhibit the expression of alpha-synuclein and its isoforms at the RNA level, the use of interference RNA represents a future challenge. The fourth strategy is based on the enhancement of inclusion body formation to accelerate the elimination of soluble alpha-synuclein oligomers. Each chapter section includes the discussion of possible strategies for the development of drugs and therapies.
Drug utilization review of cholinesterase inhibitors in Quebec.
Can J Neurol Sci. 2008 Sep; 35(4): 508-9
Massoud F, Dorais M, Charbonneau C, Lescrauwaet B, Boucher JM, LeLorier J
Effects of rivastigmine on memory and cognition in multiple sclerosis.
Can J Neurol Sci. 2008 Sep; 35(4): 476-81
Shaygannejad V, Janghorbani M, Ashtari F, Zanjani HA, Zakizade N
BACKGROUND: Cognitive dysfunction is one of the common clinical symptoms in multiple sclerosis (MS), but there is no effective treatment for it. OBJECTIVE: The aim of this study was to evaluate the effect of rivastigmine in treating memory and cognitive dysfunction in MS. METHODS: A single-center double-blind placebo-controlled randomized clinical trial conducted from October 2005 to February 2007. Sixty definite MS patients with cognitive impairment age 16 to 54 years were randomly allocated to receive a 12-week treatment course of either rivastigmine (1.5 mg once a day increment over 4 weeks to 3 mg twice daily) or placebo. Response to treatment was assessed by the Wechsler Memory Scale (WMS) at baseline and 12 weeks after start of therapy. RESULTS: A slight, but significant memory improvement occurred in both groups. Of the 30 patients treated with rivastigmine, the mean (SD) WMS general memory score increased from 60.3 (4.2) at baseline to 64.9 (5.3) at the end of study period (P
J Neurol. 2008 Oct 7;
Cucurachi L, Immovilli P, Granella F, Pavesi G, Cattaneo L
BACKGROUND : The pathogenesis of cognitive deficits in multiple sclerosis (MS) patients is the subject of debate. A causative role of grey matter impairment has been suggested. Acetylcholinesterase inhibitors have been proposed in the treatment of cognitive impairment in MS. Short-latency afferent inhibition (SAI) is a cortical phenomenon assessed by a transcranial magnetic stimulation protocol that provides an in vivo index of central cholinergic function. METHODS : We recruited 20 consecutive relapsing-remitting or secondary progressive MS patients showing normal upper limb somatosensory and motor evoked potentials. SAI of the left-hand motor cortex from median nerve stimuli was tested. A matched group of 20 healthy subjects was also assessed. All patients underwent neuropsychological assessment with Rao's Brief Repeatable Battery (BRB). Multiple regression was performed on the number of failed tests and on scores of single BRB tests as dependent variables with Extended Disability Status Scale (EDSS) score, SAI, age, gender and disease duration as regressors. Patients with impaired SAI, were reassessed after a single oral dose of rivastigmine. RESULTS : SAI was a significant predictor of the score in tests that assess verbal memory. EDSS score and age were found as predictors of the other BRB tests. SAI was significantly improved by oral rivastigmine. CONCLUSIONS : Our data confirm that cognitive impairment in MS is multifactorial. The performances in the subdomain of verbal memory are predicted by SAI. These results favour the hypothesis of grey matter involvement and suggest a role of acetylcholine dysfunction in the pathogenesis of some aspects of cognitive deficits in MS.
[Neuropsychiatric and cognitive symptoms in Parkinson disease]
Tidsskr Nor Laegeforen. 2008 Sep 25; 128(18): 2072-6
Aarsland D, Pedersen KF, Ehrt U, Bronnick K, Gjerstad MD, Larsen JP
BACKGROUND: A variety of neuropsychiatric symptoms commonly occur in Parkinson's disease. Extensive research the last 10 years has provided new knowledge in the field. MATERIAL AND METHODS: This review is based on literature retrieved from a Medline search and own research and clinical experience. RESULTS AND INTERPRETATION: Neuropsychiatric symptoms occur in the majority of patients with Parkinson's disease, and are associated with impaired quality of life for patients and relatives, additional deterioration of function and increased use of health resources. Medical and surgical therapies can induce or worsen such symptoms. Cognitive impairment and dementia are among the most common and severe complications to Parkinson's disease. No disease-modifying treatment is available, but rivastigmine was effective in one large randomised trial. Visual hallucinations are common and often persistent, but can be treated with klozapin if reducing the number and dose of antiparkinson agents are not helpful. Depression occurs frequently, usually mild, but there is little evidence of treatment efficacy. Apathy, anxiety and sleep disturbances are additional commonly occurring neuropsychiatric symptoms. Neuropsychiatric symptoms are so frequent in Parkinson's disease that they should be considered an integral part of the disease; it is important that clinicians are aware of these symptoms.
[The treatment of Alzheimer's disease in patients with comorbid somatic pathology]
Zh Nevrol Psikhiatr Im S S Korsakova. 2008; 108(7): 35-42
Selezneva ND, Gavrilova SI, Kalyn IaB, Kolykhalov IV, Fedorova IaB
To study efficacy and safety of cholinergic therapy in patients with Alzheimer's disease or combined Alzheimer's and vascular dementia and marked somatic pathology, 30 patients, aged from 54-85 years, with mild or moderate dementia have been studied. Patients were treated with rivastigmine (exelon) in dosage 3-12 mg daily during 3 months. The safety of the drug for patients with comorbid somatic pathology has been shown: during the treatment no severe aversive effects or strengthening of diseases of visceral organs were observed. The improvement of global clinical state as well as reduction of cognitive and behavioral disorders indicate the high effectiveness of exelon. The recommendations allowing to improve the tolerability of treatment with exelon of patients with comorbid pathology of visceral organs are worked out.
Diagnosis and management of Parkinson's disease dementia.
Int J Clin Pract. 2008 Oct; 62(10): 1581-7
Poewe W, Gauthier S, Aarsland D, Leverenz JB, Barone P, Weintraub D, Tolosa E, Dubois B
Parkinson's disease (PD) has long been considered predominantly a motor disorder. However, its frequent association with dementia, which contributes significantly to the morbidity and mortality of the condition, is gaining increasing recognition. PD dementia (PDD) has a unique clinical profile and neuropathology, distinct from Alzheimer's disease (AD). Cholinergic deficits, a feature of both AD and PDD, underlie the rationale for cholinesterase inhibitor therapy in both conditions. In clinical practice, it is important that PDD should be recognised and appropriately treated. This review aims to outline the recently proposed clinical diagnostic criteria for PDD and to summarise the guidelines/recommendations published since 2006 on the use of cholinesterase inhibitors in the management of PDD. Although the cholinesterase inhibitor rivastigmine has recently been approved for the management of PDD, there remains a need for the development of novel therapies that can affect key mechanisms of the disease or prevent/delay patients with PD and mild cognitive impairment from progressing to PDD.