Rivastigmine in subcortical vascular dementia

Moretti, Rita; Torre, Paola; Antonello, Rodolfo M.; Cazzato, Giuseppe; Bava, Antonio

doi:10.1016/s0022-510x(02)00280-0

Cited by 92 publications

(66 citation statements)

References 32 publications

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“…Open-label extension phase data from a preliminary study using a small number of patients with frontosubcortical VaD showed that 12-month rivastigmine treatment improved executive function and behavior compared with baseline and a control group receiving cardioaspirin. Furthermore, these beneficial effects were maintained for 22 months [104,105] . Another clinical trial, with 16 subcortical VaD patients, showed similar results, indicating that rivastigmine may provide targeted treatment to brain areas that are particularly affected in this kind of patient population [70] .…”

Section: Rivastigminementioning

confidence: 91%

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

2009

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Vascular dementia (VaD) is a progressive neurodegenerative disease with a high prevalence. Several studies have recently reported that VaD patients present cholinergic deficits in the brain and cerebrospinal fluid (CSF) that may be closely related to the pathophysiology of cognitive impairment. Moreover, cholinergic therapies have shown promising effects on cognitive improvement in VaD patients. The precise mechanisms of these cholinergic agents are currently not fully understood; however, accumulating evidence indicates that these drugs may act through the cholinergic anti-inflammatory pathway, in which the efferent vagus nerve signals suppress pro-inflammatory cytokine release and inhibit inflammation, although regulation of oxidative stress and energy metabolism, alleviation of apoptosis may also be involved. In this paper, we provide a brief overview of the cholinergic treatment strategy for VaD and its relevant mechanisms of anti-inflammation.

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Section: Rivastigminementioning

confidence: 91%

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

2009

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“…Clinical trials have con-sistently shown higher rates of adverse gastrointestinal effects in patients treated with rivastigmine, donepezil, and galantamine than in those receiving placebo. [9][10][11][12][13][14] Thus package inserts for galantamine, rivastigmine, and donepezil all warn that cholinesterase inhibitors are associated with gastrointestinal events. The most severe adverse effects occur when patients receive the agents in the early period or higher doses of cholinesterase inhibitors, when patients have low body weight, and during upward dose titration.…”

Section: Discussionmentioning

confidence: 99%

“…Controlled clinical trials with cholinesterase inhibitors, such as donepezil, galantamine, and rivastigmine, in VD, as well as in patients with AD plus VD, have demonstrated improvements in cognition, behavior and activities of daily living. [9][10][11] However, cholinesterase inhibitors may cause a broad spectrum of adverse events such as nausea, vomiting, and diarrhea, etc. [9][10][11][12][13][14] These adverse events, which make many patients stop taking cholinesterase inhibition (CHI) agents, are generally recognized as due to parasympathetic nervous system activity, while cholinesterase inhibitors ameliorate dementia by inhibiting AChE in central nervous system (CNS).…”

Section: Introductionmentioning

confidence: 99%

“…[9][10][11] However, cholinesterase inhibitors may cause a broad spectrum of adverse events such as nausea, vomiting, and diarrhea, etc. [9][10][11][12][13][14] These adverse events, which make many patients stop taking cholinesterase inhibition (CHI) agents, are generally recognized as due to parasympathetic nervous system activity, while cholinesterase inhibitors ameliorate dementia by inhibiting AChE in central nervous system (CNS). Anticholinergics have been used to treat urinary incontinence in patients tak-ing cholinesterase inhibitors for dementia.…”

Section: Introductionmentioning

confidence: 99%

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Propantheline Attenuates the Peripheral Side Effects of Donepezil without Affecting Its Antiamnestic Properties in Cerebral Ischemic Mice

Zhu

Zhang

et al. 2008

JOURNAL OF HEALTH SCIENCE

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Cholinergic deficits are found in both vascular dementia and Alzheimer's disease (AD). Cholinesterase inhibition (CHI) is the only strategy that has been proven to have beneficial effects in patients, but may cause a broad spectrum of adverse events such as nausea, vomiting, and diarrhea, etc. To investigate how to attenuate the peripheral side effects of CHI agents without affecting their efficacy, the effects of propantheline bromide (PB) co-administered with donepezil on the gastric emptying (GE), gastrointestinal transit (GIT), brain cholinesterase (ChE) activities, and maze tasks of mice with memory impairment induced by transient ischemia were observed. The results indicated that PB decreased the increase in GE and GIT, but did not change brain acetylcholinesterase (AChE) activity or the latency of escape in cerebral ischemic mice treated with donepezil. These findings suggest that PB is nearly unable to penetrate the blood-brain barrier and could attenuate the peripheral side effects of CHI agents in the peripheral nervous system and without affecting their therapeutic effects in the central nervous system.

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“…An unblinded controlled study 25 and 2 open trials have been reported in similar patients. 6,26 Although the primary outcome measure was not significantly altered by the active treatment, some secondary measures showed differences in favor of nimodipine, namely lexical production and the MMSE when a substantial 3-point change cutoff to assess improvement or worsening was used as an outcome measure. The first of these 2 results may indicate a positive effect in the executive function domain known to be selectively compromised in subcortical VaD.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Nimodipine in Subcortical Vascular Dementia

Pantoni

Ser²,

Soglian³

et al. 2005

Stroke

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Background and Purpose-Evidence of drug efficacy in vascular dementia (VaD) is scanty. Therapeutic trials should address VaD subtypes. We studied the efficacy and safety of the calcium antagonist nimodipine in subcortical VaD. Methods-242 patients defined as affected by subcortical VaD based on clinical (ICD-10) and computed tomography criteria were randomized to oral nimodipine 90 mg/d or placebo. Results-230 patients (121 nimodipine, mean age 75.2Ϯ6.1; 109 placebo, 75.4Ϯ6.0) were valid for the intention-to-treat analysis. At 52 weeks, the Sandoz Clinical Assessment Geriatric scale 5-point variation (primary outcome measure) did not differ significantly between the 2 groups. However, patients on nimodipine performed better than placebo patients in lexical production (PϽ0.01) and less frequently showed deterioration (3 or more point-drop versus baseline) on a Mini-Mental State Examination (28.1% versus 50.5%; 2 PϽ0.01) and Global Deterioration Scale (PϽ0.05). Dropouts and adverse events were all significantly more common among placebo than nimodipine patients, particularly cardiovascular (30 versus 13; RR, 2.26; 95% CI, 1.11 to 4.60) and cerebrovascular events (28 versus 10; RR, 2.48; 95% CI, 1.23 to 4.98), and behavioral disturbances requiring intervention (22 versus 5; RR, 3.88; 95% CI, 1.49 to 10.12). A worst-rank analysis, performed to correct for the effect of the high dropout rate in the placebo group, showed additional significant differences in favor of nimodipine in Set Test and MMSE total scores. Conclusions-Nimodipine may be of some benefit in subcortical VaD. Confirming previous results, the safety analysis of this study shows that in this high-risk population, nimodipine might protect against cardiovascular comorbidities.

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Rivastigmine in subcortical vascular dementia

Cited by 92 publications

References 32 publications

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

Propantheline Attenuates the Peripheral Side Effects of Donepezil without Affecting Its Antiamnestic Properties in Cerebral Ischemic Mice

Efficacy and Safety of Nimodipine in Subcortical Vascular Dementia

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