A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients

Mohs, Richard C.; Doody, Rachelle S.; Morris, John C.; Ieni, John R.; Rogers, Sherise C.; Perdomo, Carlos; Pratt, Raymond D.

doi:10.1212/wnl.57.3.481

Cited by 466 publications

(372 citation statements)

References 22 publications

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“…Improvement in ADLs (as measured by the Progressive Deterioration Scale 87 ) was seen at 52 weeks but not at earlier time points, and cognitive improvement was observed in a secondary measure (Mini-Mental State Examinationă 88 [MMSE]: scale: 0-30 points; lower scores ϭ impairment). In the study by Mohs et al, 83 which enrolled 431 patients with moderate AD, a higher proportion of patients receiving placebo (56%) compared with those receiving donepezil (41%) met criteria for clinically evident functional decline, although this difference was not significant. In addition, no difference in the mean functional status in patients completing the study was found between the donepezil and placebo groups.…”

Section: Long-term Symptomatic Efficacymentioning

confidence: 95%

“…82,83 Doody et al 79 presented results from 763 patients enrolled in a 144-week, open-label extension of 2 preceding RCTs. The deterioration in the mean change from baseline of the Alzheimer's Disease Assessment Scale 84 cognitive subscale (ADAS-Cog: 0-70 points; higher scores ϭ impairment) was 7.4 to 9.1 points for the group that received 5 mg/d and 7.9 to 10.0 points for the group that received 10 mg/d, depending on the study.…”

Section: Long-term Symptomatic Efficacymentioning

confidence: 99%

“…These studies suggest that the beneficial effects of donepezil treatment are maintained during longterm treatment, although the patient numbers involved are relatively small. Two placebo-controlled trials 82,83 assessed the efficacy of donepezil over a period of 1 year. In the study by Winblad and colleagues 82 (N ϭ 286), donepezil failed to show significant cognitive benefits over placebo at study end point in the primary analysis (intent-to-treat, last observation carried forward) on the primary efficacy measure, the Gottfries-Bråne-Steen Scale, 85 or any significant improvement in behavior (Neuropsychiatric Inventory 86 ).…”

Section: Long-term Symptomatic Efficacymentioning

confidence: 99%

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Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease:

Grossberg

2003

Current Therapeutic Research

304

156

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Background: Cholinesterase (ChE) inhibitors currently used in the treatment of Alzheimer's disease (AD) are the acetylcholinesterase (AChE)-selective inhibitors, donepezil and galantamine, and the dual AChE and butyrylcholinesterase (BuChE) inhibitor, rivastigmine. In addition to differences in selectivity for AChE and BuChE, ChE inhibitors also differ in pharmacokinetic and pharmacodynamic properties, and these differences could significantly impact on safety, tolerability, and efficacy.Objective: The aim of this article was to provide an overview of the ChE inhibitors widely used in AD, focusing on key pharmacologic differences among agents and how these may translate into important differences in safety, tolerability, and efficacy in clinical practice.Methods: Using published literature collected over time by the author, a review was conducted, focusing on the pharmacology and clinical data of donepezil, galantamine, and rivastigmine.

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Section: Long-term Symptomatic Efficacymentioning

confidence: 95%

Section: Long-term Symptomatic Efficacymentioning

confidence: 99%

Section: Long-term Symptomatic Efficacymentioning

confidence: 99%

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Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease:

Grossberg

2003

Current Therapeutic Research

304

156

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“…However, AChE inhibitors have been less promising therapeutically as they produce only modest improvements in cognitive function (Bryson and Benfield, 1997;Greenberg et al, 2000;Mohs et al, 2001;Winblad et al, 2001) along with undesirable side effects (Wilkinson, 1999;Dunn et al, 2000;Imbimbo, 2001). …”

Section: Introductionmentioning

confidence: 99%

Cognitive Enhancing Properties and Tolerability of Cholinergic Agents in Mice: A Comparative Study of Nicotine, Donepezil, and SIB-1553A, a Subtype-Selective Ligand for Nicotinic Acetylcholine Receptors

Bontempi¹,

Whelan²,

Risbrough³

et al. 2003

Neuropsychopharmacol

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Several studies have demonstrated the importance of nicotinic mechanisms in the pathophysiology of neurodegenerative and cognitive disorders, warranting the search and development of novel nicotinic ligands as potential therapeutic agents. The present study was designed to assess whether the subtype-selective nicotinic acetylcholine receptor (nAChR) ligand SIB-1553A [( 7 )-4-{[2-(1-methyl-2-pyrrolidinyl)ethyl]thio}phenol hydrochloride], with predominant agonist activity at b4 subunit-containing human nAChRs, and no activity at muscle nAChR subtypes, could enhance cognitive performance in rodents with a more desirable safety/tolerability profile as compared to the nonselective prototypic nAChR ligand nicotine. SIB-1553A was equi-efficacious to nicotine in improving working memory performance in scopolamine-treated mice as measured by increased alternation in a T-maze, and was more efficacious than nicotine in improving the baseline cognitive performance of aged mice. This effect on working memory was confirmed in a delayed nonmatching to place task using the eight-arm radial maze. SIB-1553A produced dose-dependent side effects (ie motor deficits and seizures), although these effects were observed at doses 12 to 640-fold above those required to increase cognitive performance. Overall, SIB-1553A was significantly less potent than nicotine in eliciting these undesirable effects. Thus, the subtype-selective profile of SIB-1553A appears to translate into a more efficacious and better tolerated nAChR ligand as compared to nicotine. In the present studies, cognitive enhancement induced by SIB-1553A was similar in magnitude to that produced by the clinically efficacious acetylcholinesterase inhibitor donepezil. Taken together, the present data confirm the importance of nAChR subtypes in modulating cognitive processes, and suggest that activation of nAChR subtypes by selective nAChR ligands may be a viable approach to enhance cognitive performance.

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“…One-year clinical trials in patients with mild to moderate AD showed a mean treatment difference of 1.6 points on the MMSE in favor of donepezil. 42,43 In contrast to the preservative effect seen in these clinical trials, Ms. A's cognition was greatly enhanced at the 6-and 12-month assessments of her treatment. Over the course of 1 year, her mean response to treatment was 5 points on the MMSE.…”

Section: Rivastigminementioning

confidence: 84%

Role of Cholinesterase Inhibitors in Managing Behavioral Problems in Alzheimer's Disease

Masterman¹

2004

Prim. Care Companion CNS Disord.

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A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients

Abstract: Patients with AD continue to show detectable disease progression over time, but treatment with donepezil for 1 year was associated with a 38% reduction in the risk of functional decline compared with placebo.

Cited by 466 publications

References 22 publications

Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease:

Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease:

Cognitive Enhancing Properties and Tolerability of Cholinergic Agents in Mice: A Comparative Study of Nicotine, Donepezil, and SIB-1553A, a Subtype-Selective Ligand for Nicotinic Acetylcholine Receptors

Role of Cholinesterase Inhibitors in Managing Behavioral Problems in Alzheimer's Disease

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