Cognitive, global, and functional benefits of donepezil in Alzheimer's disease and vascular dementia: results from large-scale clinical trials

Passmore, Anthony Peter; Bayer, Antony James; Steinhagen‐Thiessen, Elisabeth

doi:10.1016/j.jns.2004.11.017

Cited by 30 publications

(24 citation statements)

References 23 publications

(29 reference statements)

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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“…Recently treatment for AD has been focused on enhancing cholinergic function with AChE inhibitors, such as donepezil, rivastigmine and galantamine. Several studies showed that increasing ACh by inhibiting AChE activity to some degree ameliorates the cognitive deficits in AD patients 23,24 . Another way to increase the ACh level is to give ACh substitutes, but none is currently available.…”

Section: Discussionmentioning

confidence: 99%

Untitled

Suwanakitch¹,

Jeenapongsa²,

Watanabe³

et al. 2008

ScienceAsia

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ABSTRACT:The pathogenesis of Alzheimer' s disease (AD) is complicated and multifactorial, and is under the influence of genetic regulation. The NG108-15 cell line, a neuronal cell line, once differentiated exhibits neuron-like in morphology and intercellular synaptic junction formation. We, thus, hypothesize that the differentiation process may alter the expression patterns of AD-related genes in this cell line. This study primarily aimed to compare the expression patterns of five AD-related genes, namely AChE, COX-2, α7 nAChR, γ-secretase, and APP between undifferentiated and differentiated NG108-15 cells by RT-PCR techniques. The cyclic AMP analogue dibutyryl cAMP (Bt 2 cAMP) and 12-O-tetradecanoyl-phorbol 13-acetate (TPA) were used to induce neuronal differentiation. The differentiated NG108-15 cells exhibited neuron-like morphology and intercellular network formation. The level of AChE mRNA in differentiated cells was significantly greater than in undifferentiated cells at 2 and 3 day post-induction. Also, COX-2 mRNA expression in differentiated cells at day 1 post-induction was significantly greater than that in undifferentiated cells. In contrast, the expression of α7 nAChR mRNA was significantly down-regulated in differentiated cells at 1 and 3 days post-induction, and the expression level of γ-secretase mRNA was also significantly reduced in differentiated cells at 3 days post-induction. Interestingly, no significant difference of the expression of APP mRNA was detected. Our findings in this study indicate that the patterns of mRNA expression of AD related-genes in NG108-15 cells are changed after differentiation induction by Bt 2 cAMP and TPA.

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“…Roman et al 23 reported a combined analysis of the 2 largest randomized, double-blind, placebo-controlled, 24-week studies involving 1219 patients, and Passmore et al 24 conducted a meta-analysis of 10-clinical trials for donepezil. The donepeziltreated VaD patients had significant benefits in cognition and global function.…”

Section: Treatmentmentioning

confidence: 99%

Advances in Vascular Cognitive Impairment 2005

Chui

Skoog

2006

Stroke

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VaD is purported to be more common than AD in Asia. In a study of 34 807 persons, aged 65 or older, living in several Chinese communities, Zhang et al 4 reported a prevalence of 4.8% for AD and 1.1% for VaD. These results suggest that the prevalence of dementia subtypes in China is similar to Western countries. It should be noted, however, that the application of NINDS-AIREN criteria and the absence of brain imaging may underestimate the extent of underlying CVD.Costs related to VCI for society and individuals have been examined. According to 2 studies 5,6 annual utilization of health care resources and primary caregivers are higher for VaD than AD. In the CHS cohort, 7 median survival from dementia onset to death was shorter in VaD (3.9 year) than in AD (7.1 years) and cognitively normal controls (11.0 years). This is not surprising, because VaD would be associated with higher cardiovascular mortality.The role of inflammation, infection, and antioxidants have been explored. In the Rotterdam Study 8 levels of fibrinogen, but not C-reactive protein, were associated with an increased risk of AD and VaD. In a Japanese case-control study, 9 antibodies against Chlamydia pneumoniae were found more often in VaD than in AD. In the Canadian Study of Health and Aging, 10 subjects reporting any antioxidant vitamin-use at baseline showed a significantly lower risk for incident VCI, but not dementia or AD. These data are intriguing but preliminary. NeuroimagingAssociations between WMH, neuropsychological impairment and brain atrophy have been studied. The prospective, population-based Rotterdam Scan Study 11 observed periventricular WMH, generalized brain atrophy, and brain infarcts on MRI to be associated with steeper decline in information processing speed and executive function during 5.2 yearsmean follow-up. In a clinical study on 69 patients with dementia, those with severe WMH displayed greater executive/visuoconstructional impairment relative to memory/language disabilities, whereas those with milder white matter abnormalities displayed relatively more memory/language disabilities. 12 In a sample of 50 AD, 13 mixed AD/subcortical vascular dementia (SVD) and 77 cognitively-intact controls, WMH correlated with cortical gray matter atrophy, but not with hippocampal or entorhinal atrophy. 13 Assuming that medial temporal atrophy is a marker for AD, whereas WMH is a marker for SVD, these findings suggest AD and SVD are independent processes and that both contribute to cortical gray matter atrophy. Thus, WMH appears to contribute to cognitive decline and loss of brain volume in the elderly. PathologyHeterogeneity and overlap pose ongoing challenges for the pathological classification of VaD. Among 175 autopsied VaD cases, only 49 (28%) were classified as "pure" VaD (ie, with only 1 type of vascular brain lesion and without AD pathology). 14 Of these, 36 had small vessel disease, 7 large vessel disease, and 6 hypoxic-hypoperfusion injury. The remaining 126 cases (72%) showed, in addition to Alzheimer pathology, a mixture of ...

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Cognitive, global, and functional benefits of donepezil in Alzheimer's disease and vascular dementia: results from large-scale clinical trials

Cited by 30 publications

References 23 publications

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

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

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Advances in Vascular Cognitive Impairment 2005

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