Donepezil in patients with severe Alzheimer's disease: double-blind, parallel-group, placebo-controlled study

Winblad, Bengt; Kilander, Lena; Eriksson, Sture; Minthon, Lennart; Båtsman, Stellan; Wetterholm, A.-L.; Jansson-Blixt, C; Haglund, Anders

doi:10.1016/s0140-6736(06)68350-5

Cited by 339 publications

(270 citation statements)

References 26 publications

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“…Both are current therapies for Alzheimer's disease and have been shown to improve cognitive ability in Alzheimer's disease patients (Burns et al, 1999;Winblad et al, 2001Winblad et al, , 2006Peskind et al, 2006;Takeda et al, 2006). In the present study, both of these compounds also increased the distance moved in response to the acoustic stimulus in a similar manner to rolipram.…”

Section: Discussionsupporting

confidence: 67%

Non-Associative Learning in Larval Zebrafish

Best¹,

Berghmans²,

Hunt³

et al. 2007

Neuropsychopharmacol

216

150

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Habituation, where a response is reduced when exposed to a continuous stimulus is one of the simplest forms of non-associative learning and has been shown in a number of organisms from sea slugs to rodents. However, very little has been reported in the zebrafish, a model that is gaining popularity for high-throughput compound screens. Furthermore, since most of the studies involving learning and memory in zebrafish have been conducted in adults, we sought to determine if zebrafish larvae could display non-associative learning and whether it could be modulated by compounds identified in previous rodent studies. We demonstrated that zebrafish larvae (7 days post fertilization) exhibit iterative reduction in a startle response to a series of acoustic stimuli. Furthermore, this reduction satisfied criteria for habituation: spontaneous recovery, more rapid reductions in startle to shorter intertrial intervals and dishabituation. We then investigated the pathways mediating this behavior using established compounds in learning and memory. Administration of rolipram (PDE4 inhibitor), donepezil (acetylcholinesterase inhibitor), and memantine (N-methyl-D-aspartic acid (NMDA) receptor antagonist) all increased the acoustic startle response and decreased habituation in the larvae, similar to previous rodent studies. Further studies demonstrated that NMDA blocked the memantine response and the effect of donepezil was blocked by mecamylamine but not atropine suggesting that the donepezil response was mediated by nicotinic rather than muscarinic receptors. Zebrafish larvae possess numerous advantages for medium to high-throughput screening; the model described herein therefore offers the potential to screen for additional compounds for further study on cognition function.

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Section: Discussionsupporting

confidence: 67%

Non-Associative Learning in Larval Zebrafish

Best¹,

Berghmans²,

Hunt³

et al. 2007

Neuropsychopharmacol

216

150

View full text Add to dashboard Cite

show abstract

“…A floor effect of a test exists if more than 15% of the respondents achieved the minimum score of the test (McHorney and Tarlov, 1995), and therefore the tests are not useful in testing cognitive function in patients with severe dementia. The SIB has been used for evaluating the effect of donepezil treatment on cognition in patients with dementia in several large RCT (Winblad et al, 2006;Feldman et al, 2001), and has been found to be able to detect changes in cognitive function over time in a group of patients.…”

Section: The Validity and Reliability Of The Norwegian Version Of Thementioning

confidence: 99%

Reliability and validity of the Norwegian version of the Severe Impairment Battery (SIB)

Bergh

Selbæk

Engedal

2008

Int J Geriat Psychiatry

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ObjectiveThe Severe Impairment Battery (SIB) is developed to test cognitive function in patients with dementia of moderate to severe degree. We have conducted a study to assess the inter‐rater reliability and the validity of the Norwegian version of SIB.MethodsThe reliability study comprised 30 patients, and the validity study 59 patients in nursing homes. We assessed Cronbach's alpha coefficient of the scale and the inter‐rater reliability for the total SIB score and its nine sub scores between two testers by means of the Spearman's correlation coefficients. In the validity study we compared the SIB scores with the scores on the Clinical Dementia Rating Scale.ResultsThe mean SIB score was 72.10 (SD 25.37). The Cronbach's alpha was 0.97, and the inter‐rater reliability of total SIB score was Spearman's rho 0.85, and ranged from 0.46 to 0.76 for the nine sub‐scores. The mean SIB score for patients with a CDR score < 2 was 84.2(13.4), whereas total scores for patients with CDR 2 and 3 were 74 (18.9) and 48.4 (33.3), respectively. A cut‐off point of 80.5 points gave the highest accuracy in discriminating between patients with CDR 2 and CDR 3, while a cut‐off point of 87.5 best discriminated between CDR < 2 and CDR 3.ConclusionThe study indicates that the Norwegian version of SIB is a reliable and valid test with which to evaluate the cognition in patients with dementia of moderate to severe degree. Copyright © 2008 John Wiley & Sons, Ltd.

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“…Dysfunction of cholinergic neurotransmission may contribute to the development of amyloid plaque pathology (Caccamo et al, 2006) and toxic soluble amyloid-b (Ab) disrupts the cholinergic neurotransmission (Bales et al, 2006). Moreover, acetylcholinesterase (AChE) inhibitors, such as donepezil, improve cognitive function in AD patients to some extent (Lane et al, 2004;Petersen et al, 2005;Winblad et al, 2006). Taken altogether, supporting cholinergic neurotransmission is deemed to be a promising strategy for AD therapy, especially for patients in the early stage of the disease, when massive and irreversible brain atrophy has not yet taken place.…”

Section: Introductionmentioning

confidence: 99%

Nasal Colivelin Treatment Ameliorates Memory Impairment Related to Alzheimer's Disease

Yamada

Chiba

Sasabe

et al. 2007

Neuropsychopharmacol

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Humanin (HN) and its derivatives, such as Colivelin (CLN), suppress neuronal death induced by insults related to Alzheimer's disease (AD) by activating STAT3 in vitro. They also ameliorate functional memory impairment of mice induced by anticholinergic drugs or soluble toxic amyloid-b (Ab) in vivo when either is directly administered into the cerebral ventricle or intraperitoneally injected. However, the mechanism underlying the in vivo effect remains uncharacterized. In addition, from the standpoint of clinical application, drug delivery methods that are less invasive and specific to the central nervous system (CNS) should be developed. In this study, we show that intranasally (i.n.) administered CLN can be successfully transferred to CNS via the olfactory bulb. Using several behavioral tests, we have demonstrated that i.n. administered CLN ameliorates memory impairment of AD models in a dose-responsive manner. Attenuation of AD-related memory impairment by HN derivatives such as CLN appears to be correlated with an increase in STAT3 phosphorylation levels in the septohippocampal region, suggesting that anti-AD activities of HN derivatives may be mediated by activation of STAT3 in vivo as they are in vitro. We further demonstrate that CLN treatment inhibits an Ab induced decrease in the number of choline acetyltransferase (ChAT)-positive neurons in the medial septum. Combined with the finding that HN derivatives upregulate mRNA expression of neuronal ChAT and vesicular acetylcholine transporter (VAChT) in vitro, it is assumed that CLN may ameliorate memory impairment of AD models by supporting cholinergic neurotransmission, which is at least partly mediated by STAT3-mediated transcriptional upregulation of ChAT and VAChT.

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Donepezil in patients with severe Alzheimer's disease: double-blind, parallel-group, placebo-controlled study

Cited by 339 publications

References 26 publications

Non-Associative Learning in Larval Zebrafish

Non-Associative Learning in Larval Zebrafish

Reliability and validity of the Norwegian version of the Severe Impairment Battery (SIB)

Nasal Colivelin Treatment Ameliorates Memory Impairment Related to Alzheimer's Disease

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