Donepezil Improves Cognition and Global Function in Alzheimer Disease&lt;subtitle&gt;A 15-Week, Double-blind, Placebo-Controlled Study&lt;/subtitle&gt;

Rogers, Sherise C.

doi:10.1001/archinte.158.9.1021

Cited by 682 publications

(460 citation statements)

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“…Donepezil was developed to treat patients with Alzheimer's disease as an acetylcholinesterase inhibitor [12,13]. Donepezil prevents neurons from apoptosis and degeneration [19][20][21][22] and improves cognitive abilities in patients with Alzheimer's disease [23][24][25]. However, only few studies have focused on the angiogenesis accelerating effects of donepezil [26].…”

Section: Discussionmentioning

confidence: 99%

Donepezil, an acetylcholinesterase inhibitor against Alzheimer's dementia, promotes angiogenesis in an ischemic hindlimb model

Kakinuma

Furihata²,

Akiyama

et al. 2010

Journal of Molecular and Cellular Cardiology

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Section: Discussionmentioning

confidence: 99%

Donepezil, an acetylcholinesterase inhibitor against Alzheimer's dementia, promotes angiogenesis in an ischemic hindlimb model

Kakinuma

Furihata²,

Akiyama

et al. 2010

Journal of Molecular and Cellular Cardiology

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“…In phases II and III controlled trials with AD patients, the cholinesterase inhibitor donepezil significantly improved cognitive function, as measured with the AD Assessment Scale-Cognitive subscale and the Mini-Mental State Examination, MMSE, and global clinical assessment of change compared with placebo (Rogers, 1998;Rogers et al, 1998;Rogers and Friedhoff, 1996). A study of donepezil by Ogura et al (2000) achieved effects on water maze performance similar to the nicotine effects described in the studies by Levin et al: donepezil significantly decreased errors in the radial maze in rats with central cholinergic deficits.…”

Section: Acetylcholinesterase Inhibitorsmentioning

confidence: 99%

“…In contrast to our nicotine study, we chose to administer donepezil during a 30-day period rather than as a single dose because (1) prior studies have shown that chronic donepezil administration improves cognition of AD patients (Rogers, 1998;Rogers et al, 1998); (2) there is a lack of studies on the effects of chronic donepezil administration on cognition of healthy normal subjects; and (3) a prior study found that acute donepezil administration had no significant pharmacodynamic effects on cognition (Nathan et al, 2001). In our placebo-controlled study of donepezil, the drug group performed better on a set of complex flight simulator tasks than the placebo group after a 30-day treatment (Yesavage et al, 2002).…”

Section: Acetylcholinesterase Inhibitorsmentioning

confidence: 99%

Psychoactive Drugs and Pilot Performance: A Comparison of Nicotine, Donepezil, and Alcohol Effects

Mumenthaler

Yesavage

Taylor

et al. 2003

Neuropsychopharmacol

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The cholinergic system plays a major role in cognitive abilities that are essential to piloting an aircraft: attention, learning, and memory. In previous studies, drugs that enhance the cholinergic system through different pharmacologic mechanisms have shown beneficial effects on cognition; but dissimilar cognitive measures were used and samples were not comparable. A comparison within the same cognitive tasks, within comparable samples appears desirable. Toward this aim, we compared effect sizes (ES) of performance-enhancing doses of nicotine (a nicotinic receptor agonist) and donepezil (an acetylcholinesterase inhibitor) as found in our prior work on pilot performance. We also compared cholinergic ES to those of performance-impairing doses of alcohol. In three randomized, placebo-controlled trials, we assessed the flight performance of aircraft pilots in a Frasca 141 simulator, testing I: the acute effects of nicotine gum 2 mg; II: the effects of administration of 5 mg donepezil/day for 30 days; and III: the acute and 8 h-carryover effects of alcohol after a target peak BAC of 0.10%. We calculated the ES of nicotine, donepezil, and alcohol on a flight summary score and on four flight component scores. Compared to placebo, nicotine and donepezil significantly improved, while alcohol significantly impaired overall flight performance: ES (nicotine) ¼ 0.80; ES (donepezil) ¼ 1.02; ES (alcohol acute) ¼ À3.66; ES (alcohol 8 h) ¼ À0.82. Both cholinergic drugs showed the largest effects on flight tasks requiring sustained visual attention. Although the two tested cholinergic drugs have different pharmacologic mechanisms, their effects on flight performance were similar in kind and size. The beneficial effects of the cholinergic drugs on overall flight performance were large and the absolute (ie nondirectional) sizes were about one-fourth of the absolute ES of acute alcohol intoxication and roughly the same as the absolute 8 h-carryover ES of alcohol.

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“…Cholinergic processes in neocortical areas are affected in Alzheimer's disease (Geula and Mesulam, 1989;Heckers et al, 1992) and are particularly apparent late in the course of Alzheimer's disease when cognitive and behavioral functions are severely impaired (Davis et al, 1999). Cholinesterase inhibitors (ChEIs) that serve to increase the availability of acetylcholine have been used successfully to treat patients with MCI (Petersen et al, 2005) and early stages of Alzheimer's disease (Doody et al, 2001;Rogers et al, 1998;Winblad et al, 2001). These results suggest that there are functional changes of the cholinergic systems projecting to neocortical regions in early stages of dementia that may anticipate the later development of behavioral deficits affecting language and motor functions (Goldman et al, 1999;Pettersson et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Cholinesterase inhibitors affect brain potentials in amnestic mild cognitive impairment

et al. 2007

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Amnestic mild cognitive impairment (MCI) is an isolated episodic memory disorder that hasa high likelihood of progressing to Alzheimer's disease. Auditory sensory cortical responses (P50, N100) have been shown to be increased in amplitude in MCI compared to older controls. We tested whether (1) cortical potentials to other sensory modalities (somatosensory and visual) were also affected in MCI and (2) cholinesterase inhibitors (ChEIs), one of the therapies used in this disorder, modulated sensory cortical potentials in MCI. Somatosensory cortical potentials to median nerve stimulation and visual cortical potentials to reversing checkerboard stimulation were recorded from 15 older controls and 15 amnestic MCI subjects (single domain). Results were analyzed as a function of diagnosis (Control, MCI) and ChEIs treatment (Treated MCI, Untreated MCI). Somatosensory and visual potentials did not differ significantly in amplitude in MCI subjects compared to controls.When ChEIs use was considered, somatosensory potentials (N20, P50) but not visual potentials (N70, P100, N150) were of larger amplitude in untreated MCI subjects compared to treated MCI subjects. Three individual MCI subjects showed increased N20 amplitude while off ChEIs compared to while on ChEIs. An enhancement of N20 somatosensory cortical activity occurs in amnestic single-domain MCI and is sensitive to modulation by ChEIs. IntroductionMild cognitive impairment (MCI) describes older individuals having cognitive impairments without accompanying functional impairments that characterize dementia (Petersen et al., 1999). Recent studies have suggested criteria for distinguishing among four subtypes of MCI based on the presence of both episodic memory impairment (amnestic or non-amnestic MCI) and other cognitive impairments (single-or multipledomain MCI) (Petersen, 2004). For example, amnestic singledomain MCI refers to patients with involvement of only memory deficit whereas amnestic multiple-domain MCI refers to patients with impairment of both memory and other cognitive domains such as language or executive function. MCI subjects have a high risk of converting to Alzheimer's disease Petersen et al., 1999) and show neuropathological features of β-amyloid plaques and neurofibrillary tangles similar to early Alzheimer's disease (Kordower et al., 2001;Mufson et al., 1999). These findings suggest that MCI can be a precursor of Alzheimer's disease. Cholinergic processes in neocortical areas are affected in Alzheimer's disease (Geula and Mesulam, 1989;Heckers et al., 1992) and are particularly apparent late in the course of

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Donepezil Improves Cognition and Global Function in Alzheimer Disease<subtitle>A 15-Week, Double-blind, Placebo-Controlled Study</subtitle>

Abstract: Donepezil hydrochloride (5 and 10 mg) administered once daily is a well-tolerated and efficacious agent for treating the symptoms of mild to moderately severe Alzheimer disease.

Cited by 682 publications

References 34 publications

Donepezil, an acetylcholinesterase inhibitor against Alzheimer's dementia, promotes angiogenesis in an ischemic hindlimb model

Donepezil, an acetylcholinesterase inhibitor against Alzheimer's dementia, promotes angiogenesis in an ischemic hindlimb model

Psychoactive Drugs and Pilot Performance: A Comparison of Nicotine, Donepezil, and Alcohol Effects

Cholinesterase inhibitors affect brain potentials in amnestic mild cognitive impairment

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