Cholinergic modulation of cognitive function in healthy subjects: acute effects of donepezil, a cholinesterase inhibitor

Nathan, Pradeep J.; Baker, Allison; Carr, Elaine; Earle, J H O; Jones, Meaghan J.; Nieciecki, Michelle; Hutchison, Chris; Stough, Con

doi:10.1002/hup.323.abs

Cited by 4 publications

(4 citation statements)

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“…Furthermore, a review by Davies (1999) challenged the cholinergic hypothesis by stating that there is no correlation between cholinergic neurotransmission and AD early in its course. A double-blind, placebo controlled study (Nathan et al, 2001) examining the acute effects of donepezil on healthy human participants showed no evidence of cognitive improvement, and Belinger et al (2004) found that chronic administration of donepezil actually worsened performance on neuropsychological tests in healthy volunteers. In effect, although theories of a fundamental relationship between the cholinergic system and cognitive functioning still abound, there is little conclusive evidence of a direct causal association.…”

Section: Chis and The Cholinergic Deficiency Hypothesis In Admentioning

confidence: 99%

Acetylcholinesterase inhibitors, neuropsychiatric symptoms, and Alzheimer's disease subtypes: An alternate hypothesis to global cognitive enhancement.

Brousseau

Rourke

Burke

2007

Experimental and Clinical Psychopharmacology

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Cholinergic neurons are extensively implicated in cognitive functioning. Cholinergic deficiency is a widely accepted hypothesis of cognitive decline in Alzheimer's disease (AD) and is the impetus for the development of cholinesterase inhibitors (ChIs). Studies on the efficacy of ChIs emphasize global cognitive improvement and the amelioration of neuropsychiatric symptoms associated with AD. The authors propose that the current perception of ChIs as global cognitive enhancers may be misleading. It is hypothesized that these drugs improve cognition in specific AD subtypes primarily through psychotropic properties that facilitate attentional processing. In effect, increased attentional capacity through diminished neuropsychiatric symptoms serves to augment results on global cognitive measures: in particular, AD subtypes.

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Section: Chis and The Cholinergic Deficiency Hypothesis In Admentioning

confidence: 99%

Acetylcholinesterase inhibitors, neuropsychiatric symptoms, and Alzheimer's disease subtypes: An alternate hypothesis to global cognitive enhancement.

Brousseau

Rourke

Burke

2007

Experimental and Clinical Psychopharmacology

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“…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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“…A positive effect of donepezil was found in voluntary but not involuntary attention in one study [123]. Conflicting results were found concerning working memory [118,124,125]. Two studies found that repeated doses of donepezil (5 mg/d during 30 days) improves episodic memory [126] and complex aviation skills [127,128] but three others found no effect or even impairment in memory, attention or executive functions especially in older subjects [129][130][131].…”

Section: Acetylcholine Esterase Inhibitorsmentioning

confidence: 92%

Neuroenhancement in Healthy Adults, Part I: Pharmaceutical Cognitive Enhancement: A Systematic Review

Micoulaud¹

2015

J Clinic Res Bioeth

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The term neuroenhancement refers to improvement in the cognitive, emotional and motivational functions of healthy individuals through inter alia, the use of drugs. This popular topic attracts attention both from the general public and the scientific community. Our objective is to summarize in a synthetic review the data of randomized placebo-controlled trials that assessed cognitive effects of administration of neuroenhancers in non-sleep-deprived healthy adults compared to placebo. The major outcomes were attention, memory, learning, executive functions, and vigilance/wakefulness. Details on the pharmacological profile, effectiveness and safety for each drug are provided. We classify them according to their recognized major primary mode of action, namely catecholaminergics (methylphenidate,

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Cholinergic modulation of cognitive function in healthy subjects: acute effects of donepezil, a cholinesterase inhibitor

Cited by 4 publications

References 0 publications

Acetylcholinesterase inhibitors, neuropsychiatric symptoms, and Alzheimer's disease subtypes: An alternate hypothesis to global cognitive enhancement.

Acetylcholinesterase inhibitors, neuropsychiatric symptoms, and Alzheimer's disease subtypes: An alternate hypothesis to global cognitive enhancement.

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

Neuroenhancement in Healthy Adults, Part I: Pharmaceutical Cognitive Enhancement: A Systematic Review

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