Acute effects of donepezil in healthy young adults underline the fractionation of executive functioning

Abstract

The cholinergic system is involved in the modulation of both bottom-up and top-down attentional control. Top-down attention engages multiple executive control processes, but few studies have investigated whether all or selective elements of executive functions are modulated by the cholinergic system. To investigate the acute effects of the pro-cholinergic donepezil in young, healthy volunteers on distinct components of executive functions we conducted a double-blind, placebo-controlled, independent-groups design study including 42 young healthy male participants who were randomly assigned to one of three oral treatments: glucose (placebo), donepezil 5 mg or donepezil 7.5 mg. The test battery included measures of different executive components (shifting, updating, inhibition, dual-task performance, planning, access to long-term memory), tasks that evaluated arousal/vigilance/visuomotor performance, as well as functioning of working memory subsidiary systems. Donepezil improved sustained attention, reaction times, dual-task performance and the executive component of digit span. The positive effects in these executive tasks did not correlate with arousal/visuomotor/vigilance measures. Among the various executive domains investigated donepezil selectively increased dual-task performance in a manner that could not be ascribed to improvement in arousal/vigilance/visuomotor performance nor working memory slave systems. Other executive tasks that rely heavily on visuospatial processing may also be modulated by the cholinergic system.

Effects of Short-Term Varenicline Administration on Emotional and Cognitive Processing in Healthy, Non-Smoking Adults: A Randomized, Double-Blind, Study

“…Although the present study does not suggest any influence of varenicline on emotional processing or impulsivity, it showed cognitive-enhancing effects of varenicline on working and episodic declarative memory tasks, characteristic of cholinergic agents (Ginani et al, 2011;Rokem et al, 2010). As varenicline has no affinity for muscarinic receptors, the cognitive-enhancing effect of cholinergic agents may be at least partially mediated by nACh receptors.…”

“…In addition, varenicline increased n-back task performance among abstinent smokers , consistent with cognitive-enhancing effects of central cholinergic drugs including (A)Ch-esterase inhibitors donepezil and rivastigmine (Ginani et al, 2011;Rokem et al, 2010). Although their cholinergic effects are, in contrast to varenicline, not selective to nACh receptors, it could be hypothesized that varenicline has similar cognitive-enhancing effects.…”

Executive functioning in obstructive sleep apnea syndrome patients without comorbidities: Focus on the fractionation of executive functions

“…To select the executive domains under investigation (see Ginani et al, 2011) we followed Miyake et al (2000) who showed that it is possible to dissociate executive domains including: updating, or changes of the content of working memory by deleting information that is no longer important to the task at hand and incorporation of new data; inhibition, the ability to inhibit distracting information when selecting relevant information; and shifting, the ability to alternate between different tasks. Dual-task performance, the ability to perform two tasks in parallel (Baddeley, Della Sala, Gray, Papagno, & Spinnler, 1997;Della Sala & Logie, 2001), did not associate to performance in the other domains (Miyake et al, 2000) and could thus constitute a separate cognitive entity (e.g., see Della Sala & Logie, 2001).…”

“…Executive tasks (described as in Ginani et al, 2011) • Plus-minus task (see Miyake et al, 2000): a shifting measure consisting of three lists of 32 digits (the numbers 10-99 prerandomized without replacement). For the first list, the participants are instructed to add 3 to each number.…”

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

“…In summary, RCTs with healthy individuals have been conducted mostly with donepezil (5 mg single dose or 5 mg/d). A single dose of 5 mg donepezil has been found to improve information processing [117,118], procedural, verbal and visual spatial memory [119-121] and some executive functions [122]. A positive effect of donepezil was found in voluntary but not involuntary attention in one study [123].…”