Donepezil Effect on Visual Attention and Training

Donepezil Effect on Visual Attention and Perceptual Training in Healthy Young Adults

The present proposal investigates the role of the cholinergic system (the neurotransmitter acetylcholine) in improving vision and visual attention. Vision results from a complex processing of particular stimuli of the visual field. Attention enhances and prolongs the neural representations of visual input in the visual cortex. It has recently been shown that attention in the visual cortex depends on cholinergic mechanisms. The action of acetylcholine in the visual cortex consists in enhancement of the responsiveness to thalamocortical inputs, depression of local neuronal connections or extrastriate feedback projections and induction of gamma synchronisation. The investigators hypothesize that these effects are associated with long-term changes in functional connectivity in the visual cortex, visual attention and visual learning (improvement of the visual capacities).

In the present proposal, the investigators will test whether the administration of donepezil (Aricept, 5mg), a drug that increases the level of acetylcholine in the brain, will enhances the perceptual-cognitive abilities of young adult subjects. Perceptual-cognitive performance will be assessed in a multiple object tracking (MOT) task in a 3D automatic virtual environment. MOT is a task where observers are asked to maintain attentional focus on a limited number of preselected subgroup of elements in a dynamic scene. Multifocal attentional mechanisms are necessary to process the information. The task will be tested five time at one week interval to test whether donepezil and training improved the task performance of the subject, i.e. lead to perceptual learning. This study could help establish an intervention procedure to improve visual performance of subjects that need it.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Donepezil administration; Drug: Placebo administration

Detailed Description

Stages of a given perceptual-cognitive task (from Faubert and Sidebottom, Journal of Clinical Sport Psychology, 2012, 6, 85-102):

1. a predetermined number of spheres (typically eight) are presented in a 3D dimensional virtual volumetric cube space. The spheres are typically all identical.
2. a subset of spheres (typically four) is indexed via highlighting for a brief period of 1 s.
3. the spheres return to their original color and start moving within the restricted 3D virtual space. During this movement, the spheres can collide and consequently suddenly change direction, and they can cross over others, thus occluding their view.
4. the spheres stop moving after a predetermined time, and the observer has to identify the spheres that were initially indexed with halos. The subject is then given feedback on the response by having the spheres identified by revealing the appropriate indexed stimuli.

The main task starts at a given speed, and if all four spheres are not correctly identified, the next trial will be slower. If the four spheres are correctly identified, then the next trial will be faster. Trials are repeated like this following a staircase procedure, and ultimately, a speed threshold is established.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H3T 1P1
      • School of optometry / Université de Montréal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• good general health
• 17 < body mass index < 25
• visual acuity 6/6
• visual stereoscopy > 50
• standard visual field

Exclusion Criteria:

• pregnancy or breast feeding
• use of any drug or St John's wort
• smoking
• asthma
• pulmonary obstruction
• cardiovascular impairment
• attention troubles
• ocular diseases
• epilepsy
• lactose intolerance
• absorption of grapefruit juice

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Donepezil; Donepezil administration. In this group Donepezil (Aricept pill, 5 mg) will be orally administrated 3h before each experiment (1 week intervals)	Drug: Donepezil administration; Other Names: Aricept, Pfizer
Placebo Comparator: Lactose pill; Placebo administration. In this group, placebo (lactose pill) will be orally administrated 3h before each experiments (1 week intervals)	Drug: Placebo administration; Other Names: Lactose pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of the speed threshold, baseline	The speed of the moving spheres is increased across trials until the subject is not able anymore to track and identify the indexed spheres (speed threshold). In this baseline task, the subject will not take Donepezil or placebo	week 0
Change from baseline of the speed threshold at 1 week	The speed of the moving spheres is increased across trials. The maximal speed for which the subject is able to track and identify the indexed spheres is the speed threshold. At this time point, the effect of Donepezil (5 mg, single dose) or placebo administration on the perceptual-cognitive performance will be assessed.	week 1
Change from baseline of the speed threshold at 2 weeks	The speed of the moving spheres is increased across trials. The maximal speed for which the subject is able to track and identify the indexed spheres is the speed threshold. At this time point, the effect of Donepezil (5 mg, single dose) or placebo administration on the perceptual-cognitive performance will be assessed.	week 2
Change from baseline of the speed threshold at 3 weeks	The speed of the moving spheres is increased across trials. The maximal speed for which the subject is able to track and identify the indexed spheres is the speed threshold. At this time point, the effect of Donepezil (5 mg, single dose) or placebo administration on the perceptual-cognitive performance will be assessed.	week 3
Change from baseline of the speed threshold at 4 weeks	The speed of the moving spheres is increased across trials. The maximal speed for which the subject is able to track and identify the indexed spheres is the speed threshold. At this time point, the effect of Donepezil (5 mg, single dose) or placebo administration on the perceptual-cognitive performance will be assessed.	week 4

Collaborators and Investigators

• Sponsor: Université de Montréal
• Investigators: Study Director: Elvire Vaucher, PhD, Université de Montréal; Study Director: Jocelyn Faubert, PhD, Université de Montréal; Principal Investigator: Isabelle Legault, PhD, Université de Montréal; Principal Investigator: Mira Chamoun, MSc, Université de Montréal

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: November 20, 2012
• First Submitted That Met QC Criteria: November 27, 2012
• First Posted (Estimate): November 30, 2012

Study Record Updates

• Last Update Posted (Actual): June 5, 2017
• Last Update Submitted That Met QC Criteria: June 1, 2017
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: acetylcholine; cholinergic system; visual perception; perceptual learning; vision training; visual attention; multiple objects tracking
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: 12-084-CERES