Citicoline Improves Human Vigilance and Visual Working Memory: The Role of Neuronal Activation and Oxidative Stress

26 Oct.,2023

 

Abstract

Introduction:

Psychomotor performance task is used to assess the arousal and cognitive functions of the central nervous system. Alternatively, human visual working memory reflects the capability of the individual’s short-term memory. Psycho-mental stimuli are linked to the stimulation of Malondialdehyde (MDA) formations. Citicoline is a nootropic nucleotide agent with a favorable effect on the augmentation of human memory and cognitive function. Thus, the purpose of this study was to determine the effect of citicoline on human vigilance, visual working memory, and oxidative stress using healthy volunteers.

Methods:

40 healthy volunteers were enrolled and divided into two groups: group A: 20 volunteers received 500mg/day starch capsule for two weeks and group B: 20 volunteers received 500mg/day citicoline capsule for two weeks. Human vigilance, visual working memory, and oxidative stress markers of each volunteer were assessed before and after citicoline and placebo intake. The obtained data were analyzed by SPSS regarding P<0.05 as statistically significant.

Results:

Placebo had no significant effect on human vigilance and visual working memory after two weeks of therapy (P>0.05), whereas citicoline improved most variables of psychomotor performances and working memory (P<0.01). Placebo significantly increased serum MDA levels from 19.44±2.11 to 29.66±3.28 nmol/mL (P=0.0001), while citicoline significantly decreased MDA serum levels from 19.11±2.66 to 15.63±1.33 nmol/mL (P=0.0001).

Conclusion:

Citicoline improves human psychomotor vigilance, arousal, and visual working memory with significant amelioration of oxidative stress compared with placebo.

Keywords:

Placebo, Citicoline, Human Vigilance, Critical fusion Frequency, Working memory

Highlights

  • Citicoline improves human psychomotor performances and working memory accuracy.

  • Citicoline attenuates high vigilance induced-oxidative stress.

  • Citicoline provokes cognitive functions in normal healthy volunteers.

Plain Language Summary

Citicoline is a nootropic nucleotide agent with a positive effect on the conservation of the neurons and augmentation of human memory and cognitive functions. We examined the effect of citicoline on psychomotor performances and working memory accuracy in relation to the oxidative stress in healthy volunteers. Our results demonstrated that citicoline advances psychomotor performances and working memory precision with the noteworthy lessening of oxidative stress compared with controls in both genders.

2. Materials & Methods

This study was conducted in the Department of Clinical Pharmacology, College of Medicine, Al-Mustansiriya University and approved by the Scientific Adjudicators and Ethical Committee of Student Research Center at Medical Board, College of Medicine, Al-Mustansiriya according to the revised Helsinki Declaration 2013. All of the enrolled participants provided written informed consent permission for their contributions. In this doubleblind study, 40 healthy volunteers (22 males and 18 females) were recruited from the College of Medicine with the age range of 21–22 years and divided into two groups: Group A: 20 volunteers (10 males +10 females) receiving 500mg/day starch capsule for two consecutive weeks and group B: 20 volunteers (12 males+8 females) receiving 500mg/day citicoline capsule (Pittsburgh, PA, healthy origin) for two consecutive weeks.

Starch capsules were prepared by putting 500 mg of starch in each non-gelatin soft-gel capsule and each volunteer received an adequate amount of these capsules to ensure a daily intake of one capsule per day in the morning. This research was a single-blind study; thus, the examiner was aware but the volunteer was unaware of this agent.

In this study, vigilance, visual working memory, and oxidative stress markers of each volunteer were assessed before and after citicoline or placebo intake; i.e. before the intake of the pharmaceutical agents and two weeks after the therapy.

Human vigilance was estimated by the Leeds psychomotor tester, through which Total Reaction Time (TRT), Processing Time (PT), Recognition Reaction Time (RRT), and Movement Reaction Time (MRT) were evaluated.

2.1. Measurement of human psychomotor performances and vigilance

Each participant was asked to press the central button of the device when saw the red light as soon as possible, and the mean of five readings was displayed on the digital screen. TRT (ms) represents the time from the onset of stimuli to the end of the reaction. RRT (ms) presents the time from the onset of stimuli to commencement of motor reaction. MRT (ms) represents the time from the recognition of the stimulus to the end of motor action (MRT=TRT-RRT) and finally, PT (ms) provides the latency time between RRT and MRT (PT=RRT-MRT).

2.2. Measurement of Critical Flicker Fusion Frequency (CFFF)

After the training period, each participant was asked to focus on the four red-emitting diodes located on the black panel of the psychomotor tester device. The participant was asked to press a specific mobile key as soon as possible when he or she detects flicking or fusion of emitting red light. Critical Fusion Frequency (CFF) or ascending frequency (CFFA) represents the time needed in minutes for the red light to be perceived from flickering to be steady. Critical Flicker Frequency or Descending Frequency (CFFD) represents the time needed in minutes for the red light to be perceived from steady to be flickered. Both CFFA and CFFD reflect cortical arousal activity. The range of fusion-flicker frequency was from zero to 60 Hz. Good values for CFFA should be more than 30 Hz and less than 30Hz for CFFD (CFFF= CFFA+CFFD/2) (Al-kuraishy & Al-Gareeb, 2017; Angeli, Veres, Nagy & Schneider 2016).

2.3. Measurement of the Short-Term Working Memory Accuracy test (Computerized N-Back test)

This test was carried out on the laptop screen; the eight squares at dissimilar sites were accessible repeatedly on laptop monitor at a tempo of three seconds, a response is demanded each time, and then the single site reverses in sequence. In a one-back test, the participant detects and seeks squares site in relation to the preceding square. In a two-back test, the participant tries to find the site of a square in relation to two reverse trails of the preceding square. In the three-back test, the participant detects and seeks a square site in relation to three reverse trails of the preceding square. One-back (I-back), two-back (II-back), and three back (III-back) represent a low, moderate, and high level of memory accuracy, respectively (Alkuraishy, Al-Gareeb, Albuhadilly & ALmgoter 2014). The total time needed for the measurement of vigilance, working memory, and CFFF was 10–20 min for each volunteer. Also, 5ml of the blood sample from all volunteers was taken before and after this study for the estimation of MDA, which was assessed by a specific ELISA kit (Shanghai Yuhua Biological Technology Co., Ltd. China).

2.4. Statistical analysis

Data were analyzed using Statistical Package for the Social Sciences (SPSS) software version 20 (IBM, Statics for Window, Version 20.00; Armonk, NY, USA, IBM Corp.) and expressed as Mean±SD and percentage. The paired t-test and unpaired t-test were used to detect the significance of differences regarding a P-value of less than 0.05 as significant.

Ethical Considerations

Compliance with ethical guidelines

This study was approved by the Scientific Adjudicators and Ethical Committee of Student Research Center at Medical Board, College of Medicine, Al-Mustansiriya according to the revised Helsinki Declaration 2013 (Ethics Code: 421RT; 11/9/2016).

Footnotes

Funding

This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors.

Authors’ contributions

Both authors contributed equally in data collection, data acquisition, and analysis, data interpretations, manuscript writing. Both authors approved the final version of the manuscript for publication.

Conflict of interest

The authors declared no conflict of interest.

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