Association Test Research Articles

Understanding of death and related constructs in children with suicidal thoughts and behaviors: A review and future directions.

Despite rising rates of suicidal thoughts and behaviors in children, little is known about best practices for conducting suicide risk assessments in this population. The acquisition of the concept of death occurs during childhood, and thoughts and preoccupation with death can be developmentally normative. This review highlights a critical gap in knowledge about how children with suicide ideation understand death-a foundational issue in assessing suicide risk. First, we provide an overview of studies that examined the concept of death and related constructs (e.g., preoccupation with death) among children who experienced suicidal ideation or attempted suicide, many of which date back to the 1970s and '80s. We describe indirect methods of assessing death cognitions, such as the Death Implicit Association Test, representations of death/suicidal themes in play, and the role of exposure to these themes through screens (e.g., social media, videogames). Given the potential impact of sociocultural changes since the 1970s-1980s on how children understand death, gaining a contemporary perspective on how children think about death and its relationship to suicide risk is warranted. Guided by a developmental approach, we provide recommendations for future areas of research to advance this field and inform the design of developmentally appropriate risk assessments and interventions for children.

Neighborhood-level socioeconomic disadvantage is associated with multiple cognitive domains in a community sample of older adults.

Greater neighborhood disadvantage is associated with poorer global cognition. However, less is known about the variation in the magnitude of neighborhood effects across individual cognitive domains and whether the strength of these associations differs by individual-level factors. The current study investigated these questions in a community sample of older adults (N = 166, mean age = 72.5 years, 51% women), who reported current addresses, linked to state-level Area Deprivation Index rankings, and completed remote and validated neuropsychological tests of verbal intelligence (North American Adult Reading Test), verbal fluency (Controlled Oral Word Association Test), attention (Digit Span Forward), and working memory (Digit Span Backward and Sequencing, Letter-Number Sequencing). Linear regressions tested associations between neighborhood disadvantage and each cognitive test, controlling for individual-level factors (age, sex, education). Exploratory analyses tested moderation by each individual-level factor. Independent of individual-level factors, greater neighborhood disadvantage was associated with lower cognitive performance across domains: verbal intelligence (β = 0.30, p < .001), verbal fluency (β = -0.19, p = .014), attention (β = -0.19, p = .024), and two of three tests of working memory (β = -0.17- -0.22, ps = .004-.039). Results were robust to correction for multiple comparisons and tests of spatial autocorrelation. In addition, higher neighborhood disadvantage was associated with lower verbal fluency for older - but not younger-older adults (p = .035) and with poorer working memory in women but not men (p < .001). Education did not moderate associations. Findings suggest that older adults living in more disadvantaged neighborhoods exhibit lower cognitive performance, particularly in the domain of verbal intelligence. Continued investigation of effect modification may be fruitful for uncovering for whom associations are strongest.

Zim4rv: an R package to modeling zero-inflated count phenotype on regional-based rare variants

BackgroundWith the advance of next-generation sequencing, various gene-based rare variant association tests have been developed, particularly for binary and continuous phenotypes. In contrast, fewer methods are available for traits not following binomial or normal distributions. To address this, we previously proposed a set of burden- and kernel-based rare variant tests for count data following zero-inflated Poisson (ZIP) distributions, referred to as ZIP-b and ZIP-k tests. We sought to extend the methods to accommodate negative binomial distribution and implemented these tests in a new R package.ResultsWe introduce ZIM4rv, an R package designed to analyze the association of rare variants with zero-inflated counts outcomes. Our package offers two novel models developed by our team: our previously proposed ZIP-b and ZIP-k tests, and the newly derived Negative Binomial Burden and Kernel Test (ZINB-b, ZINB-k). Additionally, we include an ad-hoc two-stage analysis, testing zero and non-zero as a binary outcome and non-zero as a continuous outcome, respectively. To showcase the utility of our platform, we applied this program to analyze neuritic plaque count data from the ROSMAP cohort.ConclusionThe R package ZIM4rv presents an integrated workflow for conducting association tests on a set of rare variants with zero-inflated counts data.

Self-harm in women in midlife: rates, precipitating problems and outcomes following hospital presentations in the multicentre study of self-harm in England.

Suicide in women in the UK is highest among those in midlife. Given the unique changes in biological, social and economic risk factors experienced by women in midlife, more information is needed to inform care. To investigate rates, characteristics and outcomes of self-harm in women in midlife compared to younger women and identify differences within the midlife age-group. Data on women aged 40-59 years from the Multicentre Study of Self-harm in England from 2003 to 2016 were used, including mortality follow-up to 2019, collected via specialist assessments and/or emergency department records. Trends were assessed using negative binomial regression models. Comparative analysis used chi-square tests of association. Self-harm repetition and suicide mortality analyses used Cox proportional hazards models. The self-harm rate in midlife women was 435 per 100 000 population and relatively stable over time (incident rate ratio (IRR) 0.99, p < 0.01). Midlife women reported more problems with finances, alcohol and physical and mental health. Suicide was more common in the oldest midlife women (hazard ratio 2.20, p < 0.01), while psychosocial assessment and psychiatric inpatient admission also increased with age. Addressing issues relating to finances, mental health and alcohol misuse, alongside known social and biological transitions, may help reduce self-harm in women in midlife. Alcohol use was important across midlife while physical health problems and bereavement increased with age. Despite receiving more intensive follow-up care, suicide risk in the oldest women was elevated. Awareness of these vulnerabilities may help inform clinicians' risk formulation and safety planning.

Life space restriction following disruptive life events: Evidence from the COVID-19 pandemic.

Restriction of life space mobility is associated with adverse health outcomes including depression, morbidity, mortality and poorer quality of life. In this study, we aimed to determine the impact of COVID-19 and associated employment loss on the life space of older adults in Singapore. An in-person survey was administered to a cohort of older Singaporeans above 50 years old (N = 1,118). Data collected included self-report measures of life space, sensory function, well-being, cognitive function, depression, frailty, and objective measures of muscle mass and body mass index. Tests of association and linear regression were performed to test the hypotheses, while accounting for the effects of health and sociodemographic covariates. The life space of older adults have significantly diminished after the pandemic. This loss remained significant despite controlling for covariates and was more pronounced amongst those who had lost employment during the pandemic. In addition, losing employment during the pandemic was associated with having smaller life spaces. Life space assessments are a potential important noninvasive marker for not only health and longevity, but the ability to sustain employment. Public health crises like the COVID-19 pandemic and employment loss negatively impacts the life spaces of older adults. It is needful to emphasize the maintenance of life space when faced with disruptive life events and provide multidisciplinary collaborative solutions to restore the quality of life amongst vulnerable older adults.

The Effect of Using Real-Time Magnetic Resonance Imaging on the Perception of EFL Vowels

This study investigated the influence of real-time Magnetic Resonance Imaging (rtMRI) videos as an innovative tool for enhancing learners' perception of English vowel sounds among Arabic-speaking learners of English as a Foreign Language (EFL). Utilizing a pretest-intervention-posttest design, the study involved forty participants who were equally divided into two groups: an experimental group and a control group. The experimental group received targeted perception-based instruction that incorporated rtMRI videos, delivered in three weekly sessions of thirty minutes each. In contrast, the control group underwent a similar instructional approach but without the use of rtMRI technology. To assess learners' progress, two tests were administered during both the pretest and posttest phases. The first test focused on the subjects' ability to associate vowel sounds with their corresponding articulatory features, while the second test evaluated their overall perception of vowel sounds. Analysis of the post-test results revealed significant improvements in the vowel-feature association test exclusively for the experimental group. Implications of these findings are discussed.

The Impact of Using Social Media, Whatsapp and Facebook, On Communication Between Teachers and Students’ Parents, Student Performance, and Data Confidentiality

This study explored the impact of social media, particularly WhatsApp and Facebook, on teacher-parent communication, student performance, and data privacy in primary schools in Riyadh, Saudi Arabia. The study focused on primary schools in Riyadh, Saudi Arabia. The sample included 160 teachers, 300 students, and 300 parents from primary schools in Riyadh. A mixed-methods approach, combining surveys and interviews, was used to collect data. Questionnaires were administered to teachers, students, and parents to collect quantitative information about social media use, student satisfaction, student performance, and data privacy issues. Interviews were conducted with a subset of participants to gain more in-depth information about their experiences and admissions. Expressive measures and inferential tests (t-tests, ANOVA), and partial least squares auxiliary state modeling (PLS-SEM) were used to analyze the data and test for associations between factors. The study found a significant positive relationship between WhatsApp use and teacher-parent communication satisfaction. There was also a direct positive relationship between communication satisfaction and student performance. However, concerns about data confidentiality were identified, Based on the findings, recommendations are made for schools, teachers, and policymakers to enhance communication between teachers and parents, improve student performance, and address data confidentiality concerns.

Relational Victimization, Coping Styles and Depressive Symptoms: A Test of Bidirectional Associations in Adolescence.

Although evidence from previous studies suggests that adolescents with negative coping styles who experienced victimization are more likely to exhibit depressive symptoms, these associations have not yet been disentangled to separate between-person differences from within-person effects. To investigate the within-person bidirectional relationships among relational victimization, coping styles and depressive symptoms, this study conducted a four-wave random intercept cross-lagged panel model analysis. The final sample consisted of 1506 adolescents, 72.6% of whom were male, with a mean age of 10.90 years (SD = 1.12) at the first time point. The findings revealed a prospective within-person association between relational victimization and depressive symptoms, and a reciprocal within-person relationship between depressive symptoms and avoidance coping. The approach coping style negatively predicted depressive symptoms over time, whereas depressive symptoms did not affect the approach coping style. These findings show how depressive symptoms, relational victimization, and coping styles are related at the individual level, extending previous research through the demonstration of stable within-person associations over time.

Pattern of omission bias across various measures of moral judgement: Insights from the use of Young et al. (2007) vignettes.

People are more forgiving towards harmful inaction (omission) over harmful action (commission), even when the eventual outcome is identical-known as omission bias. This phenomenon is observed in a set of moral vignettes by Young et al. that was originally designed to investigate moral judgement based on the presence of harmful intent and outcome. However, studies that used this set of vignettes have never reported the "action/omission" distinction effect, thus overlooking or conflating the impact of omission bias and potentially complicating the understanding of the targeted moral construct. In this report, we demonstrate how this omission bias may have inadvertently been incorporated into Young et al. vignettes. We analysed data from two published studies by separating the values of each moral measure into action and omission, and included them as an additional two-level factor into the model used in each included study. Overall, our results revealed statistically significant effect of omission bias. Interestingly, this effect was observed only in explicit but not implicit measures (i.e., implicit association test (IAT)), though both measures were able to capture their intended effect of "intent-outcome"-based moral reasoning. Furthermore, this report offers preliminary insights into how the action-omission asymmetry relates to intent-outcome-based moral reasoning across various categories of moral judgement, suggesting avenues for future exploration.

Epidemiology, risk factors, and awareness of mycetoma among residents in Eastern Sinnar locality, Sudan, 2021.

Mycetoma is a chronic granulomatous disease affecting the skin, subcutaneous tissues, and bones, particularly in tropical and subtropical regions. Sudan, especially its Eastern Sinnar locality, experiences a significant burden due to environmental conditions and limited access to healthcare, while the population's lack of awareness and understanding often leads to delays in diagnosis and treatment. We conducted a descriptive cross-sectional, community-based study in Eastern Sinnar, Sudan, to investigate the prevalence, risk factors, and awareness of mycetoma among local residents. Using Cochran's formula, we calculated a required sample size of 400 participants from a total population of 245 201. Then, we randomly selected these participants from five villages chosen through stratified sampling. Data were collected via a validated questionnaire assessing sociodemographic characteristics and mycetoma-related information, a review of medical records to confirm infection types and prevalence, and interviews with the Directorate of the Mycetoma Centre in Sinnar. We used χ2 tests for associations in our analysis, with P-values ≤0.05 indicating statistical significance. The mycetoma prevalence was 5.4%, with males comprising 76.4% of infected cases. However, the difference in infection rates between genders was not statistically significant (P = 0.248). While infection rates were higher among certain occupational groups, such as farmers and shepherds, the association between occupation and mycetoma infection was non-significant (P = 0.107). We also found no significant associations with educational level (P = 0.104) or age (P = 0.514), but did detect significant associations for family history of infection (P < 0.001), animal ownership (P = 0.004), and not wearing shoes during work (P = 0.05). Awareness of mycetoma was relatively high, with 78.3% of respondents acknowledging the disease, though knowledge gaps remained, especially regarding its transmission, with only 36.1% believing it to be transmissible. The study highlights the need for targeted health education programmes, particularly emphasising protective footwear and safe animal-handling practices. These findings are crucial for informing public health strategies aimed at reducing the burden of mycetoma in endemic regions such as Eastern Sinnar.

Changes in Brain Functional Connectivity Underlying the Space-Number Association.

Whether small number magnitudes are inherently represented as lying to the left of larger ones, the space-number association (SNA), is an important issue in mathematical cognition. In this fMRI study, we used a go/no-go implicit association task to investigate the brain activity and functional connectivity underlying the SNA. Arabic digits lower or higher than 5 and left- or right-pointing arrows were alternated as central targets. In a single-code task condition, participants responded to a specific number magnitude and to all arrows or to a specific arrow direction and to all number magnitudes. In a joint-code (JC) condition, responses were provided after congruent, for example, "go when a number is lower than 5 or an arrow points left," or incongruent, for example, "go when a number is lower than 5 or an arrow points right," SNAs. The SNA was only found in the JC condition, where responses were faster with congruent instructions. Analyses of fMRI functional connectivity showed that the SNA was matched with enhanced excitatory inputs from ACC, the left TPJ, and the left inferior frontal gyrus to the left and right intraparietal sulcus (IPS). Incongruent JC trials were associated with enhanced excitatory modulation from ACC to the left and right IPS. These results show that the SNA is associated with enhanced activation of top-down brain control and changes in the functional interaction between the left and right IPS. We conclude that the SNA does not depend on an inherent and bottom-up spatial coding of number magnitudes.

Narrative mobile video game-based cognitive training to enhance frontal function in patients with mild cognitive impairment

Although cognitive training has been proposed as a possible therapeutic modality for mild cognitive impairment (MCI), most serious games focus on specific tasks. This study aimed to investigate the feasibility and efficacy of narrative video game-based cognitive intervention for MCI. A four-week (± 1-week) mobile game intervention was given to 17 MCI participants (mean age (SD) = 72.8(4.75)). At baseline and post-intervention, the participants received neuropsychological tests and a depression scale. Frontal function was assessed using the Corsi block-tapping test, Color Word Stroop Test, Controlled Oral Word Association Test, Digit Symbol Coding, and Trail Making Test-Elderly’s Version; depression was assessed using the Geriatric Depression Scale. User’s compliance and gaming experience were also evaluated. MCI patients showed significant improvements in frontal function, particularly in Digit Symbol Coding (mean ± SD, 0.47 ± 0.49, p = 0.007) and phonemic fluency (mean ± SD, 0.39 ± 0.55, p = 0.024). Each frontal subtest’s mean z-score was increased (mean ± SD, 0.44 ± 0.38, p = 0.008). Block span and depression scale remained unchanged. High adherence rates (122.35%) and favorable feedback on the gaming experience indicated that the game intervention’s usability boosted patients’ motivation and engagement. Our findings demonstrate that narrative game-based cognitive intervention was not only beneficial but also enjoyable for elderly MCI.

General Kernel Machine Methods for Multi-Omics Integration and Genome-Wide Association Testing With Related Individuals.

Integrating multi-omics data may help researchers understand the genetic underpinnings of complex traits and diseases. However, the best ways to integrate multi-omics data and use them to address pressing scientific questions remain a challenge. One important and topical problem is how to assess the aggregate effect of multiple genomic data types (e.g. genotypes and gene expression levels) on a phenotype, particularly while accommodating routine issues, such as having related subjects' data in analyses. In this paper, we extend an existing composite kernel machine regression model to integrate two multi-omics data types, while accommodating for general correlation structures amongst outcomes. Due to the kernel machine regression framework, our methods allow for the integration of high-dimensional omics data with small, nonlinear, and interactive effects, and accommodation of general study designs. Here, we focus on scientific questions that aim to assess the association between a functional grouping (such as a gene or a pathway) and a quantitative trait of interest. We use a kernel machine regression to integrate the two multi-omics data types, as they may relate to the trait, and perform a global test of association. We demonstrate the advantage of this approach over single data type association tests via simulation. Finally, we apply this method to a large, multi-ethnic data set to investigate how predicted gene expression and rare genetic variation may be related to two platelet traits.

Assessment of Quality of Life in Mothers of Visually Impaired Children.

To assess the factors that affect mothers' quality of life (QOL) and the association of various demographic variables with QOL of the respondents. A cross-sectional survey. Place and Duration of the Study: Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan, from April to September 2023. Mothers of visually impaired children were selected through non-probability consecutive sampling. WHO QOL-BREF was used to analyse the QOL of the respondents. The Chi-square test of association was applied to determine the factors of QOL of the respondents. Out of 264, the majority of the visually impaired children were females (n = 144, 54.5%) and belonged to 5-8 years of age (n = 115, 43.6%). It was also noted that the majority of children had mild levels of visual impairment (n = 182, 69%). More than half of the mothers of visually impaired children were married to their cousins (n = 144, 54.5%) and belonged to rural areas (n = 140, 53%). Most of the mothers perceived that they had a good quality of life (n = 96, 36%) and were satisfied with their health status (n = 107, 40%). Mothers with poor QOL were slightly more in numbers compared to those with good QOL (n = 134. 51% vs. n = 130. 49%). Mothers of visually impaired children exhibited poor QOL in all four domains. Major related factors associated with poor QOL of mothers were the age of the child, cause of disability, duration of disability, and duration of caregiving. While mother's related factors included marital status, outside family marriage, education, income level, number of children, and residence. Mothers, Quality of life, Rawalpindi, Tertiary care hospitals, Visually impaired children.

Pain Catastrophizing and Substance Misuse: A Scoping Review of the Literature

Abstract Background Pain catastrophizing, or the interpretation of pain as unbearable or intolerable, can increase pain-related anxiety and severity. High levels of pain catastrophizing have also been linked to substance use, particularly for substances with analgesic properties. Importantly, behavioral treatments can reduce pain catastrophizing, making them promising interventions for mitigating pain-related substance use. The aim of this scoping review is to summarize literature investigating the relationship between pain catastrophizing and substance use in adults. Methods We performed a scoping review of peer-reviewed literature. Included articles had both a measurement of pain catastrophizing and substance use, and reported analyses characterizing the relationship between the two. Results Of the 341 abstracts identified, 47 articles met eligibility criteria. Most studies focused on people with chronic pain. Some studies also considered samples with substance use disorders (with and without chronic pain) or acute pain, and general population samples. There was generally a positive association between pain catastrophizing and substance misuse; this association was consistent across multiple samples and substances. Most studies were cross-sectional, although associations were also detected in longitudinal studies. The magnitude of associations tended to be stronger for higher severity substance use and more proximal tests of association. More longitudinal and experimental studies are needed, however, to better delineate these effects. Discussion Findings indicate a consistent positive association between pain catastrophizing and substance use, highlighting the potential for interventions targeting pain catastrophizing to reduce negative substance-related consequences.

The relationship between the early life gastrointestinal microbiome and childhood nocturnal cough.

Nocturnal cough affects approximately 1 in 3 children, can negatively impact child health, and is often attributable to asthma. The association of the gut microbiome with nocturnal cough has not been investigated. To investigate the association between early-life gut microbiome composition and nocturnal cough overall and in the context of asthma. Gut microbiota 1-month (neonate) and 6-month (infant) specimens from 512 children in the Wayne County, Health, Environment, Allergy, and Asthma Longitudinal Study were profiled using 16S rRNA V4 sequencing. Nocturnal cough (parental-report) and asthma (parental-reported doctor diagnosis) were assessed at age 4 years. Microbiome Regression-Based Kernel Association Tests were used to assess the relationship between gut microbiota composition and nocturnal cough overall and in the context of asthma. Operational taxonomic unit (OTU) associations were conducted using negative binomial regression, adjusting for multiple comparisons using the false discovery rate (FDR). Stool microbial composition differences during infancy were associated with nocturnal cough (Weighted Unifrac p=0.045). 78 OTUs were significantly associated with nocturnal cough overall (FDR<0.05). 110 OTUs were significantly associated with nocturnal cough and differed by asthma status (interaction FDR<0.05), with predominance of Lachnospiraceae Blautia and Dorea. 32 OTU were identified as having both overall effects and differences by asthma status. Among OTUs with significant nocturnal cough-by-asthma interactions, 84 retained significance in children with asthma, with 45 exclusive to those with asthma (predominance of Bacteroidaceae Bacteroides and Lachnospiraceae Dorea). Infantile gut microbiome development is associated with nocturnal cough and differed by asthma status by age 4 years. Further studies are needed to determine if the gut microbiome may provide additional information for the early identification of children at risk for nocturnal cough, with and without asthma.

The effect of nature on creativity through mental imagery.

Immersion in nature has been linked to wide-ranging benefits on mental health and cognitive functions, from reducing stress to enhancing creativity. However, a walk in nature is not always feasible, and whether a proxy for nature immersion via a mental walk in nature can elicit the same benefits as a physical walk remains largely unknown. Accordingly, the current study utilized guided imagery to examine whether a mental walk in nature would improve creativity in general and when compared to a mental walk in an urban environment. We implemented a within-subjects design, wherein participants completed both mental walk conditions (in a nature and urban environment) at least five days apart in counterbalanced order on an online platform. During each session, participants (N = 97) completed two pre-walk tasks assessing convergent (measured by the Remote Associates Test) and divergent creative thinking (measured by the Alternate Uses Test), followed by a mental walk in either a nature or urban environment, then finally the identical two post-walk creativity tasks. After five days, they repeated the same procedure with a mental walk in the other environment. While comparisons of post-walk creativity scores between the nature and urban environment did not significantly differ from each other, the comparisons between the pre- and post-walk creativity scores revealed a significant improvement in convergent creative thinking in the nature environment condition, but not the urban environment condition. Our results suggest that taking a mental walk in nature can enhance at least one aspect of creativity, therefore providing preliminary evidence for the potential to access the creative benefits of mentally immersing ourselves in nature. These findings have important implications for those who wish to enjoy the benefits of nature but are unable to readily access nature physically.

Effect of Cashew Nut Consumption on Biomarkers of Copper and Zinc Status in Adolescents with Obesity: A Randomized Controlled Trial.

Children and adolescents with obesity have altered serum copper (Cu) and zinc (Zn) levels, which are associated with oxidative stress, inflammation, and health outcomes. The inclusion of cashew nuts in an adequate diet may provide health benefits and help improve the mineral status of individuals with obesity. To evaluate the effects of cashew nut consumption on biomarkers of Cu and Zn status in adolescents with obesity. This was a randomized controlled trial conducted in adolescents. The participants were divided into a control group (CON) and a cashew nut group (CASN). The CASN group received 30 g/day of roasted cashew nuts for 12 weeks, and both groups received nutritional counseling during the study. Anthropometric, dietary, and biochemical parameters (Zn, Cu, and superoxide dismutase (SOD)) were assessed at the baseline and at the end of the study. Association tests, within-group and between-group mean comparisons, and analyses of variation between study periods (Δ T12-T0) were performed. The sample consisted of 81 adolescents who completed the intervention period, resulting in 54 in the CASN group and 27 in the CON group. After the intervention, the CASN group presented a decrease in plasma Cu (p = 0.004) and an increase in SOD (p = 0.030). Both groups showed an increase in plasma Zn (p < 0.050) and a decrease in the Cu/Zn ratio (p < 0.001). CASN had a negative effect on the Cu concentration, which was significantly different from that of CON (p = 0.004). The consumption of cashew nuts for 12 weeks reduced plasma Cu levels in adolescents with obesity. Nutritional counseling may have contributed to the increase in plasma Zn levels in all the study participants.

Teaching Environmental Sustainability Topics with Flipped Learning Model Enriched with STEM Activities

This study aims to reveal the effect of the flipped learning model enriched with STEM activities on students' cognitive structures related to environmental sustainability concepts and to present the design, implementation, and evaluation processes of these activities. The study group consisted of 28 female students in the eighth-grade of secondary school. Word Association Test was used as a data collection tool. In the analysis of the word association tests, the cut-off points were determined by creating a frequency table of the number of words written by the students about the concepts in the word association tests. It was determined that there was a difference between the students' answers to the key concepts given in the word association test (waste, garbage, recycling, reuse, recovery, environmental pollution, sustainability) in the pre-test (f= 611) and post-test (f= 1943) and that they frequently included various concepts in the post-test that they did not include in the pre-test. In addition, it was revealed that the key concepts were meaningfully associated with the activity topics of the research in the post-test. In line with the findings obtained, it was concluded that the students' previously existing weak cognitive structures towards the concepts related to environmental sustainability improved after the activities.

The Effect of Levetiracetam on Improving Cognitive Impairment in Relapsing-Remitting Multiple Sclerosis Patients: A Pilot Double-Blind Randomized Placebo-Controlled Clinical Trial

Background: Cognitive impairment has been identified in all stages and affects all subtypes of multiple sclerosis (MS) (40 - 65% of people with clinically definite MS). A defined therapeutic strategy has not yet been determined. Objectives: This study aimed to assess the efficacy of levetiracetam (LEV) to improve cognitive impairments in patients with relapsing-remitting MS (RRMS). Methods: A Pilot randomized; double-blinded, placebo-controlled clinical trial was conducted. The patients with a definite diagnosis of RRMS treated with first-line drugs. They were assigned into two groups; LEV and the placebo for four months. The primary outcome was the changes in cognitive domains based on the minimal assessment of cognitive function in multiple sclerosis (MACFIMS) compared to baseline. The MACFIMS was accomplished by seven tests: California verbal learning test-II (CVLT-II), paced auditory serial addition test (PASAT), symbol digit modalities testing (SDMT), brief visuospatial memory test-revised (BVMT-R), delis-Kaplan executive function system (D-KEFS), controlled oral word association test (COWAT), and judgment of line orientation (JLO). Results: A total of 32 patients entered the study and 28 patients completed the trial. The change in JLO score in the LEV group was significantly greater than in the placebo group (P-value = 0.03). After intervention in the LEV group, the SDMT and JLO scores were significantly higher than the baseline scores. Conclusions: This is the study to evaluate the effects of LEV on cognitive disorders in patients with MS. Levetiracetam was significantly effective in improving the JLO and SDMT scores in patients with RRMS compared to the placebo group.