Genetic contributions to Trail Making Test performance in UK Biobank.

The Trail Making Test (TMT) is a widely used test of executive function and has been thought to be strongly associated with general cognitive function. We examined the genetic architecture of the TMT and its shared genetic aetiology with other tests of cognitive function in 23 821 participants from UK Biobank. The single-nucleotide polymorphism-based heritability estimates for trail-making measures were 7.9% (part A), 22.4% (part B) and 17.6% (part B-part A). Significant genetic correlations were identified between trail-making measures and verbal-numerical reasoning (rg>0.6), general cognitive function (rg>0.6), processing speed (rg>0.7) and memory (rg>0.3). Polygenic profile analysis indicated considerable shared genetic aetiology between trail making, general cognitive function, processing speed and memory (standardized ß between 0.03 and 0.08). These results suggest that trail making is both phenotypically and genetically strongly associated with general cognitive function and processing speed.

Cognitive Reserve Mediates the Relation between Openness to Experience and Smaller Decline in Executive Functioning.

AIMS: We investigated the mediating role of leisure activity engagement in the longitudinal relation between openness to experience and subsequent change in executive functioning over 6 years as measured through performance changes in the Trail Making Test (TMT). METHODS: We analyzed longitudinal data from 897 older adults (mean = 74.33 years in the first wave) tested on TMT parts A and B in two waves 6 years apart. Participants reported information on leisure activity engagement and openness to experience. RESULTS: Latent change score modeling revealed that 37.2% of the longitudinal relation between higher openness to experience in the first wave of data collection and a smaller subsequent increase in TMT completion time from the first to the second wave (i.e., a smaller decline in executive functioning) was mediated via a higher frequency of leisure activities in the first wave. CONCLUSION: Individuals with higher openness to experience show greater activity engagement in old age. By enhancing their cognitive reserve, this activity engagement may finally result in smaller subsequent decline in executive functioning.

Neuropsychological Test Norms in Cognitively Intact Oldest-Old.

OBJECTIVES: Individuals aged 90 or older (oldest-old), the fastest growing segment of the population, are at increased risk of developing cognitive impairment compared with younger old. Neuropsychological evaluation of the oldest-old is important yet challenging in part because of the scarcity of test norms for this group. We provide neuropsychological test norms for cognitively intact oldest-old. METHODS: Test norms were derived from 403 cognitively intact participants of The 90+ Study, an ongoing study of aging and dementia in the oldest-old. Cognitive status of intact oldest-old was determined at baseline using cross-sectional approach. Individuals with cognitive impairment no dementia or dementia (according to DSM-IV criteria) were excluded. Participants ranged in age from 90 to 102 years (mean=94). The neuropsychological battery included 11 tests (Mini-Mental Status Examination, Modified Mini-Mental State Examination, Boston Naming Test - Short Form, Letter Fluency Test, Animal Fluency Test, California Verbal Learning Test-II Short Form, Trail Making Tests A/B/C, Digit Span Forward and Backwards Test, Clock Drawing Test, CERAD Construction Subtests), and the Geriatric Depression Scale. RESULTS: Data show significantly lower scores with increasing age on most tests. Education level, sex, and symptoms of depression were associated with performance on several tests after accounting for age. CONCLUSIONS: Provided test norms will help to distinguish cognitively intact oldest-old from those with cognitive impairment. (JINS, 2019, 25, 530-545).

Effect of lamotrigine on cognitive function and serum inflammatory factors in patients with depression of recurrent bipolar disorder.

In the present study, an effort was made to investigate the effect of lamotrigine on cognitive function and serum inflammatory factors in patients with depression of recurrent bipolar disorder and to explore its possible mechanism.140 patients with depression of recurrent bipolar disorder, admitted from June 2015 to April 2017, were selected as the research subjects, followed by random division into the research group and the control group with 70 cases (n=70) in each group. The control group was treated with sodium valproate and the research group was treated with lamotrigine. After 2 months of treatment, comparison was made between the two groups for the emotional state, cognitive function and serum inflammatory factors. Results showed that the Hamilton Depression Scale(HAMD) score and Bech-Rafaelsen Mania Rating Scale BRMS score in the research group were significantly lower than in the control group (P<0.05). The time of Trail Making Test-A(TMT-A) and Trail Making Test-B(TMT-B) in the research group was significantly shorter than that of the control group, with a statistically significant difference (P < 0.05). The serum levels of MIF, IL-1ß and IL-6 in the research group were significantly lower than those in the control group and the difference was statistically significant (P<0.05). Research concluded that lamotrigine may help alleviate the clinical symptoms and improve cognitive function in patients with depression of recurrent bipolar disorder.

Trail making task performance in inpatients with anorexia nervosa and bulimia nervosa.

Set-shifting inefficiencies have been consistently identified in adults with anorexia nervosa (AN). It is less clear to what degree similar inefficiencies are present in those with bulimia nervosa (BN). It is also unknown whether perfectionism is related to set-shifting performance. We employed a commonly used set-shifting measure, the Trail Making Test (TMT), to compare the performance of inpatients with AN and BN with a healthy control sample. We also investigated whether perfectionism predicted TMT scores. Only the BN sample showed significantly suboptimal performance, while the AN sample was indistinguishable from controls on all measures. There were no differences between the AN subtypes (restrictive or binge/purge), but group sizes were small. Higher personal standards perfectionism was associated with better TMT scores across groups. Higher concern over mistakes perfectionism predicted better accuracy in the BN sample. Further research into the set-shifting profile of individuals with BN or binge/purge behaviours is needed.

Trail Making Test A improves performance characteristics of the International HIV Dementia Scale to identify symptomatic HAND.

Although HIV-associated dementia (HAD) occurs in less than 5 % of individuals with access to combination antiretroviral therapy, rates of milder forms of HIV-associated neurocognitive disorder (HAND) are much higher. We sought to define an optimal cut point for the International HIV Dementia Scale (IHDS) in Thailand for the identification of symptomatic HAND, defined as both HAD and mild neurocognitive disorder. We then sought to determine if adding a simple test from a larger neuropsychological battery could improve the performance characteristics for identifying symptomatic HAND. In this study, subjects comprising 75 seropositive adults in Bangkok, Thailand, completed neuropsychological tests and underwent a full neurological assessment. HAND diagnoses were determined by consensus conference using the 2007 Frascati criteria, blinded to the IHDS results. The optimal IHDS cut point was determined by receiver operating characteristic analysis with cross-validation. Individual neuropsychological tests were then evaluated and combined with the IHDS to test performance characteristics. The IHDS was poor at detecting symptomatic HAND at the optimized cut point of ≤ 10 (sensitivity, 53.3 %; specificity, 89.8 %). Trail Making Test A was most effective in improving performance characteristics when combined with the IHDS, with net sensitivity of 86 % and specificity of 79 %. In this setting, the IHDS performed poorly in identifying symptomatic HAND, but was substantially improved by the addition of Trail Making Test A, which typically requires less than 2 min to complete. This combination should be validated in a larger setting since it may address the critical need for HAND screening instruments in international settings.

Performance of older Japanese American adults on selected cognitive instruments.

This study examined cognitive test performance of second- and third-generation Japanese American (JA) adults, a relatively homogeneous Asian American subgroup. Sixty-five JA and 65 non-Hispanic White (NHW) adults, ages between 45 and 91, were administered the Boston Naming Test-2 (BNT), Letter Fluency Test, Semantic Fluency Test, California Verbal Learning Test (CVLT), Brief Visuospatial Memory Test-Revised (BVMT-R), and Trail Making Test. Levels of acculturation, quality of educational attainment, and generation status in the United States, were also collected. There were no significant differences in the scores between the two groups on the tests administered. JA and NHW groups, however, differed in the patterns of the associations between some of the test performance and demographic variables. JA adults showed a stronger age-score relationship on BNT, CVLT, and the BVMT-R. Furthermore, second-generation JA adults performed lower than the third-generation adults even after controlling for basic demographic variables on CVLT and Trail Making Test. Acculturation on the other hand did not explain score differences once demographic variables were considered. Our results suggest the importance of considering unique history and characteristics of ethnic groups, and interactions of the aging process and culture on tasks with different cognitive demands.

Executive functions and the down-regulation and up-regulation of emotion.

This study examined the relationship between individual differences in executive functions (EF; assessed by measures of working memory, Stroop, trail making, and verbal fluency) and ability to down-regulate and up-regulate responses to emotionally evocative film clips. To ensure a wide range of EF, 48 participants with diverse neurodegenerative disorders and 21 older neurologically normal ageing participants were included. Participants were exposed to three different movie clips that were designed to elicit a mix of disgust and amusement. While watching the films they were either instructed to watch, down-regulate, and up-regulate their visible emotional responses. Heart rate and facial behaviours were monitored throughout. Emotion regulatory ability was operationalised as changes in heart rate and facial behaviour in the down- and up-regulation conditions, controlling for responses in the watch condition. Results indicated that higher verbal fluency scores were related to greater ability to regulate emotion in both the down-regulation and up-regulation conditions. This finding remained significant even after controlling for age and general cognitive functioning. No relationships were found between emotion regulation and the other EF measures. We believe these results derive from differences among EF measures, with verbal-fluency performance best capturing the complex sequence of controlled planning, activation, and monitoring required for successful emotion regulation. These findings contribute to our understanding of emotion-cognition interaction, suggesting a link between emotion-regulatory abilities and individual differences in complex executive functions.

Two brief measures of executive function in the prediction of driving ability after acquired brain injury.

The question of fitness to drive following acquired brain injury is commonly encountered in rehabilitation settings. Pre-driving assessments are usually performed prior to on-road assessments, but there is no uniformity as to the instruments employed. Neuropsychological tests are often employed to assess different functional domains. One domain that has been suggested to be critical to driving is executive functioning. The present study examined the utility of the Frontal Assessment Battery (FAB) and the Trail Making Test Part B (TMTB) in predicting on-road driving performance after stroke or traumatic brain injury. While the TMTB has previously been demonstrated to be useful in this regard, the FAB has never been examined for this purpose. Participants were 76 patients referred for driving assessment after diagnosis of stroke or traumatic brain injury. Results indicated that scores on the TMTB, but not the FAB, were significantly predictive of on-road driving performance (p < .05). A cutoff score of 90 seconds or greater on the TMTB correctly identified 77% of those failing on-road evaluation. Implications and limitations are discussed.

Genome-wide association study identified INSC gene associated with Trail Making Test Part A and Alzheimer's disease related cognitive phenotypes.

BACKGROUND: The Trail Making Test (TMT) Part A (TMT-A) is a good measure of performance on cognitive processing speed. This study aimed to perform a genome-wide association study of TMT-A in Alzheimer's disease (AD). METHODS: A total of 757 individuals with TMT-A phenotypes and 620,901 single nucleotide polymorphisms (SNPs) were extracted from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) cohort. AD related cognitive phenotypes include TMT-A, TMT-B, Functional Activities Questionnaire (FAQ), Clinical Dementia Rating Sum of Boxes (CDR-SB), and Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS13). Multivariable linear regression analysis of TMT-A was conducted using PLINK software. The most TMT-A associated gene was tested with Color Trails Test 1 Form A (CTTA), a culturally fair analog of the TMT-A. Functional annotation of SNPs was performed using the RegulomeDB and Genotype-Tissue Expression (GTEx) databases. RESULTS: The best signal with TMT-A was rs1108010 (p = 4.34 × 10-8) at 11p15.2 within INSC gene, which was also associated with TMT-B, FAQ, CDR-SB, and ADAS13 (p = 2.47 × 10-4, 8.56 × 10-3, 0.0127 and 0.0188, respectively). Furthermore, suggestive loci were identified such as FOXD2 and CLTA with TMT-A, GBP1/GBP3 with TMT-B, GRIK2 with FAQ, BAALC and CCDC146 with CDR-SB, BAALC and NKAIN2 with ADAS13. Additionally, the best SNP within INSC associated with CTTA was rs7931705 (p = 6.15 × 10-5). Several SNPs had significant eQTLs using GTEx. CONCLUSIONS: We identified several genes/loci associated with TMT-A and AD related phenotypes. These findings offer the potential for new insights into the pathogenesis of cognitive function and Alzheimer's disease.

Normative data of neuropsychological tests of attention and executive functions in Ecuadorian adult population.

OBJECTIVE: The purpose of this study was to generate normative data for five tests of attention and executive functions (M-WCST, Stroop test, TMT, BTA, and SDMT), in a group of 322 Ecuadorian adults from Quito between the ages of 18 and 85. METHOD: Multiple regression analyzes taking into account age, education, and gender were used to generate the normative data. RESULTS: Age and education were significantly related to test performance such that scores decreased with age and improved as a function of education. An online calculator is provided to generate normative test scores. CONCLUSIONS: This is the first study that presents normative data for tests of executive functions and attention in an Ecuadorian adult population. This data will improve the clinical practice of neuropsychology and help to develop the field in the country.

Normative data for tests of attention and executive functions in a sample of European Portuguese adult population.

OBJECTIVE: The main goal of this study was to produce normative data for the Portuguese population on five neuropsychological tests frequently used to assess executive functions and attention: the Modified Wisconsin Card Sorting Test (M-WCST), the Stroop Color and Word Test, the Trail Making Test (TMT), the Brief Test of Attention (BTA), and the Symbol Digit Modalities Test (SDMT). METHOD: The study included 300 individuals aged between 18 and 93 years, who had educational backgrounds ranging from 3 to 25 years. RESULTS: The influence of age, education, and sex was explored for each measure, as well as their contribution to explain the performance variance. CONCLUSIONS: The normative data are presented as regression-based algorithms to adjust direct and derived test scores for sex, age, and education. This study provides a calculator of normative data, derived from the results of the regression models.

Effects of adult age and blood pressure on executive function and speed of processing.

Previous research has established that the effects of chronically increased blood pressure (BP) on cognition interact with adult age, but the relevant cognitive processes are not well defined. In this cross-sectional study, using a sample matched for age, years of education, and sex, 134 individuals with either normal BP (n = 71) or chronically high BP (n = 63) were categorized into younger (19-39 years), middle-aged (41-58 years), and older (60-79 years) groups. Using a between-subjects analysis of variance (ANOVA), covarying for race and years of education, composite measures of executive function and perceptual speed both exhibited age-related decline. The executive function measure, however, was associated with a differential decline in high BP older adults. This result held even when the executive function scores were covaried for speed, demonstrating an independent, age-related effect of higher BP on executive function.

Dichotomous scoring of Trails B in patients referred for a dementia evaluation.

The Trail Making Test is a popular neuropsychological test and its interpretation has traditionally used time-based scores. This study examined an alternative approach to scoring that is simply based on the examinees' ability to complete the test. If an examinee is able to complete Trails B successfully, they are coded as "completers"; if not, they are coded as "noncompleters." To assess this approach to scoring Trails B, the performance of 97 diagnostically heterogeneous individuals referred for a dementia evaluation was examined. In this sample, 55 individuals successfully completed Trails B and 42 individuals were unable to complete it. Point-biserial correlations indicated a moderate-to-strong association (r(pb)=.73) between the Trails B completion variable and the Total Scale score of the Repeatable Battery for the Assessment of Neurological Status (RBANS), which was larger than the correlation between the Trails B time-based score and the RBANS Total Scale score (r(pb)=.60). As a screen for dementia status, Trails B completion showed a sensitivity of 69% and a specificity of 100% in this sample. These results suggest that dichotomous scoring of Trails B might provide a brief and clinically useful measure of dementia status.

Normative data for the oldest old: Trail Making Test A, Symbol Digit Modalities Test, Victoria Stroop Test and Parallel Serial Mental Operations.

Normative data for evaluating cognitive function in the oldest old, aged 85 years and above, are currently sparse. The normative values used in clinical practice are often derived from younger old persons, from small sample sizes or from broad age spans (e.g. >75 years) resulting in a risk of misjudgment in assessments of cognitive decline. This longitudinal study presents normative values for the Trail Making Test A (TMT-A), the Symbol Digit Modalities Test (SDMT), the Victoria Stroop Test (VST) and the Parallel Serial Mental Operations (PaSMO) from cognitively intact Swedes aged 85 years and above. 207 participants, born in 1922, were tested at 85, 90 (n = 68) and 93 (n = 35) years of age with a cognitive screening test battery. The participants were originally recruited for participation in the Elderly in Linköping Screening Assessment. Normative values are presented as mean values and standard deviations, with and without adjustment for education. There were no clinically important differences between genders, but education had a significant effect on test results for the 85-year-olds. Age effects emerged in analyses of those participants who completed the entire study and were evident for TMT-A, SDMT, VST1 and PaSMO. When comparisons can be made, our results are in accordance with previous data for TMT-A, SDMT and VST, and we present new normative values for PaSMO.

Normative data for Farsi-speaking Iranians in the United States on measures of executive functioning.

As the Farsi-speaking Iranian population continues to grow in the United States, examination of their cognitive performance is an imperative first step to providing this group with culturally competent services. Thirty-six healthy primarily Farsi-speaking Iranian adults completed Farsi-translated and adapted versions of three frequently used measures of executive/subcortical functioning: Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT), and Color Trails Test (CTT). Participants' performance on each measure was compared to published normative data resulting in 0-85% of cognitively and medically healthy individuals being classified as impaired depending on the executive/subcortical test score examined, with the highest impairment rates for specific WCST outcome scores. These findings raise questions for the use of published norms with Farsi-speaking Iranians residing in the US. The present study provided normative data from this group of Farsi-speaking Iranians on the Farsi-translated and adapted versions of the WCST, TMT, and CTT.

Residential Proximity to Agricultural Fields and Neurological and Mental Health Outcomes in Rural Adults in Matlab, Bangladesh.

Pesticide exposure is an important rural public health concern that is linked to a spectrum of health outcomes in farmers. However, little is known about these effects on residents living in close proximity to agricultural fields and who are not involved in regular farming. This paper compared the effects of residential proximity to farming lands on a number of neurological and mental health outcomes in adults. A cross-sectional study was performed on 57 adults involved in farming only occasionally in rural Matlab in Bangladesh. A health and demographic surveillance system (HDSS) and geocoding were used to define proximity to the agricultural field. Neurological health was measured using the trail making test, vibrotactile threshold measurement, and dominant ulnar nerve conduction velocity (NCV) amplitude. An adapted Center for Epidemiological Studies Depression scale (CES-D) questionnaire was used to evaluate mental health. Results indicated that respondents living near agricultural fields had significantly higher vibrotactile threshold in big toes (p < 0.004) and needed a longer time to complete the trail making test (p < 0.004) than those living far from fields after accounting for the covariates. Results of this pilot study suggest further investigations to establish the impact of pesticide exposure among occasional and non-farmers on neurological health outcomes.

Altered cingulate white matter connectivity in panic disorder patients.

OBJECTIVE: Functional imaging studies of panic disorder subjects suggest an increased activation of the cingulate regions of the brain. Aim of the current study was to explore the white matter connectivity differences between subjects with panic disorder and healthy comparison subjects. METHOD: Structural white matter connectivity, as determined from fractional anisotropy (FA) values obtained by diffusion tensor imaging, was assessed for anterior and posterior cingulate regions in 24 panic disorder patients and 24 age and sex-matched healthy comparison subjects. RESULTS: Subjects with panic disorder exhibited significantly greater FA values in left anterior and right posterior cingulate regions (by 13.3% and 19.6%, respectively) relative to comparison subjects. White matter connectivity for these two cingulate regions was also positively correlated with clinical severity, as determined by Panic Disorder Severity Scale. FA values in left anterior cingulate region negatively correlated with the time of Trail Making Tests and positively with Digit Symbol Substitution Test. CONCLUSIONS: Findings suggest a potential 'enhancement' in white matter connectivity in left anterior and right posterior cingulate regions in panic disorder, and that these changes may play an important role in mediating clinical symptoms of panic disorder.

Rapid improvement in verbal fluency and aphasia following perispinal etanercept in Alzheimer's disease.

BACKGROUND: Recent clinical studies point to rapid and sustained clinical, cognitive, and behavioral improvement in both Alzheimer's disease and primary progressive aphasia following weekly perispinal administration of etanercept, a TNF-alpha inhibitor that acts by blocking the binding of this cytokine to its receptors. This outcome is concordant with recent basic science studies suggesting that TNF-alpha functions in vivo as a gliotransmitter that regulates synaptic function in the brain. We hypothesized that perispinal etanercept had the potential to improve verbal function in Alzheimer's disease, so we included several standarized measures of verbal ability to evaluate language skills in a clinical trial of perispinal etanercept for Alzheimer's disease. METHODS: This was a prospective, single-center, open-label, pilot study, in which 12 patients with mild-to-severe Alzheimer's disease were administered etanercept, 25-50 mg, weekly by perispinal administration for six months. Two additional case studies are presented. RESULTS: Two-tailed, paired t-tests were conducted comparing baseline performance to 6-month performance on all neuropsychological measures. Test batteries included the California Verbal Learning Test-Second Edition, Adult Version; Logical Memory I and II(WMS-LM-II) from the Wechsler Memory Scale-Abbreviated; the Comprehensive Trail Making Test (TMT); Boston Naming Test; and letter(FAS) and category verbal fluency. All measures revealed a significant effect except for the Boston Naming Test and the TMT-4, with WMS-LM-II being marginally significant at p = .05. The FAS test for letter fluency was most highly significant with a p < 0.0007. In addition, rapid improvement in verbal fluency and aphasia in two patients with dementia, beginning minutes after perispinal etanercept administration, is documented. CONCLUSION: In combination with the previously reported results of perispinal etanercept in Alzheimer's disease and primary progressive aphasia, these results further argue that larger scale studies of this therapeutic intervention, including Phase 3 trials, are warranted in dementias. In addition, these results may provide insight into the basic pathophysiologic mechanisms underlying Alzheimer's disease and related forms of dementia, and suggest the existence of novel, rapidly reversible, TNF-mediated pathophysiologic mechanisms in Alzheimer's disease which are worthy of further investigation.

Executive deficits in psychotic and bipolar disorders - implications for our understanding of schizoaffective disorder.

OBJECTIVE: Schizoaffective disorder could be considered as a form of schizophrenia, a form of bipolar disorder, an independent disorder or a disorder intermediate between bipolar disorder and schizophrenia, within a psychotic continuum. The study of cognitive deficits in subjects with those diagnoses could help differentiate between these possibilities. METHODS: We compared cognitive performances of schizoaffective (SZAff) subjects with those of subjects with schizophrenia (SZ), bipolar disorder with psychotic symptoms (life-time) (BDP), bipolar disorder without life-time occurrence of psychotic symptoms (BD) and normal controls (NC). We used two tests of executive functions - the Wisconsin Card Sorting Test (WCST) and the Trail-making Test (TMT) - that are known to be impaired in those disorders. RESULTS: The number of perseverative errors on WCST was highest in SZ subjects and gradually decreased in SZAff, BDP and, finally in BD subjects. By contrast, SZ and SZAff subjects obtained similar scores in the TMT, as did BD and BDP patients. CONCLUSIONS: These results suggest that, for some deficits, there may be a continuum between SZ, SZAff and affective disorders, whereas SZAff patients most closely resemble SZ patients for other deficits. This implies that different conceptual views about schizoaffective disorder should be seen as complementary, rather than mutually exclusive.