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 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.

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 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.

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.

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.

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).

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.

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.

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.

Diagnostic Accuracy of the Chinese Version of the Trail-Making Test for Screening Cognitive Impairment.

BACKGROUND/OBJECTIVES: The Trail-Making Test (TMT), which is commonly used to measure executive function, consists of two components (TMT-A and TMTB). There is a lack of normative TMT data for Chinese elderly adults. This study aimed to evaluate the validity of the TMT in screening for cognitive impairment. DESIGN: 2,294 Chinese-speaking adults aged 50 to 85: 1,026 with normal cognition (NC), 462 with mild cognitive impairment (MCI), 108 with Alzheimer's disease (AD), 113 with vascular mild cognitive impairment (VaMCI), 121 with vascular dementia (VaD), 282 with uncertain types of dementia, and 15 with mixed dementia. Receiver operating characteristic curve analysis was performed to test the ability of TMT scores to differentiate between NC and cognitive impairment. RESULTS: Age, education, and sex were significantly associated with TMT completion time. The TMT-A exhibited sensitivity of 77.8% and specificity of 92.0% with cut-off value of 98.5 seconds for discriminating AD from NC. The TMT-B had sensitivity of 83.3% and specificity of 91.8% with a cut-off value of 188.5 seconds for discriminating AD from NC. The TMT-A had sensitivity of 85.7% and specificity of 81.6% for discriminating NC from VaD with a cut-off value of 77.5 seconds, and the TMT-s had sensitivity of 81.6% and specificity of 83.9% with a cut-off value of 147.5 seconds. The TMT had less sensitivity distinguishing MCI from NC. CONCLUSION: The Chinese version of the TMT is reliable for detecting AD or VaD but poor at distinguishing MCI from NC.

The Trail Making Test.

The Trail Making Test (TMT) is used as an indicator of visual scanning, graphomotor speed, and executive function. The aim of this study was to examine the TMT relationships with several neuropsychological measures and to provide normative data in community-dwelling participants of 55 years and older. A population-based Spanish-speaking sample of 2,564 participants was used. The TMT, Symbol Digit Test, Stroop Color-Word Test, Digit Span Test, Verbal Fluency tests, and the MacQuarrie Test for Mechanical Ability tapping subtest were administered. Exploratory factor analyses and regression lineal models were used. Normative data for the TMT scores were obtained. A total of 1,923 participants (76.3%) participated, 52.4% were women, and the mean age was 66.5 years (Digit Span = 8.0). The Symbol Digit Test, MacQuarrie Test for Mechanical Ability tapping subtest, Stroop Color-Word Test, and Digit Span Test scores were associated in the performance of most TMT scores, but the contribution of each measure was different depending on the TMT score. Normative tables according to significant factors such as age, education level, and sex were created. Measures of visual scanning, graphomotor speed, and visuomotor processing speed were more related to the performance of the TMT-A score, while working memory and inhibition control were mainly associated with the TMT-B and derived TMT scores.

Skills of Cognitive Flexibility in Monolingual and Bilingual Younger Adults.

The current study examined skills of cognitive flexibility and sustained attention in late bilingual and monolingual younger adults. One-hundred and sixty two younger adults aged between 18 and 34 years old (M = 22.39) classified as Turkish-English late bilinguals (N = 74) and Turkish monolinguals (N = 88) completed the Trail Making Test (TMT-A and TMT-B). Results from this study showed that Turkish-English late bilinguals had shorter RTs than Turkish monolinguals on the TMT-B, however there were no significant RT differences between the groups on the TMT-A. These findings indicate that bilingualism impacts upon skills of cognitive flexibility but not sustained attention and that the amount of practice in coordinating, monitoring, and switching between languages is an important determinant of cognitive improvement.

Effects of Ncl. Basalis Meynert volume on the Trail-Making-Test are restricted to the left hemisphere.

BACKGROUND: Cortical acetylcholine released from cells in the basal forebrain facilitates cue detection and improves attentional performance. Cholinergic fibres to the cortex originate from the CH4 cell group, sometimes referred to as the Nucleus basalis of Meynert and the Nucleus subputaminalis of Ayala. The aim of this work was to investigate the effects of volumes of cholinergic nuclei on attention and executive function. METHODS: The volumes of CH4 and CH4p subregions were measured in a subgroup of 38 subjects (33.5 ± 11 years, 20 females) from a population-based cohort study of smokers and never-smokers who have undergone additional MR imaging. To define regions of interest, we applied a DARTEL-based procedure implemented in SPM8 and a validated probabilistic map of the basal forebrain. Attention and executive function were measured with Trail-Making Test (TMT A+B) and Stroop-Task. RESULTS: We found a quadratic effect of the left CH4 subregion on performance of the TMT. Extremely small as well as extremely large volumes are associated with poor test performance. CONCLUSIONS: Our results indicate that a small CH4 volume predisposes for a hypocholinergic state, whereas an extremely large volume predisposes for a hypercholinergic state. Both extremes have detrimental effects on attention. Comparable nonlinear effects have already been reported in pharmacological studies on the effects cholinergic agonists on attention.

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.

Virtual Kitchen Test. Assessing frontal lobe functions in patients with alcohol dependence syndrome.

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on "New Methodologies for Patients Rehabilitation". BACKGROUND: The ecological validity of paper-and-pencil neuropsychological tests is currently a matter of debate. Arguments in favor of alternatives indicate that paper-and-pencil forms are unable to account for both mental and functional aspects of cognitive functioning. OBJECTIVES: In this study we developed a new neuropsychological evaluation test - the Virtual Kitchen Test (VKT) - devised to evaluate frontal brain functioning in cognitively impaired individuals. We designed this test according to the rationale of the Trail Making Test (TMT), in order to capture frontal lobe abilities during a more ecologically valid task. METHODS: Forty-nine participants, 25 from a clinical sample of patients diagnosed with Alcohol Dependence Syndrome, plus 24 healthy participants. RESULTS: Execution errors and task completion time were significantly higher in the clinical sample. Also, scores on the new VKT showed moderate to high positive correlations with scores on the TMT. Furthermore, the overall discriminant performance of the VKT was high for both of its indicators. CONCLUSIONS: Overall results support the ability of the VKT to evaluate frontal lobe functions. The best cut-off scores based on this sample are discussed.

The relationship between executive functioning, processing speed, and white matter integrity in multiple sclerosis.

The primary purpose of the current study was to examine the relationship between performance on executive tasks and white matter integrity, assessed by diffusion tensor imaging (DTI) in multiple sclerosis (MS). A second aim was to examine how processing speed affects the relationship between executive functioning and fractional anisotropy (FA). This relationship was examined in two executive tasks that rely heavily on processing speed: the Color-Word Interference Test and the Trail Making Test (Delis-Kaplan Executive Function System). It was hypothesized that reduced FA is related to poor performance on executive tasks in MS, but that this relationship would be affected by the statistical correction of processing speed from the executive tasks. A total of 15 healthy controls and 25 persons with MS participated. Regression analyses were used to examine the relationship between executive functioning and FA, both before and after processing speed was removed from the executive scores. Before processing speed was removed from the executive scores, reduced FA was associated with poor performance on the Color-Word Interference Test and Trail Making Test in a diffuse network including corpus callosum and superior longitudinal fasciculus. However, once processing speed was removed, the relationship between executive functions and FA was no longer significant on the Trail Making Test, and significantly reduced and more localized on the Color-Word Interference Test.

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.

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.

Neuropsychological test performance of Spanish speakers: is performance different across different Spanish-speaking subgroups?

Even though theories and research have pointed out the importance of variables such as age, gender, or education on neuropsychological assessment, much less emphasis has been placed on language and culture. With the increasing population of Spanish speakers in North America and the limited amount of clinical and scholarly information currently available, neuropsychological assessment of this group has similarly become of increasing importance. Though several studies have been published over the last two decades, an assumption exists that all Spanish speakers, holding education and age constant, would perform similarly regardless of their origin. To address this assumption, a sample of 126 participants was tested from four different countries (Chile, Dominican Republic, Puerto Rico, and Spain). Participants were compared on the following commonly used neuropsychological tests: Verbal Serial Learning Curve, Rey- Osterrieth Complex Figure Test, Verbal Phonemic Fluency Test, the Stroop Color and Word Test, and the Trail Making Test. Analyses revealed significant differences across the groups in two of the five tests administered. Significant differences were observed in the delayed recall of the Serial Learning Test and in the Verbal Fluency Test. The findings highlight the importance of within-group differences between Spanish speakers.