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1.  The Walking Trail-Making Test is an early detection tool for mild cognitive impairment 
Background
Executive function impairment (in particular, mental flexibility) in the elderly, and in patients with mild cognitive impairment (MCI), is strongly correlated with difficulties in performing complex walking tasks. The aim of this study was to determine if the adaptation of a neuropsychological test (the Trail-Making Test), to evaluate executive functions during walking, can be an early detection tool for cognitive impairment.
Methods
Fifty subjects (15 young, 20 older, presumably healthy, and 15 MCI) were first evaluated for cognitive functions (Mini-Mental State Examination, Frontal Assessment Battery, and Trail-Making Test) and motor functions (10-meter walking test). All subjects then performed a spatial navigation, or a complex walking test (the Walking Trail-Making Test: [WTMT]), and their spatiotemporal walking variables were analyzed using cluster analysis.
Results
Following evaluation of WTMT locomotor performance, cluster analysis revealed three groups that were distinctly different in age and cognitive abilities: a group of young subjects, a group of healthy older subjects, MCI subjects with amnestic impairment, and a group of MCI subjects with executive function impairment. The WTMT enabled early detection, (ie, borderline MCI) of dysexecutive impairment, with 78% sensitivity and 90% specificity.
Conclusion
The WTMT is of interest in that it can help provide early detection of dysexecutive cognitive impairment.
doi:10.2147/CIA.S53645
PMCID: PMC3890407  PMID: 24426778
spatial navigation; walking; trail making test; detection; mild cognitive impairment
2.  Alternative Type of the Trail Making Test in Nonnative English-Speakers: The Trail Making Test-Black & White 
PLoS ONE  2014;9(2):e89078.
Objective
The Trail Making Test (TMT) has its limitations when applied to Eastern cultures due to its reliance on the alphabet. We looked for an alternative tool that is reliable and distinguishable like the TMT and devised the Trail Making Test Black & White (TMT-B&W) as a new variant. This study identifies the applicability of the TMT-B&W as a useful neuropsychological tool and determines whether the TMT-B&W could play an equivalent role as the TMT.
Methods
The TMT-B&W uses numbers encircled by black or white circles as stimuli, instead of using the alphabet. A total of 138 participants were including containing groups of 31 cognitively normal controls (NC), 55 mild cognitive impairment (MCI), and 52 people with Alzheimer’s disease (AD). Along with the TMT-B&W, the TMT and other neuropsychological tests were administered to all subjects.
Results
A considerably low dropout rate for TMT B&W demonstrates that all participants were more willingly engaged in the TMT B&W than the TMT. In particular, subjects with cognitive impairments or lower levels of education performed better on the TMT-B&W than the TMT. The difference in time-to-completion of the TMT-B&W was significant according to the level of cognitive impairment. The TMT-B&W revealed a high correlation with the TMT and frontal lobe function test.
Conclusion
The TMT-B&W is as reliable and effective as the TMT. It is worth developing a new variant of the TMT.
doi:10.1371/journal.pone.0089078
PMCID: PMC3923875  PMID: 24551221
3.  The trail making test as a screening instrument for driving performance in older drivers; a translational research 
BMC Geriatrics  2014;14(1):123.
Background
In many countries, primary care physicians determine whether or not older drivers are fit to drive. Little, however, is known regarding the effects of cognitive decline on driving performance and the means to detect it. This study explores to what extent the trail making test (TMT) can provide indications to clinicians about their older patients’ on-road driving performance in the context of cognitive decline.
Methods
This translational study was nested within a cohort study and an exploratory psychophysics study. The target population of interest was constituted of older drivers in the absence of important cognitive or physical disorders. We therefore recruited and tested 404 home-dwelling drivers, aged 70 years or more and in possession of valid drivers’ licenses, who volunteered to participate in a driving refresher course. Forty-five drivers also agreed to undergo further testing at our lab. On-road driving performance was evaluated by instructors during a 45 minute validated open-road circuit. Drivers were classified as either being excellent, good, moderate, or poor depending on their score on a standardized evaluation of on-road driving performance.
Results
The area under the receiver operator curve for detecting poorly performing drivers was 0.668 (CI95% 0.558 to 0.778) for the TMT-A, and 0.662 (CI95% 0.542 to 0.783) for the TMT-B. TMT was related to contrast sensitivity, motion direction, orientation discrimination, working memory, verbal fluency, and literacy. Older patients with a TMT-A ≥ 54 seconds or a TMT-B ≥ 150 seconds have a threefold (CI95% 1.3 to 7.0) increased risk of performing poorly during the on-road evaluation. TMT had a sensitivity of 63.6%, a specificity of 64.9%, a positive predictive value of 9.5%, and a negative predictive value of 96.9%.
Conclusion
In screening settings, the TMT would have clinicians uselessly consider driving cessation in nine drivers out of ten. Given the important negative impact this could have on older drivers, this study confirms the TMT not to be specific enough for clinicians to justify driving cessation without complementary investigations on driving behaviors.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2318-14-123) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2318-14-123
PMCID: PMC4256796  PMID: 25420615
Aging; Trail making test; Fitness to drive; On-road evaluation; Psychophysics
4.  Cross-sectional assessment of the factors associated with occupational functioning in patients with schizophrenia 
Shanghai Archives of Psychiatry  2012;24(4):222-230.
Background
Studies from other countries indicate that occupational skills training can improve the social functioning and the quality of life of patients with schizophrenia but there is little research about the relationship of occupational skills and the functional status of patients in China.
Aim
Use a translated Chinese version of the Comprehensive Occupational Therapy Evaluation scale to evaluate occupational functining in inpatients and recently discharged patients with schizophrenia and assess the relationship of occupational functioning to demographic, clinical and cognitive measures.
Methods
Thirty-five inpatiens and 29 recently discharged outpatients with schizophrenia were evaluated by trained clinicals using the COTE, the Positive and Negative Syndrome Scale (PANSS) and a neuropsychological battery that included the Wisconsin Card Sorting Test (WCST), the Continuous Perfomance Test (CPT), the digit symbol-coding subtest from the Wechsler Adult Intelligence Scale (WAIS), and Trail Making Test Parts A and B (TMT-A, TMT-B).
Results
The total score on the COTE and the three COTE dimensional scores (evaluating general behavior, interpersonal communication and task behavior) were all strongly correlated with the PANSS total score and the PANSS positive symptom, negative symptom and general pathology subscale scores (ranked correlation coefficients range from 0.40 to 0.90). The correlationship of the COTE measures was significantly greater with the PANSS negative symptom score than with the PANSS positive symptom score. The COTE scores were also significantly correlated with the Continuous Performance Test measures, the WAIS digit symbol-coding test scores and some, but not all, of the measures derived from the TMT-A, the TMT-B, and the WCST. Mutiple regression analyses found that the four COTE measures of occupational functioning were most strongly associated with either the PANSS total score or the PANSS negative symptom score and secondarily associated with time to complete TMT-B, the CPT measure on number of omissions, and the respondent's years of education.
Conclusion
Occupational functioning measures of inpatients and recently discharged outpatients with schizophrenia are closely related to the severity of psychiatric symptoms and, to a lesser extent, with cognitive functioning measures and duration of education.
doi:10.3969/j.issn.1002-08329.2012.04.003
PMCID: PMC4198858  PMID: 25324630
5.  Rosiglitazone and Cognitive Stability in Older Individuals With Type 2 Diabetes and Mild Cognitive Impairment 
Diabetes Care  2010;33(8):1706-1711.
OBJECTIVE
Studies have suggested that insulin resistance plays a role in cognitive impairment in individuals with type 2 diabetes. We aimed to determine whether an improvement in insulin resistance could explain cognitive performance variations over 36 weeks in older individuals with mild cognitive impairment (MCI) and type 2 diabetes.
RESEARCH DESIGN AND METHODS
A total of 97 older individuals (mean ± SD age 76 ± 6 years) who had recently (<2 months) started an antidiabetes treatment of metformin (500 mg twice a day) (n = 30) or metformin (500 mg/day)+rosiglitazone (4 mg/day) (n = 32) or diet (n = 35) volunteered. The neuropsychological test battery consisted of the Mini-Mental State Examination (MMSE), Rey Verbal Auditory Learning Test (RAVLT) total recall, and Trail Making Tests (TMT-A and TMT-B) performed at baseline and every 12 weeks for 36 weeks along with clinical testing.
RESULTS
At baseline, no significant differences were found between groups in clinical or neuropsychological parameters. Mean ± SD values in the entire population were as follows: A1C 7.5 ± 0.5%, fasting plasma glucose (FPG) 8.6 ± 1.3 mmol/l, fasting plasma insulin (FPI) 148 ± 74 pmol/l, MMSE 24.9 ± 2.4, TMT-A 61.6 ± 42.0, TMT-B 162.8 ± 78.7, the difference between TMT-B and TMT-A [DIFFBA] 101.2 ± 58.1, and RAVLT 24.3 ± 2.1. At follow-up, ANOVA models tested changes in metabolic control parameters (FPI, FPG, and A1C). Such parameters improved in the metformin and metformin/rosiglitazone groups (Ptrend < 0.05 in both groups). ANCOVA repeated models showed that results for the metformin/rosiglitazone group remained stable for all neuropsychological tests, and results for the diet group remained stable for the MMSE and TMT-A and declined for the TMT-B (Ptrend = 0.024), executive efficiency (DIFFBA) (Ptrend = 0.026), and RAVLT memory test (Ptrend = 0.011). Results for the metformin group remained stable for the MMSE and TMTs but declined for the RAVLT (Ptrend = 0.011). With use of linear mixed-effects models, the interaction term, FPI × time, correlated with cognitive stability on the RAVLT in the metformin/rosiglitazone group (β = −1.899; P = 0.009).
CONCLUSIONS
Rosiglitazone may protect against cognitive decline in older individuals with type 2 diabetes and MCI.
doi:10.2337/dc09-2030
PMCID: PMC2909046  PMID: 20435794
6.  TRAIL MAKING TEST PREDICTS PHYSICAL IMPAIRMENT AND MORTALITY IN OLDER PERSONS 
OBJECTIVE
To examine whether performance in Trail Making Test (TMT) predicts mobility impairment and mortality in older persons.
DESIGN
Prospective cohort study.
SETTING
Community-dwelling older persons enrolled in the InCHIANTI Study.
PARTICIPANTS
865 participants ≥65 years, free of major cognitive impairment (MMSE >21), with complete baseline data on Trail Making Test (TMT) performance. Of these, 583 performed the Short Physical Performance Battery (SPPB) both at baseline and after 6-years. Of the initial 865 participants, 222 died during 9-years of follow-up.
MEASUREMENTS
The Trail Making Test (TMT-A, TMT-B, TMT-B minus A) and the Short Physical Performance Battery for the assessment of lower extremity function were administered at baseline and at 6-years follow-up. Impaired mobility was defined as an SPPB <10. Vital status was ascertained over a 9-year follow-up.
RESULTS
Of 679 participants free of ADL disability and with SPPB ≥10 at baseline, 53 (11.0 %) developed impaired mobility (SPPB score < 10) during the follow-up. Participants in the lowest quartile of TMT-performance at baseline were significantly more likely to develop a SPPB score < 10 during the 6 years follow-up compared to those in the highest quartile. After adjusting for potential confounders this prognostic effect was substantially maintained. Also, worse performance on the TMT was associated with significantly greater decline of SPPB score over the 6-year follow- up, after adjusting for age, sex and, baseline SPPB score. During a nine-years follow-up, 222 participants (25.7 %) died. The proportion of participants who died was higher in the lowest performance quartile compared with the best performance quartile of TMT score, for TMT-A; TMT-B; and TMT B-A scores.
CONCLUSION
Performance in the Trail Making Test is a strong, independent predictor of mobility impairment, accelerated decline in lower extremity function and mortality among older adults living in the community. The Trail Making Test is a useful addition to geriatric assessment.
doi:10.1111/j.1532-5415.2010.02780.x
PMCID: PMC2935170  PMID: 20398153
Trail Making Test; neuropsychological tests; physical impairment; mortality
7.  Trail making test performance in youth varies as a function of anatomical coupling between the prefrontal cortex and distributed cortical regions 
While researchers have gained a richer understanding of the neural correlates of executive function in adulthood, much less is known about how these abilities are represented in the developing brain and what structural brain networks underlie them. Thus, the current study examined how individual differences in executive function, as measured by the Trail Making Test (TMT), relate to structural covariance in the pediatric brain. The sample included 146 unrelated, typically developing youth (80 females), ages 9–14 years, who completed a structural MRI scan of the brain and the Halstead-Reitan TMT (intermediate form). TMT scores used to index executive function included those that evaluated set-shifting ability: Trails B time (number-letter sequencing) and the difference in time between Trails B and A (number sequencing only). Anatomical coupling was measured by examining correlations between mean cortical thickness (MCT) across the entire cortical ribbon and individual vertex thickness measured at ~81,000 vertices. To examine how TMT scores related to anatomical coupling strength, linear regression was utilized and the interaction between age-normed TMT scores and both age and sex-normed MCT was used to predict vertex thickness. Results revealed that stronger Trails B scores were associated with greater anatomical coupling between a large swath of prefrontal cortex and the rest of cortex. For the difference between Trails B and A, a network of regions in the frontal, temporal, and parietal lobes was found to be more tightly coupled with the rest of cortex in stronger performers. This study is the first to highlight the importance of structural covariance in in the prediction of individual differences in executive function skills in youth. Thus, it adds to the growing literature on the neural correlates of childhood executive functions and identifies neuroanatomic coupling as a biological substrate that may contribute to executive function and dysfunction in childhood.
doi:10.3389/fpsyg.2014.00496
PMCID: PMC4077145  PMID: 25071613
executive function; anatomical covariance; cortical thickness; magnetic resonance imaging; Trail Making Test; brain; child; adolescent
8.  The trail making test in India 
Indian Journal of Psychiatry  2007;49(2):113-116.
The trail making test (TMT) is a short and convenient estimate of cognitive functions, principally attention and working memory. Like most neuropsychological tests, it is derived from and primarily applicable to English-speaking individuals. Norms for other ethnic minorities may differ significantly. The application of majority or mixed norms to specific ethnic subcultures may introduce systematic bias. To examine the impact of an English test on primarily nonEnglish-speaking individuals, outpatients attending the dermatology department of a large Indian hospital (n = 120) were asked to complete the English version of the TMT. The time taken to complete the TRAILS was unexpectedly long, although all the subjects scored within normal limits on the modified mini mental status examination and a test for general knowledge. Possible reasons for the delayed completion times are discussed below.
doi:10.4103/0019-5545.33258
PMCID: PMC2917075  PMID: 20711393
Cognitive dysfunction; schizophrenia; trail making test
9.  Cognitive correlates of HVOT performance differ between individuals with mild cognitive impairment and normal controls 
Objective
To clinically characterize performance on the Hooper Visual Organization Test (HVOT) among participants with mild cognitive impairment (MCI) and to identify naming and executive functioning correlates associated with HVOT performance among MCI participants and normal controls (NC).
Background
The HVOT is a common neuropsychological instrument that measures visuospatial skills and agnosia. It has, however, been criticized for its multifactorial nature, as several studies have reported executive or language correlates of HVOT performance. To our knowledge, simultaneous comparison of executive functioning and language demands of the HVOT has never been performed among an older cohort.
Methods
The HVOT, two tests of executive functioning [Trail Making Test, Part B (TMT-B), Controlled Oral Word Association (COWA)] and two tests of naming [abbreviated Boston Naming Test (BNT), Animal Naming] were administered to 222 NC, 166 MCI, and 68 Alzheimer’s disease (AD) individuals.
Results
HVOT scores were significantly different between all three groups in the expected direction (AD < MCI < NC). Linear regression among NC participants revealed that COWA, age, and BNT were significantly associated with HVOT scores, accounting for 12%, 6%, and 4% of HVOT variance, respectively. Among MCI participants, the BNT accounted for 43% of HVOT variance. Neither TMT-B nor Animal Naming was a significant predictor for either group.
Conclusion
Among NC participants, rapid word generation (i.e., COWA), a measure of executive functioning, is the most salient predictor of HVOT performance. In contrast, lexical retrieval (i.e., BNT) is the most salient language or executive functioning predictor of HVOT performance among MCI participants. These findings extend previous claims that the HVOT is multifactorial by suggesting that reduced HVOT performance in MCI patients may be related to mild lexical retrieval impairments.
doi:10.1016/j.acn.2006.06.001
PMCID: PMC2746420  PMID: 16893623
Object recognition; Mild cognitive impairment; Hooper Visual Organization Test
10.  Association Between Mild Anemia and Executive Function Impairment in Community-Dwelling Older Women: The Women’s Health and Aging Study II 
OBJECTIVES
To evaluate the relationship between mild anemia and executive function in community-dwelling older women.
DESIGN
Cross-sectional.
SETTING
Community-based.
PARTICIPANTS
High-functioning subjects participating in the baseline assessment of the Women’s Health and Aging Study (WHAS) II, Baltimore, Maryland, 1994 to 1996. WHAS II eligibility criteria included aged 70 to 80, a Mini-Mental State Examination score of 24 or greater, and absence of advanced disability (difficulty in no more than 1 domain of physical function). Included in this study were 364 subjects with a hemoglobin concentration 10 g/dL or greater and known executive function status.
MEASUREMENTS
Trail Making Test (TMT) Parts B and A. Tertiles of time to complete each test were used to define best (bottom), intermediate, and worst (top) performance. Tertiles of the difference TMT-B minus TMT-A were calculated. Anemia defined as hemoglobin concentration less than 12 g/dL.
RESULTS
The percentage of subjects in the worst TMT-B, TMT-A, and TMT-B minus TMT-A performance tertile was highest for those with anemia. Prevalent anemia substantially increased the likelihood of performing worst (as opposed to best) on the TMT-B (odds ratio (OR) = 5.2, 95% confidence interval (CI) = 1.3–20.5), TMT-A (OR = 4.8, 95% CI = 1.5–15.6), and TMT-B minus TMT-A (OR = 4.2, 95% CI = 1.0–17.2), even after controlling for age, education, race, prevalent diseases, and relevant physiological and functional parameters.
CONCLUSION
This study provides preliminary evidence in support of the hypothesis that mild anemia might be an independent risk factor for executive function impairment in community-dwelling older adults. Whether such an association is causal or noncausal remains to be determined.
doi:10.1111/j.1532-5415.2006.00863.x
PMCID: PMC2668150  PMID: 16970654
anemia; elderly; executive function; Trail Making Test
11.  Reduced prefrontal cortex activation using the Trail Making Test in schizophrenia 
Schizophrenia has been associated with a deficit of the prefrontal cortex, which is involved in attention, executive processes, and working memory. The Trail Making Test (TMT) is administered in two parts, TMT-A and TMT-B. It is suggested that the difference in performance between part A and part B reflects executive processes. In this study, we compared the characteristics of hemodynamic changes during TMT tasks between 14 outpatients with schizophrenia and 14 age- and gender-matched healthy control subjects. Using multichannel near-infrared spectroscopy, we measured relative changes in oxygenated hemoglobin concentration, which reflects brain activity of the prefrontal cortex during this task. In both tasks, patients showed significantly smaller activation than controls and, in an assessment of executive functions, a subtraction of oxygenated hemoglobin (oxy-Hb) changes during TMT-A from those of TMT-B showed a decrease in cerebral lateralization and hypoactivity in patients. There was a significant negative correlation between oxy-Hb changes and the severity of psychiatric symptoms. These findings may characterize disease-related features, suggesting the usefulness of oxy-Hb change measurement during TMT tasks for assessing functional outcomes in schizophrenic patients.
doi:10.2147/NDT.S43137
PMCID: PMC3658532  PMID: 23696704
Trail Making Test; multichannel near-infrared spectroscopy; schizophrenia; prefrontal cortex; executive function
12.  The Shape Trail Test: Application of a New Variant of the Trail Making Test 
PLoS ONE  2013;8(2):e57333.
Objective
The Trail making test (TMT) is culture-loaded because of reliance on the Latin alphabet, limiting its application in Eastern populations. The Shape Trail Test (STT) has been developed as a new variant. This study is to examine the applicability of the STT in a senile Chinese population and to evaluate its potential advantages and disadvantages.
Method
A total of 2470 participants were recruited, including 1151 cognitively normal control (NC), 898 amnestic mild cognitive impairment (aMCI), and 421 mild Alzheimer disease (AD) patients. Besides the STT, the Mini mental state examination and a comprehensive neuropsychological battery involving memory, language, attention, executive function and visuospatial ability were administered to all the participants. In a subgroup of 100 NC and 50 AD patients, both the STT and the Color Trail Test (CTT) were performed.
Results
In NC, the time consumed for Part A and B (STT-A and STT-B) significantly correlated with age and negatively correlated with education (p<0.01). STT-A and B significantly differed among the AD, aMCI and NC. The number that successfully connected within one minute in Part B (STT-B-1 min) correlated well with STT-B (r = 0.71, p<0.01) and distinguished well among NC, aMCI and AD. In the receiver operating characteristic curve analysis, the AUCs (area under the curve) for STT-A, STT-B, and STT-B-1min in identifying AD were 0.698, 0.694 and 0.709, respectively. The STT correlated with the CTT, but the time for completion was longer.
Conclusion
The TMT is a sensitive test of visual search and sequencing. The STT is a meaningful attempt to develop a “culture-fair” variant of the TMT in addition to the CTT.
doi:10.1371/journal.pone.0057333
PMCID: PMC3577727  PMID: 23437370
13.  Executive function on the Psychology Experiment Building Language tests 
Behavior research methods  2012;44(1):110-123.
The measurement of executive function has a long history in clinical and experimental neuropsychology. The goal of the present report was to determine the profile of behavior across the lifespan on four computerized measures of executive function contained in the recently developed Psychology Experiment Building Language (PEBL) test battery http://pebl.sourceforge.net/ and evaluate whether this pattern is comparable to data previously obtained with the non-PEBL versions of these tests. Participants (N = 1,223; ages, 5–89 years) completed the PEBL Trail Making Test (pTMT), the Wisconsin Card Sort Test (pWCST; Berg, Journal of General Psychology, 39, 15–22, 1948; Grant & Berg, Journal of Experimental Psychology, 38, 404–411, 1948), the Tower of London (pToL), or a time estimation task (Time-Wall). Age-related effects were found over all four tests, especially as age increased from young childhood through adulthood. For several tests and measures (including pToL and pTMT), age-related slowing was found as age increased in adulthood. Together, these findings indicate that the PEBL tests provide valid and versatile new research tools for measuring executive functions.
doi:10.3758/s13428-011-0096-6
PMCID: PMC3705215  PMID: 21534005
Age; Children; Adolescents; Elderly
14.  EQUIVALENCY OF SPANISH LANGUAGE VERSIONS OF THE TRAIL MAKING TEST PART B INCLUDING OR EXCLUDING “CH” 
The Clinical neuropsychologist  2008;22(4):662-665.
Spanish speakers commonly use two versions of the alphabet, one that includes the sound “Ch” between C and D and another that goes directly to D, as in English. Versions of the Trail Making Test Part B (TMT-B) have been created accordingly to accommodate this preference. The pattern and total number of circles to be connected are identical between versions. However, the equivalency of these alternate forms has not been reported. We compared the performance of 35 healthy Spanish speakers who completed the “Ch” form (CH group) to that of 96 individuals who received the standard form (D group), based on whether they mentioned “Ch” in their oral recitation of the alphabet. The groups had comparable demographic characteristics and overall neuropsychological performance. There were no significant differences in TMT-B scores between the CH and D groups, and relationships with demographic variables were comparable. The findings suggest that both versions are equivalent and can be administered to Spanish speakers based on their preference without sacrificing comparability.
doi:10.1080/13854040701476976
PMCID: PMC3059802  PMID: 17853122
Alphabet; CH; Equivalent forms; Spanish; Trails B
15.  The Relationship between Tests of Neurocognition and Performance on a Laparoscopic Simulator 
Minimally Invasive Surgery  2010;2010:486174.
Objective. To estimate if there is a relationship between the results of tests of neurocognition and performance on a laparoscopic surgery simulator. Methods and Materials. Twenty participants with no prior laparoscopic experience had baseline cognitive tests administered (Trail Making Test, Part A and B (TMT-A and TMT-B), Grooved Peg Board Test, Symbol Digit Modalities Test, Symbol Digit Recall Test, and Stroop Interference Test), completed a demographic questionnaire, and then performed laparoscopy using a simulator. We correlated the results of cognitive tests with laparoscopic surgical performance. Results. One cognitive test sensitive to frontal lobe function, TMT-A, significantly correlated with laparoscopic surgical performance on the simulator (correlation coefficient of 0.534 with P < .05). However, the correlation between performance and other cognitive tests (TMT-B, Grooved Peg Board Test, Symbol Digit Modalities Test, Symbol Digit Recall Test, and Stroop Interference Test) was not statistically significant. Conclusion. Laparoscopic performance may be related to measures of frontal lobe function. Neurocognitive tests may predict motor skills abilities and performance on laparoscopic simulator.
doi:10.1155/2010/486174
PMCID: PMC3196331  PMID: 22091352
16.  Effect of Virtual Reality on Cognitive Dysfunction in Patients With Brain Tumor 
Annals of Rehabilitation Medicine  2014;38(6):726-733.
Objective
To investigate whether virtual reality (VR) training will help the recovery of cognitive function in brain tumor patients.
Methods
Thirty-eight brain tumor patients (19 men and 19 women) with cognitive impairment recruited for this study were assigned to either VR group (n=19, IREX system) or control group (n=19). Both VR training (30 minutes a day for 3 times a week) and computer-based cognitive rehabilitation program (30 minutes a day for 2 times) for 4 weeks were given to the VR group. The control group was given only the computer-based cognitive rehabilitation program (30 minutes a day for 5 days a week) for 4 weeks. Computerized neuropsychological tests (CNTs), Korean version of Mini-Mental Status Examination (K-MMSE), and Korean version of Modified Barthel Index (K-MBI) were used to evaluate cognitive function and functional status.
Results
The VR group showed improvements in the K-MMSE, visual and auditory continuous performance tests (CPTs), forward and backward digit span tests (DSTs), forward and backward visual span test (VSTs), visual and verbal learning tests, Trail Making Test type A (TMT-A), and K-MBI. The VR group showed significantly (p<0.05) better improvements than the control group in visual and auditory CPTs, backward DST and VST, and TMT-A after treatment.
Conclusion
VR training can have beneficial effects on cognitive improvement when it is combined with computer-assisted cognitive rehabilitation. Further randomized controlled studies with large samples according to brain tumor type and location are needed to investigate how VR training improves cognitive impairment.
doi:10.5535/arm.2014.38.6.726
PMCID: PMC4280367  PMID: 25566470
Brain tumors; Cognition; Virtual reality therapy
17.  Differences in dual-task performance and prefrontal cortex activation between younger and older adults 
BMC Neuroscience  2013;14:10.
Background
The purpose of this study was to examine task-related changes in prefrontal cortex (PFC) activity during a dual-task in both healthy young and older adults and compare patterns of activation between the age groups. We also sought to determine whether brain activation during a dual-task relates to executive/attentional function and how measured factors associated with both of these functions vary between older and younger adults.
Results
Thirty-five healthy volunteers (20 young and 15 elderly) participated in this study. Near-infrared spectroscopy (NIRS) was employed to measure PFC activation during a single-task (performing calculations or stepping) and dual-task (performing both single-tasks at once). Cognitive function was assessed in the older patients with the Trail-making test part B (TMT-B). Major outcomes were task performance, brain activation during task (oxygenated haemoglobin: Oxy-Hb) measured by NIRS, and TMT-B score. Mixed ANOVAs were used to compare task factors and age groups in task performance. Mixed ANOVAs also compared task factors, age group and time factors in task-induced changes in measured Oxy-Hb. Among the older participants, correlations between the TMT-B score and Oxy-Hb values measured in each single-task and in the dual-task were examined using a Pearson correlation coefficient.
Oxy-Hb values were significantly increased in both the calculation task and the dual-task within patients in both age groups. However, the Oxy-Hb values associated with there were higher in the older group during the post-task period for the dual-task. Also, there were significant negative correlations between both task-performance accuracy and Oxy-Hb values during the dual-task and participant TMT-B scores.
Conclusions
Older adults demonstrated age-specific PFC activation in response to dual-task challenge. There was also a significant negative correlation between PFC activation during dual-task and executive/attentional function. These findings suggest that the high cognitive load induced by dual-task activity generates increased PFC activity in older adults. However, this relationship appeared to be strongest in participants with better baseline attention and executive functions.
doi:10.1186/1471-2202-14-10
PMCID: PMC3552708  PMID: 23327197
Dual-task; Near-infrared spectroscopy; Executive function; Attentional function
18.  Clinimetric properties of the Tinetti Mobility Test, Four Square Step Test, Activities-specific Balance Confidence Scale, and spatiotemporal gait measures in individuals with Huntington's disease 
Gait & posture  2014;40(4):647-651.
Background and purpose
Individuals with Huntington's disease (HD) experience balance and gait problems that lead to falls. Clinicians currently have very little information about the reliability and validity of outcome measures to determine the efficacy of interventions that aim to reduce balance and gait impairments in HD. This study examined the reliability and concurrent validity of spatiotemporal gait measures, the Tinetti Mobility Test (TMT), Four Square Step Test (FSST), and Activities-specific Balance Confidence (ABC) Scale in individuals with HD.
Methods
Participants with HD [n = 20; mean age ± SD = 50.9 ± 13.7; 7 male] were tested on spatiotemporal gait measures the TMT, FSST, and ABC Scale before and after a six week period to determine test–retest reliability and minimal detectable change (MDC) values. Linear relationships between gait and clinical measures were estimated using Pearson's correlation coefficients.
Results
Spatiotemporal gait measures, the TMT total and the FSST showed good to excellent test–retest reliability (ICC > 0.75). MDC values were 0.30 m/s and 0.17 m/s for velocity in forward and backward walking respectively, four points for the TMT, and 3 s for the FSST. The TMT and FSST were highly correlated with most spatiotemporal measures. The ABC Scale demonstrated lower reliability and less concurrent validity than other measures.
Conclusions
The high test–retest reliability over a six week period and concurrent validity between the TMT, FSST, and spatiotemporal gait measures suggest that the TMT and FSST may be useful outcome measures for future intervention studies in ambulatory individuals with HD.
doi:10.1016/j.gaitpost.2014.07.018
PMCID: PMC4230319  PMID: 25128156
Balance; Gait; Test–retest reliability; Validity; Huntington's disease
19.  Rapid improvement in verbal fluency and aphasia following perispinal etanercept in Alzheimer's disease 
BMC Neurology  2008;8:27.
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.
doi:10.1186/1471-2377-8-27
PMCID: PMC2500042  PMID: 18644112
20.  Predicting the probability of falls in community-dwelling elderly individuals using the trail-walking test 
Background
Falling is a common problem in the fast-growing elderly population. Multitasking or engaging in two or more activities at the same time is common in daily living.
Objective
To determine the usefulness of the trail-walking test (TWT) for predicting a fall in community-dwelling elderly individuals.
Methods
This was a prospective study in which the TWT was used to evaluate the risk of falling among a group of community-dwelling elderly individuals (n = 171) with a mean age of 80.5 ± 5.6 years. The following tests were conducted: TWT, trail-making test (TMT), timed-up-and-go test (TUG), functional reach (FR) test, one-leg standing (OLS) test, and 10-m walking time test. Test–retest reliability was assessed by repeating the TWT within 2 weeks of the first trial, and there was a 1-year follow-up. Stepwise logistic regression analysis was used to analyze whether the TWT, TMT, TUG, FR, OLS, or 10-m walking tests predicted falling.
Results
The test–retest reliability of TWT was high (intraclass correlation coefficient 0.945, p < 0.001). Fifty-nine participants (34.5%) had reported a fall during the year preceding the 1-year follow-up. The stepwise logistic regression analysis revealed that only the TWT was significantly related to falling (odds ratio 1.160, 95% confidence interval 1.107–1.214; p < 0.001). In total, 77.8% of cases were correctly classified.
Conclusion
When reliability and validity were considered, the TWT was most useful test of those evaluated for assessing the risk of fall among our elderly cohort.
doi:10.1007/s12199-010-0154-1
PMCID: PMC2955901  PMID: 21432571
Fall; Elderly; Trail-walking test; Predictor; Complex-task condition
21.  Computerised cognitive assessment of concussed Australian Rules footballers 
Background—"Paper and pencil" neuropsychological tests play an important role in the management of sports related concussions. They provide objective information on the athlete's cognitive function and thus facilitate decisions on safe return to sport. It has been proposed that computerised cognitive tests have many advantages over such conventional tests, but their role in this domain is yet to be established.
Objectives—To measure cognitive impairment after concussion in a case series of concussed Australian Rules footballers, using both computerised and paper and pencil neuropsychological tests. To investigate the role of computerised cognitive tests in the assessment and follow up of sports related concussions.
Methods—Baseline measures on the Digit Symbol Substitution Test (DSST), Trail Making Test-Part B (TMT), and a simple reaction time (SRT) test from a computerised cognitive test battery (CogState) were obtained in 240 players. Tests were repeated in players who had sustained a concussive injury. A group of non-injured players were used as matched controls.
Results—Six concussions were observed over a period of nine weeks. At the follow up, DSST and TMT scores did not significantly differ from baseline scores in both control and concussed groups. However, analysis of the SRT data showed an increase in response variability and latency after concussion in the injured athletes. This was in contrast with a decrease in response variability and no change in latency on follow up of the control players (p<0.02).
Conclusion—Increased variability in response time may be an important cognitive deficit after concussion. This has implications for consistency of an athlete's performance after injury, as well as for tests used in clinical assessment and follow up of head injuries.
Key Words: concussion; football; neuropsychology; cognitive; head injury
doi:10.1136/bjsm.35.5.354
PMCID: PMC1724390  PMID: 11579074
22.  A Bias Against Disconfirmatory Evidence Is Associated With Delusion Proneness in a Nonclinical Sample 
Schizophrenia Bulletin  2007;33(4):1023-1028.
Previous work has suggested that a bias against disconfirmatory evidence (BADE) may be associated with the schizophrenia spectrum. The current investigation focused on whether a BADE (1) overlaps with traditional measures of memory and executive functions or selectively taps into a unique aspect of cognition and (2) is correlated with delusional ideation but not with other aspects of schizotypy. Sixty-eight undergraduate students were administered the Schizotypal Personality Questionnaire (SPQ), the BADE test, the Rey Auditory Verbal Learning Test (RAVLT), the Wisconsin Card Sorting Test (WCST), the Trail Making Tests A and B (TMT), and tests used to estimate IQ. Factor analysis of all cognition measures resulted in a 6-factor solution, 4 of which reflected the 4 domains of neuropsychological tests (WCST, RAVLT, TMT, and IQ), and 2 of which reflected different aspects of the BADE test: Initial Belief and Integration of Disconfirmatory Evidence. This solution suggests that BADE measures were independent from the other cognitive domains measured. Integration of Disconfirmatory Evidence was the only factor that correlated with delusion-content subscales of the SPQ, providing support for the contribution of a BADE to delusional ideation.
doi:10.1093/schbul/sbm013
PMCID: PMC2632321  PMID: 17347526
schizotypy; delusions; cognition; decision making; reasoning
23.  The use of Ginkgo biloba for the prevention of chemotherapy-related cognitive dysfunction in women receiving adjuvant treatment for breast cancer, N00C9 
Purpose
Patients undergoing treatment for cancer often report problems with their cognitive function, which is an essential component of health-related quality of life. Pursuant to this, a two-arm randomized, placebo-controlled, double-blind, phase III clinical trial was conducted to evaluate Ginkgo biloba (EGB 761) for the prevention of chemotherapy-related cognitive dysfunction in patients with breast cancer.
Methods
Previously chemotherapy naïve women about to receive adjuvant chemotherapy for breast cancer were randomized to receive 60 mg of EGB 761 or a matching placebo twice daily. The study agent was to begin before their second cycle of chemotherapy and to be taken throughout chemotherapy and 1 month beyond completion. The primary measure for cognitive function was the High Sensitivity Cognitive Screen (HSCS), with a secondary measure being the Trail Making Tests (TMT) A and B. Subjective assessment of cognitive function was evaluated by the cognitive subscale of the Perceived Health Scale (PHS) and the Profile of Mood States (POMS). Data were collected at baseline and at intervals throughout and after chemotherapy, up to 24 months after completion of adjuvant treatment. The primary statistical analysis included normalized area under the curve (AUC) comparisons of the HSCS, between the arms. Secondary analyses included evaluation of the other measures of cognition as well as correlational analyses between self-report and cognitive testing.
Results
One hundred and sixty-six women provided evaluable data. There were no significant differences in AUC up to 12 months on the HSCS between arms at the end of chemotherapy or at any other time point after adjuvant treatment. There were also no significant differences in TMT A or B at any data point. Perceived cognitive functions, as measured by the PHS and confusion/bewilderment subscale of the POMS, were not different between arms at the end of chemotherapy. There was also little correlation between self-reported cognition and cognitive testing. No differences were observed in toxicities per Common Terminology Criteria for Adverse Events (CTCAE) assessment between Ginkgo biloba and placebo throughout the study; however, after chemotherapy, the placebo group reported worse nausea (p = .05).
Conclusion
This study did not provide any support for the notion that Ginkgo biloba, at a dose of 60 mg twice a day, can help prevent cognitive changes from chemotherapy. These analyses do provide data to further support the low associations between patients’ self-report of cognition and cognitive performance, based on more formal testing.
doi:10.1007/s00520-012-1647-9
PMCID: PMC3587364  PMID: 23150188
Ginkgo biloba; Chemotherapy-related cognitive dysfunction; Adjuvant treatment; Breast cancer; Dietary supplements
24.  Poor Trail Making Test Performance Is Directly Associated with Altered Dual Task Prioritization in the Elderly – Baseline Results from the TREND Study 
PLoS ONE  2011;6(11):e27831.
Background
Deterioration of executive functions in the elderly has been associated with impairments in walking performance. This may be caused by limited cognitive flexibility and working memory, but could also be caused by altered prioritization of simultaneously performed tasks. To disentangle these options we investigated the associations between Trail Making Test performance—which specifically measures cognitive flexibility and working memory—and dual task costs, a measure of prioritization.
Methodology and Principal Findings
Out of the TREND study (Tuebinger evaluation of Risk factors for Early detection of Neurodegenerative Disorders), 686 neurodegeneratively healthy, non-demented elderly aged 50 to 80 years were classified according to their Trail Making Test performance (delta TMT; TMT-B minus TMT-A). The subjects performed 20 m walks with habitual and maximum speed. Dual tasking performance was tested with walking at maximum speed, in combination with checking boxes on a clipboard, and subtracting serial 7 s at maximum speeds. As expected, the poor TMT group performed worse when subtracting serial 7 s under single and dual task conditions, and they walked more slowly when simultaneously subtracting serial 7 s, compared to the good TMT performers. In the walking when subtracting serial 7 s condition but not in the other 3 conditions, dual task costs were higher in the poor TMT performers (median 20%; range −6 to 58%) compared to the good performers (17%; −16 to 43%; p<0.001). To the contrary, the proportion of the poor TMT performance group that made calculation errors under the dual tasking situation was lower than under the single task situation, but higher in the good TMT performance group (poor performers, −1.6%; good performers, +3%; p = 0.035).
Conclusion
Under most challenging conditions, the elderly with poor TMT performance prioritize the cognitive task at the expense of walking velocity. This indicates that poor cognitive flexibility and working memory are directly associated with altered prioritization.
doi:10.1371/journal.pone.0027831
PMCID: PMC3218043  PMID: 22114705
25.  A Combination of Schwann-Cell Grafts and Aerobic Exercise Enhances Sciatic Nerve Regeneration 
PLoS ONE  2014;9(10):e110090.
Background
Despite the regenerative potential of the peripheral nervous system, severe nerve lesions lead to loss of target-organ innervation, making complete functional recovery a challenge. Few studies have given attention to combining different approaches in order to accelerate the regenerative process.
Objective
Test the effectiveness of combining Schwann-cells transplantation into a biodegradable conduit, with treadmill training as a therapeutic strategy to improve the outcome of repair after mouse nerve injury.
Methods
Sciatic nerve transection was performed in adult C57BL/6 mice; the proximal and distal stumps of the nerve were sutured into the conduit. Four groups were analyzed: acellular grafts (DMEM group), Schwann cell grafts (3×105/2 µL; SC group), treadmill training (TMT group), and treadmill training and Schwann cell grafts (TMT + SC group). Locomotor function was assessed weekly by Sciatic Function Index and Global Mobility Test. Animals were anesthetized after eight weeks and dissected for morphological analysis.
Results
Combined therapies improved nerve regeneration, and increased the number of myelinated fibers and myelin area compared to the DMEM group. Motor recovery was accelerated in the TMT + SC group, which showed significantly better values in sciatic function index and in global mobility test than in the other groups. The TMT + SC group showed increased levels of trophic-factor expression compared to DMEM, contributing to the better functional outcome observed in the former group. The number of neurons in L4 segments was significantly higher in the SC and TMT + SC groups when compared to DMEM group. Counts of dorsal root ganglion sensory neurons revealed that TMT group had a significant increased number of neurons compared to DMEM group, while the SC and TMT + SC groups had a slight but not significant increase in the total number of motor neurons.
Conclusion
These data provide evidence that this combination of therapeutic strategies can significantly improve functional and morphological recovery after sciatic injury.
doi:10.1371/journal.pone.0110090
PMCID: PMC4198198  PMID: 25333892

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