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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.  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
3.  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
4.  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
5.  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
6.  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
7.  Executive ability and physical performance in urban Black older adults 
Abstract
Executive dysfunction is correlated with disability in tasks of daily living. Less is known about the relationship between cognition, particularly executive dysfunction, and physical performance. This study investigated how executive ability, measured by the Trail Making Test, Part B (TMT-B), Controlled Oral Word Association test (COWA) and Animal Naming (AN), related to completion of physical tasks on the Short Physical Performance Battery (SPPB). The sample included 68 urban-dwelling Black adults ages 59–95. AN and TMT-B accounted for 6.2% and 7.1% of the variance, respectively, in SPPB total score after controlling for general cognitive functioning (Mini Mental Status Exam) and demographics. COWA and the MMSE did not obtain significance. Only the TMT-B remained significant after accounting for illness burden. Findings suggest that executive ability is related to physical performance in older urban Black adults more than general cognitive functioning. This relationship is attenuated by illness burden.
doi:10.1016/j.acn.2008.06.003
PMCID: PMC2577195  PMID: 18650058
Disability; Executive function; Short Physical Performance Battery; Cognition; Older adults
8.  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
9.  Executive functions in schizophrenia 
Indian Journal of Psychiatry  2005;47(1):21-26.
Background:
Executive functions constitute the core deficit in schizophrenic illness and have been related to structural and functional deficits, cognitive impairments and final outcome.
Aim:
To study the various dimensions of executive functions such as goal formulation, planning, behavioural programming and effective performance.
Methods:
By using direct and indirect clinical neuropsychological methods, 31 patients were studied neuropsychologically by the trail-making test (TMT), Raven matrices and fluency tests, and their symptom patterns were quantified using the Positive and Negative Syndrome Scale (PANSS).
Results:
The patients had varying degrees of involvement of different dimensions of executive functions. There was an inverse relationship to TMT and a positive correlation with Raven matrices and fluency tests.
Conclusion:
The dimensions of executive functions did not show any significant relationship with age, duration of illness or most scores in PANSS. Our findings are relevant for remediation and rehabilitation measures.
doi:10.4103/0019-5545.46069
PMCID: PMC2918311
Executive functions; neurocognition; schizophrenia
10.  Trail Making Test Part A and Brain Perfusion Imaging in Mild Alzheimer's Disease 
Background/Aims
The Trail Making Test (TMT) has long been used to investigate deficits in cognitive processing speed and executive function in humans. However, there are few studies that elucidate the neural substrates of the TMT. The aim of the present study was to identify the regional perfusion patterns of the brain associated with performance on the TMT part A (TMT-A) in patients with Alzheimer's disease (AD).
Methods
Eighteen AD patients with poor performance on the TMT-A and 36 age- and sex-matched AD patients with good performance were selected. All subjects underwent brain single photon emission computed tomography.
Results
No significant differences between the good and poor performance groups were found with respect to years of education and revised Addenbrooke's Cognitive Examination scores. However, higher z-scores for hypoperfusion in the bilateral superior parietal lobule were observed in the group that scored poorly on the TMT-A compared with the good performance group.
Conclusion
Our results suggest that functional activity of the bilateral superior parietal lobules is closely related to performance time on the TMT-A. Thus, the performance time on the TMT-A might be a promising index of dysfunction of the superior parietal area among mild AD patients.
doi:10.1159/000350806
PMCID: PMC3721127  PMID: 23888166
Alzheimer's disease; Cerebral blood flow; Single photon emission computed tomography; Trail Making Test

11.  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
12.  Prediction of conversion from mild cognitive impairment to Alzheimer's disease dementia based upon biomarkers and neuropsychological test performance 
Neurobiology of Aging  2010;33(7):1203-1214.e2.
The current study tested the accuracy of primary MRI and cerebrospinal fluid (CSF) biomarker candidates and neuropsychological tests for predicting the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia. In a cross-validation paradigm, predictor models were estimated in the training set of AD (N = 81) and elderly control subjects (N = 101). A combination of CSF t-tau/Aβ1-4 ratio and MRI biomarkers or neuropsychological tests (free recall and trail making test B (TMT-B)) showed the best statistical fit in the AD vs. HC comparison, reaching a classification accuracy of up to 64% when applied to the prediction of MCI conversion (3.3-year observation interval, mean = 2.3 years). However, several single-predictor models showed a predictive accuracy of MCI conversion comparable to that of any multipredictor model. The best single predictors were right entorhinal cortex (prediction accuracy = 68.5% (95% CI (59.5, 77.4))) and TMT-B test (prediction accuracy 64.6% (95% CI (55.5, 73.4%))). In conclusion, short-term conversion to AD is predicted by single marker models to a comparable degree as by multimarker models in amnestic MCI subjects.
doi:10.1016/j.neurobiolaging.2010.10.019
PMCID: PMC3328615  PMID: 21159408
Alzheimer's disease; Dementia; Mild cognitive impairment; Mild cognitive impairment (MCI); Autopsy-confirmation; Biomarkers; Early detection; Cerebrospinal fluid; Cerebrospinal fluid (CSF); Aβ1-42; Tau; p-tau; MRI; Hippocampus; Volumetry; Entorhinal cortex; Prodromal; ADNI
13.  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
14.  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
15.  Cognitive Impairment in Relapsing Remitting and Secondary Progressive Multiple Sclerosis Patients: Efficacy of a Computerized Cognitive Screening Battery 
ISRN Neurology  2014;2014:151379.
Objective. To investigate the pattern of cognitive impairment in relapsing remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) patients using a computerized battery. Methods. RRMS patients (N = 50), SPMS patients (N = 30), and controls (N = 31) were assessed by Central Nervous System Vital Signs (CNS VS) computerized battery, Trail Making Tests (TMT) A and B, and semantic and phonological verbal fluency tasks. Results. The overall prevalence of cognitive dysfunction was 53.75% (RRMS 38%, SPMS 80%). RRMS patients differed from controls with large effect size on reaction time, medium effect size on TMT A and small on TMT B, phonological verbal fluency, composite memory, psychomotor speed, and cognitive flexibility. SPMS patients differed from controls in all neuropsychological measures (except complex attention) with large effect sizes on TMT A and B, phonological verbal fluency, composite memory, psychomotor speed, reaction time, and cognitive flexibility. Between patient groups, medium effect sizes were present on TMT B and psychomotor speed, while small effect sizes were present on composite memory and processing speed. Conclusion. CNS VS is sensitive in detecting cognitive impairment in RRMS and SPMS patients. Significant impairment in episodic memory, executive function, and processing speed were identified, with gradual increment of the frequency as disease progresses.
doi:10.1155/2014/151379
PMCID: PMC3976849
16.  The Contribution of Trail Making to the Prediction of Performance-Based IADLs in Parkinson’s Disease Without Dementia 
Performance on part B of the Trail Making Test (TMT) contributes to the prediction of ability to complete instrumental activities of daily living (IADLs) in Parkinson’s disease (PD). Although this suggests that cognitive flexibility is important in the everyday functioning of individuals with PD, this may not be that case as the TMT is multifactorial, involving motor speed, visual scanning, sequencing, and cognitive flexibility. The purpose of the current study was to determine which elements of the task contribute to the prediction of IADLs in a sample of 30 non-demented individuals with PD. Correlational analyses indicated strong relationships between a performance-based measure of IADLs and measures involving scanning, sequencing, and cognitive flexibility from the Delis-Kaplan Executive Function System (D-KEFS) TMT. Results from standard regressions indicated that measures of sequencing and level of depression but not scanning, cognitive flexibility, or demographic variables made a significant, independent contribution to the prediction of IADLs. These results suggest that the sequencing element of the TMT is paramount in the prediction of IADLs in PD.
doi:10.1080/13803395.2013.798397
PMCID: PMC3674142  PMID: 23663116
Parkinson’s disease; cognitive flexibility; trail making; IADLs
17.  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
18.  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
19.  Assessment of cognitive function in patients with essential hypertension treated with lercanidipine 
Objectives
The aim of this longitudinal, open-label, comparative, multicenter study was to assess cognitive function in hypertensive patients receiving mid-term treatment with lercanidipine.
Methods
Hypertensive patients aged 40 years or older were treated with lercanidipine (10mg daily) after 7–10 days washout period. The duration of the study was 6 months. Blood pressure (BP) was measured every 4 weeks (JNC 6th report). In patients with inadequate BP control, doxazosin was added and up-titrated. At baseline and after 6 months of treatment, cognitive function was evaluated using the Spanish validated version of the Mini-Mental State Examination (MMSE) and the Trail Making Test (TMT).
Results
In the study population of 467 patients, BP decreased from 154.4/95.3 mmHg at baseline to 134.8/80.7 mmHg at 6 months. At the end of the study, 98% of patients were receiving lercanidipine, 20% an angiotensin-converting enzyme inhibitor, and 6% doxazosin. Adequate BP control was obtained in 68% of patients. The mean (standard deviation) MMSE scores improved from 32.35 (2.59) to 33.25 (2.36) (p<0.0001). Patients with good BP control scored significantly better than those with inadequate BP control (p<0.05), which was already observed at the first month.
Conclusions
The third-generation calcium channel antagonist, lercanidipine, improved cognitive function after 6 months of treatment especially in patients with good BP control, suggesting that improvements in cognitive function may be associated with a decrease in BP.
PMCID: PMC1994004  PMID: 17323604
lercanidipine; hypertension; cognitive function
20.  Differences in executive functioning in children with heavy prenatal alcohol exposure or attention-deficit/hyperactivity disorder 
Children with either fetal alcohol spectrum disorder (FASD) or attention-deficit/hyperactivity disorder (ADHD) display deficits in attention and executive function (EF) and differential diagnosis of these two clinical groups may be difficult, especially when information about prenatal alcohol exposure is unavailable. The current study compared EF performance of three groups: children with heavy prenatal alcohol exposure (ALC); nonexposed children with attention-deficit/hyperactivity disorder (ADHD); and typically developing controls (CON). Both clinical groups met diagnostic criteria for ADHD. The EF tasks used were the Wisconsin Card Sorting Test (WCST), the Controlled Oral Word Association Test (COWAT), and the Trail Making Test (TMT). Results indicated different patterns of deficit; both clinical groups displayed deficits on the WCST and a relative weakness on letter versus category fluency. Only the ALC group displayed overall deficits on letter fluency and a relative weakness on TMT-B versus TMT-A. In addition, WCST performance was significantly lower than expected based on IQ in the ADHD group and significantly higher than expected in the ALC group. These results, which indicate that, although EF deficits occurred in both clinical groups, the degree and pattern of deficit differed between the ALC and ADHD groups, may improve differential diagnosis.
doi:10.1017/S1355617708080144
PMCID: PMC3713496  PMID: 18078538
Fetal alcohol syndrome; Fetal alcohol spectrum disorders; Differential diagnosis; FAS; ADHD; Neuropsychological function
21.  Cognitive Functions across the GNB3 C825T Polymorphism in an Elderly Italian Population 
To verify whether the C825T polymorphism of the GNB3 influences the response to neuropsychological tests, mini-mental state examination, digit span (DS), immediate and delayed prose memory, memory with interference at 10 and 30 seconds (MI 10 and 30), trail making tests (TMTs) A and B, abstraction task, verbal fluency (VF) test, figure drawing and copying, overlapping figures test and clock test were performed in 220 elderly men and women free from clinical dementia and from neurological and psychiatric diseases randomly taken from the Italian general population and analysed across the C825T polymorphism. The performance of DS, immediate and delayed prose memory, VF, and TMTs was worse in subjects who were TT for the polymorphism in comparison to the C-carriers. The performance of all tests declined with age. In the case of DS, immediate and delayed prose memory, MI 10 and VF, this trend was maintained in the C-carriers but not in TT. In the case of prose memory, of memory with interference, and of VF, schooling reduced the detrimental interaction between age and genotype. The C825T polymorphism of GNB3 gene therefore influences memory and verbal fluency, being additive to the effects of age and partially mitigated by schooling.
doi:10.1155/2013/597034
PMCID: PMC3819753  PMID: 24251036
22.  Impaired Set-Shifting Ability in Patients with Eating Disorders, Which Is Not Moderated by Their Catechol-O-Methyltransferase Val158Met Genotype 
Psychiatry Investigation  2010;7(4):298-301.
The aim of this study was to examine the set-shifting ability in women with both anorexia nervosa (AN) and bulimia nervosa (BN) and to investigate whether it is contributed by the catechol-O-methyltransferase (COMT) Val158Met genotype. A total of 102 Korean participants-40 women with lifetime AN, 28 women with lifetime BN, and 34 healthy women of comparable age and intelligence quotient- were examined. A neuropsychological battery of tests was applied and blood samples were obtained for COMT Val158Met genotyping. Set-shifting impairments Trail Making Test (TMT, Part B) were found in patients with AN and BN, respectively. Furthermore, the eating disorders were also linked to deficits in attentional mechanisms (TMT, Part A) and motor skills (Finger Tapping Test). Finally, set-shifting and its link to eating disorders were not moderated by COMT Val158Met genotype.
doi:10.4306/pi.2010.7.4.298
PMCID: PMC3022318  PMID: 21253415
Eating disorders; Set-shifting ability; Anorexia nervosa; Bulimia nervosa; Catechol-O-methyltransferase
23.  Is the N-Back Task a Valid Neuropsychological Measure for Assessing Working Memory? 
The n-back is a putative working memory task frequently used in neuroimaging research; however, literature addressing n-back use in clinical neuropsychological evaluation is sparse. We examined convergent validity of the n-back with an established measure of working memory, digit span backward. The relationship between n-back performance and scores on measures of processing speed was also examined, as was the ability of the n-back to detect potential between-groups differences in control and Parkinson's disease (PD) groups. Results revealed no correlation between n-back performance and digit span backward. N-back accuracy significantly correlated with a measure of processing speed (Trail Making Test Part A) at the 2-back load. Relative to controls, PD patients performed less accurately on the n-back and showed a trend toward slower reaction times, but did not differ on any of the neuropsychological measures. Results suggest the n-back is not a pure measure of working memory, but may be able to detect subtle differences in cognitive functioning between PD patients and controls.
doi:10.1093/arclin/acp063
PMCID: PMC2770861  PMID: 19767297
Working memory; Executive function; Information processing speed; Parkinson's disease; Neuropsychology
24.  A reappraisal of the association between Dysbindin (DTNBP1) and schizophrenia in a large combined case-control and family-based sample of German ancestry 
Schizophrenia research  2010;118(1-3):98-105.
Background
Dysbindin (DTNBP1) is a widely-studied candidate gene for schizophrenia (SCZ); however, inconsistent results across studies triggered skepticism towards the validity of the findings. In this HapMap-based study, we reappraised the association between Dysbindin and SCZ in a large sample of German ethnicity.
Method
Six hundred thirty-four cases with DSM-IV SCZ, 776 controls, and 180 parent-offspring trios were genotyped for 38 Dysbindin SNPs. We also studied two phenotypically-defined subsamples: 147 patients with a positive family history of SCZ (FH-SCZ+) and SCZ patients characterized for cognitive performance with Trail-Making Tests A and B (TMT-A: n=219; TMT-B: n=247). Given previous evidence of gene-gene interactions in SCZ involving the COMT gene, we also assessed epistatic interactions between Dysbindin markers and 14 SNPs in COMT.
Results
No association was detected between Dysbindin markers and SCZ, or in the FH-SCZ+ subgroup. Only one marker (rs1047631, previously reported to be part of a risk haplotype), showed a nominally significant association with performance on TMT-A and TMT-B; these findings did not remain significant after correction for multiple comparisons. Similarly, no pairwise epistatic interactions between Dysbindin and COMT markers remained significant after correction for 504 pairwise comparisons.
Conclusions
Our results, based on one of the largest sample of European Caucasians and using narrowly-defined criteria for SCZ, do not support the etiological involvement of Dysbindin markers in SCZ. Larger samples may be needed in order to unravel Dysbindin's possible role in the genetic basis of proposed intermediate phenotypes of SCZ or to detect epistatic interactions.
doi:10.1016/j.schres.2009.12.025
PMCID: PMC2856768  PMID: 20083391
polymorphism; COMT; epistasis; endophenotype; cognitive function
25.  Predictors of Decision-Making on the Iowa Gambling Task: Independent Effects of Lifetime History of Substance Use Disorders and Performance on the Trail Making Test 
Brain and cognition  2007;66(3):243-252.
Poor decision-making and executive function deficits are frequently observed in individuals with substance use disorders (SUDs), and executive deficits may contribute to poor decision-making in this population. This study examined the influence of lifetime history of an alcohol, cocaine, heroin, or polysubstance use disorder on decision-making as measured by the Iowa Gambling Task (IGT) after controlling for executive ability, demographic characteristics, and current substance use. Participants (131 with lifetime history of SUD and 37 controls) completed the IGT and two neuropsychological tests: the Trail Making Test and the Controlled Oral Word Association Test. Control participants performed significantly better than those with a lifetime SUD history on the IGT, but performance on the neuropsychological tests was comparable for the two groups. A lifetime SUD diagnosis was associated with performance on the IGT after controlling for covariates, and Trail Making Test performance was associated with IGT performance in both SUD and control participants.
doi:10.1016/j.bandc.2007.09.001
PMCID: PMC2292486  PMID: 17942206
decision-making; substance use disorder; executive ability; neuropsychological tests; Iowa Gambling Task; Trail Making Test; Controlled Oral Word Association Test

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