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PubMed2006

Diffusion tensor imaging of frontal white matter and executive functioning in cocaine-exposed children.

BACKGROUND: Although animal studies have demonstrated frontal white matter and behavioral changes resulting from prenatal cocaine exposure, no human studies have associated neuropsychological deficits in attention and inhibition with brain structure. We used diffusion tensor imaging to investigate frontal white matter integrity and executive functioning in cocaine-exposed children. METHODS: Six direction diffusion tensor images were acquired using a Siemens 3T scanner with a spin-echo echo-planar imaging pulse sequence on right-handed cocaine-exposed (n = 28) and sociodemographically similar non-exposed children (n = 25; mean age: 10.6 years) drawn from a prospective, longitudinal study. Average diffusion and fractional anisotropy were measured in the left and right frontal callosal and frontal projection fibers. Executive functioning was assessed using two well-validated neuropsychological tests (Stroop color-word test and Trail Making Test). RESULTS: Cocaine-exposed children showed significantly higher average diffusion in the left frontal callosal and right frontal projection fibers. Cocaine-exposed children were also significantly slower on a visual-motor set-shifting task with a trend toward lower scores on a verbal inhibition task. Controlling for gender and intelligence, average diffusion in the left frontal callosal fibers was related to prenatal exposure to alcohol and marijuana and an interaction between cocaine and marijuana exposure. Performance on the visual-motor set-shifting task was related to prenatal cocaine exposure and an interaction between cocaine and tobacco exposure. Significant correlations were found between test performance and fractional anisotropy in areas of the frontal white matter. CONCLUSIONS: Prenatal cocaine exposure, alone and in combination with exposure to other drugs, is associated with slightly poorer executive functioning and subtle microstructural changes suggesting less mature development of frontal white matter pathways. The relative contribution of postnatal environmental factors, including characteristics of the caregiving environment and stressors associated with poverty and out-of-home placement, on brain development and behavioral functioning in polydrug-exposed children awaits further research.

Child↗

PubMed1994

Oral physostigmine and impaired memory in adults with brain injury.

The purpose of this study was to examine the effects of physostigmine, a cholinergic agonist, on memory loss after traumatic brain injury (TBI), as compared to placebo or scopolamine, a cholinergic antagonist, using a double-blind, placebo-controlled design. Each subject received each active drug and placebo. Neuropsychological measures (Wechsler Memory Scale I and II, Selective Reminding Test, Trail-Making Test, Parts A and B, Digit Symbol, and Memory Questionnaire) and measures of clinical balance were completed at baseline, after each drug phase, and at 1 month follow-up. Thirty-six subjects completed the study with results showing an improvement in memory scores in 44% of subjects (responders) while taking oral physostigmine. The most sensitive measure was the Selective Reminding Test, specifically Long-term Storage. The impact of drugs on standing balance as compared to placebo was improved standing time in the responders: (1) with physostigmine when standing tandem with eyes closed (p < 0.05), and (2) with scopolamine when standing on one foot with eyes closed (p < 0.05). Results support the potential benefit of cholinergic agonists on memory after TBI and the need for further research of possible clinical markers for the drug.

Administration, Cutaneous↗

PubMed2000

[Spanish verbal fluency. Normative data in Argentina].

Letter and category fluency tasks are used to assess semantic knowledge, retrieval ability, and executive functioning. The original normative data have been obtained mainly from English speaking populations; there are few papers on norms in other languages. The purpose of this study was to collect normative scores in Argentina and to evaluate the effects of sex, age, education and cognitive status on the letter and category fluency tasks, in 266 healthy Spanish-speaking participants (16 to 86 years). Mean education span was 12.8 +/- 4 years. In each subject a neuropsychological battery (Minimental State Exam, Signoret Memory Battery, Boston Naming Test and Trail Making Test) was carried out as well as category fluency (naming animals in one minute) and letter fluency (words beginning with letter "p" in one minute). The sample was arranged into a group of subjects with less than 45 years and further groups up to 10 more years, until 75 years (or more) with three different levels of education. Significant effects were found for age, education, and Minimental State Exam on performance of both fluencies. Mean performance scores are presented for each group to be used in Argentina.

Adolescent↗

PubMedDate not supplied

[Factorial structure of the executive functions in young university students].

INTRODUCTION: Several studies have proposed a multiple dimensional theoretical model for executive function. OBJECTIVE: To identify the factor structure of the executive function in a sample of young university students of different modalities of learning in their careers. METHODS: 100 participants of both sexes, age 16 to-21-year old and normal Full Scale IQ were selected in a randomized and representative approach from private universities of Medellin Colombia. They were student of verbal, visuospatial and mathematical careers. A executive function assessment battery were applied, which included: Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT) A and B, verbal fluency test (FAS) by phonologic and semantic guides, and Stroop test. RESULTS: A structure of four factor was found, which explained 74.9% of variance. Factors were: 1. Organization and flexibility, which explained 26.6% of variance; 2. Processing speed, 19.7%; 3. Inhibitory control, 15.1%; and 4. Verbal fluency 13.4%. CONCLUSION: A multiple factor structure of the executive function in young university students was demonstrated.

Adolescent↗

PubMed1987

An experimental evaluation of the efficacy of suloctidil in the treatment of primary degenerative dementia.

A double-blind, placebo-controlled randomized design was employed to test the efficacy and optimal dosage of Suloctidil in the treatment of primary degenerative dementia (PDD i.e., Alzheimer's disease). Initially, 30 geriatric patients with a diagnosis of PDD were matched for age, education, and handedness, and randomly assigned to one of three groups: (a) 600 mg. Suloctidil daily; (b) 450 mg. Suloctidil daily; (c) or placebo, for 12 weeks. All patients were administered individually a brief neuropsychological battery at pretreatment and at 12-week posttreatment. The tests were the Boston Naming Test, the Thurstone Word Fluency Test, the Trail Making Test, and the Grooved Pegboard. While there was differential attrition across the three groups, the results of the Boston Naming Test suggest a medication-dosage effect.

Clinical Trial↗

PubMed2002

High-functioning autism and schizophrenia: a comparison of an early and late onset neurodevelopmental disorder.

Autism and schizophrenia are separate neurodevelopmental disorders that share a number of interpersonal and cognitive deficits. The symptoms of autism first appear during early life while schizophrenic symptoms do not typically appear until adolescence at the earliest. Efforts have been made to characterize the pattern of cognitive function in both disorders, and certain resemblances have become apparent such as deficits in abstract reasoning and the more complex aspects of memory and language. The present study provided a comparison of cognitive function between the two disorders. The autistic sample consisted of well-diagnosed individuals with high-functioning autism (IQ> or =70). The schizophrenic sample was divided into four subgroups using Ward's method of cluster analysis. Participants received the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the Halstead Category Test, the Trail Making test, and the Wisconsin Card Sorting test (WCST). The profile of the autism sample was compared with the four schizophrenia cluster profiles. The autism group resembled only one of the schizophrenia clusters, with both showing elevations on the WAIS-R Information and Block Design subtests and depressions on Comprehension and Digit Symbol. It was concluded that individuals with high-functioning autism have a cognitive profile that resembles that of an empirically derived subgroup of schizophrenia patients but that does not resemble profiles found in other schizophrenia subgroups. The pattern itself, marked by a relatively depressed score on the Comprehension subtest among the Verbal subtests and a relatively elevated score on Block Design among the Performance subtests, has been characterized in the past as a prototypic profile for high-functioning autism.

Journal Article↗

PubMed1998

A comparison of clustering solutions for cognitive heterogeneity in schizophrenia.

A cluster analytic solution based upon a battery of tests consisting of the Halstead Category and Tactual Performance Tests, the Trail Making Test, and the Wisconsin Card Sorting Test was compared with a solution based on the subtests of the Wechsler intelligence scales, utilizing a sample of 221 schizophrenic patients. Both analyses permitted four-cluster solutions, and we found a weak but significant degree of association between solutions. Examination of external validity of the two solutions revealed stronger associations with clinical variables for the Wechsler-scale-based solution. The major conclusions were that the existence of cognitive heterogeneity in schizophrenia exists across a broad range of abilities, and appears to reflect a combination of continuity of ability level and existence of possible subtypes requiring further neuropsychological and neurobiological verification.

Adult↗

PubMed1997

Cognitive impairment in the euthymic phase of chronic unipolar depression.

Cognitive functioning in the nonsymptomatic phase and the long-term cognitive outcome of patients with mood disorders are both heuristic and important clinical issues in the study of mood disorders. Literature findings are inconsistent because of design confounds. We tried to address these issues while controlling for several confounds including age, education, gender differences in neurobehavioral functioning, and diagnosis. Nonsymptomatic patients with a history of chronic unipolar depression and bipolar affective disorder and healthy male individuals were administered neuropsychological tests to assess attention, visual-motor tracking, executive abilities, and immediate verbal memory. Subjects had comparable depression scores at the time of testing. Disease duration was 7.5 years (SD 5.1) for unipolar and 11 years (SD 7.3) for bipolar patients. Unipolar patients were more impaired than healthy normal comparison subjects on measures of visual-motor sequencing (Trail Making Test A, p < .05), executive function (Trail Making Test B, Stroop Test Color/Word Trial, p < .05), and immediate memory and attention (CERAD 1st trial, WAIS Digit Symbol subtest, p < .05). Differences between bipolar patients and normal comparison subjects did not reach significance in any of the selected measures. Male patients with a history of chronic unipolar disorder are at risk for cognitive impairment in the nonsymptomatic phase of their disease. Cognitive disturbance is the type seen with prefrontal dysfunction and may be assessed with standard neuropsychological assessments.

Bipolar Disorder↗

PubMed2004

An analysis of an older driver evaluation program.

OBJECTIVES: To identify elements of an older driver evaluation program that predict driving performance in older adults. SETTING: Outpatient medical clinic in an academic medical center. DESIGN: A retrospective analysis. PARTICIPANTS: Six hundred sixty-four older adults who were referred to an older driver evaluation program. MEASUREMENTS: A physician trained in geriatric medicine and a clinical geriatric nurse specialist oversaw an experienced driving evaluator and an occupational therapist who conducted assessments of older persons' functional status; reaction time; driving skills; and cognitive, hearing, and vision abilities. Self-report data along with a medical history submitted by patients' primary care physicians supplemented the clinical assessments. RESULTS: A multinomial logistic regression revealed that the Mini-Mental State Examination (MMSE), cues needed with the Trail Making Test, Part B, grip strength, and an interaction effect between the MMSE and reaction time constituted the most parsimonious model for predicting on-the-road performance. A receiver operating characteristic analysis indicated that this index had good sensitivity but low specificity. A binomial regression comparing imperfect and perfect drivers demonstrated the significance of the Traffic Sign and Visual Perception tests. CONCLUSION: Clinicians should employ a multilevel screening process that includes initial cognitive tests, such as the MMSE and the Trail Making Test, Part B, although more studies of driving evaluation programs in medical settings that include random samples of older drivers are needed.

Aged↗

PubMed1998

Neuropsychological and pharmacokinetic assessment of hospice inpatients receiving morphine.

Eighteen inpatients receiving morphine for cancer pain in a palliative care unit were recruited to a study employing a range of neuropsychological tests to assess cognitive function. The tests employed were National Adult Reading Test, Williams Delayed Recall Test, Immediate Memory for Digits, Trailing Making Test, and the Digit Symbol Substitution Test. These data were correlated with biochemical tests of renal and hepatic function, morphine dose, route of administration, plasma morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) concentrations. Despite having no clinical evidence of impairment of cognitive function, the level of current intellectual functioning (Symbol Digit Substitution Test) was on average two standard deviations below normal. Immediate memory appeared to be well preserved, but Delayed Recall and Trailing Making Test scores were significantly above normal. There was no significant correlation between morphine dose, or plasma morphine and M3G and M6G concentrations, and the neuropsychological test results, although a weak correlation was found between plasma morphine concentration and digits forward (r = -0.47, p < 0.05) and Digit Symbol Substitution scores (r = -0.46, p < 0.05). Seven patients had some degree of nausea or vomiting, ascribed as an opioid adverse effect, and had higher serum creatinine concentrations, worse neuropsychological performance, and significantly higher plasma M3G concentrations (p < 0.05). These data provide some evidence to suggest that cognitive functioning in patients with advanced cancer receiving morphine may be significantly impaired despite apparent clinical normality. From these data it is not possible to determine what relative causal contribution the disease and the drug made to these observations, although renal function, plasma morphine, and M3G concentrations may be important. Future research should address a broad range of neuropsychological testing to assist in the modification of practices aimed at enhancement of quality of life, such as opioid substitution or rotation.

Adult↗

PubMed2005

Cognitive deficits associated with restless legs syndrome (RLS).

BACKGROUND AND PURPOSE: Restless legs syndrome produces significant chronic sleep loss, which despite not causing expected profound sleepiness, might nonetheless produce cognitive deficits similar to those seen with acute sleep deprivation, i.e. involving mostly pre-frontal cortical (PFC) functioning. PATIENTS AND METHODS: Sixteen patients off RLS treatment for at least 2 weeks and 15 age- and gender-matched control subjects had polysomnograms (PSGs) on two consecutive nights. Cognitive tests were given in the morning after the second night. Six cognitive tests were used: two Verbal Fluency tests and the Trail Making tests were selected to be particularly sensitive to PFC function and sleep loss. Porteus Mazes and the Stroop Test were selected to reflect more general frontal and executive function. The Colored Progressive Matrices were used to assess general cognitive skills. RESULTS: RLS patients compared to controls showed significant (P<0.05) and sizeable (20-40%) deficits on two of the three PFC tests and marginally non-significant deficit (P<0.1) on the third. The other three tests showed no significant differences. CONCLUSIONS: The results indicate that RLS patients show cognitive deficits similar to that reported for one night of sleep loss.

Aged↗

PubMed2006

A four-year prospective study of cognitive functioning in Huntington's disease.

The contribution of neurologic, genetic, and demographic variables to decline in cognition was examined in 70 early- to mid-stage patients with Huntington's disease (HD) using random effects modeling. Study participants were followed prospectively at baseline and at four annual reevaluations. Only modest decline was noted on most neuropsychological variables. Neurologic dysfunction, assessed using the Quantified Neurologic Examination (QNE), proved to be the strongest predictor of cognitive decline. While significantly predictive of more rapid decline in neurologic functioning, CAG repeat length was not generally related to cognitive decline after adjusting for QNE, with the exception of performance on a single test of visual scanning and psychomotor speed (i.e., Trail Making Test, Part A). We propose that CAG repeat length is more closely linked with changes in basal ganglia that predominate in early- to mid-stage HD than with cortical degeneration seen later in disease progression. Such a relationship would explain the predictive value that CAG repeat length plays in changes associated with automatic motor response programs (e.g., QNE and Trail Making Test, Part A) but not in dysfunction on tasks requiring higher-order processing.

Adult↗

PubMed2006

Increased inattentional blindness in severe traumatic brain injury: evidence for reduced distractibility?

PRIMARY OBJECTIVE: To examine the role of selective attention and visual perception in medicating inattentional blindness in a severe traumatic brain injured sample. RESEARCH DESIGN: Cross-sectional design with age and education matched control sample. METHODS AND PROCEDURES: Twenty participants with severe traumatic brain injury (n = 10) and matched controls (n = 10) completed a series of tests of focused attention (Stroop test), divided attention (Trail Making Test), visual perception (Visual Object and Space Perception Battery) and two tasks of inattentional blindness. MAIN OUTCOMES AND RESULTS: The group with severe TBI were significantly slower on the Stroop test and TMT and displayed significantly elevated Stroop interference and TMT ratio scores. On the inattentional blindness tasks, fewer TBI participants identified a distracting stimulus. CONCLUSION: The results indicate severe TBI is associated with deficits to focused and divided attention with the finding of a potentially more debilitating impairment arising from reduced distractibility following severe TBI.

Adult↗

PubMed2007

Utility of behavioral versus cognitive measures in differentiating between subtypes of frontotemporal lobar degeneration and Alzheimer's disease.

We hypothesized that a modified version of the Frontal Behavioral Inventory (FBI-mod), along with a few cognitive tests, would be clinically useful in distinguishing between clinically defined Alzheimer's disease (AD) and subtypes of frontotemporal lobar degeneration (FTLD): frontotemporal dementia (dysexecutive type), progressive nonfluent aphasia, and semantic dementia. We studied 80 patients who were diagnosed with AD (n = 30) or FTLD (n = 50), on the basis of a comprehensive neuropsychological battery, imaging, neurological examination, and history. We found significant between-group differences on the FBI-mod, two subtests of the Rey Auditory Verbal Learning Test (verbal learning and delayed recall), and the Trail Making Test Part B (one measure of 'executive functioning'). AD was characterized by relatively severe impairment in verbal learning, delayed recall, and executive functioning, with relatively normal scores on the FBI-mod. Frontotemporal dementia was characterized by relatively severe impairment on the FBI-mod and executive functioning in the absence of severe impairment in verbal learning and recall. Progressive nonfluent aphasia was characterized by severe impairment in executive functioning with relatively normal scores on verbal learning and recall and FBI-mod. Finally, semantic dementia was characterized by relatively severe deficits in delayed recall, but relatively normal performance on new learning, executive functioning, and on FBI-mod. Discriminant function analysis confirmed that the FBI-mod, in conjunction with the Rey Auditory Verbal Learning Test, and the Trail Making Test Part B categorized the majority of patients as subtypes of FTLD or AD in the same way as a full neuropsychological battery, neurological examination, complete history, and imaging. These tests may be useful for efficient clinical diagnosis, although progressive nonfluent aphasia and semantic dementia are likely to be best distinguished by language tests not included in standard neuropsychological test batteries.

Aged↗

PubMed1993

Cognitive functioning and anhedonia in subjects at risk for schizophrenia.

This study investigated the performance of individuals with familiar loading of schizophrenia (healthy siblings of schizophrenic inpatients) on three neuropsychological tasks assumed to require frontal lobe functions: Trail Making Test (TMT), verbal fluency and Wisconsin Card Sorting Test (WCST). Healthy siblings of schizophrenics differed in performance from healthy controls not only on the WCST, but also on the Trail Making Test and the verbal fluency task. Furthermore, scores of physical anhedonia, assessed in a self-report rating scale (Chapman et al., 1976) were also significantly higher in the high risk group than in the control sample. However, healthy siblings of schizophrenics did not differ from controls with regard to experiences of perceptual aberrations, measured by the same method (Chapman et al., 1978). Neuropsychological performance and elevated anhedonia scores in the high risk group were interpreted under the conceptual framework of vulnerability markers: they were supposed to represent a trait shared by family members of schizophrenic probands. Amongst the neuropsychological tests, there were significant correlations between the physical anhedonia score and WCST and Trail Making test performance in the group of healthy siblings of schizophrenics, but not in the control group.

Adult↗

PubMed2000

Trail making across languages.

The effects of different language backgrounds on trail making tasks were examined in this study. The measures adopted were the Color Trails Test (CTT) and the Trail Making Test (TMT), the former being the culturally fair analogue of the latter. Eighty-four right-handed participants belonging to the Chinese-English Bilingual (CEB) and English Monolingual (EM) groups participated in this study. The results of between-group comparisons revealed no significant differences in performance on the two measures between our Chinese bilingual and English monolingual participants, except on the TMT-A. However, a within-group correlation indicated that performances on the TMT and CTT were highly correlated for the English sample, but not for the Chinese. These observations suggest that trail making tasks like the TMT and CTT are themselves generally fair across Chinese and English, but equivalence between them may be more language-specific. Furthermore, mastery of a language loaded on temporal sequencing like English may give an advantage in the completion of trail making tasks.

Adult↗

PubMed2006

Acute effects of the ampakine farampator on memory and information processing in healthy elderly volunteers.

Ampakines act as positive allosteric modulators of AMPA-type glutamate receptors and facilitate hippocampal long-term potentiation (LTP), a mechanism associated with memory storage and consolidation. The present study investigated the acute effects of farampator, 1-(benzofurazan-5-ylcarbonyl) piperidine, on memory and information processes in healthy elderly volunteers. A double-blind, placebo-controlled, randomized, cross-over study was performed in 16 healthy, elderly volunteers (eight male, eight female; mean age 66.1, SD 4.5 years). All subjects received farampator (500 mg) and placebo. Testing took place 1 h after drug intake, which was around Tmax for farampator. Subjects performed tasks assessing episodic memory (wordlist learning and picture memory), working and short-term memory (N-back, symbol recall) and motor learning (maze task, pursuit rotor). Information processing was assessed with a tangled lines task, the symbol digit substitution test (SDST) and the continuous trail making test (CTMT). Farampator (500 mg) unequivocally improved short-term memory but appeared to impair episodic memory. Furthermore, it tended to decrease the number of switching errors in the CTMT. Drug-induced side effects (SEs) included headache, somnolence and nausea. Subjects with SEs had significantly higher plasma levels of farampator than subjects without SEs. Additional analyses revealed that in the farampator condition the group without SEs showed a significantly superior memory performance relative to the group with SEs. The positive results on short-term memory and the favorable trends in the trail making test (CTMT) are interesting in view of the development of ampakines in the treatment of Alzheimer's disease and schizophrenia.

Adult↗

PubMed2006

Predictors of driving exposure and avoidance in a field study of older drivers from the state of Maryland.

Using structural equation modeling techniques, this study examines causal models of driving avoidance and exposure among older adults. Prior studies have revealed that past incidence of falls, Useful Field of View (UFOV) test performance, and Trails Making test performance are predictive of subsequent motor vehicle crash involvement [Owsley, C., Ball, K., McGwin Jr., G., Sloane, M.E., Roenker, D.L., White, M.F., Overley, E.T., 1998. Visual processing impairment and risk of motor vehicle crash among older adults. J. Am. Med. Assoc. 279 (14), 1083-1088; Sims, R.V., McGwin, G., Pulley, L., Roseman, J.M., 2001. Mobility impairments in crash-involved older drivers. J. Aging Health 13 (3), 430-438; Stutts, J.C., 1998. Do older drivers with visual nd cognitive impairments drive less? J. Am. Geriatr. Soc. 46, 854-861]. Data analyses used these indices, along with age, health, measures of physical functioning, and additional measures of cognitive functioning, to examine driving exposure and avoidance behaviors. A field sample of 4,234 drivers, 55 years of age and older, were recruited from the Maryland Motor Vehicles Administration after renewing their driver's licenses. A performance-based assessment, which included the Gross Impairment Screening battery and task 2 of the UFOV test, was completed by participants. A sub-sample of participants (n=815) were interviewed by telephone about their health and mobility 3-6 months following the initial assessment at a renewal center. In addition to age and gender, latent variables for health status, physical functioning, cognitive functioning, driving exposure, and driving avoidance were created. Direct and indirect causal paths were specified. Age, gender, health status, and cognitive functioning had direct effects on both driving exposure and driving avoidance; physical functioning did not have a direct effect on driving exposure or avoidance. The implications of these findings are discussed as they relate to designing interventions to promote mobility.

Accidents, Traffic↗