D-KEFS trail making test as an embedded performance validity measure.

OBJECTIVE: The Delis-Kaplan Executive Function System (D-KEFS) Trail Making Test (TMT) is a commonly used measure of processing speed and executive functioning that may also be useful as an embedded performance validity test (PVT). We evaluated the utility of several multi-condition indices on the D-KEFS TMT in three independent samples to determine an optimal multi-condition index and cutoff on the D-KEFS TMT. METHOD: Classification accuracy statistics for multiple multi-condition indices on the D-KEFS TMT were evaluated in three independent samples, including a sample with history of mild traumatic brain injury (TBI; n = 267) classified into psychometrically defined performance-valid and performance-invalid subgroups, the D-KEFS national normative sample (n = 1713), and a sample of middle- and older-aged adults diagnosed with mild cognitive impairment (MCI; n = 70). RESULTS: The D-KEFS TMT Conditions 1-5 summation index maximized sensitivity at .31 while maintaining adequate specificity at ≥.9. This index also had acceptable classification accuracy in both the D-KEFS national normative and MCI cross-validation samples, with the exception of the oldest subgroup of the national norming sample (i.e., individuals' ages 80-89), in which the observed failure rates for all multi-condition indices tested were greater than 10%. CONCLUSION: Our study provides support for the use the D-KEFS TMT Conditions 1-5 summation index as an embedded PVT among individuals younger than 80 years-old and from a range of conditions spanning from cognitively normal to mildly impaired; however, further validation is necessary.

Passive smoking acutely affects the microcirculation in healthy non-smokers.

OBJECTIVE: Acute effects of passive smoking on microcirculation have not been sufficiently studied. The aim of the present study was to detect microcirculatory alterations in healthy non-smokers after passive exposure to cigarette smoke, utilizing the Near Infrared Spectroscopy method combined with the vascular occlusion technique. METHODS: Sixteen (9 females, age: 34 ±â€¯9 years) non-smoking, healthy volunteers were exposed to passive smoking for 30 min in a temperature-controlled environment. Smoke concentration was monitored with a real-time particle counter. The following microcirculatory parameters were estimated: baseline tissue oxygen saturation (StO2); StO2 decrement after vascular occlusion (indicating the oxygen consumption rate); StO2incremental response after vascular occlusion release (reperfusion rate); the time period where the StO2 signal returns to the baseline values after the hyperemic response. RESULTS: Baseline StO2 (79.6 ±â€¯6.4 vs. 79 ±â€¯8%, p = 0.53) as well as the time needed for StO2 to return to baseline levels (138.2 ±â€¯26.5 vs. 142.1 ±â€¯34.6 s, p = 0.64) did not significantly differ before vs. after passive smoking exposure. Oxygen consumption rate decreased after 30 min exposure to passive smoking (from 12.8 ±â€¯4.2 to 11.3 ±â€¯2.8%/min, p = 0.04); Reperfusion rate also significantly decreased (from 5.6 ±â€¯1.8 to 5 ±â€¯1.7%/s, p = 0.04). CONCLUSIONS: Our results suggest that acute exposure to passive smoking delays peripheral tissue oxygen consumption and adversely affects microcirculatory responsiveness after stagnant ischemia in healthy non-smokers.

Elevated pulse pressure is associated with age-related decline in language ability.

Recent research suggests that pulse pressure (PP), a putative marker of vascular integrity, may be associated with brain microvascular damage and age-related cognitive decline. Thus, the present study examined the relationship between PP and cognition in a sample of healthy nondemented older adults. One hundred nine participants were administered neurological and neuropsychological evaluations and determined to be nondemented. Regression analyses were used to examine the relationships among pulse pressure (PP) [systolic blood pressure (SBP)--diastolic blood pressure (DBP)], age, and cognition. PP and related measures were inversely correlated with global cognitive functioning and scores on a composite measure of language function, even after adjusting for age, education, and relevant vascular risk factors. Results indicate that increases in the pulsatile component of blood pressure may convey added risk of global cognitive decline and specific impairment in language abilities.

Treatment of paediatric visceral leishmaniasis: amphotericin B or pentavalent antimony compounds?

Pentavalent antimony compounds and amphotericin B lipid formulations have been found highly active for the treatment of visceral leishmaniasis. This study focuses on which treatment is preferable in the best interests of the child. Records were reviewed of children in our hospital aged 0-14 years, diagnosed with visceral leishmaniasis, during the last 4 years. Twenty-nine children were identified. Ten were treated with meglumine antimonate (20 mg/kg/day for 21 days) and remained in hospital for 11-28 days (median 19 days), while 19 patients received liposomal amphotericin B at four different dosage schemes and were in hospital for 6-11 days (median 7 days). All of the patients were cured regardless of the treatment regime they followed. No relapses were noted. Liposomal amphotericin B would be preferable to meglumine antimonate if the reduction in hospital stay and hence the convenience of the patient balance the cost of medication. The optimal duration of treatment with liposomal amphotericin B remains to be determined.

Detection of mild cognitive deficits in Parkinson's disease patients with the WAIS-R NI.

The relative insensitivity of traditional IQ tests to mild cognitive deficits has led investigators to develop a version of the widely used Wechsler intelligence scales that allows quantitative analysis of underlying qualitative responses. This instrument, the Wechsler Adult Intelligence Scale-Revised as a Neuropsychological Instrument (WAIS-R NI) was administered to 16 Parkinson's disease (PD) patients and 30 normal controls (NC). The 2 groups did not differ significantly in mean age or education, or on their mean Mattis Dementia Rating Scale score. Relative to NC participants, PD patients showed decreased visual attention span, longer response latencies, slower visuomotor processing, and more stimulus-bound errors. Many of the WAIS-R NI measures were able to detect cognitive impairment in a greater percentage of patients than the traditional WAIS-R measures, making it easier to identify deficits that could affect quality of life early in the course of the disease.

Verbal and design fluency in patients with frontal lobe lesions.

The ability to generate items belonging to categories in verbal fluency tasks has been attributed to frontal cortex. Nonverbal fluency (e.g., design fluency) has been assessed separately and found to rely on the right hemisphere or right frontal cortex. The current study assessed both verbal and nonverbal fluency in a single group of patients with focal, frontal lobe lesions and age- and education-matched control participants. In the verbal fluency task, participants generated items belonging to both letter cues (F, A, and S) and category cues (animals and boys' names). In the design fluency task, participants generated novel designs by connecting dot arrays with 4 straight lines. A switching condition was included in both verbal and design fluency tasks and required participants to switch back and forth between different sets (e.g., between naming fruits and furniture). As a group, patients with frontal lobe lesions were impaired, compared to control participants, on both verbal and design fluency tasks. Patients with left frontal lesions performed worse than patients with right frontal lesions on the verbal fluency task, but the 2 groups performed comparably on the design fluency task. Both patients and control participants were impacted similarly by the switching conditions. These results suggest that verbal fluency is more dependent on left frontal cortex, while nonverbal fluency tasks, such as design fluency, recruit both right and left frontal processes.

A Phase II study of docetaxel and carboplatin in the treatment of non-small cell lung cancer.

We investigated the efficacy of docetaxel (D) in combination with carboplatin (C) in the treatment of non-small cell lung cancer (NSCLC) patients. Since 1996, 123 with inoperable NSCLC were enrolled in the study; 120 (108 males, 12 females; mean age 58.0+/-8.3 years) were evaluated. Of those, 46 patients had squamous carcinoma, 44 adenocarcinoma, 11 large cell carcinoma and 19 undifferentiated tumours. Eligibility criteria included, documented inoperable NSCLC, WHO performance status (PS) 0-1, age up to 70 years, and normal renal and hepatic function. A total of 622 cycles of chemotherapy (CHT) (median 7 (95% CI 6.2-7.47), courses per patient) were administered. Each cycle consisted of 100 mg/m(2) of docetaxel in a 2-h infusion with C at a dose of area under the curve (AUC) of 6 on day 1. This regimen was repeated every 28 days up to eight cycles. Of the patients, five (4%) achieved complete response, 49 (40%) partial response, 47 (39%) had stable disease and 19 (15%) had progressive disease. The median survival was 12 months for all patients, 12 for the four patients with stage IIb disease, 18 for the patients with stage IIIa disease, 20 for the 29 patients with stage IIIb disease, and 11 for the 65 stage IV patients. The median time to progression was 8 months (90 patients). Toxicity was, grade 3/4 neutropenia, 18 patients (15%); grade 3/4 anaemia, 6 patients (5%); and tolerable peripheral neuropathy, 16 patients (13.3%). Responders received radiotherapy (total dose, 50 Gy in 4 weeks) between the 6th and 8th cycle. Among responders with initial stage IIIb disease, 7 (5%) underwent surgical resection. Patients with early progression of the disease received the same dose of radiotherapy between 2nd and 3rd cycle. The study is ongoing, and six patients (5%) are still alive (after 3 years). Preliminary results indicate that the D/C combination is very active in the treatment of NSCLC with tolerable toxicity. It appears that this drug combination is also good as neoadjuvant therapy in inoperable NSCLC patients.

Verbal and nonverbal fluency in children with heavy prenatal alcohol exposure.

OBJECTIVE: Executive function deficits, including verbal fluency, have been documented in children with histories of prenatal alcohol exposure. Whereas nonverbal fluency impairments have been reported in adults with such exposure, these abilities have not been tested in children. Deficits in both verbal and nonverbal fluency were predicted and assessed in children and adolescents with histories of heavy prenatal alcohol exposure. METHOD: There was a total of 28 (54% female) subjects; children with heavy prenatal alcohol exposure with (n = 10) and without (n = 8) fetal alcohol syndrome (FAS) were compared to nonexposed controls (n = 10) on the design and verbal fluency measures from the Delis-Kaplan Executive Function System. Both fluency measures consist of three conditions, including a new set-shifting task. All tests require the generation of multiple responses within both rule and time constraints. RESULTS: Data were analyzed using repeated measures analyses of variance and hierarchical regression analyses. Compared to controls, children with heavy prenatal alcohol exposure with and without FAS displayed deficits in both fluency domains, but did not differ from each other. In addition, prenatal alcohol exposure was a significant predictor of performance on the set-shifting design fluency task above and beyond performance on more traditional fluency tasks. IQ was not a significant predictor for the traditional or set-shifting fluency measures, whereas diagnostic group remained a significant predictor when IQ was included in the model. CONCLUSIONS: This study adds to the literature on the integrity of executive functions in children with heavy prenatal alcohol exposure, documenting fluency impairment in both verbal and nonverbal domains. It is important to note that these impairments were demonstrated in higher functioning alcohol-exposed children, both with and without FAS, and that diagnostic group explained such deficiencies above and beyond general intellectual ability.

Do subgroups of patients with Alzheimer's disease exhibit asymmetric deficits on memory tests?

Several studies have reported asymmetric cognitive profiles in patients with Alzheimer's disease (AD), but these results have almost exclusively been found using non-memory cognitive instruments. The present study investigated whether AD patients who display lateralized profiles on non-memory cognitive instruments also exhibit asymmetric deficits on verbal versus spatial memory tests. Sixty-eight AD patients participated in the study: 36 with a "High Verbal" cognitive profile, and 32 with a "High Spatial" profile. The results indicated that the High Verbal AD patients performed significantly better than the High Spatial AD patients on verbal memory tests, but the two subgroups failed to differ on spatial memory tests. Implications of these findings for understanding the heterogeneous nature of cognitive profiles in AD patients are discussed.

Improved memory functioning and frontal lobe maturation between childhood and adolescence: a structural MRI study.

Previous studies conducted by our group have provided evidence for age-related reductions in cortical thickness in dorsal frontal and parietal regions between childhood and adulthood, and gray matter volume increases of mesial temporal and anterior diencephalic structures. The purpose of this study was to describe neurobehavioral correlates of these brain maturational changes using morphometric analyses of brain magnetic resonance images (MRI) and two tests of cognitive abilities. Participants were 35 normal children roughly stratified by age (7 to 16 years) and sex (20 boys and 15 girls) and frontal and mesial temporal regions were anatomically defined in each subjects' MRI data. The California Verbal Learning Test-Children's Version and the Rey-Osterrieth Complex Figure test were used as measures of verbal and visuospatial memory and organizational abilities. Analyses designed to show regionally specific relationships between the brain and behavioral measures revealed interesting results. Specifically, frontal lobe gray matter thinning was more strongly predictive of delayed verbal memory functioning than was the mesial temporal lobe gray matter volume, and this relationship did not appear to be mediated by factors indexed in chronological age. Similar, but less regionally specific relationships were observed for measures of visuospatial memory abilities and frontal lobe maturation. Functional imaging studies in the literature consistently report activation in frontal regions in adults during retrieval tasks. The relationship between frontal lobe maturation and delayed recall observed here may be reflective of the children's development towards the more adult-like frontal lobe function revealed in the functional imaging studies.

Age effects on executive ability.

Heterogeneity of executive tasks has made it difficult to determine whether there are age-related declines in executive functioning. To address this issue, 112 individuals, 20-79 years old, took the California Trail Making Test (CTMT) and the California Stroop Test (CST), subtests of the Delis-Kaplan Executive Function Scale (D. C. Delis, E. Kaplan, & J. H. Kramer, in press) that include measurement of component skills embedded in the executive function tasks. Multiple regression analyses revealed that after controlling for component skills, age had a significant effect on the executive requirement of the CST, namely speed on the interference condition. Age did not affect switching performance on the letter-number condition of the CTMT. Additional analyses revealed that age was significantly associated with commission of certain types of errors. This study confirms the importance of partialing out components in the assessment of multidimensional cognitive tasks, particularly when making age comparisons. It also emphasizes specificity over generalizability when examining the impact of age on cognition.

Attentional dysfunction associated with posttraumatic stress disorder among rape survivors.

Posttraumatic stress disorder (PTSD) is characterized by subjective reports of decreased concentration and an inability to sustain attention. Some empirical validation of these symptoms has been demonstrated via reduced performance on attentional tests among war veterans with PTSD. However, the significance of such findings is unclear given high co-morbidity with other psychiatric, neurologic, and substance abuse disorders among veterans. The present study examined neuropsychological functioning among rape survivors with PTSD, a patient population with comparatively low rates of psychiatric co-morbidity. Rape survivors with PTSD (PTSD+; n = 15) were compared to rape survivors without PTSD (PTSD-; n = 16) and age- and education-matched nontraumatized controls (CTRL; n = 16) on tests of attention. Performance of the PTSD+ group was significantly worse than the other groups on measures of sustained and divided attention, but not on shifting of visuospatial selective attention. Performance differences were not attributable to co-morbid psychiatric disorders or substance abuse. The implications of these findings regarding the effects of trauma on attentional functions are discussed.

Comparison of the serial position effect in very mild Alzheimer's disease, mild Alzheimer's disease, and amnesia associated with electroconvulsive therapy.

Individuals given a series of words to memorize normally show better immediate recall for items from the beginning and end of the list than for mid-list items. This phenomenon, known as the serial position effect, is thought to reflect the concurrent contributions of secondary and primary memory, respectively, to recall performance. The present study compared the serial position effects produced on Trial 1 of the California Verbal Learning Test (CVLT) in mildly demented (N = 25; M MMSE = 20.0) and very mildly demented (N = 25; M MMSE = 25.5) patients with Alzheimer's disease (AD), and age- and education-matched normal control (NC) participants (N = 50). In addition, the serial position effects of the very mildly demented AD patients were compared to those of patients with a transient, circumscribed amnesia arising from a prescribed series of electroconvulsive therapy (ECT) treatments for the relief of depressive illness (N = 11). While the NC group exhibited the typical serial position effect, AD patients recalled significantly fewer words than NC participants overall, and exhibited a significantly reduced primacy effect (i.e., recall of the first 2 list items) with a normal recency effect (i.e., recall of the last 2 list items). Patients with circumscribed amnesia due to ECT were as impaired as the very mildly demented AD patients on most standard CVLT measures of learning and memory, but exhibited primacy and recency effects, which were within normal limits. These results suggest that a reduction in the primacy effect, but not the recency effect, is an early and ubiquitous feature of the memory impairment of AD. It is not, however, a necessary feature of all causes of memory impairment.

Isepamicin versus amikacin for the treatment of acute pyelonephritis in children.

In this study we compared the efficacy and safety of isepamicin versus amikacin at a dose of 7.5 mg/kg i.v. q12h for 10-14 days in children with pyelonephritis. Sixteen children were enrolled in the study; ten received isepamicin and six amikacin. Urine cultures grew Escherichia coli in all patients. All patients were treated successfully with either isepamicin or amikacin. Clinical and bacteriological response rates were 100% for both groups. No adverse events occurred. Peak serum levels ranged from 9.05 to 30.70 mg/l (median: 16.165) and from 12.20 to 25.90 mg/l (median: 19.05) for isepamicin and amikacin, respectively. Trough serum levels ranged from 0.11 to 3.20 mg/l (median: 0.75) and from 0.1 to 2.1 mg/l (median: 0.655), respectively. Isepamicin was shown to be as effective and safe as amikacin in the treatment of children with pyelonephritis and might prove an advantageous alternative in areas with high incidence of resistance to other aminoglycosides.

Neurocognitive functioning of adolescents: effects of protracted alcohol use.

BACKGROUND: The present study examined associations between alcohol involvement in early to middle adolescence and neuropsychological (NP) functioning. METHODS: Alcohol-dependent adolescents (n = 33) with over 100 lifetime alcohol episodes and without dependence on other substances were recruited from alcohol/drug abuse treatment facilities. Comparison (n = 24) adolescents had no histories of alcohol or drug problems and were matched to alcohol-dependent participants on age (15 to 16 years), gender, socioeconomic status, education, and family history of alcohol dependence. NP tests and psychosocial measures were administered to alcohol-dependent participants following 3 weeks of detoxification. RESULTS: Alcohol-dependent and comparison adolescents demonstrated significant differences on several NP scores. Protracted alcohol use was associated with poorer performance on verbal and nonverbal retention in the context of intact learning and recognition discriminability. Recent alcohol withdrawal among adolescents was associated with poor visuospatial functioning, whereas lifetime alcohol withdrawal was associated with poorer retrieval of verbal and nonverbal information. CONCLUSIONS: Deficits in retrieval of verbal and nonverbal information and in visuospatial functioning were evident in youths with histories of heavy drinking during early and middle adolescence.

Verbal memory impairments in dyslexia.

Although verbal memory deficits are frequently reported in reading disabled children, the specific mechanisms underlying these impairments have yet to be clearly defined. The present study used the California Verbal Learning Test-Children's Version (CVLT-C) to assess verbal learning in 57 dyslexic children and 114 controls matched for gender, age, and WISC-R Vocabulary score. Three areas of verbal memory were investigated: Recall and recognition, use of learning strategies, and interference effects. The dyslexic group learned the list items more slowly, recalled fewer words on the last learning trial and the delayed trials, and performed less well on the recognition condition. Dyslexics and controls displayed similar vulnerability to interference, but group differences were evident in serial position effects. Taken together, our data suggest that dyslexics have less efficient rehearsal and encoding mechanisms, resulting in deficient encoding of new information, but normal retention and retrieval.

Executive functioning in children with heavy prenatal alcohol exposure.

BACKGROUND: Children with heavy prenatal alcohol exposure have well documented deficits in overall cognitive ability. Recently, attention has turned to the executive function (EF) domain in this population. Until recently, comprehensive measures of EF have not been available within one test battery. This study used a battery of tests to assess four domains of EF in alcohol-exposed children. METHODS: The Delis-Kaplan Executive Function Scale was used to evaluate EF in 18 children with heavy prenatal alcohol exposure, with and without a diagnosis of fetal alcohol syndrome (FAS), and 10 nonexposed controls. Children ranged in age from 8 to 15 years. Measures from four domains of executive functioning were analyzed: planning ability, cognitive flexibility, selective inhibition, and concept formation and reasoning. Tasks consisted of primary EF measures as well as measures of secondary component skills. RESULTS: Alcohol-exposed children were deficient on EF measures compared with nonexposed controls. Furthermore, in most cases, children with and without the FAS diagnosis did not differ from one another. These deficits were not entirely explainable by concomitant deficits on component skills. Specific impairments were identified within the domains of planning and response inhibition, with additional deficits in abstract thinking and flexibility. CONCLUSIONS: Deficits in executive functioning were observed in alcohol-exposed children with or without the diagnosis of FAS and in the absence of mental retardation. Performance on these EF tasks provides insight into the cognitive processes driving overall performance and has implications for adaptive and daily functions. These results are consistent with anecdotal and empirical reports of deficits in behavioral control and with neuroanatomical evidence of volumetric reductions in structures within the frontal-subcortical system in children with heavy prenatal alcohol exposure.

Global-local processing in schizophrenia: hemispheric asymmetry and symptom-specific interference.

The hypothesis of atypical functional hemispheric asymmetry in schizophrenia is tested using the directed global-local paradigm, a lateralizing measure of visual perception. Results indicate low error rates (< 2%) for schizophrenia and normal control groups, but longer response times for the schizophrenia group. In the normal group, detection speed of global and local forms did not differ. In contrast, the schizophrenia group responded significantly faster to local relative to global forms, which supports the asymmetry hypotheses of left hemisphere overactivity-right hemisphere underactivity in schizophrenia. The normal group exhibited a global interference effect (slowed response latency to the local target in the presence of a dissimilar global distractor). When the schizophrenia group was examined according to symptom type and severity, high positive symptom severity was associated with local interference (slowed response latency to the global target in the presence of dissimilar local distractors). Negative symptoms were not associated with interference from the competing local or global forms. Patients with a combination of high positive and low negative symptoms showed significantly greater local interference than patients with high negative and low positive symptoms. Interconnected temporal and frontal systems are postulated to contribute to this pattern of perceptual processing efficiency and distractibility in schizophrenia.