OBJECTIVE To determine whether unihemispheral hemodynamic failure is independently associated with cognitive impairment among participants in the National Institute of Neurological Disorders and Stroke-sponsored, multicenter, randomized clinical trial, Randomized Evaluation of Carotid Occlusion and Neurocognition (RECON). METHODS Forty-three patients were randomized into RECON after recent symptomatic carotid artery occlusion and asymmetrically increased oxygen extraction fraction (OEF) by PET (OEF ratio >1.13), indicating stage II hemodynamic failure on the side of occlusion. The PET-positive patients were compared with 28 RECON-enrolled patients who met all clinical and radiographic inclusion/exclusion criteria but had no OEF asymmetry. A multivariable regression compared patients with PET OEF >1.13 or ≤1.13, stratifying by TIA vs. stroke as the qualifying event. The dependent variable was a composite neurocognitive score derived from averaging age-normalized z scores on a test battery that included global and internal carotid artery (ICA) side-relevant hemisphere-specific tests. RESULTS There were no differences in demographic, clinical, or radiologic characteristics between the PET-positive and PET-negative patients except for PET OEF asymmetry. The unadjusted average neurocognitive z score was -1.45 for the PET-positive and -1.25 for the PET-negative patients, indicating cognitive impairment in both groups but no difference between them (p = 0.641). After adjustment for age, education, side of occlusion, depression, and previous stroke, there was a significant difference between PET-positive and PET-negative patients among those with TIA as a qualifying event (average z score =-1.41 vs.-0.76, p = 0.040). Older age and right ICA side were also significant in this model. CONCLUSION Hemodynamic failure is independently associated with cognitive impairment in patients with carotid occlusion. This finding establishes the physiologic parameter upon which the extracranial-intracranial bypass will be tested.

A randomized double blind clinical comparison of neomycin and lactulose was performed in 33 cirrhotic patients with chronic portal-systemic encephalopathy (PSE) at seven cooperating hospitals. In order to maintain double blindness, sorbitol syrup was used as a control solution along with neomycin and was compared with lactulose syrup and placebo tablets in a double drug protocol. Twenty-nine patients were studied in a crossover investigation in which each received both therapeutic regimens preceded and followed by control periods. Four additional patients received one or the other agent, but did not receive both. Serial, semiquantitative assessments were made in all patients of mental status, asterixis, and the trailmaking test (TMT) and electroencephalograms (EEG) and arterial ammonia levels. Both neomycin-sorbitol and lactulose were effective in the majority of patients (83 and 90%, respectively). Each of these parameters (mental state, asterixis, TMT, EEG, and NH3) was improved significantly by neomycin-sorbitol and lactulose. The post-treatment levels for each of these measures were similar in the neomycin and lactulose-treated groups. Mean stool pH was reduced by neomycinsorbitol to 6.1 and by lactulose to 5.5. This difference was highly significant statistically. Bowel activity was similar in the two groups. Both drugs were free of toxicity. These investigations demonstrate that both lactulose and neomycin-sorbitol are effective in the treatment of chronic portal-systemic encephalopathy.

BACKGROUND Normal aging is accompanied by a decline of cognitive abilities, and executive skills may be affected selectively, but the underlying mechanisms remain obscure and preventive strategies are lacking. It has been suggested that cortical "disconnection" due to the loss of white matter fibers may play an important role. But, to date, there has been no direct demonstration of structural disconnection in humans in vivo. METHODS The authors used diffusion tensor MRI to look for evidence of ultrastructural changes in cerebral white matter in a group of 20 elderly volunteers with normal conventional MRI scans, and a group of 10 younger controls. The older group also underwent neuropsychological assessment. RESULTS Diffusional anisotropy, a marker of white matter tract integrity, was reduced in the white matter of older subjects and fell linearly with increasing age in the older group. Mean diffusivity was higher in the older group and increased with age. These changes were maximal in anterior white matter. In the older group, anterior mean diffusivity correlated with executive function assessed by the Trail Making Test. CONCLUSIONS These findings provide direct evidence that white matter tract disruption occurs in normal aging and would be consistent with the cortical disconnection hypothesis of age-related cognitive decline. Maximal changes in anterior white matter provide a plausible structural basis for selective loss of executive functions. In addition to providing new information about the biological basis of cognitive abilities, diffusion tensor MRI may be a sensitive tool for assessing interventions aimed at preventing cognitive decline.

The usefulness of frontal lobe (FL) dysfunction as a conceptual model for Attention Deficit Hyperactivity Disorder (ADHD) was investigated. Twenty-four ADHD and 24 normal control (NC) children were tested using two batteries of tasks. The first was sensitive to FL deficits in motor control and problem solving skills. The second consisted of memory tasks sensitive to temporal lobe dysfunction. ADHD children differed significantly from NCs on measures of FL function, but not on tests of temporal lobe functions. Where norms were available for normal children on the same FL tests, ADHDs performed like 6- to 7-year-olds, despite their mean age of 10 years and minimum age of 8 years. The differential performance of ADHDs on tasks sensitive to FL and temporal lobe dysfunction supports the hypothesis that ADHD deficits are analogous to FL dysfunction and demonstrates that the children's deficits do not reflect generalized cognitive impairment.

OBJECTIVE: This study was designed to ascertain the degree and specificity of cognitive impairments in patients with schizophrenia and patients with affective disorders. METHOD: Cognitive function was assessed with a neuropsychological test battery in consecutively admitted patients with schizophrenia (N = 57), unipolar depression (N = 29), and bipolar disorder (N = 16). RESULTS: The performance of the schizophrenic group was significantly below that of the groups with affective disorders on measures of attention and psychomotor speed, verbal and visual memory, and problem solving and abstraction. IQ was lower in the schizophrenic group and appeared to have deteriorated from a normal premorbid level that was not different from that of the affective disorder groups, as determined by the Wide Range Achievement Test--Revised reading test, a putative measure of premorbid intelligence. When IQ was controlled, differences between the groups in problem solving and visual memory remained. Psychiatric symptoms had a larger impact on test performance in the affective disorder groups than in the schizophrenic group. CONCLUSIONS: These results suggest that patients with schizophrenia perform systematically worse on cognitive measures than patients with affective disorders, which is consistent with their generally poorer outcome. The results also indicate that schizophrenia and affective disorders are qualitatively distinguishable in neuropsychological terms, given differences in apparent intellectual deterioration, profiles of cognitive impairment, and associations between cognitive performance and psychopathology.

Two neuropsychological tests were administered to 227 men and women, ages 25 to 69 years, before and after coronary bypass and cardiac valve operations to provide current information regarding the incidence of postoperative decrements in neuropsychological dysfunction and the factors associated with them. Biographical, psychological, and medical-surgical data were studied together with changes in scores on the Trail Making Tests and the Visual Reproduction (VR) Test of the Wechsler Memory Scale (WMS). Postoperative decrements greater than one standard deviation were observed in each of the four scores derived from these testings for 11% to 17% of the patients. Yet 70% of all patients remained within one standard deviation of original performance on all four scores. Among the preoperative correlates of significantly reduced test performance were age greater than 60 years, end-diastolic pressure greater than 30 mm Hg, moderate to severely enlarged heart size on preoperative x-ray film, and use of propranolol or chlordiazepoxide hydrochloride. Significant perioperative correlates included measure of duration of operation (such as total time of operation greater than 7 hours, time on the pump greater than 2 hours, and aortic cross-clamp time greater than 2 hours), total estimate of blood loss greater than 2,000 ml, hypotension, difficult intubation, and insertion of an intra-aortic balloon. Postoperative factors significantly associated with declines in test scores included electrolyte (Na+, K+, Cl-) abnormalities, longer stay in the intensive care unit, bizarre behavior or disorientation, and depression score. These findings suggest that those patients with more precarious heart function, a more protracted operation, and/or increased metabolic disturbances are especially prone to neuropsychological dysfunction following cardiac operations.

Although there are increasing reports of methamphetamine use, studies examining the cognitive consequences of methamphetamine have not been performed on a population currently using the drug. To characterize this population, 65 people currently using MA regularly and 65 non-users were given a battery of cognitive tests. The battery included recall, recognition, Digit Symbol, Trail Making A & B, Stroop, Wisconsin Card Sort, backward digit span, and the FAS test of verbal fluency. The methamphetamine users were significantly more impaired on recall tasks, digit symbol, Stroop color words, and Trail Making B, but scores fell within the normal ranges on the other measures.

Three neuropsychological tests were administered to 245 men and women, ages 25 to 69 years, before and 6 months after coronary bypass and cardiac valve operations to provide current information regarding the incidence of long-term postoperative decrements in neuropsychological function and the factors associated with them. Biographical, psychological and medical-surgical data were studied together with changes on the Trail Making Test from the Halstead-Reitan Battery, and Visual Reproduction (VR) and Logical Memory tests, both from the Wechsler Memory Scale (WMS). Although 28% of this group showed a deterioration in one or more test scores at a 9 day postoperative examination as compared to their preoperative scores, over 80% of these patients had returned to normal range by 6 months. Similarly, the majority of the 19% of patients showing a significant decrease in one or more of four scores at 6 months had incurred their performance decrements subsequent to the 9 day examination. Hence it seems inappropriate to attribute these latter dysfunctions to the surgical epidose per se, as others have reported. Only 5% of patients showed consistent postoperative test score deterioration both at 9 days and 6 months. Decrements of function at 6 months appear to be associated with total estimated blood loss greater than 3,000 ml and administration of propranolol during the operation plus several postoperative factors including higher levels of fatigue, depression, and worries related to the operation and the recovery process. These findings underscore the need for clinicians and investigators studying neuropsychological dysfunction following cardiac operations to take concurrent emotional and physical states into account, and to make repeated measures well separated in time, before interpreting the presence or absence of residual neuropsychological problems.

To evaluate the benefits of coronary artery bypass graft (CABG) surgery, we interviewed and tested 318 patients (268 men and 50 women) younger than age 70 before and six months after elective CABG at four university medical centers. Biomedical, psychoneurological, physical function, role function, occupational, social, family, sexual, emotional, and attitudinal variables were assessed. Quantitative comparisons showed improvement on many factors. Angina was completely relieved for 69% to 85% of persons, depending on whether it had been induced by exertion or other events. Disability days were reduced more than 80%. Seventy-five percent of employed persons had returned to work. Anxiety, depression, fatigue, and sleep problems declined. Vigor and well-being scores rose significantly. When losses were expected (eg, psychoneurological function, marital adjustment), they generally were not found. For none of the more than 60 outcome variables was widespread serious worsening found. The findings suggest that the great majority of patients are able to resume normal economic and social functioning within six months after CABG.

Variation in mental performance under different levels of heat stress-induced dehydration was recorded in 11 subjects heat acclimatized to the tropicals. Dehydration was induced by a combination of water restriction and exercise in heat. The psychological functions--arithmetic ability, short-term memory, and visuomotor tracking--were assessed in a thermoneutral room after the subjects recovered fully from the effects of exercise in heat, as reflected by their oral temperature and heart rate. The results indicated significant deterioration in mental functions at 2% or more body dehydration levels.