Cognitive impairment in hemodialysis patients is common.

BACKGROUND: Hemodialysis patients are at high risk for cognitive impairment due to their older age and high prevalence of stroke and cardiovascular risk factors. METHODS: Using a cross-sectional design, the authors measured cognitive function in 374 hemodialysis patients aged 55 years and older and an age-matched comparison group in Minneapolis and St. Paul, MN. Cognitive performance was measured in three domains: memory, executive function, and language. Subjects were classified as having no, mild, moderate, or severe cognitive impairment. RESULTS: Of 338 subjects who completed testing in at least two of the three cognitive domains, 13.9% (95% CI 10.4, 18.1) were classified with mild impairment, 36.1% (31.0, 41.5) with moderate impairment, 37.3% (32.1, 42.7) with severe impairment, and 12.7% (9.4, 16.8) with normal cognition. Only 2.9% had a documented history of cognitive impairment. Factors associated with severe cognitive impairment on adjusted logistic regression were stroke (adjusted OR [AOR] 1.95; 95% CI 1.08, 3.49; p < 0.03), equilibrated Kt/V > 1.2 (1.67; 1.01, 2.75; p < 0.05), and education >12 years (0.32; 0.14, 0.72; p < 0.01). The AOR for severe cognitive impairment in a random sample of 101 hemodialysis patients vs an age-matched comparison group was 3.54 (1.28, 9.78; p < 0.02). CONCLUSIONS: Moderate to severe cognitive impairment is common and undiagnosed in hemodialysis patients. Further studies are needed to determine whether dialysis exacerbates the cognitive impairment attributable to underlying disease. Cognitive testing in hemodialysis patients before dialysis initiation and periodically may be warranted.

Introduction: neuropsychological assessment après Luria.

Neuropsychological assessment since Alexander R. Luria's death in 1977 has demonstrated increased sophistication and advancement, and a number of models or approaches to neuropsychological assessment are available worldwide today. This article reviews, in the context of this special issue, Luria's influence on the further development of neuropsychological assessment approaches and methods. Contemporary approaches are summarized and contrasted, and a discussion of neo-Lurian adaptations and extensions of his neuropsychological model is presented. Brief comments about the succeeding articles in this issue help to demonstrate the wide influence sustained by Luria's ideas in various regions of the world.

Introduction: Alexander Luria's continuing influence on worldwide neuropsychology.

As an introduction to this special issue, this article provides an overview of the worldwide influence of the work of Alexander R. Luria, a noted Russian neuropsychologist. Major themes and issues that he studied are reviewed, and the reasons for his strong worldwide influence are discussed. An overview of subsequent articles in this issue is provided.

Converging impressions in Russian and American neuropsychology: discussion of a clinical case.

We report the case of FR, a 50-year-old woman who suffered a closed head injury in a motor vehicle accident. FR was evaluated approximately two months post-injury using a combined Russian and North American assessment approach with test methods applied from each country. The case is thoroughly discussed qualitatively and quantitatively using the Lurian principle of syndrome analysis to illustrate the findings. The logical-conceptual understanding of the case as different findings were revealed is presented to demonstrate the benefit of the application of a process oriented analysis to assist in the functional description of the case and the development of rehabilitative strategies. We believe that this is one of the first cases to be described that has used a combined Russian and American approach to assessment.

Synthesis of disulfide-bridged fragments of omega-conotoxins GVIA and MVIIA. Use of Npys as a protecting/activating group for cysteine in Fmoc syntheses.

The 3-nitro-2-pyridinesulphenyl (Npys) moiety is finding increasing utility as a protecting-activating group for cysteine, particularly in the synthesis of cyclic and unsymmetrical disulfides using the Boc strategy. This chemistry has been extended to peptides assembled by the Fmoc strategy. N-Terminal Cys(Npys) is introduced via Boc-Cys(Npys)-OPfp. Non-N-terminal Cys(Npys) is incorporated by reacting a resin-bound, fully protected Cys(Acm) peptide with NpysCl. This approach has been applied to the synthesis of four disulfide-bridged fragments of omega-conotoxins GVIA and MVIIA.

Synthesis and dopamine antagonist activity of 2-thioether derivatives of the ergoline ring system.

A series of 2-thioether derivatives of a number of clavine alkaloid (ergoline) ring systems have been synthesized and tested for dopamine antagonist activity. Of the compounds tested 2-(methylthio)-agroclavine (8,9-didehydro-6,8-dimethyl-2-(methylthio)ergoline) (6) was the most potent and had a profile of activity in animal models indicative of potential antipsychotic activity. The synthesis and biological activity of a number of metabolites of 6, including the 13-hydroxy derivative, are also reported.

Some observations on the use of the Woodcock-Johnson Tests of Cognitive Ability in adults with head injury.

Current research specifies the varied cognitive and psychoeducational deficits in the adult with head injury, and the clinical assessment of this population is widespread, though often only traditional intellectual measures are used. This article provides descriptive data in the first reported study using the Woodcock-Johnson Tests of Cognitive Ability (WJTCA) (Woodcock & Johnson, 1977) in an outpatient sample of 39 adults with closed head injury. The study also addressed (a) the relationships between the various cognitive clusters of the WJTCA and a measure of injury severity (coma duration) and (b) the relationships between the WJTCA and several Halstead-Reitan neuropsychological measures. Correlational analyses indicated significant relationships between coma duration and performance on the Perceptual Speed and Memory clusters of the WJTCA. No relationships were found between the Halstead Category test and any of the WJTCA cognitive clusters, though the Trail Making test correlated significantly with many of the WJTCA clusters. Time since injury did not correlate with any of the WJTCA test results. Other findings are presented, and the advantages and disadvantages of this set of cognitive tests in relation to other psychoeducational and cognitive measures are reviewed.

Methodological considerations in the use of attribute variables in neuropsychological research.

This paper examines the conceptual and statistical difficulties created when neuropsychological research uses attribute variables in traditional orthogonal experimental designs. It is argued that attribute variables, as a result of their statistical and theoretical nonindependence, break the underlying assumptions of these traditional designs, and may lead to incorrect inferences being drawn. These difficulties are illustrated in a consideration of the typical use of analysis of variance designs, matched groups designs, and the analysis of covariance. Finally, a plea is made for the explicit consideration of the assumptions underlying the design models used in neuropsychological research, and a suggestion is made regarding the more appropriate use of correlational techniques in neuropsychology.

4-Piperazinyl-10H-thieno[2,3-b][1,5]benzodiazepines as potential neuroleptics.

A series of 4-substituted 10H-theino[2,3-b][1,5]benzodiazepines has been synthesized. These compounds have been assessed for their ability to block a conditioned avoidance response (CAR) and to produce catalepsy in rats and have been compared with several typical and atypical neuroleptics. The compounds which inhibit CAR at doses which produce no catalepsy are believed to cause less extrapyramidal side effects in the clinic. A number of compounds (9, 12, 17, 29, and 34) show potent neuroleptic activity, yet maintain a favorable separation of activity on these two parametrs. Three 5-piperazinyl-10H-thieno[2,3-b][1,4]benzodiazepine derivatives (46-48) analogous to compounds in the [1,5] series have been prepared for comparison and were found to be inactive.

10-Piperazinyl-4H-theino[3,2-b][1,5]- and -[3,4-b][1,5]benzodiazepines as potential neuroleptics.

The synthesis of 10-piperazinyl-4H-thieno[3,2-b][1,5]benzodiazepines is described. The activity of these compounds has been assessed on the basis of their ability to produce hypothermia in mice and block a conditioned avoidance response (CAR) and produce catalepsy in rats, and the results are compared with various classical and nonclassical neuroleptic drugs. A number of compounds (6, 17, 21, and 22) demonstrate potency greater than clozapine and also show low degree of catalepsy. It is believed that this profile of activity, unlike standard neuroleptics, is associated with the relative lack of extrapyramidal side effects in the clinic. The corresponding 9-piperazinyl-4H-thieno[1,4]benzodiazepines (12 and 35, limited analogues prepared in the respective series, were inactive.

Utility of the neurological examination in rats.

This study presents general observations of neurological examination in rats after various CNS manipulations. The examination consisted of neurologic reactions as described in Bures and co-workers. Subjects studied were controls, hippocampal irradiates, and animals with cerebellar lesions or midline cerebellar transplants. Utility of the procedure as an adjunct to more detailed testing is discussed.

Adamantane and protoadamantanealkanamines as potential anti-Parkinson agents.

The synthesis of 2-halo-1-adamantanemethanamines, 4-protoadamantanemethanamines, and 4-protoadamantaneamines is described. The anti-Parkinson activity of these amines in terms of reversal of reserpine-induced catalepsy in rats has been evaluated and compared with amantadine. 2-Bromo- and 2-chloro-1-adamantanemethanamines are shown to be twice as active as amantadine.