Serum anticholinergic activity and postoperative cognitive dysfunction in elderly patients.

BACKGROUND: Cerebral cholinergic transmission plays a key role in cognitive function, and anticholinergic drugs administered during the perioperative phase are a hypothetical cause of postoperative cognitive dysfunction (POCD). We hypothesized that a perioperative increase in serum anticholinergic activity (SAA) is associated with POCD in elderly patients. METHODS: Seventy-nine patients aged >65 years undergoing elective major surgery under standardized general anesthesia (thiopental, sevoflurane, fentanyl, and atracurium) were investigated. Cognitive functions were assessed preoperatively and 7 days postoperatively using the extended version of the CERAD-Neuropsychological Assessment Battery. POCD was defined as a postoperative decline >1 z-score in at least 2 test variables. SAA was measured preoperatively and 7 days postoperatively at the time of cognitive testing. Hodges-Lehmann median differences and their 95% confidence intervals were calculated for between-group comparisons. RESULTS: Of the patients who completed the study, 46% developed POCD. Patients with POCD were slightly older and less educated than patients without POCD. There were no relevant differences between patients with and without POCD regarding gender, demographically corrected baseline cognitive functions, and duration of anesthesia. There were no large differences between patients with and without POCD regarding SAA preoperatively (pmol/mL, median [interquartile range]/median difference [95% CI], P; 1.14 [0.72, 2.37] vs 1.13 [0.68, 1.68]/0.12 [-0.31, 0.57], P = 0.56), SAA 7 days postoperatively (1.32 [0.68, 2.59] vs 0.97 [0.65, 1.83]/0.25 [-0.26, 0.81], P = 0.37), or changes in SAA (0.08 [-0.50, 0.70] vs -0.02 [-0.53, 0.41]/0.1 [-0.31, 0.52], P = 0.62). There was no significant relationship between changes in SAA and changes in cognitive function (Spearman rank correlation coefficient preoperatively of 0.03 [95% CI, -0.21, 0.26] and postoperatively of -0.002 [95% CI, -0.24, 0.23]). CONCLUSIONS: In this panel of patients with low baseline SAA and clinically insignificant perioperative anticholinergic burden, although a relationship cannot be excluded in some patients, our analysis suggests that POCD is probably not a substantial consequence of anticholinergic medications administered perioperatively but rather due to other mechanisms.

Sexual protection behavior in HIV-positive gay men: testing a modified information-motivation-behavioral skills model.

This study on determinants of sexual protection behavior among HIV-positive gay men used the empirically tested information-motivation-behavioral skills (IMB) model. HIV-specific variables were added to the model to determine factors decisive for condom use with steady and casual partners. Data were collected using an anonymous, standardized self-administered questionnaire. Study participants were recruited at HIV outpatient clinics associated with the Eurosupport Study Group and the Swiss HIV Cohort Study. To identify factors associated with condom use, backward elimination regression analyses were performed. Overall, 838 HIV-infected gay men from 14 European countries were included in this analysis. About 53% of them reported at least one sexual contact with a steady partner; 62.5% had sex with a casual partner during the last 6 months. Forty-three percent always used condoms with steady partners and 44% with casual partners. High self-efficacy and subjective norms in favor of condom-use were associated with increased condom use with casual and steady partners, whereas feeling depressed was associated with decreased condom use with casual partners. Condoms were used less often with HIV-positive partners. Self-efficacy as an important behavioral skill to perform protection behavior was influenced by lower perceived vulnerability, higher subjective norms, and more positive safer sex attitudes. The IMB-model constructs appeared to be valid; however, not all the model predictors could be determined as hypothesized. Besides the original IMB constructs, HIV-specific variables, including sexual partners' serostatus and mental health, explained condom use. Such factors should be considered in clinical interventions to promote "positive prevention."

The Costs of Caring for People with Dementia and Related Cognitive Impairments

The National Council on Ageing and Older People has undertaken a programme of research into dementia in Ireland. An Action Plan for Dementia provided a framework for the provision and planning of services for people with dementia in Ireland The Costs of Caring for People with Dementia and Related Cognitive Impairments is a complementary report to the Action Plan but with a more quantitative focus. The role of carers is one that is often taken for granted and is seen by many as a free resource. Dr Oâ?TShea explores what caring for a person with dementia entails in terms of the carers time, finances and stress. Evaluating the cost of caring for a person with dementia is the main focus of this study Download the Report here

Troubles cognitifs séquellaires de la rupture d'anévrysmes de l'artère communicante antérieure et de l'artère cérébrale antérieure. Etude rétrospective de 56 cas [Cognitive sequelae following rupture of aneurysms of the anterior communicating artery and the anterior cerebral artery. Retrospective study of 56 cases].

The neuropsychological records of 56 patients operated for clipping were studied. Almost every patient remained autonomous and without invalidating motor defect. The present study was aimed at specifying the type and frequency of neuropsychological sequelae and, to a lesser extent, the role of various pathophysiological factors. A main concern was to examine to what extent and at what post-operative interval the neuropsychological assessment can predict the intellectual and socioprofessional outcome of each individual patient. The neuropsychological assessment performed beyond the acute phase showed evidence of intellectual sequelae in about two thirds of the patients. Only one case of permanent anterograde amnesia was observed, probably due to unavoidable inclusion of a hypothalamic artery in the clip during surgery. Transient anterograde amnesia and confabulations were occasionally observed, generally for less than three weeks. A common finding was impaired performance on memory and/or executive tests. In a minority of patients, language disorders, visuoperceptive and visuoconstructive disabilities were found, probably in relation with hemodynamic changes at distance from the aneurysm. Global impairment of intellectual function was not uncommon in the acute post-operative phase but it evolved in most cases towards a more selective impairment, for instance restricted to executive and memory functions, in the chronic phase. The neuropsychological investigation carried out 4 to 15 weeks post-operatively provided satisfactory information about possible long-lasting intellectual disturbances and professional resumption. In particular, persistent global intellectual impairment, persistent amnesia and confabulations 4-15 weeks post-operative were associated with cessation of professional activity; executive and memory impairment, behavioral disturbances such as those encountered in patients with frontal lobe damage were associated with a decreased probability of full-time employment. Pre- and post-operative angiography were not good predictors of long-term cognitive outcome: normal angiography was not necessarily followed by normal neuropsychological outcome, conversely abnormal angiography could be found together with normal neuropsychological outcome. By contrast, there was a relationship between left-lateralised abnormalities on post-operative angiography and occurrence of language disorders; similarly, there was a relationship between side of craniotomy and type of deficits, that is language disorders versus visuoperceptive-visuoconstructive impairments.

History of offending behavior in first episode psychosis patients: A marker of specific clinical needs and a call for early detection strategies among young offenders.

OBJECTIVES: Previous literature suggests that early psychosis (EP) patients with a history of offending behavior (HOB) have specific clinical needs. The aims of this study were to assess: (1) the prevalence of HOB in a representative sample of EP; (2) the premorbid and baseline characteristics of patients with HOB, and (3) the potential differences in short-term outcome of such patients when compared to patients without HOB. METHODS: The Early Psychosis Prevention and Intervention Centre (EPPIC) admitted 786 EP patients between 1998 and 2000. Data were collected from patients' files using a standardized questionnaire. Data of 647 patients could be analyzed. RESULTS: HOB patients (29% of the sample) were more likely to be male with lower level of premorbid functioning and education, have used illicit substances and have attempted suicide. They presented with a more complex clinical picture and had poorer 18-month outcome. Most importantly, they had a significantly longer duration of untreated psychosis. CONCLUSIONS: On the basis of the high prevalence and specific features of EP patients with HOB, our study confirms a need for additional research in this domain and for the development of specific treatment strategies. Most importantly, it suggests a need for the promotion of early detection strategies among the populations of young offenders, considering that some of them may be going through the early phases of a psychotic disorder and that reduction of treatment delay and provision of well adapted interventions may have a significant impact at numerous levels in such patients.

Severe childhood encephalopathy with dyskinesia and prolonged cognitive disturbances: evidence for anti-N-methyl-d-aspartate receptor encephalitis.

Aim We report four cases of acquired severe encephalopathy with massive hyperkinesia, marked neurological and cognitive regression, sleep disturbance, prolonged mutism, and a remarkably delayed recovery (time to full recovery between 5 and 18mo) with an overall good outcome, and its association with anti-N-methyl-d-aspartate (anti-NMDA) receptor antibodies. Method We reviewed the four cases retrospectively and we also reviewed the literature. Results Anti-NMDA receptor antibodies (without ovarian teratoma detected so far) were found in the two children tested in this study. Interpretation The clinical features are similar to those first reported in 1992 by Sebire et al.,(1) and rarely recognized since. Sleep disturbance was not emphasized as part of the disorder, but appears to be an important feature, whereas coma is less certain and difficult to evaluate in this setting. The combination of symptoms, evolution (mainly seizures at onset), severity, paucity of abnormal laboratory findings, very slow recovery, and difficult management justify its recognition as a specific entity. The neuropathological substrate may be anatomically close to that involved in encephalitis lethargica, in which the same target functions (sleep and movement) are affected but in reverse, with hypersomnolence and bradykinesia. This syndrome closely resembles anti-NMDA receptor encephalitis, which has been reported in adults and is often paraneoplastic.

Connexin 30 sets synaptic strength by controlling astroglial synapse invasion.

Astrocytes play active roles in brain physiology by dynamic interactions with neurons. Connexin 30, one of the two main astroglial gap-junction subunits, is thought to be involved in behavioral and basic cognitive processes. However, the underlying cellular and molecular mechanisms are unknown. We show here in mice that connexin 30 controls hippocampal excitatory synaptic transmission through modulation of astroglial glutamate transport, which directly alters synaptic glutamate levels. Unexpectedly, we found that connexin 30 regulated cell adhesion and migration and that connexin 30 modulation of glutamate transport, occurring independently of its channel function, was mediated by morphological changes controlling insertion of astroglial processes into synaptic clefts. By setting excitatory synaptic strength, connexin 30 plays an important role in long-term synaptic plasticity and in hippocampus-based contextual memory. Taken together, these results establish connexin 30 as a critical regulator of synaptic strength by controlling the synaptic location of astroglial processes.

Postoperative cognitive dysfunction POCD, serum anticholinergic activity and intraoperative cerebral perfusion in geriatric patients

Background: Inadequate intraoperative cerebral perfusion and increased serum anticholinergic activity (SAA) have been suggested as possible causes of postoperative cognitive dysfunction (POCD). Methods: 53 patients aged >65 yrs undergoing elective major surgical procedures under standardized general anaesthesia. Cerebral perfusion was monitored with transcranial Doppler and near-infrared spectroscopy. Mx, an index of cerebral autoregulation was calculated based on the correlation of spontaneous changes inmean arterial blood pressure (MAP) and cerebral blood flow velocity. Cognitive function was measured preoperatively and 7 days postoperatively using the CERAD-Neuropsychological Battery. A postoperative decline >1 z-score in at least 2 cognitive variables was defined as POCD. SAA was measured preoperatively and 7 days postoperatively (data available for 38 patients). CRP was measured at the same time points and 2 days postoperatively. Results: Age was 75_7 yrs (mean_SD). 23 patients (43%) developed POCD. There were no statistical significant differences between patients with POCD and without POCD in age (77_7 vs 73_6 yrs), MAP (74_12 vs 78_11 mmHg), cerebral tissue oxygenation indices (67_6 vs 69_4 %) SAA preoperatively (1.74_1.52 vs 1.74_1.21) and 7 days postoperatively (1.90_1.63 vs 1.84_1.39) and CRP preoperatively (32_72 vs 7_9), 2 days postoperatively (176_129 vs 111_69) and 7days postoperatively (53_43 vs 48_25). Patients with POCD had less efficient autoregulation than patients without POCD (Mx 0.55_0.15 vs 0.45_0.20, p = 0.046). However, the percentage of patients with clearly impaired autoregulation (ie, Mx>0.5) was statistically not different between groups (with POCD: 65%; without POCD: 38%; p = 0.06) but there seems to be a trend. Conclusions: Our data on the association between cerebral perfusion and POCD in elderly patients are inconclusive and more patients need to be investigated. In this small group of patients SAA seems not to be associated with POCD.

Translating cognitive neuroscience to fitness to drive using a neuroergonomic approach

Non-pathological or normal ageing is accompanied by brain alterations that are the result of natural changes occurring with age and our ability to compensate for them. Compared to younger adults, older adults have reduced vision, more difficulties in detecting relevant information they are not intending to and require more time to process sensorial information. Little is known on how these changes affect behaviour in a natural environment. Relying on a translational approach at the frontiers between neurobiology, psychophysics, neuropsychology and epidemiology, we were able to: explore the needs for innovative instrumentations to detect cerebral decline in clinical settings; develop and validate a new computed neuropsychological instrument designed to measure cerebral decline in healthy older adults; explore the link between processing speed and on-road driving performance; and investigate the effects of being able to anticipate on visual processing speed.

Attachment and temperament in early childhood; implications for later behavior problems.

In the context of a French validation study, the Child Behavior Checklist (CBCL) was administered to more than 3000 French speaking mothers of 5-year-old children. Scores were factor-analyzed. Principal components analysis revealed four dimensions: externalizing and internalizing behavior problems, immaturity and somatoform disorders. Another sample of 40 mothers participated in a longitudinal study, filling in the CBCL when their children were 5 years old. These children had been observed previously in the Strange Situation (SSP) at 21 months. Several dichotomous variables derived from the SSP (e.g. secure versus insecure, proximal versus distal interaction with the mother, avoidant behavior) have been used as predictors of the four dimensions extracted from the CBCL. Hierarchical regressions showed that proximal behaviors with the mother, which reflect temperamental characteristics independently of the quality of attachment, predicted internalizing problems, whereas avoidance of the mother, or insecure-avoidant attachment, predicted internalizing as well as externalizing problems at 5 years of age. These results show that attachment and temperament, as assessed by the SSP, may each have specific implications for later behavior problems.

Genetic and epigenetic analysis of SSAT gene dysregulation in suicidal behavior.

It has recently been proposed that the SSAT gene plays a role in the predisposition to suicidal behavior. SSAT expression was found to be down-regulated in the brain of suicide completers. In addition, a single nucleotide polymorphism (SNP) rs6526342 was associated both with variation in SSAT expression and with suicidal behavior. In this study, we aimed to characterize the relationship between SSAT dysregulation and suicide behavior. To this end, we measured SSAT expression levels in the ventral prefrontal cortex (VPFC) of suicide completers (n = 20) and controls (n = 20) and found them to be significantly down-regulated in suicide victims (P = 0.007). To identify the basis of the regulation of SSAT expression, we performed an association analysis of 309 SNPs with SSAT transcript levels in 53 lymphoblastoid cell lines from the CEPH collection. We then examined the methylation status of the SSAT promoter region in males and females suicide completers and control subjects whose SSAT brain expression had been measured. We found no evidence to support a role for SNPs in controlling the level of SSAT expression. SSAT promoter methylation levels were not different between suicide completers and controls and did not correlate with SSAT expression levels. In addition, we found no indication of a genetic association between suicidal behavior and SNPs located within the SSAT gene. Our study provides new results which show that dysregulation of SSAT expression does play a role in suicide behavior. However, our data do not support any association between rs6526342 and variation in SSAT expression or suicidal behavior.

Trypanosoma cruzi: genetic group with peculiar biochemical and biological behavior

Thirty-two Trypanosoma cruzi strains, isolated from chronic chagasic patients in the northwest of the state of Paraná (Brazil), were analyzed using molecular, biochemical and biological characteristics. Genotypic analysis using randomly amplified polymorphic DNA and simple sequence repeat-anchored polymerase chain reaction amplified profiles showed a large, genetically well-correlated group that contained the majority of the strains and a divergent group that included the PR-150 strain. For glycoconjugate composition, the PR-150 strain was different from the other strains considering the absence or presence of specific bands in aqueous or detergent phases. This strain was also totally different from the others in one out of the six parameters related to in vitro and in vivo biological behavior. We highlight the fact that the PR-150 was totally resistant to benznidazole. For the other biological parameters this strain was not totally distinct from the others, but it showed a peculiar behavior.

Detection of cognitive impairment with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in adolescents with psychotic symptomatology.

Cognitive impairment has been identified in the early phase of schizophrenia spectrum disorders, and is a major contributor to disease-related disability. While screening tools assessing cognitive impairment have been validated for adult schizophrenic populations, there is a need for brief, easily administered, standardized instruments that provide clinically relevant information for adolescents. This study examines the utility of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in identifying and quantifying neurocognitive impairment in adolescents with schizophrenia spectrum disorders and other serious psychiatric illnesses. 112 adolescents, including 32 healthy subjects and 80 patients, were administered the RBANS. Patients with psychotic disorders demonstrated significant impairment on the RBANS total score compared to patients with other disorders and healthy controls, but this impairment appeared somewhat less severe than is typically reported for in adult patients with schizophrenia on this measure. The RBANS appears to be sensitive in the detection of neurocognitive impairment in a psychiatric population of adolescents with psychotic symptomatology, and may therefore have utility as a clinical screening instrument and/or neurocognitive outcome measure in this population.