Executive dysfunction correlates with impaired functional status in older adults with varying degrees of cognitive impairment

Background: Previous studies have reported an association between executive dysfunction and the ability to perform activities of daily living (ADL)s among older adults. This study aims to examine the association between executive functions and functional status in a cross-section of older adults with varying degrees of cognitive impairment. Methods: 89 individuals (mean age 73.8 years) were recruited at a memory clinic in Sao Paulo, Brazil. Subjects underwent evaluation, and were allocated into three diagnostic groups according to cognitive status: normal controls (NC, n = 32), mild cognitive impairment (MCI, n = 3 1) and mild Alzheimer`s disease (AD, n=26). Executive functions were assessed with the 25-item Executive Interview (EXIT25), and functional status was measured with the Direct Assessment of Functional Status test (DAFS-R). Results: Significantly different total DAFS-R scores were observed across the three diagnostic groups. Patients with AD performed significantly worse in EXIT25 compared with subjects without dementia, and no significant differences were detected between NC and MCI patients. We found a robust negative correlation between the DAFS-R and the EXIT25 scores (r=-0.872, p < 0.001). Linear regression analyses suggested a significant influence of the EXIT-25 and the CAMCOG on the DAFS-R scores. Conclusion: Executive dysfunction and decline in general measures of cognitive functioning are associated with a lower ability to undertake instrumental ADLs. MCI patients showed worse functional status than NC subjects. MCI patients may show subtle changes in functional status that may only be captured by objective measures of ADLs.

Language impairment in euthymic, elderly patients with bipolar disorder but no dementia

Background: Neurocognitive impairment is known to occur in euthymic bipolar patients, but language alterations have not been thoroughly investigated. The aim of this study is to examine the performance in language tests of a sample of elderly patients with bipolar disorder. Methods: We studied 33 eurthymic elderly patients with bipolar disorder but no dementia and 33 healthy individuals, matched for age and education, who were compared in terms of their CAMCOG global score and its subitems. Results: The scores obtained in language-related abilities for patients and controls, respectively, were: language (total): 27.3 (1) and 28.5 (1), p < 0.0001)comprehension: 8.6 (0.5) and 8.9 (0.3), p = 0.006; production: 18.7 (1) and 19.6 (0.9), p = < 0.0001; abstraction: 6.8 (1.1) and 7.3 (0.7), p = 0.016; verbal fluency: 16.3 (4.3) and 19.6 (4.1), p = 0.003. Conclusion: A mild but significant impairment in language-related ability scores was detected when comparing patients and controls.

High prevalence of dementia among older adults from poor socioeconomic backgrounds in Sao Paulo, Brazil

Background: The aim of this study was to determine the prevalence of dementia in a socioeconomically disadvantaged population of older adults living in the city of Sao Paulo, Brazil. Methods: A cross-sectional one-phase population-based study was carried out among all residents aged >= 65 in defined census sectors of an economically disadvantaged area of Sao Paulo. Identification of cases of dementia followed the protocol developed by the 10/66 Dementia Research Group. Results: Of 2072 individuals in the study, 105 met the criteria for a diagnosis of dementia, yielding a prevalence of 5.1%. Prevalence increased with age for both men and women after age 75 years, but was stable from 65 to 74 years. Low education and income were associated with increased risk of dementia. Conclusions: The prevalence of dementia among older adults from low socioeconomic backgrounds is high. This may be partly due to adverse socioeconomic conditions and consequent failure to compress morbidity into the latter stages of life. The increasing survival of poorer older adults with dementia living in developing countries may lead to a rapid increase in the prevalence of dementia worldwide.

A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression

Preliminary findings suggest that transcranial direct current stimulation (tDCS) can have antidepressant effects. We sought to test this further in a parallel-group, double-blind clinical trial with 40 patients with major depression, medication-free randomized into three groups of treatment: anodal tDCS of the left dorsolateral prefrontal cortex (active group-`DLPFC`); anodal tDCS of the occipital cortex (active control group-`occipital`) and sham tDCS (placebo control group-`sham`). tDCS was applied for 10 sessions during a 2-wk period. Mood was evaluated by a blinded rater using the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). The treatment was well tolerated with minimal side-effects that were distributed equally across all treatment groups. We found significantly larger reductions in depression scores after DLPFC tDCS [HDRS reduction of 40.4 % (+/-25.8%)] compared to occipital [HDRS reduction of 21.3 % ( +/-12.9%)] and sham tDCS [HDRS reduction of 10.4 % (+/-36.6%)]. The beneficial effects of tDCS in the DLPFC group persisted for 1 month after the end of treatment. Our findings support further investigation on the effects of this novel potential therapeutic approach - tDCS - for the treatment of major depression.

Altered endothelial function following the Fontan procedure

Objective: Thrombosis has been widely described after the Fontan procedure. The vascular endothelium plays a central role in the control of coagulation and fibrinolysis. The aim of this study was to investigate if patients undergoing a modified Fontan procedure have impaired endothelial function and fibrinolysis in the late postoperative course. Patients and methods: We compared 23 patients aged from 7 to 26 years with age-matched healthy volunteers, collecting blood samples prior to and following standardized venous occlusion testing. Plasma levels of von Willebrand factor antigen, tissue-type plasminogen activator antigen, plasminogen activator inhibitor-1, and D-dimer were measured with enzyme-linked immunosorbent assay. Results: We found increased plasma levels of von Willebrand factor antigen in patients when compared to controls (p = 0.003). At the basal condition, concentrations of tissue-type plasminogen activator antigen and plasminogen activator inhibitor-1 antigen in the plasma, as well as their activity, were not significantly different between patients and controls. Following venous occlusion, concentrations of tissue-type plasminogen activator antigen in the plasma were significantly increased both in patients and controls, compared to pre-occlusion values. D-dimer was within the reference range. Multivariate discriminant analysis differentiated patients and their controls on the basis of differences for plasminogen activator inhibitor-1 and von Willebrand factor antigen (p = 0.0016). Conclusions: Our data suggest that patients with the Fontan circulation may have endothelial dysfunction, as indicated by raised levels of von Willebrand factor. Fibrinolysis seems to be relatively preserved, as suggested by appropriate response to venous occlusion.

Atrioventricular septal defect with coexisting tricuspid atresia

We describe two infants having an atrioventricular septal defect in the setting of a double inlet atrioventricular connection, but with patency of the left-sided valvar orifice and an imperforate right-sided valvar component, and a further case with atrioventricular septal defect and an imperforate Ebstein`s malformation, all producing the haemodynamic effect of tricuspid atresia. We make comparisons with the arrangement in trisomy 16 mice, in whom deficient atrioventricular septation is seen at times with the common atrioventricular junction exclusively connected to the left ventricle, a situation similar to that seen in two of our infants. We also review previous reports emphasising the important theoretical implication of the findings despite their rarity.

Effects of creatine supplementation on homocysteine levels and lipid peroxidation in rats

Hyperhomocysteinaemia is an independent risk factor for CVD. Recent data show a relationship between homocysteine (Hcy) and free radical formation. Since creatine synthesis is responsible for most of the methyl group transfers that result in Hcy formation, creatine supplementation might inhibit Hcy production and reduce free radical formation. The present study investigated the effects of creatine supplementation on Hcy levels and lipid peroxidation biomarkers. Thirty rats were divided into three groups: control group; diet with creatine group (DCr; 2% creatine in the diet for 28 d); creatine overload plus diet with creatine group (CrO + D; 5 g creatine/kg by oral administration for 5 d + 2 % in the diet for 23 d). Plasma Hcy was significantly lower (P<0.05) in DCr (7.5 (SD 1.2) mu mol/l) and CrO + D (7.2 (SD 1.7) mu mol/l) groups compared with the control group (12.4 (SD 2.2) mu mol/l). Both plasma thiobarbituric acid-reactive species (TBARS) (control, 10 (SD 3.4); DCr, 4.9 (So 0.7); CrO + D, 2.4 (SD 1) mu mol/l) and plasma total glutathione (control, 4.3 (SD 1.9); DCr, 2.5 (SD 0.8); CrO + D, 1.8 (SD 0.5) mu mol/l) were lower in the groups that received creatine (P<0.05). In addition, Hcy showed significant negative correlation (P<0.05) with plasma creatine (r - 0.61) and positive correlation with plasma TBARS (r 0.74). Plasma creatine was negatively correlated with plasma TBARS (r - 0.75) and total peroxide (r - 0.40). We conclude that creatine supplementation reduces plasma Hcy levels and lipid peroxidation biomarkers, suggesting a protective role against oxidative damage. Modulating Hcy fort-nation may, however, influence glutathione synthesis and thereby affect the redox state of the cells.

Cannabinoid CB(1) receptors in the medial prefrontal cortex modulate the expression of contextual fear conditioning

The ventral portion of the medial prefrontal cortex (vMPFC) has been related to the expression of contextual fear conditioning. This study investigated the possible involvement of CB(1) receptors in this aversive response. Male Wistar rats were submitted to a contextual aversive conditioning session and 48 h later re-exposed to the aversive context in which freezing and cardiovascular responses (increase of arterial pressure and heart rate) were recorded. The expression of CB(1) receptor-mRNA in the vMPFC was also measured using real time-PCR. In the first experiment intra-vMPFC administration of the CB(1) receptor agonist anandamide (AEA, 5 pmol/200 nl) or the AEA transport inhibitor AM404 (50 pmol/200 nl) prior to re-exposure to the aversive context attenuated the fear-conditioned responses. These effects were prevented by local pretreatment with the CB(1) receptor antagonist AM251 (100 pmol/200 nl). Using the same conditioning protocol in another animal group, we observed that CB(1) receptor mRNA expression increased in the vMPFC 48 h after the conditioning session. Although AM251 did not cause any effect by itself in the first experiment, this drug facilitated freezing and cardiovascular responses when the conditioning session employed a lesser aversive condition. These results indicated that facilitation of cannabinoid-mediated neurotransmission in the vMPFC by local CB(1) receptor activation attenuates the expression of contextual fear responses. Together they suggest that local endocannabinoid-mediated neurotransmission in the vMPFC can modulate these responses.

Panicolytic-like effect of BDNF in the rat dorsal periaqueductal grey matter: the role of 5-HT and GABA

A wealth of evidence suggests a role for brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) in the aetiology of depression and in the mode of action of antidepressant drugs. Less clear is the involvement of this neurotrophin in other stress-related pathologies such as anxiety disorders. The dorsal periaqueductal grey matter (DPAG), a midbrain area rich in BDNF and TrkB receptor mRNAs and proteins, has been considered a key structure in the pathophysiology of panic disorder. In this study we investigated the effect of intra-DPAG injection of BDNF in a proposed animal model of panic: the escape response evoked by the electrical stimulation of the same midbrain area. To this end, the intensity of electrical current that needed to be applied to DPAG to evoke escape behaviour was measured before and after microinjection of BDNF. We also assessed whether 5-HT- or GABA-related mechanisms may account for the putative behavioural/autonomic effects of the neurotrophin. BDNF (0.05, 0.1, 0.2 ng) dose-dependently inhibited escape performance, suggesting a panicolytic-like effect. Local microinjection of K252a, an antagonist of TrkB receptors, or bicuculline, a GABA(A) receptor antagonist, blocked this effect. Intra-DPAG administration of WAY-100635 or ketanserin, respectively 5-HT(1A) and 5-HT(2A/2c) receptor antagonists, did not alter BDNF`s effects on escape. Bicuculline also blocked the inhibitory effect of BDNF on mean arterial pressure increase caused by electrical stimulation of DPAG. Therefore, in the DPAG, BDNF-TrkB signalling interacts with the GABAergic system to cause a panicolytic-like effect.

P2X4 receptors interact with both P2X2 and P2X7 receptors in the form of homotrimers

BACKGROUND AND PURPOSE The P2X receptor family consists of seven subunit types - P2X1-P2X7. All but P2X6 are able to assemble as homotrimers. In addition, various subunit permutations have been reported to form heterotrimers. Evidence for heterotrimer formation includes co-localization, co-immunoprecipitation and the generation of receptors with novel functional properties; however, direct structural evidence for heteromer formation, such as chemical cross-linking and single-molecule imaging, is available in only a few cases. Here we examined the nature of the interaction between two pairs of subunits - P2X2 and P2X4, and P2X4 and P2X7. EXPERIMENTAL APPROACH We used several experimental approaches, including in situ proximity ligation, co-immunoprecipitation, co-isolation on affinity beads, chemical cross-linking and atomic force microscopy (AFM) imaging. KEY RESULTS Both pairs of subunits co-localize upon co-transfection, interact intimately within cells, and can be co-immunoprecipitated and co-isolated from cell extracts. Despite this, chemical cross-linking failed to show evidence for heteromer formation. AFM imaging of isolated receptors showed that all three subunits had the propensity to form receptor dimers. This self-association is likely to account for the observed close interaction between the subunit pairs, in the absence of true heteromer formation. CONCLUSIONS AND IMPLICATIONS We conclude that both pairs of receptors interact in the form of distinct homomers. We urge caution in the interpretation of biochemical evidence indicating heteromer formation in other cases.

Global poly(A) mRNA expression profile measured in individual bovine oocytes and cleavage embryos

The objective of this article was to estimate quantitative differences for GAPDH transcripts and poly(A) mRNA: (i) between oocytes collected from cumulus-oocyte complexes (COCs) qualified morphologically as grades A and B; (ii) between grade A oocytes before and after in vitro maturation (IVM); and (iii) among in vitro-produced embryos at different developmental stages. To achieve this objective a new approach was developed to estimate differences between poly(A) mRNA when using small samples. The approach consisted of full-length cDNA amplification (acDNA) monitored by real-time PCR, in which the cDNA from half of an oocyte or embryo was used as a template. The GAPDH gene was amplified as a reverse transcription control and samples that were not positive for GAPDH transcripts were discarded. The fold differences between two samples were estimated using delta Ct and statistical analysis and were obtained using the pairwise fixed reallocation randomization test. It was found that the oocytes recovered from grade B COCs had quantitatively less poly(A) mRNA (p < 0.01) transcripts compared with grade A COCs (1 arbitrary unit expression rate). In the comparison with immature oocytes (I arbitrary unit expression rate), the quantity of poly(A) mRNA did not change during IVM, but declined following IVF and varied with embryo culture (p < 0.05). Amplification of cDNA by real-time PCR was an efficient method to estimate differences in the amount of poly(A) mRNA between oocytes and embryos. The results obtained from individual oocytes suggested an association between poly(A) mRNA abundance and different morphological qualities of oocytes from COCs. In addition, a poly(A) mRNA profile was characterized from oocytes undergoing IVM, fertilization and blastocyst heating.

Modulation of effective connectivity during emotional processing by Delta(9)-tetrahydrocannabinol and cannabidiol

Cannabis sativa, the most widely used illicit drug, has profound effects on levels of anxiety in animals and humans. Although recent studies have helped provide a better understanding of the neurofunctional correlates of these effects, indicating the involvement of the amygdala and cingulate cortex, their reciprocal influence is still mostly unknown. In this study dynamic causal modelling (DCM) and Bayesian model selection (BMS) were used to explore the effects of pure compounds of C. sativa [600 mg of cannabidiol (CBD) and 10 mg Delta(9)-tetrahydrocannabinol (Delta(9)-THC)] on prefrontal-subcortical effective connectivity in 15 healthy subjects who underwent a double-blind randomized, placebo-controlled fMRI paradigm while viewing faces which elicited different levels of anxiety. In the placebo condition, BMS identified a model with driving inputs entering via the anterior cingulate and forward intrinsic connectivity between the amygdala and the anterior cingulate as the best fit. CBD but not Delta(9)-THC disrupted forward connectivity between these regions during the neural response to fearful faces. This is the first study to show that the disruption of prefrontal-subocrtical connectivity by CBD may represent neurophysiological correlates of its anxiolytic properties.

Amygdala activation to masked happy facial expressions

The amygdala has a key role in automatic non-conscious processing of emotions. Highly salient emotional stimuli elicit amygdala activity, and happy faces are among the most rapidly perceived facial expressions. In backward masking paradigms, an image is presented briefly and then masked by another stimulus. However, reports of amygdala responses to masked happy faces have been mixed. In the present Study, we used functional magnetic resonance imaging (fMRI) to examine amygdala activation to masked happy, sad, and neutral facial expressions. Masked happy faces elicited greater amygdala activation bilaterally as compared to masked sad faces. Our findings indicate that the amygdala is highly responsive to non-consciously perceived happy facial expressions. (JINS, 2010, 16, 383-387.)

Depersonalization and personality in panic disorder

Background: Prevalence and clinical correlates of depersonalization symptoms have been associated with panic disorder. Personality traits might increase the likelihood of experiencing depersonalization symptoms or depersonalization disorder in panic patients. Aims: The objectives of this study are to establish the prevalence of depersonalization symptoms during the panic attack and in depersonalization disorder and to examine the personality factors associated with the presence of depersonalization in patients with panic disorder. Methods: The sample comprised 104 consecutive adult outpatients with panic disorder, diagnosed according to the Semistructured Clinical Interview for DSM-IV (Axis I/II disorders). Participants were assessed with the Cambridge Depersonalization Scales, the Temperament and Character Inventory, and the Panic and Agoraphobia Scale. Results: Forty-eight percent of the sample had depersonalization symptoms during the panic attack, whereas 20% of patients had a depersonalization disorder. Women presented more depersonalization disorders than did men (P = .036). Patients with panic disorder with depersonalization disorder had a more severe panic disorder (P = .002). Logistic regression analysis showed that self-transcendence trait (odds ratio, 1.089; 95% confidence interval, 1.021-1.162; P = .010) and severity of panic (odds ratio, 1.056; 95% confidence interval, 1.005-1.110; P = .032) were independently associated with depersonalization disorder. Conclusions: A high prevalence of depersonalization symptoms and depersonalization disorder was confirmed in patients with panic disorder, supporting a dosage effect model for understanding depersonalization pathology. Self-transcendence trait and severity of panic disorder were reported as risk factors for depersonalization disorder. (C) 2011 Elsevier Inc. All rights reserved.

Histological effects of intratympanic gentamicin on the vestibular organ of guinea pigs

Background: Transtympanic administration of gentamicin may be suitable to achieve unilateral vestibular ablation, in order to control unilateral Meniere`s disease. In low doses, gentamicin appears to affect selectively the vestibular system, with relative sparing of the cochlea. An experimental study on guinea pigs was conducted to determine what single dose of gentamicin would produce a unilateral vestibular organ lesion when applied to the middle ear. Study design: Experimental and prospective. Methods: Four groups of guinea pigs received different gentamicin doses ( 1, 5, 10 and 25 mg) administered to the middle ear. The animals` vestibular organs were then assessed by scanning electron microscopy, in order to quantify the level of vestibular damage. Results: Study of the utricular macula and the ampullar crista of the lateral semicircular canal revealed vestibular neuroepithelial lesions in all infused ears. Conclusions: The severity of the vestibular neuroepithelial lesions was dose-dependent. Lower gentamicin doses were observed to damage vestibular structures more than cochlear structures.