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Mild Impairment (mild + impairment)
Selected AbstractsSynaptic plasticity in the basolateral amygdala in transgenic mice expressing dominant-negative cAMP response element-binding protein (CREB) in forebrainEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2000G. Rammes Abstract Electrophysiological and behavioural experiments were performed in transgenic mice expressing a dominant-negative form of cAMP response element-binding protein (CREBA133) in the limbic system. In control littermate in vitro slice preparation, tetanizing the lateral amygdala,basolateral amygdala (BLA) pathway with a single train (100 Hz for 1 s) produced short-term potentiation (STP) in the BLA. Five trains (10-s interstimulus interval) induced long-term potentiation (LTP), which was completely blocked by the N-methyl- d -aspartate (NMDA) receptor antagonist d(,)-2-amino-5-phosphonopentanoic acid (AP5; 50 ,m). When GABAergic (,-aminobutyric acid) inhibition was blocked by picrotoxin (10 ,m), LTP became more pronounced. Low-frequency stimulation (1 Hz for 15 min) induced either long-term depression (LTD) or depotentiation. LTD remained unaffected by AP5 (50 ,m) or by the L- and T-type Ca2+ -channel blockers nifedipine (20 ,m) and Ni2+ (50 ,m), but was prevented by picrotoxin (10 ,m), indicating a GABAergic link in the expression of LTD in the BLA. When conditioned fear was tested, a mild impairment was seen in one of three transgenic lines only. Although high levels of mRNA encoding CREBA133 lead to downregulation of endogenous CREB, expression of LTP and depotentiation were unaltered in BLA of these transgenic animals. These results could suggest that residual CREB activity was still present or that CREB per se is dispensable. Alternatively, other CREB-like proteins were able to compensate for impaired CREB function. [source] Performance deficit of ,7 nicotinic receptor knockout mice in a delayed matching-to-place task suggests a mild impairment of working/episodic-like memoryGENES, BRAIN AND BEHAVIOR, Issue 6 2006C. Fernandes Patients with schizophrenia exhibit deficits in a range of cognitive functions, particularly working and episodic memory, which are thought to be core features of the disorder. Memory dysfunction in schizophrenia is familial and thus a promising endophenotype for genetic studies. Both human and animal studies suggest a role for the neural nicotinic acid receptor family in cognition and specifically the ,7-receptor subunit in schizophrenia and its endophenotypes. Consequently, we tested mice lacking the ,7 subunit of the neural nicotinic receptor (B6.129S7-Chrna7tm1Bay/J) in the delayed matching-to-place (DMP) task of the Morris water maze, a measure of working/episodic memory akin to human episodic memory. We report that a minor impairment in ,7 knockout mice was observed in the DMP task, with knockout mice taking longer to find the hidden platform than their wildtype controls. This suggests a role for the ,7 subunit in working/episodic memory and a potential role for the ,7 neural nicotinic receptor gene (CHRNA7) in schizophrenia and its endophenotypes. [source] Dynamic Balance and Stepping Versus Tai Chi Training to Improve Balance and Stepping in At-Risk Older AdultsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 12 2006Joseph O. Nnodim MD OBJECTIVES: To compare the effect of two 10-week balance training programs, Combined Balance and Step Training (CBST) versus tai chi (TC), on balance and stepping measures. DESIGN: Prospective intervention trial. SETTING: Local senior centers and congregate housing facilities. PARTICIPANTS: Aged 65 and older with at least mild impairment in the ability to perform unipedal stance and tandem walk. INTERVENTION: Participants were allocated to TC (n= 107, mean age 78) or CBST, an intervention focused on improving dynamic balance and stepping (n=106, mean age 78). MEASUREMENTS: At baseline and 10 weeks, participants were tested in their static balance (Unipedal Stance and Tandem Stance (TS)), stepping (Maximum Step Length, Rapid Step Test), and Timed Up and Go (TUG). RESULTS: Performance improved more with CBST than TC, ranging from 5% to 10% for the stepping tests (Maximum Step Length and Rapid Step Test) and 9% for TUG. The improvement in TUG represented an improvement of more than 1 second. Greater improvements were also seen in static balance ability (in TS) with CBST than TC. CONCLUSION: Of the two training programs, in which variants of each program have been proven to reduce falls, CBST results in modest improvements in balance, stepping, and functional mobility versus TC over a 10-week period. Future research should include a prospective comparison of fall rates in response to these two balance training programs. [source] Cognitive Impairment and Mortality in Older Primary Care PatientsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 7 2001Timothy E. Stump MA OBJECTIVE: To assess the impact of cognitive impairment on mortality in older primary care patients after controlling for confounding effects of demographic and comorbid chronic conditions. DESIGN: Prospective cohort study. SETTING: Academic primary care group practice. PARTICIPANTS: Three thousand nine hundred and fifty-seven patients age 60 and older who completed the Short Portable Mental Status Questionnaire (SPMSQ) during routine office visits. MEASUREMENTS: Cognitive impairment measured at baseline using the SPMSQ, demographics, problem drinking, history of smoking, clinical data (including weight, cholesterol level, and serum albumin), and comorbid chronic conditions collected at baseline; survival time measured during the 5 to 7 years after baseline. RESULTS: Eight hundred and eighty-six patients (22.4%) died during the 5 to 7 years of follow-up. Cognitive impairment was categorized as having no impairment (84.3%), mild impairment (10.5%), and moderate-to-severe impairment (5.2%) based on SPMSQ score. Chi-square tests revealed that patients with moderate-to-severe impairment were significantly more likely to die compared with patients with mild impairment (40.8% vs 21.5%) and those with no impairment (40.8% vs 21.4%). No significant difference in crude mortality was found between patients with no impairment and those with mild impairment. After analyzing time to death using the Kaplan-Meier method, patients with moderate-to-severe cognitive impairment were at increased risk of death compared with those with no or mild impairment (Log-rank ,2 = 55.5; P < .0001). Even in multivariable analyses using Cox proportional hazards to control for confounding factors, compared with those with no impairment, moderately-to-severely impaired patients had an increased risk of death, with a hazard ratio (HR) of 1.70. Increased risk of death was also associated with older age (HR = 1.03 for each year), a history of smoking (HR = 1.48), having a serum albumin level <3.5 g/L (HR = 1.29), and weighing less than 90% of the ideal body weight (HR = 1.98). Outpatient diagnoses associated with increased mortality risk were diabetes mellitus, coronary artery disease, congestive heart failure, cerebrovascular disease, cancer, anemia, and chronic obstructive pulmonary disease (HR range 1.36,1.67). Factors protective of mortality risk included female gender (HR = 0.67) and black race (HR = 0.73). CONCLUSIONS: Moderate-to-severe cognitive impairment is associated with an increased risk of mortality, even after controlling for confounding effects of demographic and clinical characteristics. Mild cognitive impairment is not associated with mortality risk, but a longer follow-up period may be necessary to identify this risk if it exists. [source] Activation of the PI3K/Akt signal transduction pathway and increased levels of insulin receptor in protein repair-deficient miceAGING CELL, Issue 1 2005Christine Farrar Summary Protein l -isoaspartate (d -aspartate) O -methyltransferase is an enzyme that catalyses the repair of isoaspartyl damage in proteins. Mice lacking this enzyme (Pcmt1,/, mice) have a progressive increase in brain size compared with wild-type mice (Pcmt1+/+ mice), a phenotype that can be associated with alterations in the PI3K/Akt signal transduction pathway. Here we show that components of this pathway, including Akt, GSK3, and PDK-1, are more highly phosphorylated in the brains of Pcmt1,/, mice, particularly in cells of the hippocampus, in comparison with Pcmt1+/+ mice. Examination of upstream elements of this pathway in the hippocampus revealed that Pcmt1,/, mice have increased activation of insulin-like growth factor-I (IGF-I) receptor and/or insulin receptor. Western blot analysis revealed an approximate 200% increase in insulin receptor protein levels and an approximate 50% increase in IGF-I receptor protein levels in the hippocampus of Pcmt1,/, mice. Higher levels of the insulin receptor protein were also found in other regions of the adult brain and in whole tissue extracts of brain, liver, heart and testes of both juvenile and adult Pcmt1,/, mice. There were no significant differences in plasma insulin levels for adult Pcmt1,/, mice during glucose tolerance tests. However, they did show higher peak levels of blood glucose, suggesting a mild impairment in glucose tolerance. We propose that Pcmt1,/, mice have altered regulation of the insulin pathway, possibly as a compensatory response to altered glucose uptake or metabolism or as an adaptive response to a general accumulation of isoaspartyl protein damage in the brain and other tissues. [source] Complement 3 deficiency impairs early pregnancy in miceMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 7 2009Wang-Ngai Chow Human oviductal cells produce complement-3 (C3) and its derivative, iC3b. These molecules are important in immune responses. Our recent study suggested that iC3b also possessed embryotrophic activity and it stimulates the blastulation and hatching rates of in vitro cultured mouse embryos. The objective is to study the impact of C3 deficiency on early pregnancy in vivo using homozygous C3-deficient (C3KO) and wild-type (C3WT) mice. C3 protein was undetectable in the reproductive tissues of C3KO mice. Deficiency in C3 is associated with significantly longer estrous cycle (P,=,0.037). No significant difference was found in the ovulation rate, total cell count in blastocysts and implantation rate between the wild-type and the C3KO mice, though C3KO mice tended to have lower values in the latter two parameters. On day 15 of pregnancy, C3KO mice had fewer conceptus (P,<,0.001) and higher resorption rate (P,<,0.001) than that of C3WT mice. The fetal and placental weights (P,<,0.001) were lower in the C3KO mice. The placenta of C3KO mice had smaller spongiotrophoblast (P,=,0.001) and labyrinth (P,=,0.037). Deficiency in C3 is associated with mild impairment in early pregnancy including longer estrous cycle and higher resorption rates after implantation. The impairment may be related to compromised placental development leading to under-developed fetuses. Mol. Reprod. Dev. 76: 647,655, 2009. © 2009 Wiley-Liss, Inc. [source] Does anthracycline administration by infusion in children affect late cardiotoxicity?BRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2004G. A. Levitt Summary The severity of late cardiotoxicity after anthracycline treatment for childhood cancer relates mainly to the cumulative anthracycline dose received, but all dose ranges cause some cardiac dysfunction. Anthracycline administration by infusion in order to lower peak drug concentration has been used in an attempt to reduce cardiotoxicity. Cardiac performance was assessed by echocardiography in children who were relapse-free survivors of treatment for acute lymphoblastic leukaemia (ALL). They received the same cumulative anthracycline dose (daunorubicin 180 mg/m2) either by bolus injection (UKALL X protocol, n = 40) or by infusion (UKALL XI protocol, n = 71) with a follow-up duration of 5·3 ± 2·0 and 5·4 ± 1·0 years respectively. On analysis, both the bolus administration and infusion groups showed similar mild impairment of cardiac performance, characterized by increased left ventricular end systolic stress and impaired left ventricular function. In conclusion, subclinical abnormality of left ventricular performance was confirmed in both groups despite the relatively modest cumulative anthracycline dose received. We were unable to demonstrate an advantage of anthracycline administration by 6-h infusion with respect to late cardiotoxicity at this dose. [source] Does the medial orbitofrontal cortex have a role in social valuation?EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2010M. P. Noonan Abstract It has been claimed that social behaviour changes after lesions of the ventromedial prefrontal cortex (vmPFC). However, lesions in humans are rarely restricted to a well defined cortical area. Although vmPFC lesions usually include medial orbitofrontal cortex (mOFC), they typically also affect subgenual and/or perigenual anterior cingulate cortex. The purpose of the current study is to investigate the role of mOFC in social valuation and decision-making. We tested four macaque monkeys prior to and after focal lesions of mOFC. Comparison of the animals' pre- and postoperative performance revealed that, unlike lesions of anterior cingulate gyrus (ACCg), lesions of mOFC did not induce alterations in social valuation. MOFC lesions did, however, induce mild impairments in a probabilistic two-choice decision task, which were not seen after ACCg lesions. In summary, the double dissociation between the patterns of impairment suggest that vmPFC involvement in both decision-making and social valuation may be mediated by distinct subregions centred on mOFC and ACCg respectively. [source] Progressive Cerebral Disease in Lymphomatoid Granulomatosis Causes Anterograde Amnesia and Neuropsychiatric DisorderJOURNAL OF NEUROIMAGING, Issue 2 2006Dominic A. Carone PhD ABSTRACT The authors report neuropsychological (NP) and serial quantitative magnetic resonance imaging (MRI) findings of a 29-year-old woman with lymphomatoid granulomatosis (LG). Disease course was characterized by acute psychosis, tremor, fever, seizures, and progressive cognitive impairment. At the time of symptom onset, brain MRI revealed mild lesion volume and normal parenchymal volume. This was followed by dramatic progression of brain lesions and atrophy over 2 years, at which point the patient expired. Atrophy was most prominent in the mesial temporal lobes. NP testing revealed marked amnesia and mild impairments in other cognitive domains. To our knowledge, this is the first recorded case of LG in which bilateral temporal lobe atrophy is evident and accompanied by anterograde amnesia. We speculate that temporal lobe atrophy was influenced by the established susceptibility of this region in various neurological diseases. [source] | |||||||||||||