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[PMID]: 26967228
[Au] Autor:Silbert LC; Dodge HH; Lahna D; Promjunyakul NO; Austin D; Mattek N; Erten-Lyons D; Kaye JA
[Ad] Address:NIA-Layton Aging & Alzheimer's Disease Center, Department of Neurology, Oregon Health & Science University, Portland, OR, USA....
[Ti] Title:Less Daily Computer Use is Related to Smaller Hippocampal Volumes in Cognitively Intact Elderly.
[So] Source:J Alzheimers Dis;52(2):713-7, 2016 Mar 9.
[Is] ISSN:1875-8908
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:BACKGROUND: Computer use is becoming a common activity in the daily life of older individuals and declines over time in those with mild cognitive impairment (MCI). The relationship between daily computer use (DCU) and imaging markers of neurodegeneration is unknown. OBJECTIVE: The objective of this study was to examine the relationship between average DCU and volumetric markers of neurodegeneration on brain MRI. METHODS: Cognitively intact volunteers enrolled in the Intelligent Systems for Assessing Aging Change study underwent MRI. Total in-home computer use per day was calculated using mouse movement detection and averaged over a one-month period surrounding the MRI. Spearman's rank order correlation (univariate analysis) and linear regression models (multivariate analysis) examined hippocampal, gray matter (GM), white matter hyperintensity (WMH), and ventricular cerebral spinal fluid (vCSF) volumes in relation to DCU. A voxel-based morphometry analysis identified relationships between regional GM density and DCU. RESULTS: Twenty-seven cognitively intact participants used their computer for 51.3 minutes per day on average. Less DCU was associated with smaller hippocampal volumes (r = 0.48, p = 0.01), but not total GM, WMH, or vCSF volumes. After adjusting for age, education, and gender, less DCU remained associated with smaller hippocampal volume (p = 0.01). Voxel-wise analysis demonstrated that less daily computer use was associated with decreased GM density in the bilateral hippocampi and temporal lobes. CONCLUSIONS: Less daily computer use is associated with smaller brain volume in regions that are integral to memory function and known to be involved early with Alzheimer's pathology and conversion to dementia. Continuous monitoring of daily computer use may detect signs of preclinical neurodegeneration in older individuals at risk for dementia.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.3233/JAD-160079

  2 / 281130 MEDLINE  
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[PMID]: 26967211
[Au] Autor:Jefferson AL; Gifford KA; Acosta LM; Bell SP; Donahue MJ; Davis LT; Gottlieb J; Gupta DK; Hohman TJ; Lane EM; Libon DJ; Mendes LA; Niswender K; Pechman KR; Rane S; Ruberg FL; Su YR; Zetterberg H; Liu D
[Ad] Address:Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA....
[Ti] Title:The Vanderbilt Memory & Aging Project: Study Design and Baseline Cohort Overview.
[So] Source:J Alzheimers Dis;52(2):539-59, 2016 Mar 8.
[Is] ISSN:1875-8908
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:BACKGROUND: Vascular health factors frequently co-occur with Alzheimer's disease (AD). A better understanding of how systemic vascular and cerebrovascular health intersects with clinical and pathological AD may inform prevention and treatment opportunities. OBJECTIVE: To establish the Vanderbilt Memory & Aging Project, a case-control longitudinal study investigating vascular health and brain aging, and describe baseline methodology and participant characteristics. METHODS: From September 2012 to November 2014, 335 participants age 60- 92 were enrolled, including 168 individuals with mild cognitive impairment (MCI, 738 years, 41% female) and 167 age-, sex-, and race-matched cognitively normal controls (NC, 727 years, 41% female). At baseline, participants completed a physical and frailty examination, fasting blood draw, neuropsychological assessment, echocardiogram, cardiac MRI, and brain MRI. A subset underwent 24-hour ambulatory blood pressure monitoring and lumbar puncture for cerebrospinal fluid (CSF) collection. RESULTS: As designed, participant groups were comparable for age (p = 0.31), sex (p = 0.95), and race (p = 0.65). MCI participants had greater Framingham Stroke Risk Profile scores (p = 0.008), systolic blood pressure values (p = 0.008), and history of left ventricular hypertrophy (p = 0.04) than NC participants. As expected, MCI participants performed worse on all neuropsychological measures (p-values < 0.001), were more likely to be APOEɛ4 carriers (p = 0.02), and had enhanced CSF biomarkers, including lower A42 (p = 0.02), higher total tau (p = 0.004), and higher p-tau (p = 0.02) compared to NC participants. CONCLUSION: Diverse sources of baseline and longitudinal data will provide rich opportunities to investigate pathways linking vascular and cerebrovascular health, clinical and pathological AD, and neurodegeneration contributing to novel strategies to delay or prevent cognitive decline.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.3233/JAD-150914

  3 / 281130 MEDLINE  
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[PMID]: 27031477
[Au] Autor:Edmonds EC; Delano-Wood L; Jak AJ; Galasko DR; Salmon DP; Bondi MW; Alzheimer's Disease Neuroimaging Initiative
[Ad] Address:Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA....
[Ti] Title:"Missed" Mild Cognitive Impairment: High False-Negative Error Rate Based on Conventional Diagnostic Criteria.
[So] Source:J Alzheimers Dis;52(2):685-91, 2016 Mar 31.
[Is] ISSN:1875-8908
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Mild cognitive impairment (MCI) is typically diagnosed using subjective complaints, screening measures, clinical judgment, and a single memory score. Our prior work has shown that this method is highly susceptible to false-positive diagnostic errors. We examined whether the criteria also lead to "false-negative" errors by diagnostically reclassifying 520 participants using novel actuarial neuropsychological criteria. Results revealed a false-negative error rate of 7.1%. Participants' neuropsychological performance, cerebrospinal fluid biomarkers, and rate of decline provided evidence that an MCI diagnosis is warranted. The impact of "missed" cases of MCI has direct relevance to clinical practice, research studies, and clinical trials of prodromal Alzheimer's disease.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.3233/JAD-150986

  4 / 281130 MEDLINE  
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[PMID]: 26656786
[Au] Autor:Pattacini L; Baeten JM; Thomas KK; Fluharty TR; Murnane PM; Donnell D; Bukusi E; Ronald A; Mugo N; Lingappa JR; Celum C; McElrath MJ; Lund JM; Partners PrEP Study Team
[Ad] Address:*Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Departments of Global Health; Epidemiology; Medicine, University of Washington, Seattle, WA; ‖Statistical Center for HIV-1/AIDS Research and Prevention, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya; #Department of Obstetrics and Gynecology, University of Washington, Seattle, WA; **Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada; Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya; and Department of Pediatrics, University of Washington, Seattle, WA.
[Ti] Title:Regulatory T-Cell Activity But Not Conventional HIV-Specific T-Cell Responses Are Associated With Protection From HIV-1 Infection.
[So] Source:J Acquir Immune Defic Syndr;72(2):119-28, 2016 Jun 1.
[Is] ISSN:1944-7884
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVE: Two distinct hypotheses have been proposed for T-cell involvement in protection from HIV-1 acquisition. First, HIV-1-specific memory T-cell responses generated on HIV-1 exposure could mount an efficient response to HIV-1 and inhibit the establishment of an infection. Second, a lower level of immune activation could reduce the numbers of activated, HIV-1-susceptible CD4 T cells, thereby diminishing the likelihood of infection. METHODS: To test these hypotheses, we conducted a prospective study among high-risk heterosexual men and women, and tested peripheral blood samples from individuals who subsequently acquired HIV-1 during follow-up (cases) and from a subset of those who remained HIV-1 uninfected (controls). RESULTS: We found no difference in HIV-1-specific immune responses between cases and controls, but Treg frequency was higher in controls as compared with cases and was negatively associated with frequency of effector memory CD4 T cells. CONCLUSIONS: Our findings support the hypothesis that low immune activation assists in protection from HIV-1 infection.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM; X
[St] Status:In-Data-Review
[do] DOI:10.1097/QAI.0000000000000919

  5 / 281130 MEDLINE  
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[PMID]: 27028955
[Au] Autor:Soman S; Prasad G; Hitchner E; Massaband P; Moseley ME; Zhou W; Rosen AC
[Ad] Address:Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School Boston, Massachusetts....
[Ti] Title:Brain structural connectivity distinguishes patients at risk for cognitive decline after carotid interventions.
[So] Source:Hum Brain Mapp;37(6):2185-94, 2016 Jun.
[Is] ISSN:1097-0193
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:While brain connectivity analyses have been demonstrated to identify ill patients for a number of diseases, their ability to predict cognitive impairment after brain injury is not well established. Traditional post brain injury models, such as stroke, are limited for this evaluation because pre-injury brain connectivity patterns are infrequently available. Patients with severe carotid stenosis, in contrast, often undergo non-emergent revascularization surgery, allowing the collection of pre and post-operative imaging, may experience brain insult due to perioperative thrombotic/embolic infarcts or hypoperfusion, and can suffer post-operative cognitive decline. We hypothesized that a distributed function such as memory would be more resilient in patients with brains demonstrating higher degrees of modularity. To test this hypothesis, we analyzed preoperative structural connectivity graphs (using T1 and DWI MRI) for 34 patients that underwent carotid intervention, and evaluated differences in graph metrics using the Brain Connectivity Toolbox. We found that patients with lower binary component number, binary community number and weighted community number prior to surgery were at greater risk for developing cognitive decline. These findings highlight the promise of brain connectivity analyses to predict cognitive decline following brain injury and serve as a clinical decision support tool. Hum Brain Mapp 37:2185-2194, 2016. 2016 Wiley Periodicals, Inc.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1002/hbm.23166

  6 / 281130 MEDLINE  
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[PMID]: 26991358
[Au] Autor:Proskovec AL; Heinrichs-Graham E; Wilson TW
[Ad] Address:Department of Psychology, University of Nebraska - Omaha, Omaha, Nebraska....
[Ti] Title:Aging modulates the oscillatory dynamics underlying successful working memory encoding and maintenance.
[So] Source:Hum Brain Mapp;37(6):2348-61, 2016 Jun.
[Is] ISSN:1097-0193
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Working memory is central to the execution of many daily functions and is typically divided into three phases: encoding, maintenance, and retrieval. While working memory performance has been repeatedly shown to decline with age, less is known regarding the underlying neural processes. We examined age-related differences in the neural dynamics that serve working memory by recording high-density magnetoencephalography (MEG) in younger and older adults while they performed a modified, high-load Sternberg working memory task with letters as stimuli. MEG data were evaluated in the time-frequency domain and significant oscillatory responses were imaged using a beamformer. A hierarchical regression was performed to investigate whether age moderated the relationship between oscillatory activity and accuracy on the working memory task. Our results indicated that the spatiotemporal dynamics of oscillatory activity in language-related areas of the left fronto-temporal cortices were similar across groups. Age-related differences emerged during early encoding in the right-hemispheric homologue of Wernicke's area. Slightly later, group differences emerged in the homologue of Broca's area and these persisted throughout memory maintenance. Additionally, occipital alpha activity during maintenance was stronger, occurred earlier, and involved more cortical tissue in older adults. Finally, age significantly moderated the relationship between accuracy and neural activity in the prefrontal cortices. In younger adults, as prefrontal activity decreased, accuracy tended to increase. Our results are consistent with predictions of the compensation-related utilization of neural circuits hypothesis (CRUNCH). Such differences in the oscillatory dynamics could reflect compensatory mechanisms, which would aid working memory performance in older age. Hum Brain Mapp 37:2348-2361, 2016. 2016 Wiley Periodicals, Inc.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1002/hbm.23178

  7 / 281130 MEDLINE  
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[PMID]: 26578623
[Au] Autor:Dubinski D; Wlfer J; Hasselblatt M; Schneider-Hohendorf T; Bogdahn U; Stummer W; Wiendl H; Grauer OM
[Ad] Address:Department of Neurology, University Hospital of Regensburg, Regensburg, Germany (D.D., U.B.); Department of Neurosurgery, University Hospital of Muenster, Muenster, Germany (J.W., W.S.); Institute of Neuropathology, University Hospital of Muenster, Muenster, Germany (M.H.); Department of Neurology, ...
[Ti] Title:CD4+ T effector memory cell dysfunction is associated with the accumulation of granulocytic myeloid-derived suppressor cells in glioblastoma patients.
[So] Source:Neuro Oncol;18(6):807-18, 2016 Jun.
[Is] ISSN:1523-5866
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Myeloid-derived suppressor cells (MDSCs) comprise a heterogeneous population of myeloid cells that are significantly expanded in cancer patients and are associated with tumor progression. METHODS: Multicolor flow cytometry was used to study the frequency, phenotype, and function of MDSCs in peripheral blood and freshly resected tumors of 52 participants with primary glioblastoma (GBM). RESULTS: The frequency of CD14(high)CD15(pos) monocytic and CD14(low)CD15(pos) granulocytic MDSCs was significantly higher in peripheral blood of GBM participants compared with healthy donors. The majority of granulocytic MDSCs consisted of CD14(low)CD15(high) neutrophilic MDSCs with high T-cell suppressive capacities. At the tumor side, we found an increase in CD14(high)CD15(pos) monocytic MDSCs and high frequencies of CD14(low)CD15(pos) granulocytic MDSCs that displayed an activated phenotype with downregulation of CD16 and upregulation of HLA-DR molecules, which did not inhibit T-cell proliferative responses in vitro. However, a strong association between granulocytic MDSCs and CD4(+) effector memory T-cells (TEM) within the tumors was detected. Tumor-derived CD4(+) TEM expressed high levels of PD-1 when compared with their blood-derived counterparts and were functionally exhausted. The respective ligand, PD-L1, was significantly upregulated on tumor-derived MDSCs, and T-cell co-culture experiments confirmed that glioma-infiltrating MDSCs can induce PD-1 expression on CD4(+) TEM. CONCLUSIONS: Our findings provide a detailed characterization of different MDSC subsets in GBM patients and indicate that both granulocytic MDSCs in peripheral blood and at the tumor site play a major role in GBM-induced T-cell suppression.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1093/neuonc/nov280

  8 / 281130 MEDLINE  
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[PMID]: 26663222
[Au] Autor:Armstrong C; Wang J; Yeun Lee S; Broderick J; Bezaire MJ; Lee SH; Soltesz I
[Ad] Address:Irvine Department of Anatomy & Neurobiology, University of California, Irvine, California....
[Ti] Title:Target-selectivity of parvalbumin-positive interneurons in layer II of medial entorhinal cortex in normal and epileptic animals.
[So] Source:Hippocampus;26(6):779-93, 2016 Jun.
[Is] ISSN:1098-1063
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The medial entorhinal cortex layer II (MEClayerII ) is a brain region critical for spatial navigation and memory, and it also demonstrates a number of changes in patients with, and animal models of, temporal lobe epilepsy (TLE). Prior studies of GABAergic microcircuitry in MEClayerII revealed that cholecystokinin-containing basket cells (CCKBCs) select their targets on the basis of the long-range projection pattern of the postsynaptic principal cell. Specifically, CCKBCs largely avoid reelin-containing principal cells that form the perforant path to the ipsilateral dentate gyrus and preferentially innervate non-perforant path forming calbindin-containing principal cells. We investigated whether parvalbumin containing basket cells (PVBCs), the other major perisomatic targeting GABAergic cell population, demonstrate similar postsynaptic target selectivity as well. In addition, we tested the hypothesis that the functional or anatomic arrangement of circuit selectivity is disrupted in MEClayerII in chronic TLE, using the repeated low-dose kainate model in rats. In control animals, we found that PVBCs innervated both principal cell populations, but also had significant selectivity for calbindin-containing principal cells in MEClayerII . However, the magnitude of this preference was smaller than for CCKBCs. In addition, axonal tracing and paired recordings showed that individual PVBCs were capable of contacting both calbindin and reelin-containing principal cells. In chronically epileptic animals, we found that the intrinsic properties of the two principal cell populations, the GABAergic perisomatic bouton numbers, and selectivity of the CCKBCs and PVBCs remained remarkably constant in MEClayerII . However, miniature IPSC frequency was decreased in epilepsy, and paired recordings revealed the presence of direct excitatory connections between principal cells in the MEClayerII in epilepsy, which is unusual in normal adult MEClayerII . Taken together, these findings advance our knowledge about the organization of perisomatic inhibition both in control and in epileptic animals. 2015 Wiley Periodicals, Inc.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1002/hipo.22559

  9 / 281130 MEDLINE  
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[PMID]: 27153191
[Au] Autor:Startin CM; Rodger E; Fodor-Wynne L; Hamburg S; Strydom A
[Ad] Address:UCL Division of Psychiatry, University College London, London, United Kingdom....
[Ti] Title:Developing an Informant Questionnaire for Cognitive Abilities in Down Syndrome: The Cognitive Scale for Down Syndrome (CS-DS).
[So] Source:PLoS One;11(5):e0154596, 2016.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Down syndrome (DS) is the most common genetic cause of intellectual disability (ID). Abilities relating to executive function, memory and language are particularly affected in DS, although there is a large variability across individuals. People with DS also show an increased risk of developing dementia. While assessment batteries have been developed for adults with DS to assess cognitive abilities, these batteries may not be suitable for those with more severe IDs, dementia, or visual / hearing difficulties. Here we report the development of an informant rated questionnaire, the Cognitive Scale for Down Syndrome (CS-DS), which focuses on everyday abilities relating to executive function, memory and language, and is suitable for assessing these abilities in all adults with DS regardless of cognitive ability. Complete questionnaires were collected about 128 individuals with DS. After final question selection we found high internal consistency scores across the total questionnaire and within the executive function, memory and language domains. CS-DS scores showed a wide range, with minimal floor and ceiling effects. We found high interrater (n = 55) and test retest (n = 36) intraclass correlations. CS-DS scores were significantly lower in those aged 41+ with significant cognitive decline compared to those without decline. Across all adults without cognitive decline, CS-DS scores correlated significantly to measures of general abilities. Exploratory factor analysis suggested five factors within the scale, relating to memory, self-regulation / inhibition, self-direction / initiation, communication, and focussing attention. The CS-DS therefore shows good interrater and test retest reliability, and appears to be a valid and suitable informant rating tool for assessing everyday cognitive abilities in a wide range of individuals with DS. Such a questionnaire may be a useful outcome measure for intervention studies to assess improvements to cognition, in addition to detecting dementia-related cognitive decline. The CS-DS may also be a useful tool for other populations with ID.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0154596

  10 / 281130 MEDLINE  
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[PMID]: 27152422
[Au] Autor:Valentin LS; Pereira VF; Pietrobon RS; Schmidt AP; Oses JP; Portela LV; Souza DO; Vissoci JR; Luz VF; Trintoni LM; Nielsen KC; Carmona MJ
[Ad] Address:Department of Anesthesia, LIM 8 -Laboratory of Anesthesiology, Faculdade de Medicina da Universidade de So Paulo, So Paulo, So Paulo, Brazil....
[Ti] Title:Effects of Single Low Dose of Dexamethasone before Noncardiac and Nonneurologic Surgery and General Anesthesia on Postoperative Cognitive Dysfunction-A Phase III Double Blind, Randomized Clinical Trial.
[So] Source:PLoS One;11(5):e0152308, 2016.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:UNLABELLED: Postoperative cognitive dysfunction (POCD) is a multifactorial adverse event most frequently in elderly patients. This study evaluated the effect of dexamethasone on POCD incidence after noncardiac and nonneurologic surgery. METHODS: One hundred and forty patients (ASA I-II; age 60-87 years) took part in a prospective phase III, double blind, randomized study involving the administration or not of 8 mg of IV dexamethasone before general anesthesia under bispectral index (BIS) between 35-45 or 46-55. Neuropsychological tests were applied preoperatively and on the 3rd, 7th, 21st, 90th and 180th days after surgery and compared with normative data. S100 was evaluated before and 12 hours after induction of anesthesia. The generalized estimating equations (GEE) method was applied, followed by the posthoc Bonferroni test considering P<0.05 as significant. RESULTS: On the 3rd postoperative day, POCD was diagnosed in 25.2% and 15.3% of patients receiving dexamethasone, BIS 35-45, and BIS 46-55 groups, respectively. Meanwhile, POCD was present in 68.2% and 27.2% of patients without dexamethasone, BIS 35-45 and BIS 46-55 groups (p<0.0001). Neuropsychological tests showed that dexamethasone associated to BIS 46-55 decreased the incidence of POCD, especially memory and executive function. The administration of dexamethasone might have prevented the postoperative increase in S100 serum levels. CONCLUSION: Dexamethasone can reduce the incidence of POCD in elderly patients undergoing surgery, especially when associated with BIS 46-55. The effect of dexamethasone on S100 might be related with some degree of neuroprotection. TRIAL REGISTRATION: www.clinicaltrials.gov NCT01332812.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0152308


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