Sample records for gak function impairs

  1. GAK, a regulator of clathrin-mediated membrane traffic, also controls centrosome integrity and chromosome congression.

    PubMed

    Shimizu, Hiroyuki; Nagamori, Ippei; Yabuta, Norikazu; Nojima, Hiroshi

    2009-09-01

    Cyclin G-associated kinase (GAK) is an association partner of clathrin heavy chain (CHC) and is essential for clathrin-mediated membrane trafficking. Here, we report two novel functions of GAK: maintenance of proper centrosome maturation and of mitotic chromosome congression. Indeed, GAK knockdown by siRNA caused cell-cycle arrest at metaphase, which indicates that GAK is required for proper mitotic progression. We found that this impaired mitotic progression was due to activation of the spindle-assembly checkpoint, which senses protruded, misaligned or abnormally condensed chromosomes in GAK-siRNA-treated cells. GAK knockdown also caused multi-aster formation, which was due to abnormal fragmentation of pericentriolar material, but not of the centrioles. Moreover, GAK and CHC cooperated in the same pathway and interacted in mitosis to regulate the formation of a functional spindle. Taken together, we conclude that GAK and clathrin function cooperatively not only in endocytosis, but also in mitotic progression.

  2. Disruption of zebrafish cyclin G-associated kinase (GAK) function impairs the expression of Notch-dependent genes during neurogenesis and causes defects in neuronal development

    PubMed Central

    2010-01-01

    Background The J-domain-containing protein auxilin, a critical regulator in clathrin-mediated transport, has been implicated in Drosophila Notch signaling. To ask if this role of auxilin is conserved and whether auxilin has additional roles in development, we have investigated the functions of auxilin orthologs in zebrafish. Results Like mammals, zebrafish has two distinct auxilin-like molecules, auxilin and cyclin G-associated kinase (GAK), differing in their domain structures and expression patterns. Both zebrafish auxilin and GAK can functionally substitute for the Drosophila auxilin, suggesting that they have overlapping molecular functions. Still, they are not completely redundant, as morpholino-mediated knockdown of the ubiquitously expressed GAK alone can increase the specification of neuronal cells, a known Notch-dependent process, and decrease the expression of Her4, a Notch target gene. Furthermore, inhibition of GAK function caused an elevated level of apoptosis in neural tissues, resulting in severe degeneration of neural structures. Conclusion In support of the notion that endocytosis plays important roles in Notch signaling, inhibition of zebrafish GAK function affects embryonic neuronal cell specification and Her4 expression. In addition, our analysis suggests that zebrafish GAK has at least two functions during the development of neural tissues: an early Notch-dependent role in neuronal patterning and a late role in maintaining the survival of neural cells. PMID:20082716

  3. Can apricot kernels fatty acids delay the atrophied hepatocytes from progression to fibrosis in dimethylnitrosamine (DMN)-induced liver injury in rats?

    PubMed

    Abdel-Rahman, Manal K

    2011-07-07

    The present study was aimed to analyze the chemical composition of ground apricot kernel (GAK) and examine its effect on hepatic fibrosis in vivo induced by dimethylnitrosamine (DMN) in rats. Hepatic fibrosis was induced by intraperitoneal injections of 10 mg/kg DMN for 3 consecutive days each week over a period of 4 wk. The rats were randomly assigned to five groups of nine rats each: the negative control group (NC), the hepatic fibrosis group (PC), hepatic fibrosis supplemented with GAK (0.5 mg/kg/BW/rat), hepatic fibrosis supplemented with GAK (1 mg/kg/BW/rat) and hepatic fibrosis supplemented with GAK (1.5 mg/kg/BW/rat). Rats were killed, blood was collected and livers were excised for biochemical measurements and histological examination. Results indicate that the diet supplemented with GAK led to improving liver function, lipid peroxides, and liver CAT, SOD and GSH. These results were confirmed by liver histology. Hierarchically high levels f GAK (1.5 mg/kg/BW/rat) gave the best results compared to other tested levels. This study demonstrates that GAK administration specifically (1.5 mg/kg/BW/rat) can effectively improve liver fibrosis caused by DMN, and may be used as a therapeutic option and preventive measure against hepatic fibrosis. Furthermore, a human trial would be applied specially GAK is a part of Egyptian diet. The act of why high amounts of GAK was improved biochemical values compared to low or moderate levels tested in this study may be due to increase levels of oleic acid and other polyphenols in apricot kernels.

  4. Can apricot kernels fatty acids delay the atrophied hepatocytes from progression to fibrosis in dimethylnitrosamine (DMN)-induced liver injury in rats?

    PubMed Central

    2011-01-01

    Background and aims The present study was aimed to analyze the chemical composition of ground apricot kernel (GAK) and examine its effect on hepatic fibrosis in vivo induced by dimethylnitrosamine (DMN) in rats. Methods and results Hepatic fibrosis was induced by intraperitoneal injections of 10 mg/kg DMN for 3 consecutive days each week over a period of 4 wk. The rats were randomly assigned to five groups of nine rats each: the negative control group (NC), the hepatic fibrosis group (PC), hepatic fibrosis supplemented with GAK (0.5 mg/kg/BW/rat), hepatic fibrosis supplemented with GAK (1 mg/kg/BW/rat) and hepatic fibrosis supplemented with GAK (1.5 mg/kg/BW/rat). Rats were killed, blood was collected and livers were excised for biochemical measurements and histological examination. Results indicate that the diet supplemented with GAK led to improving liver function, lipid peroxides, and liver CAT, SOD and GSH. These results were confirmed by liver histology. Hierarchically high levels f GAK (1.5 mg/kg/BW/rat) gave the best results compared to other tested levels. Conclusion This study demonstrates that GAK administration specifically (1.5 mg/kg/BW/rat) can effectively improve liver fibrosis caused by DMN, and may be used as a therapeutic option and preventive measure against hepatic fibrosis. Furthermore, a human trial would be applied specially GAK is a part of Egyptian diet. The act of why high amounts of GAK was improved biochemical values compared to low or moderate levels tested in this study may be due to increase levels of oleic acid and other polyphenols in apricot kernels PMID:21736706

  5. Anticancer kinase inhibitors impair intracellular viral trafficking and exert broad-spectrum antiviral effects.

    PubMed

    Bekerman, Elena; Neveu, Gregory; Shulla, Ana; Brannan, Jennifer; Pu, Szu-Yuan; Wang, Stanley; Xiao, Fei; Barouch-Bentov, Rina; Bakken, Russell R; Mateo, Roberto; Govero, Jennifer; Nagamine, Claude M; Diamond, Michael S; De Jonghe, Steven; Herdewijn, Piet; Dye, John M; Randall, Glenn; Einav, Shirit

    2017-04-03

    Global health is threatened by emerging viral infections, which largely lack effective vaccines or therapies. Targeting host pathways that are exploited by multiple viruses could offer broad-spectrum solutions. We previously reported that AAK1 and GAK, kinase regulators of the host adaptor proteins AP1 and AP2, are essential for hepatitis C virus (HCV) infection, but the underlying mechanism and relevance to other viruses or in vivo infections remained unknown. Here, we have discovered that AP1 and AP2 cotraffic with HCV particles in live cells. Moreover, we found that multiple viruses, including dengue and Ebola, exploit AAK1 and GAK during entry and infectious virus production. In cultured cells, treatment with sunitinib and erlotinib, approved anticancer drugs that inhibit AAK1 or GAK activity, or with more selective compounds inhibited intracellular trafficking of HCV and multiple unrelated RNA viruses with a high barrier to resistance. In murine models of dengue and Ebola infection, sunitinib/erlotinib combination protected against morbidity and mortality. We validated sunitinib- and erlotinib-mediated inhibition of AAK1 and GAK activity as an important mechanism of antiviral action. Additionally, we revealed potential roles for additional kinase targets. These findings advance our understanding of virus-host interactions and establish a proof of principle for a repurposed, host-targeted approach to combat emerging viruses.

  6. Anticancer kinase inhibitors impair intracellular viral trafficking and exert broad-spectrum antiviral effects

    PubMed Central

    Bekerman, Elena; Shulla, Ana; Brannan, Jennifer; Wang, Stanley; Barouch-Bentov, Rina; Bakken, Russell R.; Mateo, Roberto; Govero, Jennifer; Nagamine, Claude M.; Diamond, Michael S.; De Jonghe, Steven; Herdewijn, Piet; Dye, John M.; Randall, Glenn

    2017-01-01

    Global health is threatened by emerging viral infections, which largely lack effective vaccines or therapies. Targeting host pathways that are exploited by multiple viruses could offer broad-spectrum solutions. We previously reported that AAK1 and GAK, kinase regulators of the host adaptor proteins AP1 and AP2, are essential for hepatitis C virus (HCV) infection, but the underlying mechanism and relevance to other viruses or in vivo infections remained unknown. Here, we have discovered that AP1 and AP2 cotraffic with HCV particles in live cells. Moreover, we found that multiple viruses, including dengue and Ebola, exploit AAK1 and GAK during entry and infectious virus production. In cultured cells, treatment with sunitinib and erlotinib, approved anticancer drugs that inhibit AAK1 or GAK activity, or with more selective compounds inhibited intracellular trafficking of HCV and multiple unrelated RNA viruses with a high barrier to resistance. In murine models of dengue and Ebola infection, sunitinib/erlotinib combination protected against morbidity and mortality. We validated sunitinib- and erlotinib-mediated inhibition of AAK1 and GAK activity as an important mechanism of antiviral action. Additionally, we revealed potential roles for additional kinase targets. These findings advance our understanding of virus-host interactions and establish a proof of principle for a repurposed, host-targeted approach to combat emerging viruses. PMID:28240606

  7. The clathrin-binding and J-domains of GAK support the uncoating and chaperoning of clathrin by Hsc70 in the brain

    PubMed Central

    Park, Bum-Chan; Yim, Yang-In; Zhao, Xiaohong; Olszewski, Maciej B.; Eisenberg, Evan; Greene, Lois E.

    2015-01-01

    ABSTRACT Cyclin-G-associated kinase (GAK), the ubiquitously expressed J-domain protein, is essential for the chaperoning and uncoating of clathrin that is mediated by Hsc70 (also known as HSPA8). Adjacent to the C-terminal J-domain that binds to Hsc70, GAK has a clathrin-binding domain that is linked to an N-terminal kinase domain through a PTEN-like domain. Knocking out GAK in fibroblasts caused inhibition of clathrin-dependent trafficking, which was rescued by expressing a 62-kDa fragment of GAK, comprising just the clathrin-binding and J-domains. Expressing this fragment as a transgene in mice rescued the lethality and the histological defects caused by knocking out GAK in the liver or in the brain. Furthermore, when both GAK and auxilin (also known as DNAJC6), the neuronal-specific homolog of GAK, were knocked out in the brain, mice expressing the 62-kDa GAK fragment were viable, lived a normal life-span and had no major behavior abnormalities. However, these mice were about half the size of wild-type mice. Therefore, the PTEN-like domains of GAK and auxilin are not essential for Hsc70-dependent chaperoning and uncoating of clathrin, but depending on the tissue, these domains appear to increase the efficiency of these co-chaperones. PMID:26345367

  8. Essential Role of Cyclin-G–associated Kinase (Auxilin-2) in Developing and Mature Mice

    PubMed Central

    Lee, Dong-won; Zhao, Xiaohong; Yim, Yang-In; Eisenberg, Evan

    2008-01-01

    Hsc70 with its cochaperone, either auxilin or GAK, not only uncoats clathrin-coated vesicles but also acts as a chaperone during clathrin-mediated endocytosis. However, because synaptojanin is also involved in uncoating, it is not clear whether GAK is an essential gene. To answer this question, GAK conditional knockout mice were generated and then mated to mice expressing Cre recombinase under the control of the nestin, albumin, or keratin-14 promoters, all of which turn on during embryonic development. Deletion of GAK from brain, liver, or skin dramatically altered the histology of these tissues, causing the mice to die shortly after birth. Furthermore, by expressing a tamoxifen-inducible promoter to express Cre recombinase we showed that deletion of GAK caused lethality in adult mice. Mouse embryonic fibroblasts in which the GAK was disrupted showed a lack of clathrin-coated pits and a complete block in clathrin-mediated endocytosis. We conclude that GAK deletion blocks development and causes lethality in adult animals by disrupting clathrin-mediated endocytosis. PMID:18434600

  9. Disruption of clathrin-mediated trafficking causes centrosome overduplication and senescence.

    PubMed

    Olszewski, Maciej B; Chandris, Panagiotis; Park, Bum-Chan; Eisenberg, Evan; Greene, Lois E

    2014-01-01

    The Hsc70 cochaperone, G cyclin-associated kinase (GAK), has been shown to be essential for the chaperoning of clathrin by Hsc70 in the cell. In this study, we used conditional GAK knockout mouse embryonic fibroblasts (MEFs) to determine the effect of completely inhibiting clathrin-dependent trafficking on the cell cycle. After GAK was knocked out, the cells developed the unusual phenotype of having multiple centrosomes, but at the same time failed to divide and ultimately became senescent. To explain this phenotype, we examined the signaling profile and found that mitogenic stimulation of the GAK KO cells and the control cells were similar except for increased phosphorylation of Akt. In addition, the disruption of intracellular trafficking caused by knocking out GAK destabilized the lysosomal membranes, resulting in DNA damage due to iron leakage. Knocking down clathrin heavy chain or inhibiting dynamin largely reproduced the GAK KO phenotype, but inhibiting only clathrin-mediated endocytosis by knocking down adaptor protein (AP2) caused growth arrest and centrosome overduplication, but no DNA damage or senescence. We conclude that disruption of clathrin-dependent trafficking induces senescence accompanied by centrosome overduplication because of a combination of DNA damage and changes in mitogenic signaling that uncouples centrosomal duplication from DNA replication. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  10. Effect of Gum Arabic karroo as a Water-Reducing Admixture in Concrete

    PubMed Central

    Mbugua, Rose; Salim, Ramadhan; Ndambuki, Julius

    2016-01-01

    Concrete is one of the most popular construction materials in the world. Chemical admixtures are ingredients added to concrete to enhance its properties. However, most chemical admixtures on the market today are expensive, thereby making them out of reach for small consumers of concrete. In Africa, use of chemical admixtures is rare despite the harsh weather conditions. In the current study, Gum from Acacia karroo (GAK) was used as a water-reducing admixture in concrete. A slump test, density and compressive strength were studied using different dosages of GAK while neat concrete was the control. Results showed that slump increased by 200% at a 2% dosage of GAK. This enabled reduction of water-to-binder (w/b) ratio from 0.61 to 0.48 for samples with a 3% dosage. Reduction in w/b resulted in increased compressive strength of 37.03% above the control after 180 days of curing for a 3% dosage. XRD studies also showed a decreased rate of hydration in the presence of GAK in concrete. It was concluded that GAK can be used in concrete as a water-reducing admixture, which is environmentally-friendly, thus producing sustainable and greener concrete. PMID:28787879

  11. Effect of Gum Arabic karroo as a Water-Reducing Admixture in Concrete.

    PubMed

    Mbugua, Rose; Salim, Ramadhan; Ndambuki, Julius

    2016-01-28

    Concrete is one of the most popular construction materials in the world. Chemical admixtures are ingredients added to concrete to enhance its properties. However, most chemical admixtures on the market today are expensive, thereby making them out of reach for small consumers of concrete. In Africa, use of chemical admixtures is rare despite the harsh weather conditions. In the current study, Gum from Acacia karroo (GAK) was used as a water-reducing admixture in concrete. A slump test, density and compressive strength were studied using different dosages of GAK while neat concrete was the control. Results showed that slump increased by 200% at a 2% dosage of GAK. This enabled reduction of water-to-binder (w/b) ratio from 0.61 to 0.48 for samples with a 3% dosage. Reduction in w/b resulted in increased compressive strength of 37.03% above the control after 180 days of curing for a 3% dosage. XRD studies also showed a decreased rate of hydration in the presence of GAK in concrete. It was concluded that GAK can be used in concrete as a water-reducing admixture, which is environmentally-friendly, thus producing sustainable and greener concrete.

  12. Investigating AAK1-and GAK-Regulated Virus-Host Interactions Uncovers Broad-Spectrum Antivirals

    DTIC Science & Technology

    2017-02-16

    trans-Golgi network 100 (TGN) transport (9-12). Specifically, AAK1 and GAK phosphorylate the μ subunits of AP1 and 101 AP2, thereby enhancing their...Figure 2) (35). Isothiazolo[5,4-b]pyridines, 12g and 12i (Figure 2K), are potent (Kd = ~8 nM), 205 selective, ATP- competitive GAK inhibitors capable of...with combinations of the two 225 drugs revealed synergistic inhibition of DENV2 infection with a synergy volume of 36.7 μM2% 226 at the 95% confidence

  13. The Afghanistan National Railway: A Plan of Opportunity

    DTIC Science & Technology

    2014-01-01

    surface. Seven iron and copper mining “areas of interest” would produce the majority of the country’s export earn- ings: Haji Gak, Syadara, and Zarkashan...and 2040. Minerals from Haji Gak, acclaimed as one of the world’s largest iron reserves, account for most of the anticipated freight demand for a...proposed southern line. Haji Gak’s output is expected to be four times that of all the other mining areas combined. Afghanistan offers many

  14. An Analysis of the Published Mineral Resource Estimates of the Haji-Gak Iron Deposit, Afghanistan

    USGS Publications Warehouse

    Sutphin, D.M.; Renaud, K.M.; Drew, L.J.

    2011-01-01

    The Haji-Gak iron deposit of eastern Bamyan Province, eastern Afghanistan, was studied extensively and resource calculations were made in the 1960s by Afghan and Russian geologists. Recalculation of the resource estimates verifies the original estimates for categories A (in-place resources known in detail), B (in-place resources known in moderate detail), and C 1 (in-place resources estimated on sparse data), totaling 110. 8 Mt, or about 6% of the resources as being supportable for the methods used in the 1960s. C 2 (based on a loose exploration grid with little data) resources are based on one ore grade from one drill hole, and P 2 (prognosis) resources are based on field observations, field measurements, and an ore grade derived from averaging grades from three better sampled ore bodies. C 2 and P 2 resources are 1,659. 1 Mt or about 94% of the total resources in the deposit. The vast P 2 resources have not been drilled or sampled to confirm their extent or quality. The purpose of this article is to independently evaluate the resources of the Haji-Gak iron deposit by using the available geologic and mineral resource information including geologic maps and cross sections, sampling data, and the analog-estimating techniques of the 1960s to determine the size and tenor of the deposit. ?? 2011 International Association for Mathematical Geology (outside the USA).

  15. Fragment screening of cyclin G-associated kinase by weak affinity chromatography.

    PubMed

    Meiby, Elinor; Knapp, Stefan; Elkins, Jonathan M; Ohlson, Sten

    2012-11-01

    Fragment-based drug discovery (FBDD) has become a new strategy for drug discovery where lead compounds are evolved from small molecules. These fragments form low affinity interactions (dissociation constant (K(D)) = mM - μM) with protein targets, which require fragment screening methods of sufficient sensitivity. Weak affinity chromatography (WAC) is a promising new technology for fragment screening based on selective retention of fragments by a drug target. Kinases are a major pharmaceutical target, and FBDD has been successfully applied to several of these targets. In this work, we have demonstrated the potential to use WAC in combination with mass spectrometry (MS) detection for fragment screening of a kinase target-cyclin G-associated kinase (GAK). One hundred seventy fragments were selected for WAC screening by virtual screening of a commercial fragment library against the ATP-binding site of five different proteins. GAK protein was immobilized on a capillary HPLC column, and compound binding was characterized by frontal affinity chromatography. Compounds were screened in sets of 13 or 14, in combination with MS detection for enhanced throughput. Seventy-eight fragments (46 %) with K(D) < 200 μM were detected, including a few highly efficient GAK binders (K(D) of 2 μM; ligand efficiency = 0.51). Of special interest is that chiral screening by WAC may be possible, as two stereoisomeric fragments, which both contained one chiral center, demonstrated twin peaks. This ability, in combination with the robustness, sensitivity, and simplicity of WAC makes it a new method for fragment screening of considerable potential.

  16. Genomewide association study for susceptibility genes contributing to familial Parkinson disease

    PubMed Central

    Pankratz, Nathan; Wilk, Jemma B.; Latourelle, Jeanne C.; DeStefano, Anita L.; Halter, Cheryl; Pugh, Elizabeth W.; Doheny, Kimberly F.; Gusella, James F.; Nichols, William C.

    2009-01-01

    Five genes have been identified that contribute to Mendelian forms of Parkinson disease (PD); however, mutations have been found in fewer than 5% of patients, suggesting that additional genes contribute to disease risk. Unlike previous studies that focused primarily on sporadic PD, we have performed the first genomewide association study (GWAS) in familial PD. Genotyping was performed with the Illumina HumanCNV370Duo array in 857 familial PD cases and 867 controls. A logistic model was employed to test for association under additive and recessive modes of inheritance after adjusting for gender and age. No result met genomewide significance based on a conservative Bonferroni correction. The strongest association result was with SNPs in the GAK/DGKQ region on chromosome 4 (additive model: p = 3.4 × 10−6; OR = 1.69). Consistent evidence of association was also observed to the chromosomal regions containing SNCA (additive model: p = 5.5 × 10−5; OR = 1.35) and MAPT (recessive model: p = 2.0 × 10−5; OR = 0.56). Both of these genes have been implicated previously in PD susceptibility; however, neither was identified in previous GWAS studies of PD. Meta-analysis was performed using data from a previous case–control GWAS, and yielded improved p values for several regions, including GAK/DGKQ (additive model: p = 2.5 × 10−7) and the MAPT region (recessive model: p = 9.8 × 10−6; additive model: p = 4.8 × 10−5). These data suggest the identification of new susceptibility alleles for PD in the GAK/DGKQ region, and also provide further support for the role of SNCA and MAPT in PD susceptibility. PMID:18985386

  17. Selective AAK1 and GAK Inhibitors for Combating Dengue and Other Emerging Viral Infections

    DTIC Science & Technology

    2017-10-01

    Hemorrhagic Fever Viruses, Santa Fe, New Mexico , December 2016. 7. PARTICIPANTS & OTHER COLLABORATING ORGANIZATIONS Individuals who have worked on the... varicella -zoster virus glycoprotein I, a protein localized in the trans-Golgi network. EMBO J. 1996;15(22):6096–6110. 18. Bhattacharyya S, Hope TJ

  18. Kinase inhibition by the Jamaican ball moss, Tillandsia recurvata L.

    PubMed

    Lowe, Henry I C; Watson, Charah T; Badal, Simone; Toyang, Ngeh J; Bryant, Joseph

    2012-10-01

    This research was undertaken in order to investigate the inhibitory potential of the Jamaican ball moss, Tillandsia recurvata against several kinases. The inhibition of these kinases has emerged as a potential solution to restoring the tight regulation of normal cellular growth, the loss of which leads to cancer cell formation. Kinase inhibition was investigated using competition binding (to the ATP sites) assays, which have been previously established and authenticated. Four hundred and fifty one kinases were tested against the Jamaican ball moss extract and a dose-response was tested on 40 kinases, which were inhibited by more than 35% compared to the control. Out of the 40 kinases, the Jamaican ball moss selectively inhibited 5 (CSNK2A2, MEK5, GAK, FLT and DRAK1) and obtained Kd(50)s were below 20 μg/ml. Since MEK5 and GAK kinases have been associated with aggressive prostate cancer, the inhibitory properties of the ball moss against them, coupled with its previously found bioactivity towards the PC-3 cell line, makes it promising in the arena of drug discovery towards prostate cancer.

  19. Optical follow-up observation of AT2018cow/ATLAS18qqn

    NASA Astrophysics Data System (ADS)

    Im, Myungshin; Lim, Gu; Seo, Jinguk; Paek, Gregory S.; Kim, Hwara; Kim, Joonho; Choi, Changsu; Sung, Hyun-Il

    2018-06-01

    At 2018-06-20 UT, we observed the transient, AT2018cow/ATLAS18qqn (Smartt et al. ATel #11727) using various telescopes including the SNU Astronomical Observatory (SAO) 1m telescope, the LOAO 1m telescope, the McDonald 0.8 m telescope, and the Lee Sang Gak Telescope (LSGT) at SSO. A series of BVRI and griz data were obtained.

  20. Local-area-enhanced, 2.5-meter resolution natural-color and color-infrared satellite-image mosaics of the Haji-Gak mineral district in Afghanistan: Chapter C in Local-area-enhanced, high-resolution natural-color and color-infrared satellite-image mosaics of mineral districts in Afghanistan

    USGS Publications Warehouse

    Davis, Philip A.; Cagney, Laura E.; Arko, Scott A.; Harbin, Michelle L.

    2012-01-01

    The U.S. Geological Survey (USGS), in cooperation with the U.S. Department of Defense Task Force for Business and Stability Operations, prepared databases for mineral-resource target areas in Afghanistan. The purpose of the databases is to (1) provide useful data to ground-survey crews for use in performing detailed assessments of the areas and (2) provide useful information to private investors who are considering investment in a particular area for development of its natural resources. The set of satellite-image mosaics provided in this Data Series (DS) is one such database. Although airborne digital color-infrared imagery was acquired for parts of Afghanistan in 2006, the image data have radiometric variations that preclude their use in creating a consistent image mosaic for geologic analysis. Consequently, image mosaics were created using ALOS (Advanced Land Observation Satellite; renamed Daichi) satellite images, whose radiometry has been well determined (Saunier, 2007a,b). This part of the DS consists of the locally enhanced ALOS image mosaics for the Haji-Gak mineral district, which has iron ore deposits. ALOS was launched on January 24, 2006, and provides multispectral images from the AVNIR (Advanced Visible and Near-Infrared Radiometer) sensor in blue (420-500 nanometer, nm), green (520-600 nm), red (610-690 nm), and near-infrared (760-890 nm) wavelength bands with an 8-bit dynamic range and a 10-meter (m) ground resolution. The satellite also provides a panchromatic band image from the PRISM (Panchromatic Remote-sensing Instrument for Stereo Mapping) sensor (520-770 nm) with the same dynamic range but a 2.5-m ground resolution. The image products in this DS incorporate copyrighted data provided by the Japan Aerospace Exploration Agency ((c)JAXA,2006,2007), but the image processing has altered the original pixel structure and all image values of the JAXA ALOS data, such that original image values cannot be recreated from this DS. As such, the DS products match JAXA criteria for value added products, which are not copyrighted, according to the ALOS end-user license agreement. The selection criteria for the satellite imagery used in our mosaics were images having (1) the highest solar-elevation angles (near summer solstice) and (2) the least cloud, cloud-shadow, and snow cover. The multispectral and panchromatic data were orthorectified with ALOS satellite ephemeris data, a process which is not as accurate as orthorectification using digital elevation models (DEMs); however, the ALOS processing center did not have a precise DEM. As a result, the multispectral and panchromatic image pairs were generally not well registered to the surface and not coregistered well enough to perform resolution enhancement on the multispectral data. For this particular area, PRISM image orthorectification was performed by the Alaska Satellite Facility, applying its photogrammetric software to PRISM stereo images with vertical control points obtained from the digital elevation database produced by the Shuttle Radar Topography Mission (Farr and others, 2007) and horizontal adjustments based on a controlled Landsat image base (Davis, 2006). The 10-m AVNIR multispectral imagery was then co-registered to the orthorectified PRISM images and individual multispectral and panchromatic images were mosaicked into single images of the entire area of interest. The image-coregistration was facilitated using an automated control-point algorithm developed by the USGS that allows image coregistration to within one picture element. Before rectification, the multispectral and panchromatic images were converted to radiance values and then to relative-reflectance values using the methods described in Davis (2006). Mosaicking the multispectral or panchromatic images started with the image with the highest sun-elevation angle and the least atmospheric scattering, which was treated as the standard image. The band-reflectance values of all other multispectral or panchromatic images within the area were sequentially adjusted to that of the standard image by determining band-reflectance correspondence between overlapping images using linear least-squares analysis. The resolution of the multispectral image mosaic was then increased to that of the panchromatic image mosaic using the SPARKLE logic, which is described in Davis (2006). Each of the four-band images within the resolution-enhanced image mosaic was individually subjected to a local-area histogram stretch algorithm (described in Davis, 2007), which stretches each band's picture element based on the digital values of all picture elements within a 500-m radius. The final databases, which are provided in this DS, are three-band, color-composite images of the local-area-enhanced, natural-color data (the blue, green, and red wavelength bands) and color-infrared data (the green, red, and near-infrared wavelength bands). All image data were initially projected and maintained in Universal Transverse Mercator (UTM) map projection using the target area's local zone (42 for Haji-Gak) and the WGS84 datum. The final image mosaics were subdivided into three overlapping tiles or quadrants because of the large size of the target area. The three image tiles (or quadrants) for the Haji-Gak area are provided as embedded geotiff images, which can be read and used by most geographic information system (GIS) and image-processing software. The tiff world files (tfw) are provided, even though they are generally not needed for most software to read an embedded geotiff image. Within the Haji-Gak study area, three subareas were designated for detailed field investigations (that is, the Haji-Gak Prospect, Farenjal, and NE Haji-Gak subareas); these subareas were extracted from the area's image mosaic and are provided as separate embedded geotiff images.

  1. Selective AAK1 and GAK Inhibitors for Combating Dengue and Other Emerging Viral Infections

    DTIC Science & Technology

    2017-10-01

    accomplishments. This year, USAMRIID has tested nine candidate inhibitors. Inhibitors were evaluated for their impact on in vitro viability prior to...evaluation of inhibitory capacity against Ebola virus (EBOV), Marburg virus (MARV) and/or chikungunya virus (CHIKV). For viability assessment, compounds...were applied to cells at a range of doses, and a commercially available kit was used to measure ATP content as a marker of viability . Only

  2. Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease

    PubMed Central

    Hamza, Taye H; Zabetian, Cyrus P; Tenesa, Albert; Laederach, Alain; Montimurro, Jennifer; Yearout, Dora; Kay, Denise M; Doheny, Kimberly F; Paschall, Justin; Pugh, Elizabeth; Kusel, Victoria I; Collura, Randall; Roberts, John; Griffith, Alida; Samii, Ali; Scott, William K; Nutt, John; Factor, Stewart A; Payami, Haydeh

    2010-01-01

    Parkinson disease (PD) is a common disorder that leads to motor and cognitive disability. We performed a genome-wide association study (GWAS) with 2000 PD and 1986 control Caucasian subjects from NeuroGenetics Research Consortium.1–5 We confirmed SNCA2,6–8 and MAPT3,7–9; replicated GAK9 (PPankratz+NGRC=3.2×10−9); and detected a novel association with HLA (PNGRC=2.9×10−8) which replicated in two datasets (PMeta-analysis=1.9×10−10). We designate the new PD genes PARK17 (GAK) and PARK18 (HLA). PD-HLA association was uniform across genetic and environmental risk strata, and strong in sporadic (P=5.5×10−10) and late-onset (P=2.4×10−8) PD. The association peak was at rs3129882, a non-coding variant in HLA-DRA. Two studies suggested rs3129882 influences expression of HLA-DR and HLA-DQ.10,11 PD brains exhibit up-regulation of DR antigens and presence of DR-positive reactive microglia.12 Moreover, non-steroidal anti-inflammatory drugs (NSAID) reduce PD risk.4,13 The genetic association with HLA coalesces the evidence for involvement of the immune system and offers new targets for drug development and pharmacogenetics. PMID:20711177

  3. Geologic map of the Haji-Gak iron deposit, Bamyan Province, Afghanistan, modified from the 1965 original map compilation of M.S. Smirnov and I.K. Kusov

    USGS Publications Warehouse

    Renaud, Karine M.; Tucker, Robert D.; Peters, Stephen G.; Stettner, Will R.; Masonic, Linda M.; Moran, Thomas W.

    2011-01-01

    This map is a modified version of Geological-structural map of Hajigak iron-ore deposit, scale 1:10,000, which was compiled by M.S. Smirnov and I.K. Kusov in 1965. (Refer to the References Cited section in the Map PDF for complete citations of the original map and a related report.) USGS scientists, in cooperation with the Afghan Geological Survey and the Task Force for Business and Stability Operations of the U.S. Department of Defense, studied the original documents and also visited the field area in November 2009. This modified map illustrates the geological structure of the Haji-Gak iron deposit and includes cross sections of the same area. The map reproduces the topology (contacts, faults, and so forth) of the original Soviet map and cross sections and includes modifications based on our examination of these documents. Elevations on the cross sections are derived from the original Soviet topography and may not match the newer topography used on the current map. We have attempted to translate the original Russian terminology and rock classification into modern English geologic usage as literally as possible without changing any genetic or process-oriented implications in the original descriptions. We also use the age designations from the original map. The unit colors on the map and cross sections differ from the colors shown on the original version. The units are colored according to the color and pattern scheme of the Commission for the Geological Map of the World (CGMW) (http://www.ccgm.org).

  4. Geologic map of the western Haji-Gak iron deposit, Bamyan Province, Afghanistan, modified from the 1965 original map compilation of V.V. Reshetniak and I.K. Kusov

    USGS Publications Warehouse

    Renaud, Karine M.; Tucker, Robert D.; Peters, Stephen G.; Stettner, Will R.; Masonic, Linda M.; Moran, Thomas W.

    2011-01-01

    This map is a modified version of Geologic-prospecting plan of western area of Hajigak iron-ore deposit, scale 1:2,000, which was compiled by V.V. Reshetniak and I.K. Kusov in 1965. (Refer to the References Cited section in the Map PDF for complete citations of the original map and related reports.) USGS scientists, in cooperation with the Afghan Geological Survey and the Task Force for Business and Stability Operations of the U.S. Department of Defense, studied the original documents and also visited the field area in November 2009. This modified map illustrates the geological structure of the western Haji-Gak iron deposit and includes cross sections of the same area. The map reproduces the topology (contacts, faults, and so forth) of the original Soviet map and includes modifications based on our examination of that document. We constructed the cross sections from data derived from the original map. Elevations on the cross sections are derived from the original Soviet topography and may not match the newer topography used on the current map. We have attempted to translate the original Russian terminology and rock classification into modern English geologic usage as literally as possible without changing any genetic or process-oriented implications in the original descriptions. We also use the age designations from the original map. The unit colors on the map and cross sections differ from the colors shown on the original version. The units are colored according to the color and pattern scheme of the Commission for the Geological Map of the World (CGMW) (http://www.ccgm.org).

  5. Association of Parkinson Disease Risk Loci With Mild Parkinsonian Signs in Older Persons

    PubMed Central

    Shulman, Joshua M.; Yu, Lei; Buchman, Aron S.; Evans, Denis A.; Schneider, Julie A.; Bennett, David A.; De Jager, Philip L.

    2014-01-01

    IMPORTANCE Parkinsonian motor signs are common in the aging population and are associated with adverse health outcomes. Compared with Parkinson disease (PD), potential genetic risk factors for mild parkinsonian signs have been largely unexplored. OBJECTIVE To determine whether PD susceptibility loci are associated with parkinsonism or substantia nigra pathology in a large community-based cohort of older persons. DESIGN, SETTING, AND PARTICIPANTS Eighteen candidate single-nucleotide polymorphisms from PD genome-wide association studies were evaluated in a joint clinicopathologic cohort. Participants included 1698 individuals and a nested autopsy collection of 821 brains from the Religious Orders Study and the Rush Memory and Aging Project, 2 prospective community-based studies. MAIN OUTCOMES AND MEASURES The primary outcomes were a quantitative measure of global parkinsonism or component measures of bradykinesia, rigidity, tremor, and gait impairment that were based on the motor Unified Parkinson’s Disease Rating Scale. In secondary analyses, we examined associations with additional quantitative motor traits and postmortem indices, including substantia nigra Lewy bodies and neuronal loss. RESULTS Parkinson disease risk alleles in the MAPT (rs2942168; P = .0006) and CCDC62 (rs12817488; P = .004) loci were associated with global parkinsonism, and these associations remained after exclusion of patients with a PD diagnosis. Based on motor Unified Parkinson’s Disease Rating Scale subscores, MAPT (P = .0002) and CCDC62 (P = .003) were predominantly associated with bradykinesia, and we further discovered associations between SREBF1 (rs11868035; P = .005) and gait impairment, SNCA (rs356220; P = .04) and rigidity, and GAK (rs1564282; P = .03) and tremor. In the autopsy cohort, only NMD3 (rs34016896; P = .03) was related to nigral neuronal loss, and no associations were detected with Lewy bodies. CONCLUSIONS AND RELEVANCE In addition to the established link to PD susceptibility, our results support a broader role for several loci in the development of parkinsonian motor signs and nigral pathology in older persons. PMID:24514572

  6. Automatic Clock and Time Signal System of the Astronomical Agency in East Asia Area

    NASA Astrophysics Data System (ADS)

    Lee, Yong Sam

    2009-09-01

    We analysed the old automatic clock and time signal system that was used by the national astronomical agency in East Asian Area. Jagyeongnu is a kind of water clock that was operated by the flowing water in Joseon Dynasty. Seowoongwan managed the water clock so as to keep the standard time system in the dynasty from the 16th year (1434) of King Sejong's reign. In 1438 the Okru that was invented in the period. Such kind of clock system already was used in China, which was Shui yun i hsiang t'ai (?) in 1092. During the period Joseon Dynasty, China and Japan had been kept the time system that one day is divided into 12 shin (?2?) or 100 gak (?). However detailed part of the system had a little difference among the three countries. Though the whole system of water clock in Joseon had manufactured on the basis of Chinese, it had been gradually developed by own method and idea. In this study we show the historical records of the standard time keeping system in East Asian history. And then we can inform materials on the structure and functional devises for the purpose of new restoration models about the automatic clock and time system.

  7. Identification and Targeting of an Interaction between a Tyrosine Motif within Hepatitis C Virus Core Protein and AP2M1 Essential for Viral Assembly

    PubMed Central

    Ziv-Av, Amotz; Gerber, Doron; Jacob, Yves; Einav, Shirit

    2012-01-01

    Novel therapies are urgently needed against hepatitis C virus infection (HCV), a major global health problem. The current model of infectious virus production suggests that HCV virions are assembled on or near the surface of lipid droplets, acquire their envelope at the ER, and egress through the secretory pathway. The mechanisms of HCV assembly and particularly the role of viral-host protein-protein interactions in mediating this process are, however, poorly understood. We identified a conserved heretofore unrecognized YXXΦ motif (Φ is a bulky hydrophobic residue) within the core protein. This motif is homologous to sorting signals within host cargo proteins known to mediate binding of AP2M1, the μ subunit of clathrin adaptor protein complex 2 (AP-2), and intracellular trafficking. Using microfluidics affinity analysis, protein-fragment complementation assays, and co-immunoprecipitations in infected cells, we show that this motif mediates core binding to AP2M1. YXXΦ mutations, silencing AP2M1 expression or overexpressing a dominant negative AP2M1 mutant had no effect on HCV RNA replication, however, they dramatically inhibited intra- and extracellular infectivity, consistent with a defect in viral assembly. Quantitative confocal immunofluorescence analysis revealed that core's YXXΦ motif mediates recruitment of AP2M1 to lipid droplets and that the observed defect in HCV assembly following disruption of core-AP2M1 binding correlates with accumulation of core on lipid droplets, reduced core colocalization with E2 and reduced core localization to trans-Golgi network (TGN), the presumed site of viral particles maturation. Furthermore, AAK1 and GAK, serine/threonine kinases known to stimulate binding of AP2M1 to host cargo proteins, regulate core-AP2M1 binding and are essential for HCV assembly. Last, approved anti-cancer drugs that inhibit AAK1 or GAK not only disrupt core-AP2M1 binding, but also significantly inhibit HCV assembly and infectious virus production. These results validate viral-host interactions essential for HCV assembly and yield compounds for pharmaceutical development. PMID:22916011

  8. Nanorods on surface of GaN-based thin-film LEDs deposited by post-annealing after photo-assisted chemical etching

    NASA Astrophysics Data System (ADS)

    Chen, Lung-Chien; Lin, Wun-Wei; Liu, Te-Yu

    2017-01-01

    This study investigates the optoelectronic characteristics of gallium nitride (GaN)-based thin-film light-emitting diodes (TF-LEDs) that are formed by a two-step transfer process that involves wet etching and post-annealing. In the two-step transfer process, GaN LEDs were stripped from sapphire substrates by the laser lift-off (LLO) method using a KrF laser and then transferred onto ceramic substrates. Ga-K nanorods were formed on the surface of the GaN-based TF-LEDs following photo-assisted chemical etching and photo-enhanced post-annealing at 100 °C for 1 min. As a result, the light output power of GaN-based TF-LEDs with wet etching and post-annealing was over 72% more than that of LEDs that did not undergo these treatments.

  9. Nanorods on surface of GaN-based thin-film LEDs deposited by post-annealing after photo-assisted chemical etching.

    PubMed

    Chen, Lung-Chien; Lin, Wun-Wei; Liu, Te-Yu

    2017-12-01

    This study investigates the optoelectronic characteristics of gallium nitride (GaN)-based thin-film light-emitting diodes (TF-LEDs) that are formed by a two-step transfer process that involves wet etching and post-annealing. In the two-step transfer process, GaN LEDs were stripped from sapphire substrates by the laser lift-off (LLO) method using a KrF laser and then transferred onto ceramic substrates. Ga-K nanorods were formed on the surface of the GaN-based TF-LEDs following photo-assisted chemical etching and photo-enhanced post-annealing at 100 °C for 1 min. As a result, the light output power of GaN-based TF-LEDs with wet etching and post-annealing was over 72% more than that of LEDs that did not undergo these treatments.

  10. Structural equation modeling of motor impairment, gross motor function, and the functional outcome in children with cerebral palsy.

    PubMed

    Park, Eun-Young; Kim, Won-Ho

    2013-05-01

    Physical therapy intervention for children with cerebral palsy (CP) is focused on reducing neurological impairments, improving strength, and preventing the development of secondary impairments in order to improve functional outcomes. However, relationship between motor impairments and functional outcome has not been proved definitely. This study confirmed the construct of motor impairment and performed structural equation modeling (SEM) between motor impairment, gross motor function, and functional outcomes of regarding activities of daily living in children with CP. 98 children (59 boys, 39 girls) with CP participated in this cross-sectional study. Mean age was 11 y 5 mo (SD 1 y 9 mo). The Manual Muscle Test (MMT), the Modified Ashworth Scale (MAS), range of motion (ROM) measurement, and the selective motor control (SMC) scale were used to assess motor impairments. Gross motor function and functional outcomes were measured using the Gross Motor Function Measure (GMFM) and the Functional Skills domain of the Pediatric Evaluation of Disability Inventory (PEDI) respectively. Measurement of motor impairment was consisted of strength, spasticity, ROM, and SMC. The construct of motor impairment was confirmed though an examination of a measurement model. The proposed SEM model showed good fit indices. Motor impairment effected gross motor function (β=-.0869). Gross motor function and motor impairment affected functional outcomes directly (β=0.890) and indirectly (β=-0.773) respectively. We confirmed that the construct of motor impairment consist of strength, spasticity, ROM, and SMC and it was identified through measurement model analysis. Functional outcomes are best predicted by gross motor function and motor impairments have indirect effects on functional outcomes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Functional Impairment and Changes in Depression Subtypes for Women in STAR*D: A Latent Transition Analysis

    PubMed Central

    Rothschild, Anthony J.; Lapane, Kate L.

    2016-01-01

    Abstract Objective: To characterize the association between functional impairment and major depression subtypes at baseline and to characterize changes in subtypes by functional impairment level in women receiving citalopram in level 1 of the Sequenced Treatment Alternatives to Relieve Depression trial. Method: Women who completed baseline and week 12 study visits were included. Items from the self-reported Quick Inventory of Depressive Symptomatology were used to define the latent depression subtypes. The Work and Social Adjustment Scale was used to classify baseline functional impairment. A latent transition analysis model provided estimates of the prevalence of subtype membership and transition probabilities by functional impairment level. Results: Of the 755 women included, 69% had major functional impairment at baseline. Regardless of functional impairment level, the subtypes were differentiated by depression severity, appetite changes, psychomotor disturbances, and insomnia. Sixty-seven percent of women with normal/significant functional impairment and 60% of women with major impairment were likely to transition to a symptom resolution subtype at week 12. Women with baseline major impairment who were in the severe with psychomotor agitation subtype at the beginning of the study were least likely to transition to the symptom resolution subtype (4% chance). Conclusions: Functional impairment level was related to both the baseline depression subtype and the likelihood of moving to a different subtype. These results underscore the need to incorporate not only depression symptoms but also functioning in the assessment and treatment of depression. PMID:26488110

  12. Neurocognition, functional competence and self-reported functional impairment in psychometrically defined schizotypy.

    PubMed

    Xavier, Shannon; Best, Michael W; Schorr, Emily; Bowie, Christopher R

    2015-01-01

    Schizotypy is phenologically and genetically related to schizophrenia-spectrum illness. Previous studies find cognitive function to be mildly impaired, but specific impairments and their relationship to functioning are not well understood. In this study, we sought to examine how cognitive load affects performance in schizotypy and to examine whether impairments might manifest in functional capacity and quality of life. Undergraduate students were screened for abnormally high levels of schizotypy (N = 72) and compared to those without psychopathology (N = 80) on a standard battery of neuropsychological tests, cognitive tests with varying cognitive load, functional capacity measures and quality of life. The high schizotypy group did not differ from controls on traditional measures of neuropsychological functioning, but an interaction of group by cognitive load was observed, where those with schizotypy manifested a greater decline in performance as information processing load was parametrically increased. Differences in functioning were observed and cognitive impairment was associated with impaired functioning. Cognitive and functional impairment can be observed in those with high schizotypal traits who are non-treatment seeking. The sensitivity of cognitive tests to impairment in this population might be a function of their ability to parametrically increase cognitive load.

  13. Arthritis and Risk of Cognitive and Functional Impairment in Older Mexican Adults.

    PubMed

    Veeranki, Sreenivas P; Downer, Brian; Jupiter, Daniel; Wong, Rebeca

    2017-04-01

    This study investigated the risk of cognitive and functional impairment in older Mexicans diagnosed with arthritis. Participants included 2,681 Mexicans, aged ≥60 years, enrolled in the Mexican Health and Aging Study cohort. Participants were categorized into arthritis and no arthritis exposure groups. Primary outcome included participants categorized into "cognitively impaired" or "cognitively normal" groups. Secondary outcomes included participants categorized into Normal, Functionally Impaired only, Cognitively Impaired only, or Dementia (both cognitively and functionally impaired) groups. Multivariable logistic and multinomial regression models were used to assess the relationships. Overall, 16% or 7% were diagnosed with cognitive impairment or dementia. Compared with older Mexicans without arthritis, those who were diagnosed with arthritis had significantly increased risk of functional impairment (adjusted odds ratio [OR] 1.82, 95% confidence interval [CI] = [1.45, 2.29]), but not of dementia. Arthritis is associated with increased risk of functional impairment, but not with dementia after 11 years in older Mexicans.

  14. Effectiveness of the second-stage rehabilitation in stroke patients with cognitive impairment.

    PubMed

    Milinavičienė, Eglė; Rastenytė, Daiva; Kriščiūnas, Aleksandras

    2011-01-01

    The aim of this study was to evaluate the recovery of functional status and effectiveness of the second-stage rehabilitation depending on the degree of cognitive impairment in stroke patients. The study sample comprised 226 stroke patients at the Viršužiglis Hospital of rehabilitation, Hospital of Lithuanian University of Health Sciences. Functional status was evaluated with the Functional Independence Measure, cognitive function with the Mini-Mental Status Examination scale, and severity of neurologic condition with the National Institutes of Health Stroke Scale. The patients were divided into 4 study groups based on cognitive impairment: severe, moderate, mild, or no impairment. More than half (53%) of all cases were found to have cognitive impairment, while patients with different degree of cognitive impairment were equally distributed: mild impairment (18%), moderate impairment (17%), and severe impairment (18%). Improvement of functional status was observed in all study groups (P<0.001). In the patients with moderate and severe cognitive impairment, cognitive recovery was significantly more expressed than in other study groups (P<0.001). Insufficient recovery of functional status was significantly associated with hemiplegia (OR, 11.15; P=0.015), urinary incontinence (OR, 14.91; P<0.001), joint diseases (OR, 5.52; P=0.022), heart diseases (OR, 4.10; P=0.041), and severe cognitive impairment (OR, 15.18; P<0.001), while moderate and mild cognitive impairment was not associated with the recovery of functional status. During the second-stage rehabilitation of stroke patients, functional status as well as cognitive and motor skills were improved both in patients with and without cognitive impairment; however, the patients who were diagnosed with severe or moderate cognitive impairment at the beginning of second-stage rehabilitation showed worse neurological and functional status during the whole second-stage rehabilitation than the patients with mild or no cognitive impairment.

  15. Association between pulmonary function and renal function: findings from China and Australia.

    PubMed

    Yu, Dahai; Chen, Tao; Cai, Yamei; Zhao, Zhanzheng; Simmons, David

    2017-05-01

    The relationship between obstructive lung function and impaired renal function is unclear. This study investigated the dose-response relationship between obstructive lung function and impaired renal function. Two independent cross-sectional studies with representative sampling were applied. 1454 adults from rural Victoria, Australia (1298 with normal renal function, 156 with impaired renal function) and 5824 adults from Nanjing, China (4313 with normal renal function, 1511 with impaired renal function). Pulmonary function measurements included forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Estimated glomerular filtration rate (eGFR), and impaired renal function marked by eGFR <60 mL/min/1.73m 2 were used as outcome. eGFR increased linearly with FEV1 in Chinese participants and with FVC in Australians. A non-linear relationship with peaked eGFR was found for FEV1 at 2.65 L among Australians and for FVC at 2.78 L among Chinese participants, respectively. A non-linear relationship with peaked eGFR was found for the predicted percentage value of forced expiratory volume in 1 s (PFEV1) at 81-82% and for the predicted percentage value of forced vital capacity (PFVC) at 83-84% among both Chinese and Australian participants, respectively. The non-linear dose-response relationships between lung capacity measurements (both for FEV1 and FVC) and risk of impaired renal function were consistently identified in both Chinese and Australian participants. An increased risk of impaired renal function was found below 3.05 L both for FEV1 and FVC, respectively. The non-linear relationship between PFEV and PVC and the risk of impaired renal function were consistently identified in both Chinese and Australian participants. An increased risk of impaired renal function was found below 76-77% for PFEV1 and 79-80% for PFVC, respectively. In both Australian and Chinese populations, the risk of impaired renal function increased both with FEV1 and FVC below 3.05 L, with PFEV1 below 76-77% or with PFVC below 79-80%, respectively. Obstructive lung function was associated with increased risk of reduced renal function. The screen for impaired renal function in patients with obstructive lung disease might be useful to ensure there was no impaired renal function before the commencement of potentially nephrotoxic medication where indicated (eg diuretics).

  16. Structural Equation Modeling of Motor Impairment, Gross Motor Function, and the Functional Outcome in Children with Cerebral Palsy

    ERIC Educational Resources Information Center

    Park, Eun-Young; Kim, Won-Ho

    2013-01-01

    Physical therapy intervention for children with cerebral palsy (CP) is focused on reducing neurological impairments, improving strength, and preventing the development of secondary impairments in order to improve functional outcomes. However, relationship between motor impairments and functional outcome has not been proved definitely. This study…

  17. Gender differences in associations between DSM-5 posttraumatic stress disorder symptom clusters and functional impairment in war veterans.

    PubMed

    Meyer, Eric C; Konecky, Brian; Kimbrel, Nathan A; DeBeer, Bryann B; Marx, Brian P; Schumm, Jeremiah; Penk, Walter E; Gulliver, Suzy Bird; Morissette, Sandra B

    2018-05-01

    Understanding the links between posttraumatic stress disorder (PTSD) symptoms and functional impairment is essential for assisting veterans in transitioning to civilian life. Moreover, there may be differences between men and women in the relationships between PTSD symptoms and functional impairment. However, no prior studies have examined the links between functional impairment and the revised symptom clusters as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5; American Psychiatric Association, 2013) or whether the associations between PTSD symptom clusters and functional impairment differ by gender. We examined the associations between the DSM-5 PTSD symptom clusters and functional impairment in 252 trauma-exposed Iraq and Afghanistan war veterans (79 females). Regression analyses included demographic factors and exposure to both combat and military sexual trauma as covariates. In the total sample, both the intrusions cluster (β = .18, p = .045) and the negative alterations in cognition and mood cluster (β = .45, p < .001) were associated with global functional impairment. Among male veterans, global functional impairment was associated only with negative alterations in cognition and mood (β = .52, p < .001). However, by contrast, among female veterans, only marked alterations in arousal and reactivity were associated with global functional impairment (β = .35, p = .027). These findings suggest that there may be important gender differences with respect to the relationship between PTSD symptoms and functional impairment. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  18. Eating disorder severity and functional impairment: moderating effects of illness duration in a clinical sample.

    PubMed

    Davidsen, Annika Helgadóttir; Hoyt, William T; Poulsen, Stig; Waaddegaard, Mette; Lau, Marianne

    2017-09-01

    The aim was to examine duration of illness and body mass index as possible moderators of the relationship between eating disorder severity and functional impairment, as well as psychological distress as a possible mediator of this relationship. The study included 159 patients diagnosed with bulimia nervosa, binge eating disorder or eating disorder not otherwise specified. Regression analysis was applied to assess the effect of the hypothesized moderators and mediators. Eating disorder severity was measured with the Eating Disorder Examination Questionnaire, functional impairment was measured with the Sheehan Disability Scale, and psychological distress was measured with the Symptom Check List-90-R. Duration of illness and body mass index were assessed clinically. Duration of illness significantly moderated the relationship between eating disorder severity and functional impairment; the relationship was strongest for patients with a shorter duration of illness. Psychological distress partly mediated the relationship between eating disorder severity and functional impairment. Duration of illness significantly moderated the relationship between psychological distress and functional impairment; the strongest relationship was seen for patients with a shorter duration of illness. Body mass index was not a significant moderator of the relationship between ED severity and functional impairment. Overall, this study established a link between ED severity, psychological distress and functional impairment indicating that both eating disorder severity and psychological distress are more strongly related to impaired role functioning for patients with more recent onset of an eating disorder. More research in the complex relationship between ED severity and functional impairment is needed.

  19. Associations of smoking and alcohol consumption with impaired β-cell function in Chinese men.

    PubMed

    Xu, Min; Zhou, Yulin; Xu, Baihui; Sun, Jichao; Wang, Tiange; Lu, Jieli; Lai, Shenghan; Bi, Yufang; Wang, Weiqing; Ning, Guang

    2016-05-01

    The aims of the present study were to examine the association of cigarette smoking and alcohol consumption with impaired β-cell function in Chinese men, particularly the interaction of smoking and alcohol consumption on impaired insulin secretion. A population-based cross-sectional study was performed in 3957 Chinese men aged ≥40 years. The homeostatic model assessment of β-cell function (HOMA-β) was calculated, and impaired β-cell function was defined as less than the lowest quartile HOMA-βcut-off point. The prevalence of impaired β-cell function in current smokers and heavy drinkers (≥200 g/week) was significantly higher than in non-smokers and non-drinkers, respectively. Compared with non-smoking, current smoking had an exacerbating relationship with impaired β-cell function (odds ratio [OR] 1.78; 95% confidence interval [CI] 1.47-2.15; P < 0.001). No significant association was found between impaired β-cell function and former smoking (P = 0.21), although low and heavy drinking were associated with an increased risk of impaired β-cell function (OR 1.40 [95% CI 1.07-1.81] and 2.14 [95% CI 1.77-2.58], respectively) compared with non-drinking. The combination of current smoking and heavy drinking was associated with the highest risk of impaired β-cell function (OR 3.16; 95% CI 2.43-4.12; P < 0.0001) after adjustment for confounders. We did not detect an additive interaction between current smoking and heavy drinking on the association with impaired β-cell function. Cigarette smoking and alcohol consumption were significantly and independently associated with impaired β-cell function in Chinese men. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  20. Sensory Impairments and Cognitive Function in Middle-Aged Adults.

    PubMed

    Schubert, Carla R; Cruickshanks, Karen J; Fischer, Mary E; Chen, Yanjun; Klein, Barbara E K; Klein, Ronald; Pinto, A Alex

    2017-08-01

    Hearing, visual, and olfactory impairments have been associated with cognitive impairment in older adults but less is known about associations with cognitive function in middle-aged adults. Sensory and cognitive functions were measured on participants in the baseline examination (2005-2008) of the Beaver Dam Offspring Study. Cognitive function was measured with the Trail Making tests A (TMTA) and B (TMTB) and the Grooved Peg Board test. Pure-tone audiometry, Pelli-Robson letter charts, and the San Diego Odor Identification test were used to measure hearing, contrast sensitivity, and olfaction, respectively. There were 2,836 participants aged 21-84 years with measures of hearing, visual, olfactory, and cognitive function at the baseline examination. Nineteen percent of the cohort had one sensory impairment and 3% had multiple sensory impairments. In multivariable adjusted linear regression models that included all three sensory impairments, hearing impairment, visual impairment, and olfactory impairment were each independently associated with poorer performance on the TMTA, TMTB, and Grooved Peg Board (p < .05 for all sensory impairments in all models). Participants with a sensory impairment took on average from 2 to 10 seconds longer than participants without the corresponding sensory impairment to complete these tests. Results were similar in models that included adjustment for hearing aid use. Hearing, visual and olfactory impairment were associated with poorer performance on cognitive function tests independent of the other sensory impairments and factors associated with cognition. Sensory impairments in midlife are associated with subtle deficits in cognitive function which may be indicative of early brain aging. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. A prospective study of the impact of diabetes mellitus on restrictive and obstructive lung function impairment: The Saku study.

    PubMed

    Sonoda, Nao; Morimoto, Akiko; Tatsumi, Yukako; Asayama, Kei; Ohkubo, Takayoshi; Izawa, Satoshi; Ohno, Yuko

    2018-05-01

    To assess the impact of diabetes on restrictive and obstructive lung function impairment. This 5-year prospective study included 7524 participants aged 40-69years without lung function impairment at baseline who underwent a comprehensive medical check-up between April 2008 and March 2009 at Saku Central Hospital. Diabetes was defined by fasting plasma glucose ≥7.0mmol/l (126mg/dl), HbA1c≥6.5% (48mmol/mol), or a history of diabetes, as determined by interviews conducted by the physicians. Restrictive and obstructive lung function impairment were defined as forced vital capacity (FVC) <80% predicted and forced expiratory volume in 1s (FEV 1 ) to FVC ratio (FEV 1 /FVC) <0.70, respectively. Participants were screened until they developed restrictive or obstructive lung function impairment or until March 2014. During the follow-up period, 171 and 639 individuals developed restrictive and obstructive lung function impairment, respectively. Individuals with diabetes had a 1.6-fold higher risk of restrictive lung function impairment than those without diabetes after adjusting for sex, age, height, abdominal obesity, smoking status, exercise habits, systolic blood pressure, HDL-cholesterol, log-transformed high-sensitivity C-reactive protein, and baseline lung function [multivariable-adjusted HR and 95% CI; 1.57 (1.04-2.36)]. In contrast, individuals with diabetes did not have a significantly higher risk of obstructive lung function impairment [multivariable-adjusted HR and 95% CI; 0.93 (0.72-1.21)]. Diabetes was associated with restrictive lung function impairment but not obstructive lung function impairment. Copyright © 2017. Published by Elsevier Inc.

  2. Interactive effects of diabetes and impaired kidney function on cognitive performance in old age: a population-based study.

    PubMed

    Yin, Zhaoxue; Yan, Zhongrui; Liang, Yajun; Jiang, Hui; Cai, Chuanzhu; Song, Aiqin; Feng, Lei; Qiu, Chengxuan

    2016-01-12

    The interactive effect between diabetes and impaired kidney function on cognitive impairment in older adults has not yet been reported. The aim of this study was to investigate the association of diabetes and impaired kidney function with cognitive impairment among Chinese older people living in a rural area. This cross-sectional study included 1,358 participants (age ≥60 years; 60.5% women) in the population-based Confucius Hometown Aging Project in Shandong, China. Data on demographics, lifestyle factors, health history, use of medications, global cognitive function, and kidney function were collected through structured interviews, clinical examinations, and blood tests. We defined diabetes as a fasting plasma glucose level ≥7.0 mmol/l or use of hypoglycemic agents, impaired kidney function as glomerular filtration rate estimated from cystatin C (eGFRcys) <60 ml/min/1.73 m(2). Cognitive impairment was defined using the education-based cut-off scores of Mini-Mental State Examination (MMSE). Data were analyzed using multiple general linear and logistic regression models. Cognitive impairment was defined in 197 (14.5%) persons. The multi-adjusted β coefficient of MMSE score associated with diabetes was -0.06 (95% confidence interval [CI], -0.16, 0.03); the corresponding figures associated with eGFRcys <60, 60-89.9, and ≥90 ml/min/1.73 m(2) were -0.15 (-0.28, -0.02), -0.01 (-0.10, 0.08), and 0 (reference) (Ptrend = 0.046), respectively. Diabetes and impaired kidney function showed an interactive effect on cognitive impairment ( interaction = 0.02). Compared with individuals having neither diabetes nor impaired kidney function, those with both conditions had a multi-adjusted odds ratio of 4.23 (95% CI, 2.10-8.49) for cognitive impairment. The relative excess risk due to interaction was 2.74. This study suggests that concurrent presence of diabetes and impaired kidney function is associated with a substantial likelihood for cognitive impairment in older adults.

  3. Arthritis and Risk of Cognitive and Functional Impairment in Older Mexican Adults

    PubMed Central

    Veeranki, Sreenivas P.; Downer, Brian; Jupiter, Daniel; Wong, Rebeca

    2016-01-01

    Objective This study investigated the risk of cognitive and functional impairment in older Mexicans diagnosed with arthritis. Participants included 2,681 Mexicans, aged ≥60 years, enrolled in the Mexican Health and Aging Study cohort. Method Participants were categorized into arthritis and no arthritis exposure groups. Primary outcome included participants categorized into “cognitively impaired” or “cognitively normal” groups. Secondary outcomes included participants categorized into Normal, Functionally Impaired only, Cognitively Impaired only, or Dementia (both cognitively and functionally impaired) groups. Multivariable logistic and multinomial regression models were used to assess the relationships. Results Overall, 16% or 7% were diagnosed with cognitive impairment or dementia. Compared with older Mexicans without arthritis, those who were diagnosed with arthritis had significantly increased risk of functional impairment (adjusted odds ratio [OR] 1.82, 95% confidence interval [CI] = [1.45, 2.29]), but not of dementia. Conclusion Arthritis is associated with increased risk of functional impairment, but not with dementia after 11 years in older Mexicans. PMID:26965081

  4. Risk factors for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory: a matched case-control study.

    PubMed

    Conway, Aaron; Page, Karen; Rolley, John; Fulbrook, Paul

    2013-08-01

    Side effects of the medications used for procedural sedation and analgesia in the cardiac catheterisation laboratory are known to cause impaired respiratory function. Impaired respiratory function poses considerable risk to patient safety as it can lead to inadequate oxygenation. Having knowledge about the conditions that predict impaired respiratory function prior to the procedure would enable nurses to identify at-risk patients and selectively implement intensive respiratory monitoring. This would reduce the possibility of inadequate oxygenation occurring. To identify pre-procedure risk factors for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory. Retrospective matched case-control. 21 cases of impaired respiratory function were identified and matched to 113 controls from a consecutive cohort of patients over 18 years of age. Conditional logistic regression was used to identify risk factors for impaired respiratory function. With each additional indicator of acute illness, case patients were nearly two times more likely than their controls to experience impaired respiratory function (OR 1.78; 95% CI 1.19-2.67; p = 0.005). Indicators of acute illness included emergency admission, being transferred from a critical care unit for the procedure or requiring respiratory or haemodynamic support in the lead up to the procedure. Several factors that predict the likelihood of impaired respiratory function were identified. The results from this study could be used to inform prospective studies investigating the effectiveness of interventions for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory.

  5. Telephone Crisis Support Workers' Intentions to Use Recommended Skills While Experiencing Functional Impairment.

    PubMed

    Kitchingman, Taneile A; Wilson, Coralie J; Woodward, Alan; Caputi, Peter; Wilson, Ian

    2018-05-01

    Empathic engagement with distressed others can lead to elevated symptoms of psychological distress and functional impairment, which preclude helping professionals' delivery of optimal patient care. Whether telephone crisis support workers are impacted in a similar way is not currently reported in the literature. This study examined the relationship between functional impairment and intentions to use recommended support skills in a representative national sample of 210 telephone crisis support workers. Participants completed an online survey including measures of functional impairment and intentions to use recommended telephone crisis support skills with callers reporting suicidal ideation, symptoms of depression, and anxiety. As a group, participants who experienced greater functional impairment during the past month reported significantly lower intentions to use recommended support skills with callers than those who reported lower functional impairment. Future research is needed to clarify the extent to which results generalize to telephone crisis support workers from other organizations. Results warrant further research to (a) identify determinants of telephone crisis support workers' functional impairment, and (b) for the deliberate management of telephone crisis support workers' functional impairment through developing and/or modifying existing service strategies to optimize workers' psychological well-being and delivery of support to callers.

  6. Evaluating the role of functional impairment in personality psychopathology.

    PubMed

    Boland, Jennifer K; Damnjanovic, Tatjana; Anderson, Jaime L

    2018-03-22

    DSM-5's Section III Alternative Model for Personality Disorder (AMPD) model states that an individual must show impairment in self and interpersonal functioning for PD diagnosis. The current study investigated dimensional personality trait associations with impairment, including differential patterns of impairment across specific PDs, and whether traits have improved our assessment of functional impairment in PDs. Two-hundred and seventy-seven participants were administered measures of Antisocial PD, Avoidant PD, Borderline PD, Narcissistic PD, Obsessive-Compulsive PD, and Schizotypal PD from the perspectives of Section II (PDQ-4) and Section III (PID-5) PD models, as well as measures of functional impairment in interpersonal and intrapersonal domains. Pearson correlations showed associations between ratings of impairment and most Section II and Section III PDs and trait facets, with the exception of narcissistic PD. Hierarchical regression analyses revealed that Section III PDs added predictive validity beyond Section II PDs in predicting impairment, except narcissistic PD. These findings provide support both for the impairment criterion in the AMPD and for the association between trait-based PDs and impairment, and suggest that this trait-based measurement adds uniquely to the understanding of functional impairment. Copyright © 2018. Published by Elsevier B.V.

  7. Treatment of Functional Impairment in Patients with Bipolar Disorder.

    PubMed

    Sanchez-Moreno, Jose; Martinez-Aran, Anabel; Vieta, Eduard

    2017-01-01

    Traditionally, functional impairment has received little attention in bipolar disorder, despite the fact that many patients experience significant impairments in daily life. In the last decade, research has changed its focus from clinical remission to functional recovery in bipolar patients as a priority. A literature review of this topic will allow us provide an overview of the relevance of functional impairment as well as the potential factors that can predict or contribute to low functioning in bipolar disorder (BD). Treatment approaches should consider not only euthymia as a goal but also cognitive and functional improvement of patients with such a complex disorder. Functional remediation and psychoeducation among psychological interventions may help to enhance functioning. The combination of cognitive enhancers and cognitive/functional remediation programs may help in improving cognitive and functional impairments. Early interventions are essential to prevent cognitive deficits and disability.

  8. Does visual impairment lead to additional disability in adults with intellectual disabilities?

    PubMed

    Evenhuis, H M; Sjoukes, L; Koot, H M; Kooijman, A C

    2009-01-01

    This study addresses the question to what extent visual impairment leads to additional disability in adults with intellectual disabilities (ID). In a multi-centre cross-sectional study of 269 adults with mild to profound ID, social and behavioural functioning was assessed with observant-based questionnaires, prior to expert assessment of visual function. With linear regression analysis the percentage of variance, explained by levels of visual function, was calculated for the total population and per ID level. A total of 107/269 participants were visually impaired or blind (WHO criteria). On top of the decrease by ID visual impairment significantly decreased daily living skills, communication & language, recognition/communication. Visual impairment did not cause more self-absorbed and withdrawn behaviour or anxiety. Peculiar looking habits correlated with visual impairment and not with ID. In the groups with moderate and severe ID this effect seems stronger than in the group with profound ID. Although ID alone impairs daily functioning, visual impairment diminishes the daily functioning even more. Timely detection and treatment or rehabilitation of visual impairment may positively influence daily functioning, language development, initiative and persistence, social skills, communication skills and insecure movement.

  9. Inappropriate Prescription and Renal Function Among Older Patients with Cognitive Impairment.

    PubMed

    Sönnerstam, Eva; Sjölander, Maria; Gustafsson, Maria

    2016-12-01

    Older people are more sensitive to drugs and adverse drug reactions than younger people because of age-related physiological changes such as impaired renal function. As people with dementia are particularly vulnerable to the effects of drugs, it is especially important to evaluate the dosages of renally cleared medications in this group. The aim of this study was to estimate the prevalence of impaired renal function and inappropriate prescriptions on the basis of renal function among older patients with dementia or cognitive impairment. The medical records of 428 patients aged ≥65 years who were admitted to two hospitals in northern Sweden were reviewed and renally cleared medications were identified. The Cockcroft-Gault equation was used to evaluate renal function. Doses were evaluated according to the Geriatric Dosage Handbook. Renal function was impaired (estimated glomerular filtration rate <60 ml/min) in 65.4 % of the study population. Impaired renal function was associated with increasing age. Among 547 prescriptions identified as renally cleared medications, 9.1 % were inappropriate based on the patient's renal function; 13.5 % of the 326 patients prescribed renally cleared medications had inappropriate prescriptions. Inappropriate prescriptions were more common among patients living in nursing homes. Impaired renal function is common and inappropriate prescription is prevalent among old people with cognitive impairment in northern Sweden. Continuous consideration of renal function is important when prescribing medications to this group.

  10. Validation of DSM-5 age-of-onset criterion of attention deficit/hyperactivity disorder (ADHD) in adults: Comparison of life quality, functional impairment, and family function.

    PubMed

    Lin, Yu-Ju; Lo, Kuan-Wu; Yang, Li-Kuang; Gau, Susan Shur-Fen

    2015-12-01

    The newly published Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) elevates the threshold of the ADHD age-of-onset criterion from 7 to 12 years. This study evaluated the quality of life and functional impairment of adults with ADHD who had symptoms onset by or after 7 years and examined the mediation effect of family function and anxiety/depression symptoms between ADHD diagnosis and quality of life and functional impairment. We assessed 189 adults with ADHD and 153 non-ADHD controls by psychiatric interview and self-administered reports on the Adult ADHD Quality of Life Scale, Weiss Functional Impairment Rating Scale, Family APGAR, and Adult Self Report Inventory-4. The ADHD group was divided into early-onset ADHD (onset <7 years, n=147) and late-onset ADHD (onset between 7 and 12 years, n=42). The mediation analysis was conducted to verify the mediating factors from ADHD to functional impairment and quality of life. The late-onset ADHD had more severe functional impairment at work and poorer family support than early-onset ADHD while they had comparable impairment at other domains. Less perceived family support and current anxiety/depressive symptoms partially mediated the link between ADHD diagnosis and quality of life/functional impairment both in early- and late-onset ADHD. Our data support decreased quality of life and increased functional impairment in adult ADHD, regardless of age of onset, and these adverse outcomes may be mediated by family support and anxiety/depression at adulthood. Our findings also imply that the new DSM-5 ADHD criteria do not over-include individuals without impairment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Quantifying the Clinical Significance of Cannabis Withdrawal

    PubMed Central

    Allsop, David J.; Copeland, Jan; Norberg, Melissa M.; Fu, Shanlin; Molnar, Anna; Lewis, John; Budney, Alan J.

    2012-01-01

    Background and Aims Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt. Methods and Results A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001). Conclusions Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes. PMID:23049760

  12. Levomilnacipran Extended-Release Treatment in Patients With Major Depressive Disorder: Improvements in Functional Impairment Categories

    PubMed Central

    Gommoll, Carl P.; Chen, Changzheng; Greenberg, William M.; Ruth, Adam

    2015-01-01

    Objective: In this post hoc analysis, improvement in functional impairment in patients with major depressive disorder (MDD) treated with levomilnacipran extended release (ER) was evaluated by assessing shifts from more severe to less severe functional impairment categories on individual Sheehan Disability Scale (SDS) subscales. Method: SDS data were pooled from 5 phase II/III studies conducted between December 2006 and March 2012 of levomilnacipran ER versus placebo in adult patients with MDD (DSM-IV-TR criteria). Proportions of patients shifting from moderate-extreme baseline impairment (score ≥ 4) to mild-no impairment (score ≤ 3) at end of treatment were assessed for each SDS subscale. Proportions of patients shifting from marked-extreme (score ≥ 7) baseline impairment to moderate-no (score ≤ 6) or mild-no impairment (score ≤ 3) at end of treatment, and shifts in which patients worsened from moderate-no to marked-extreme impairment, were also evaluated. Results: A significantly higher proportion of patients treated with levomilnacipran ER than placebo-treated patients improved from more severe categories of functional impairment at baseline to less severe impairment categories across all SDS subscales: work/school, social life, and family life/home responsibilities (P < .01). Depending on the SDS subscale, 48%–55% of levomilnacipran ER–treated patients with moderate-extreme impairment at baseline improved to mild or no impairment, compared with no more than 40% of placebo patients on any subscale. Almost half (42%–47%) of levomilnacipran ER–treated patients versus only about one-third (29%–34%) of placebo patients improved from marked-extreme to mild or no impairment across functional domains. Conclusions: These results suggest that functional improvement was observed across the SDS functional domains. To our knowledge, this is the first such categorical analysis of functional improvement, as measured by the SDS, for an antidepressant. Trial Registration: ClinicalTrials.gov identifiers: NCT00969709, NCT01377194, NCT00969150, and NCT01034462 and EudraCT identifier: 2006–002404-34 PMID:26644957

  13. Functional impairment and mental health functioning among Vietnamese children.

    PubMed

    Dang, Hoang-Minh; Weiss, Bahr; Trung, Lam T

    2016-01-01

    Functional impairment is a key indicator of need for mental health services among children and adolescents, often a stronger predictor of service usage than mental health symptoms themselves. Functional impairment may be of particular importance in low- and middle-income countries (LMIC) because of its potential to focus policy on treatment of child mental health problems which is generally given low priority in LMIC. However, few studies have assessed functional impairment in LMIC. The present study assessed rates of functional impairment among children in Vietnam, as a case example of an LMIC, as well as effects of other risk/protective factors of particular relevance to LMIC (e.g., whether the family lived in an urban or rural area; family structure variables such as grandparents living with the family). 1314 parents of children 6-16 years old from 10 Vietnamese provinces were interviewed. The overall rate of functional impairment among Vietnamese children was 20 %, similar to rates in high-income countries such as Germany and the United States, suggesting that LMIC status may not be associated with dramatic increases in functional impairment in children. Functional impairment was significantly greater among mental health cases than non-cases, with increases of over 550 % associated with mental health caseness. A number of other risk factors (e.g., marital status) had smaller but significant effects. Mental health problems are a major but not the sole contributor to functional impairment among Vietnamese children. The pragmatic significance of this research lies in its potential to affect public awareness and policy related to child mental health in LMIC.

  14. Functional impairment and mental health functioning among Vietnamese children

    PubMed Central

    Dang, Hoang-Minh; Weiss, Bahr; Trung, Lam T.

    2015-01-01

    Purpose Functional impairment is a key indicator of need for mental health services among children and adolescents, often a stronger predictor of service usage than mental health symptoms themselves. Functional impairment may be of particular importance in low and middle income countries (LMIC) because of its potential to focus policy on treatment of child mental health problems which is generally given low priority in LMIC. However, few studies have assessed functional impairment in LMIC. The present study assessed rates of functional impairment among children in Vietnam, as a case example of an LMIC, as well as effects of other risk/protective factors of particular relevance to LMIC (e.g., whether the family lived in an urban or rural area; family structure variables such as grandparents living with the family). Methods 1,314 parents of children 6–16 years old from 10 Vietnamese provinces were interviewed. Results The overall rate of functional impairment among Vietnamese children was 20%, similar to rates in high income countries such as Germany and the United States, suggesting that LMIC status may not be associated with dramatic increases in functional impairment in children. Functional impairment was significantly greater among mental health cases than non-cases, with increases of over 550% associated with mental health caseness. A number of other risk factors (e.g., marital status) had smaller but significant effects. Conclusions Mental health problems are a major but not the sole contributor to functional impairment among Vietnamese children. The pragmatic significance of this research lies in its potential to affect public awareness and policy related to child mental health in LMIC. PMID:26315942

  15. Functional Impairment and Hospital Readmission in Medicare Seniors

    PubMed Central

    Greysen, S. Ryan; Cenzer, Irena Stijacic; Auerbach, Andrew D.; Covinsky, Kenneth E.

    2015-01-01

    Importance Medicare currently penalizes hospitals for high rates of readmission for seniors but does not account for common age-related syndromes such as functional impairment. Objectives Given the high prevalence of functional impairments in community-dwelling seniors, we assessed effects of functional impairment on Medicare hospital readmissions. Study Design, Participants, and Setting We created a nationally-representative cohort of 7,854 community-dwelling seniors in the Health and Retirement Study (HRS) with 22,289 Medicare hospitalizations from 2000–2010. Main Outcome and Measurements Outcome was 30-day readmission, assessed by Medicare claims. Main predictor was functional impairment determined from HRS interview preceding hospitalization, stratified into 5 levels: no functional impairments, difficulty with ≥1 instrumental activity of daily living (IADL), difficulty with ≥1 activity of daily living (ADL), dependency (need for help) in 1–2 ADLs, and dependency in ≥3 ADLs. Adjustment variables included age, race, gender, income, and net worth and comorbid conditions (Elixhauser score from Medicare claims), and prior admission. We performed multivariable logistic regression adjusted for clustering at patient level to characterize the association of functional impairments and readmission. Results Mean age 79 (±8; 65–105), 58% female, 85% White, 90% reported ≥3 comorbidities, 86% had ≥1 hospitalization in previous year. Overall, 48% had some level of functional impairment prior to admission and 15% experienced a 30-day readmission. We found a progressive increase in adjusted risk of readmission as the degree of functional impairment increased: 13.5% with no functional impairment, 14.3% with ≥ 1 IADL difficulty (OR 1.06; 95% CI 0.94–1.20), 14.4% with ≥1 ADL difficulty (OR 1.08; 0.96–1.21), 16.5% with dependency in 1–2 ADLs (OR 1.26; 1.11–1.44), and 18.2% with dependency in ≥3 ADLs (1.42; 1.20–1.69). Sub-analysis restricted to patients admitted with conditions targeted by Medicare (heart failure, myocardial infarction, and pneumonia) revealed a parallel trend with larger effects for the most-impaired (16.9% readmission rate for no impairment vs. 25.7% for dependency in ≥3 ADLs, OR 1.70; 1.04–2.78). Conclusions Functional impairment is associated with increased risk of 30-day, all-cause hospital readmission in Medicare seniors, especially those admitted for heart failure, myocardial infarction or pneumonia. Functional impairment on admission may be an overlooked but highly suitable target for interventions to reduce Medicare hospital readmissions. Relevance Functional impairment may be an important but under-addressed factor in preventing readmissions for Medicare seniors. PMID:25642907

  16. The Reliability of the CVI Range: A Functional Vision Assessment for Children with Cortical Visual Impairment

    ERIC Educational Resources Information Center

    Newcomb, Sandra

    2010-01-01

    Children who are identified as visually impaired frequently have a functional vision assessment as one way to determine how their visual impairment affects their educational performance. The CVI Range is a functional vision assessment for children with cortical visual impairment. The purpose of the study presented here was to examine the…

  17. Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function.

    PubMed

    Li, Yan; Wang, Xiaomin; O'Mara, Edward; Dimopoulos, Meletios A; Sonneveld, Pieter; Weisel, Katja C; Matous, Jeffrey; Siegel, David S; Shah, Jatin J; Kueenburg, Elisabeth; Sternas, Lars; Cavanaugh, Chloe; Zaki, Mohamed; Palmisano, Maria; Zhou, Simon

    2017-01-01

    Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM) in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK) model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide concentration data collected on dialysis days from both the withdrawal (arterial) side and from the returning (venous) side of the dialyzer, from rrMM patients with severely impaired renal function requiring dialysis, were used to assess the extent to which dialysis contributes to the removal of pomalidomide from blood circulation. PPK analyses demonstrated that moderate to severe renal impairment not requiring dialysis has no influence on pomalidomide clearance or plasma exposure, as compared to those patients with normal renal function, while pomalidomide exposure increased approximately 35% in patients with severe renal impairment requiring dialysis on nondialysis days. In addition, dialysis increased total body pomalidomide clearance from 5 L/h to 12 L/h, indicating that dialysis will significantly remove pomalidomide from the blood circulation. Thus, pomalidomide should be administered post-dialysis on the days of dialysis.

  18. The Association Between Higher Social Support and Lower Depressive Symptoms Among Aging Services Clients is Attenuated at Higher Levels of Functional Impairment

    PubMed Central

    Van Orden, Kimberly A.; Yan, Li; Podgorski, Carol A.; Conwell, Yeates

    2015-01-01

    Objective Adults seeking services from the Aging Services Provider Network (ASPN) are at risk for depression. ASPN clients also have high prevalence of both functional impairments and social morbidities. Study of the relationships between these factors may inform the development of interventions for depression in this service setting. Methods We interviewed 373 older adults accessing ASPN services and assessed depression symptom severity, functional impairment (instrumental activities of daily living and activities of daily living), and social support. Results Lower social support and greater functional impairment were associated with greater depressive symptoms. At a high level of functional impairment, the inverse associations between indices of social support and depressive symptoms were attenuated. Conclusions Results suggest that older adults with more severe functional impairment may benefit somewhat less from increased social support with respect to depression symptom severity. PMID:25663607

  19. Consumption of meat in relation to physical functioning in the Seniors-ENRICA cohort.

    PubMed

    Struijk, Ellen A; Banegas, José R; Rodríguez-Artalejo, Fernando; Lopez-Garcia, Esther

    2018-04-05

    Meat is an important source of high-quality protein and vitamin B but also has a relatively high content of saturated and trans fatty acids. Although protein and vitamin B intake seems to protect people from functional limitations, little is known about the effect of habitual meat consumption on physical function. The objective of this study was to examine the prospective association between the intake of meat (processed meat, red meat, and poultry) and physical function impairment in older adults. Data were collected for 2982 participants in the Seniors-ENRICA cohort, who were aged ≥60 years and free of physical function impairment. In 2008-2010, their habitual diet was assessed through a validated computer-assisted face-to-face diet history. Study participants were followed up through 2015 to assess self-reported incident impairment in agility, mobility, and performance-based lower-extremity function. Over a median follow-up of 5.2 years, we identified 625 participants with impaired agility, 455 with impaired mobility, and 446 with impaired lower-extremity function. After adjustment for potential confounders, processed meat intake was associated with a higher risk of impaired agility (hazard ratio [HR] for highest vs. lowest tertile: 1.33; 95% confidence interval [CI]: 1.08-1.64; p trend = 0.01) and of impaired lower-extremity function (HR for highest vs. lowest tertile: 1.31; 95% CI: 1.02-1.68; p trend = 0.04). No significant associations were found for red meat and poultry. Replacing one serving per day of processed meat with one serving per day of red meat, poultry, or with other important protein sources (fish, legumes, dairy, and nuts) was associated with lower risk of impaired agility and lower-extremity function. A higher consumption of processed meat was associated with a higher risk of impairment in agility and lower-extremity function. Replacing processed meat by other protein sources may slow the decline in physical functioning in older adults.

  20. Functional Literacy for Students with Visual Impairments and Significant Cognitive Disabilities: The Perspective of Teachers of Students with Visual Impairments

    ERIC Educational Resources Information Center

    Zebehazy, Kim T.

    2014-01-01

    This study reports opinions and practices of teachers of students with visual impairments (TSVIs) in 34 states regarding functional literacy for students with visual impairments (VIs) and significant cognitive disabilities (SCDs). The survey asked TSVIs to select a definition of functional literacy, indicate agreement with a series of literacy…

  1. Prevalence and correlates of hearing and visual impairments in European nursing homes: results from the SHELTER study.

    PubMed

    Yamada, Yukari; Vlachova, Martina; Richter, Tomas; Finne-Soveri, Harriet; Gindin, Jacob; van der Roest, Henriëtte; Denkinger, Michael D; Bernabei, Roberto; Onder, Graziano; Topinkova, Eva

    2014-10-01

    Visual and hearing impairments are known to be related to functional disability, cognitive impairment, and depression in community-dwelling older people. The aim of this study was to examine the prevalence of sensory impairment in nursing home residents, and whether sensory impairment is related to other common clinical problems in nursing homes, mediated by functional disability, cognitive impairment, and depressive symptoms. Cross-sectional data of 4007 nursing home residents in 59 facilities in 8 countries from the SHELTER study were analyzed. Visual and hearing impairments were assessed by trained staff using the interRAI instrument for Long-Term Care Facilities. Generalized linear mixed models adjusted for functional disability, cognitive impairment, and depressive symptoms were used to analyze associations of sensory impairments with prevalence of clinical problems, including behavioral symptoms, incontinence, fatigue, falls, problems with balance, sleep, nutrition, and communication. Of the participants, 32% had vision or hearing impairment (single impairment) and another 32% had both vision and hearing impairments (dual impairment). Residents with single impairment had significantly higher rates of communication problems, fatigue, balance problems, and sleep problems, as compared with residents without any sensory impairment. Those with dual impairment had significantly higher rates of all clinical problems assessed in this study as compared with those without sensory impairment. For each clinical problem, the magnitude of the odds ratio for specific clinical problems was higher for dual impairment than for single impairment. Visual and hearing impairments are associated with higher rates of common clinical problems among nursing home residents, independent of functional disability, cognitive impairment, and depressive symptoms. Copyright © 2014 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  2. Cognitive Impairment Precedes and Predicts Functional Impairment in Mild Alzheimer's Disease.

    PubMed

    Liu-Seifert, Hong; Siemers, Eric; Price, Karen; Han, Baoguang; Selzler, Katherine J; Henley, David; Sundell, Karen; Aisen, Paul; Cummings, Jeffrey; Raskin, Joel; Mohs, Richard

    2015-01-01

    The temporal relationship of cognitive deficit and functional impairment in Alzheimer's disease (AD) is not well characterized. Recent analyses suggest cognitive decline predicts subsequent functional decline throughout AD progression. To better understand the relationship between cognitive and functional decline in mild AD using autoregressive cross-lagged (ARCL) panel analyses in several clinical trials. Data included placebo patients with mild AD pooled from two multicenter, double-blind, Phase 3 solanezumab (EXPEDITION/2) or semagacestat (IDENTITY/2) studies, and from AD patients participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cognitive and functional outcomes were assessed using AD Assessment Scale-Cognitive subscale (ADAS-Cog), AD Cooperative Study-Activities of Daily Living instrumental subscale (ADCS-iADL), or Functional Activities Questionnaire (FAQ), respectively. ARCL panel analyses evaluated relationships between cognitive and functional impairment over time. In EXPEDITION, ARCL panel analyses demonstrated cognitive scores significantly predicted future functional impairment at 5 of 6 time points, while functional scores predicted subsequent cognitive scores in only 1 of 6 time points. Data from IDENTITY and ADNI programs yielded consistent results whereby cognition predicted subsequent function, but not vice-versa. Analyses from three databases indicated cognitive decline precedes and predicts subsequent functional decline in mild AD dementia, consistent with previously proposed hypotheses, and corroborate recent publications using similar methodologies. Cognitive impairment may be used as a predictor of future functional impairment in mild AD dementia and can be considered a critical target for prevention strategies to limit future functional decline in the dementia process.

  3. Cognitive and motor function of neurologically impaired extremely low birth weight children.

    PubMed

    Bernardo, Janine; Friedman, Harriet; Minich, Nori; Taylor, H Gerry; Wilson-Costello, Deanne; Hack, Maureen

    2015-01-01

    Rates of neurological impairment among extremely low birth weight children (ELBW [<1 kg]) have decreased since 2000; however, their functioning is unexamined. To compare motor and cognitive functioning of ELBW children with neurological impairment, including cerebral palsy and severe hypotonia/hypertonia, between two periods: 1990 to 1999 (n=83) and 2000 to 2005 (n=34). Measures of function at 20 months corrected age included the Mental and Psychomotor Developmental Indexes of the Bayley Scales of Infant Development and the Gross Motor Functional Classification System as primary outcomes and individual motor function items as secondary outcomes. Analysis failed to reveal significant differences for the primary outcomes, although during 2000 to 2005, sitting significantly improved in children with neurological impairment (P=0.003). Decreases in rates of neurological impairment among ELBW children have been accompanied by a suggestion of improved motor function, although cognitive function has not changed.

  4. Impact of Sensory Impairments on Functional Disability in Adults With Arthritis

    PubMed Central

    Fisher, Diana E.; Ward, Michael M.; Hoffman, Howard J.; Li, Chuan-Ming; Cotch, Mary Frances

    2015-01-01

    Introduction Mobility is reduced in people with sensory impairments and those with arthritis. The joint impact of these conditions may be underappreciated. This study examines the associations between impairments in vision, hearing, and balance and functional ability in adults with versus without arthritis. Methods Using National Health and Nutrition Examination Survey data from 1999–2004, arthritis status, functional ability, and sensory impairments (vision, hearing, and balance) were assessed from self-reported responses by 6,654 individuals aged ≥50 years (mean age, 63.4 years; 46.3% male). Multivariable regression analyses, conducted in 2014, assessed the associations between sensory impairment and arthritis on functional ability and mobility. Results Among study participants, 41.8% reported having arthritis; of these, 27.1%, 44.9%, and 35.1% reported impaired vision, hearing, or balance, respectively. Having multiple sensory impairments was significantly associated with reduced functional ability in people with arthritis; individuals with three sensory impairments reported the highest levels of disability for all functional domains (compared with no impairment; lower extremity mobility, 80.2% vs 39.1%; general physical activities, 94.7% vs 75.9%; activities of daily living, 69.7% vs 27.2%; instrumental activities of daily living, 77.2% vs 37.4%; leisure and social activities, 66.3% vs 30.6%; impaired gait speed, 48.1% vs 16.3%; all p<0.001). Importantly, visual deficits, in combination with arthritis, had the greatest impact on mobility, with odds of impaired mobility at least twice as high as for individuals without arthritis. Conclusions Addressing sensory deficits, especially difficulties with vision, may improve functional ability, which may be particularly helpful for adults with arthritis. PMID:26410186

  5. Progressively Disrupted Brain Functional Connectivity Network in Subcortical Ischemic Vascular Cognitive Impairment Patients.

    PubMed

    Sang, Linqiong; Chen, Lin; Wang, Li; Zhang, Jingna; Zhang, Ye; Li, Pengyue; Li, Chuanming; Qiu, Mingguo

    2018-01-01

    Cognitive impairment caused by subcortical ischemic vascular disease (SIVD) has been elucidated by many neuroimaging studies. However, little is known regarding the changes in brain functional connectivity networks in relation to the severity of cognitive impairment in SIVD. In the present study, 20 subcortical ischemic vascular cognitive impairment no dementia patients (SIVCIND) and 20 dementia patients (SIVaD) were enrolled; additionally, 19 normal controls were recruited. Each participant underwent a resting-state functional MRI scan. Whole-brain functional networks were analyzed with graph theory and network-based statistics (NBS) to study the functional organization of networks and find alterations in functional connectivity among brain regions. After adjustments for age, gender, and duration of formal education, there were significant group differences for two network functional organization indices, global efficiency and local efficiency, which decreased (NC > SIVCIND > SIVaD) as cognitive impairment worsened. Between-group differences in functional connectivity (NBS corrected, p  < 0.01) mainly involved the orbitofrontal, parietal, and temporal cortices, as well as the basal ganglia. The brain connectivity network was progressively disrupted as cognitive impairment worsened, with an increased number of decreased connections between brain regions. We also observed more reductions in nodal efficiency in the prefrontal and temporal cortices for SIVaD than for SIVCIND. These findings indicated a progressively disrupted pattern of the brain functional connectivity network with increased cognitive impairment and showed promise for the development of reliable biomarkers of network metric changes related to cognitive impairment caused by SIVD.

  6. The aftermath of terrorism: posttraumatic stress and functional impairment after the 2011 Oslo bombing

    PubMed Central

    Solberg, Øivind; Blix, Ines; Heir, Trond

    2015-01-01

    Objective: In the present study we wanted to investigate the link between exposure, posttraumatic stress symptomatology, and functional impairment in the aftermath of terrorism. Method: Posttraumatic stress symptomatology and functional impairment related to the Oslo bombing 22nd of July, 2011, in directly and indirectly exposed individuals (N = 1927) were assessed together with demographics, exposure, peri-traumatic reactions, and event centrality approximately 1 year after the attack. Results: Directly and indirectly exposed individuals qualifying for posttraumatic stress disorder (PTSD) reported similar peri-traumatic reactions, event centrality, and functional impairment. However, clusters within the PTSD symptomatology were differentially associated with impairment as a function of their exposure. In the directly exposed group, all clusters within the PTSD symptomatology were associated with impairment in function, while only emotional numbing was associated with impairment within the indirectly exposed group. Conclusion: Considering that terror attacks frequently involve directly exposed individuals and a larger population of indirectly exposed individuals, this finding is of importance, especially in the design of intervention programs and the development of treatment policies. PMID:26300833

  7. Functional Impairment: An Unmeasured Marker of Medicare Costs for Postacute Care of Older Adults.

    PubMed

    Greysen, S Ryan; Stijacic Cenzer, Irena; Boscardin, W John; Covinsky, Kenneth E

    2017-09-01

    To assess the effects of preadmission functional impairment on Medicare costs of postacute care up to 365 days after hospital discharge. Longitudinal cohort study. Health and Retirement Study (HRS). Nationally representative sample of 16,673 Medicare hospitalizations of 8,559 community-dwelling older adults from 2000 to 2012. The main outcome was total Medicare costs in the year after hospital discharge, assessed according to Medicare claims data. The main predictor was functional impairment (level of difficulty or dependence in activities of daily living (ADLs)), determined from HRS interview preceding hospitalization. Multivariable linear regression was performed, adjusted for age, race, sex, income, net worth, and comorbidities, with clustering at the individual level to characterize the association between functional impairment and costs of postacute care. Unadjusted mean Medicare costs for 1 year after discharge increased with severity of impairment in a dose-response fashion (P < .001 for trend); 68% had no functional impairment ($25,931), 17% had difficulty with one ADL ($32,501), 7% had dependency in one ADL ($39,928), and 8% had dependency in two or more ADLs ($45,895). The most severely impaired participants cost 77% more than those with no impairment; adjusted analyses showed attenuated effect size (33% more) but no change in trend. Considering costs attributable to comorbidities, only three conditions were more expensive than severe functional impairment (lymphoma, metastatic cancer, paralysis). Functional impairment is associated with greater Medicare costs for postacute care and may be an unmeasured but important marker of long-term costs that cuts across conditions. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  8. Ten-Year Review of Rating Scales, VII: Scales Assessing Functional Impairment

    ERIC Educational Resources Information Center

    Winters, Nancy C.; Collett, Brent R.; Myers, Kathleen M.

    2005-01-01

    Objective: This is the seventh in a series of 10-year reviews of rating scales. Here the authors present scales measuring functional impairment, a sequela of mental illness. The measurement of functional impairment has assumed importance with the recognition that symptom resolution does not necessarily correlate with functional improvement.…

  9. Dissociative symptoms mediate the relation between PTSD symptoms and functional impairment in a sample of military members, veterans, and first responders with PTSD.

    PubMed

    Boyd, Jenna E; Protopopescu, Alina; O'Connor, Charlene; Neufeld, Richard W J; Jetly, Rakesh; Hood, Heather K; Lanius, Ruth A; McKinnon, Margaret C

    2018-01-01

    Background : Posttraumatic Stress Disorder (PTSD) is associated with significant functional impairment in important areas, including interpersonal relationships and occupational or educational roles. Preliminary evidence suggests that the dissociative subtype of PTSD (PTSD+DS), characterized by marked symptoms of depersonalization and derealization, is associated with increased functional impairment and disease severity, including among military members and veterans diagnosed with PTSD. Similarly, first responders (e.g. police, fire, paramedics) have also been found to experience dissociative symptoms. Despite these findings, little work has investigated whether dissociative symptoms are related to heightened functional impairment among these populations. Objective : We examined the relation between functional impairment and symptom level variables, including dissociative symptoms of depersonalization and derealization among military members, veterans, and first responders with probable PTSD. We further investigated the hypothesis that dissociative symptoms mediate the relation between PTSD symptomatology and functional impairment. Method : Eighty-one medical charts of inpatients at a residential PTSD treatment programme were accessed via retrospective review. Sixty-two were included in the present analyses. Comparison of means on symptom measures between first responders and military members/veterans were conducted, followed by correlational and mediation analyses. Results : Compared with first responders, military members and veterans showed higher levels of derealization, functional impairment, alexithymia, anxiety, and depression. Within the total sample, dissociative symptoms emerged as the strongest correlate of functional impairment and, among the dissociative symptom clusters, derealization symptoms demonstrated the strongest relation with impairment. Mediation analyses revealed that total dissociative symptoms and derealization symptoms significantly mediated the relation between PTSD symptoms and functional impairment. Conclusions : These findings highlight the importance of assessing and treating dissociative symptoms, consistent with the dissociative subtype of PTSD, among military members, veterans, and first responders with PTSD. Successful recovery on a functional and symptomatic level may necessitate treatment of dissociative symptoms, particularly derealization.

  10. Dissociative symptoms mediate the relation between PTSD symptoms and functional impairment in a sample of military members, veterans, and first responders with PTSD

    PubMed Central

    Protopopescu, Alina; O’Connor, Charlene; Neufeld, Richard W. J.; Jetly, Rakesh; Hood, Heather K.; Lanius, Ruth A.; McKinnon, Margaret C.

    2018-01-01

    ABSTRACT Background: Posttraumatic Stress Disorder (PTSD) is associated with significant functional impairment in important areas, including interpersonal relationships and occupational or educational roles. Preliminary evidence suggests that the dissociative subtype of PTSD (PTSD+DS), characterized by marked symptoms of depersonalization and derealization, is associated with increased functional impairment and disease severity, including among military members and veterans diagnosed with PTSD. Similarly, first responders (e.g. police, fire, paramedics) have also been found to experience dissociative symptoms. Despite these findings, little work has investigated whether dissociative symptoms are related to heightened functional impairment among these populations. Objective: We examined the relation between functional impairment and symptom level variables, including dissociative symptoms of depersonalization and derealization among military members, veterans, and first responders with probable PTSD. We further investigated the hypothesis that dissociative symptoms mediate the relation between PTSD symptomatology and functional impairment. Method: Eighty-one medical charts of inpatients at a residential PTSD treatment programme were accessed via retrospective review. Sixty-two were included in the present analyses. Comparison of means on symptom measures between first responders and military members/veterans were conducted, followed by correlational and mediation analyses. Results: Compared with first responders, military members and veterans showed higher levels of derealization, functional impairment, alexithymia, anxiety, and depression. Within the total sample, dissociative symptoms emerged as the strongest correlate of functional impairment and, among the dissociative symptom clusters, derealization symptoms demonstrated the strongest relation with impairment. Mediation analyses revealed that total dissociative symptoms and derealization symptoms significantly mediated the relation between PTSD symptoms and functional impairment. Conclusions: These findings highlight the importance of assessing and treating dissociative symptoms, consistent with the dissociative subtype of PTSD, among military members, veterans, and first responders with PTSD. Successful recovery on a functional and symptomatic level may necessitate treatment of dissociative symptoms, particularly derealization. PMID:29805778

  11. Evaluation of Parkinson Disease Risk Variants as Expression-QTLs

    PubMed Central

    Latourelle, Jeanne C.; Dumitriu, Alexandra; Hadzi, Tiffany C.; Beach, Thomas G.; Myers, Richard H.

    2012-01-01

    The recent Parkinson Disease GWAS Consortium meta-analysis and replication study reports association at several previously confirmed risk loci SNCA, MAPT, GAK/DGKQ, and HLA and identified a novel risk locus at RIT2. To further explore functional consequences of these associations, we investigated modification of gene expression in prefrontal cortex brain samples of pathologically confirmed PD cases (N = 26) and controls (N = 24) by 67 associated SNPs in these 5 loci. Association between the eSNPs and expression was evaluated using a 2-degrees of freedom test of both association and difference in association between cases and controls, adjusted for relevant covariates. SNPs at each of the 5 loci were tested for cis-acting effects on all probes within 250 kb of each locus. Trans-effects of the SNPs on the 39,122 probes passing all QC on the microarray were also examined. From the analysis of cis-acting SNP effects, several SNPs in the MAPT region show significant association to multiple nearby probes, including two strongly correlated probes targeting the gene LOC644246 and the duplicated genes LRRC37A and LRRC37A2, and a third uncorrelated probe targeting the gene DCAKD. Significant cis-associations were also observed between SNPs and two probes targeting genes in the HLA region on chromosome 6. Expanding the association study to examine trans effects revealed an additional 23 SNP-probe associations reaching statistical significance (p<2.8×10−8) including SNPs from the SNCA, MAPT and RIT2 regions. These findings provide additional context for the interpretation of PD associated SNPs identified in recent GWAS as well as potential insight into the mechanisms underlying the observed SNP associations. PMID:23071545

  12. Curcumin derivatives as metal-chelating agents with potential multifunctional activity for pharmaceutical applications.

    PubMed

    Ferrari, Erika; Benassi, Rois; Sacchi, Stefania; Pignedoli, Francesca; Asti, Mattia; Saladini, Monica

    2014-10-01

    Curcuminoids represent new perspectives for the development of novel therapeutics for Alzheimer's disease (AD), one probable mechanism of action is related to their metal complexing ability. In this work we examined the metal complexing ability of substituted curcuminoids to propose new chelating molecules with biological properties comparable with curcumin but with improved stability as new potential AD therapeutic agents. The K2T derivatives originate from the insertion of a -CH2COOC(CH3)3 group on the central atom of the diketonic moiety of curcumin. They retain the diketo-ketoenol tautomerism which is solvent dependent. In aqueous solution the prevalent form is the diketo one but the addition of metal ion (Ga(3+), Cu(2+)) causes the dissociation of the enolic proton creating chelate complexes and shifting the tautomeric equilibrium towards the keto-enol form. The formation of metal complexes is followed by both NMR and UV-vis spectroscopy. The density functional theory (DFT) calculations on K2T21 complexes with Ga(3+) and Cu(2+) are performed and compared with those on curcumin complexes. [Ga(K2T21)2(H2O)2](+) was found more stable than curcumin one. Good agreement is detected between calculated and experimental (1)H and (13)C NMR data. The calculated OH bond dissociation energy (BDE) and the OH proton dissociation enthalpy (PDE), allowed to predict the radical scavenging ability of the metal ion complexed with K2T21, while the calculated electronic affinity (EA) and ionization potential (IP) represent yardsticks of antioxidant properties. Eventually theoretical calculations suggest that the proton-transfer-associated superoxide-scavenging activity is enhanced after binding metal ions, and that Ga(3+) complexes display possible superoxide dismutase (SOD)-like activity. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Visual impairment at baseline is associated with future poor physical functioning among middle-aged women: The Study of Women's Health Across the Nation, Michigan Site.

    PubMed

    Chandrasekaran, Navasuja; Harlow, Sioban; Moroi, Sayoko; Musch, David; Peng, Qing; Karvonen-Gutierrez, Carrie

    2017-02-01

    Emerging evidence suggests that the prevalence rates of poor functioning and of disability are increasing among middle-aged individuals. Visual impairment is associated with poor functioning among older adults but little is known about the impact of vision on functioning during midlife. The objective of this study was to assess the impact of visual impairment on future physical functioning among middle-aged women. In this longitudinal study, the sample consisted of 483 women aged 42 to 56 years, from the Michigan site of the Study of Women's Health Across the Nation. At baseline, distance and near vision were measured using a Titmus vision screener. Visual impairment was defined as visual acuity worse than 20/40. Physical functioning was measured up to 10 years later using performance-based measures, including a 40-foot timed walk, timed stair climb and forward reach. Women with impaired distance vision at baseline had 2.81 centimeters less forward reach distance (95% confidence interval (CI): -4.19, -1.42) and 4.26s longer stair climb time (95% CI: 2.73, 5.79) at follow-up than women without impaired distance vision. Women with impaired near vision also had less forward reach distance (2.26 centimeters, 95% CI: -3.30, -1.21) than those without impaired near vision. Among middle-aged women, visual impairment is a marker of poor physical functioning. Routine eye testing and vision correction may help improve physical functioning among midlife individuals. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Visual Impairment at Baseline is Associated with Future Poor Physical Functioning Among Middle-Aged Women: The Study of Women's Health Across the Nation, Michigan site

    PubMed Central

    Chandrasekaran, Navasuja; Harlow, Sioban; Moroi, Sayoko; Musch, David; Peng, Qing; Karvonen-Gutierrez, Carrie

    2016-01-01

    Objectives Emerging evidence suggests that the prevalence rates of poor functioning and of disability are increasing among middle-aged individuals. Visual impairment is associated with poor functioning among older adults but little is known about the impact of vision on functioning during midlife. The objective of this study was to assess the impact of visual impairment on future physical functioning among middle-aged women. Study design In this longitudinal study, the sample consisted of 483 women aged 42 to 56 years, from the Michigan site of the Study of Women's Health Across the Nation. Main Outcome Measures At baseline, distance and near vision were measured using a Titmus vision screener. Visual impairment was defined as visual acuity worse than 20/40. Physical functioning was measured up to 10 years later using performance-based measures, including a 40-foot timed walk, timed stair climb and forward reach. Results Women with impaired distance vision at baseline had 2.81 centimeters less forward reach distance (95% confidence interval (CI): −4.19,−1.42) and 4.26 seconds longer stair climb time (95% CI: 2.73, 5.79) at follow-up than women without impaired distance vision. Women with impaired near vision also had less forward reach distance (2.26 centimeters, 95% CI: −3.30,−1.21) than those without impaired near vision. Conclusion Among middle-aged women, visual impairment is a marker of poor physical functioning. Routine eye testing and vision correction may help improve physical functioning among midlife individuals. PMID:28041592

  15. Functional impairment and hospital readmission in Medicare seniors.

    PubMed

    Greysen, S Ryan; Stijacic Cenzer, Irena; Auerbach, Andrew D; Covinsky, Kenneth E

    2015-04-01

    Medicare currently penalizes hospitals for high readmission rates for seniors but does not account for common age-related syndromes, such as functional impairment. To assess the effects of functional impairment on Medicare hospital readmissions given the high prevalence of functional impairments in community-dwelling seniors. We created a nationally representative cohort of 7854 community-dwelling seniors in the Health and Retirement Study, with 22,289 Medicare hospitalizations from January 1, 2000, through December 31, 2010. Outcome was 30-day readmission assessed by Medicare claims. The main predictor was functional impairment determined from the Health and Retirement Study interview preceding hospitalization, stratified into the following 5 levels: no functional impairments, difficulty with 1 or more instrumental activities of daily living, difficulty with 1 or more activities of daily living (ADL), dependency (need for help) in 1 to 2 ADLs, and dependency in 3 or more ADLs. Adjustment variables included age, race/ethnicity, sex, annual income, net worth, comorbid conditions (Elixhauser score from Medicare claims), and prior admission. We performed multivariable logistic regression to adjust for clustering at the patient level to characterize the association of functional impairments and readmission. Patients had a mean (SD) age of 78.5 (7.7) years (range, 65-105 years); 58.4% were female, 84.9% were white, 89.6% reported 3 or more comorbidities, and 86.0% had 1 or more hospitalizations in the previous year. Overall, 48.3% had some level of functional impairment before admission, and 15.5% of hospitalizations were followed by readmission within 30 days. We found a progressive increase in the adjusted risk of readmission as the degree of functional impairment increased: 13.5% with no functional impairment, 14.3% with difficulty with 1 or more instrumental activities of daily living (odds ratio [OR], 1.06; 95% CI, 0.94-1.20), 14.4% with difficulty with 1 or more ADL (OR, 1.08; 95% CI, 0.96-1.21), 16.5% with dependency in 1 to 2 ADLs (OR, 1.26; 95% CI, 1.11-1.44), and 18.2% with dependency in 3 or more ADLs (OR, 1.42; 95% CI, 1.20-1.69). Subanalysis restricted to patients admitted with conditions targeted by Medicare (ie, heart failure, myocardial infarction, and pneumonia) revealed a parallel trend with larger effects for the most impaired (16.9% readmission rate for no impairment vs 25.7% for dependency in 3 or more ADLs [OR, 1.70; 95% CI, 1.04-2.78]). Functional impairment is associated with increased risk of 30-day all-cause hospital readmission in Medicare seniors, especially those admitted for heart failure, myocardial infarction, or pneumonia. Functional impairment may be an important but underaddressed factor in preventing readmissions for Medicare seniors.

  16. Functional impairment in patients with major depressive disorder: the 2-year PERFORM study

    PubMed Central

    Hammer-Helmich, Lene; Haro, Josep Maria; Jönsson, Bengt; Tanguy Melac, Audrey; Di Nicola, Sylvie; Chollet, Julien; Milea, Dominique; Rive, Benoît; Saragoussi, Delphine

    2018-01-01

    Background The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (PERFORM) study describes the course of depressive symptoms, perceived cognitive symptoms, and functional impairment over 2 years in outpatients with major depressive disorder (MDD) and investigates the patient-related factors associated with functional impairment. Methods This was a 2-year observational study in 1,159 outpatients with MDD aged 18–65 years who were either initiating antidepressant monotherapy or undergoing their first switch of antidepressant. Functional impairment was assessed by the Sheehan Disability Scale and the Work Productivity and Activity Impairment questionnaire. Patients assessed depression severity using the nine-item Patient Health Questionnaire and severity of perceived cognitive symptoms using the five-item Perceived Deficit Questionnaire. To investigate which patient-related factors were associated with functional impairment, univariate analyses of variance were performed to identify relevant factors that were then included in multivariate analyses of covariance at baseline, month 2, months 6 and 12 combined, and months 18 and 24 combined. Results The greatest improvement in depressive symptoms, perceived cognitive symptoms, and functional impairment was seen immediately (within 2 months) following initiation or switch of antidepressant therapy, followed by more gradual improvement and long-term stabilization. Improvement in perceived cognitive symptoms was less marked than improvement in depressive symptoms during the acute treatment phase. Functional impairment in patients with MDD was not only associated with severity of depressive symptoms but also independently associated with severity of perceived cognitive symptoms when adjusted for depression severity throughout the 2 years of follow-up. Conclusion These findings highlight the burden of functional impairment in MDD and the importance of recognizing and managing cognitive symptoms in daily practice. PMID:29386897

  17. Functional impairment in patients with major depressive disorder: the 2-year PERFORM study.

    PubMed

    Hammer-Helmich, Lene; Haro, Josep Maria; Jönsson, Bengt; Tanguy Melac, Audrey; Di Nicola, Sylvie; Chollet, Julien; Milea, Dominique; Rive, Benoît; Saragoussi, Delphine

    2018-01-01

    The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (PERFORM) study describes the course of depressive symptoms, perceived cognitive symptoms, and functional impairment over 2 years in outpatients with major depressive disorder (MDD) and investigates the patient-related factors associated with functional impairment. This was a 2-year observational study in 1,159 outpatients with MDD aged 18-65 years who were either initiating antidepressant monotherapy or undergoing their first switch of antidepressant. Functional impairment was assessed by the Sheehan Disability Scale and the Work Productivity and Activity Impairment questionnaire. Patients assessed depression severity using the nine-item Patient Health Questionnaire and severity of perceived cognitive symptoms using the five-item Perceived Deficit Questionnaire. To investigate which patient-related factors were associated with functional impairment, univariate analyses of variance were performed to identify relevant factors that were then included in multivariate analyses of covariance at baseline, month 2, months 6 and 12 combined, and months 18 and 24 combined. The greatest improvement in depressive symptoms, perceived cognitive symptoms, and functional impairment was seen immediately (within 2 months) following initiation or switch of antidepressant therapy, followed by more gradual improvement and long-term stabilization. Improvement in perceived cognitive symptoms was less marked than improvement in depressive symptoms during the acute treatment phase. Functional impairment in patients with MDD was not only associated with severity of depressive symptoms but also independently associated with severity of perceived cognitive symptoms when adjusted for depression severity throughout the 2 years of follow-up. These findings highlight the burden of functional impairment in MDD and the importance of recognizing and managing cognitive symptoms in daily practice.

  18. [Evaluation of mental and communication functions in mapuche and non mapuche elderly subjects in rural communities in Southern Chile].

    PubMed

    Mella, Rebeca; Alvear, María; Carrillo, Berta; Caire, Victor

    2003-11-01

    The main predictors of functional impairment in the elderly are alterations in mental or communication functions. To study mental and communication functions in rural elderly subjects of Mapuche and non Mapuche origin. Elderly subjects coming from a rural Mapuche community and a non Mapuche community were studied. Subjects were interviewed at their homes. The communication and mental function assessments of the Functional Autonomy Measurement System were applied. Fifty one Mapuche and 49 non Mapuche subjects with a mean age of 71 +/- 7 and 74 +/- 8 years respectively, were studied. Fifty four percent were female and 31% were illiterate. Twenty six percent had impairment in mental functions. The item with the highest difficulty was memory. The visual function was the most severely impaired among communication items. Mapuche elderly subjects had significantly higher degrees of impairment in mental and communication functions. There is a higher degree of mental and communication impairment among rural Mapuche elderly subjects than in their non Mapuche counterparts.

  19. Contrasting Olfaction, Vision, and Audition as Predictors of Cognitive Change and Impairment in Non-Demented Older Adults

    PubMed Central

    MacDonald, Stuart W.S.; Keller, Connor J.C.; Brewster, Paul W.H.; Dixon, Roger A.

    2017-01-01

    Objective This study examines the relative utility of a particular class of non-invasive functional biomarkers -- sensory functions -- for detecting those at risk of cognitive decline and impairment. Three central research objectives were examined including whether: (1) olfactory function, vision, and audition exhibited significant longitudinal declines in non-demented older adults, (2) multi-wave change for these sensory function indicators predicted risk of mild cognitive impairment, and (3) change within persons for each sensory measure shared dynamic time-varying associations with within-person change in cognitive functioning. Method A longitudinal sample (n=408) from the Victoria Longitudinal Study was assembled. Three cognitive status subgroups were identified: not impaired cognitively (NIC), single assessment mild cognitive impairment (SA-MCI), and multiple assessment mild cognitive impairment (MA-MCI). Results We tested independent predictive associations, contrasting change in sensory function as predictors of cognitive decline and impairment, utilizing both linear mixed models and logistic regression analysis. Olfaction and, to a lesser extent, vision were identified as the most robust predictors of cognitive status and decline; audition showed little predictive influence. Conclusions These findings underscore the potential utility of deficits in olfactory function, in particular, as an early marker of age- and pathology-related cognitive decline. Functional biomarkers may represent potential candidates for use in the early stages of a multi-step screening approach for detecting those at risk of cognitive impairment, as well as for targeted intervention. PMID:29809033

  20. Impact of neurocognition on social and role functioning in individuals at clinical high risk for psychosis.

    PubMed

    Carrión, Ricardo E; Goldberg, Terry E; McLaughlin, Danielle; Auther, Andrea M; Correll, Christoph U; Cornblatt, Barbara A

    2011-08-01

    Cognitive deficits have been well documented in schizophrenia and have been shown to impair quality of life and to compromise everyday functioning. Recent studies of adolescents and young adults at high risk for developing psychosis show that neurocognitive impairments are detectable before the onset of psychotic symptoms. However, it remains unclear how cognitive impairments affect functioning before the onset of psychosis. The authors assessed cognitive impairment in adolescents at clinical high risk for psychosis and examined its impact on social and role functioning. A sample of 127 treatment-seeking patients at clinical high risk for psychosis and a group of 80 healthy comparison subjects were identified and recruited for research in the Recognition and Prevention Program. At baseline, participants were assessed with a comprehensive neurocognitive battery as well as measures of social and role functioning. Relative to healthy comparison subjects, clinical high-risk patients showed significant impairments in the domains of processing speed, verbal memory, executive function, working memory, visuospatial processing, motor speed, sustained attention, and language. Clinical high-risk patients also displayed impaired social and role functioning at baseline. Among patients with attenuated positive symptoms, processing speed was related to social and role functioning at baseline. These findings demonstrate that cognitive and functional impairments are detectable in patients at clinical high risk for psychosis before the onset of psychotic illness and that processing speed appears to be an important cognitive predictor of poor functioning.

  1. Impact of Neurocognition on Social and Role Functioning in Individuals at Clinical High Risk for Psychosis

    PubMed Central

    Carrión, Ricardo E.; Goldberg, Terry E.; McLaughlin, Danielle; Auther, Andrea M.; Correll, Christoph U.; Cornblatt, Barbara A.

    2011-01-01

    Objective Cognitive deficits have been well documented in schizophrenia and have been shown to impair quality of life and to compromise everyday functioning. Recent studies of adolescents and young adults at high risk for developing psychosis show that neurocognitive impairments are detectable before the onset of psychotic symptoms. However, it remains unclear how cognitive impairments affect functioning before the onset of psychosis. The authors assessed cognitive impairment in adolescents at clinical high risk for psychosis and examined its impact on social and role functioning. Method A sample of 127 treatment-seeking patients at clinical high risk for psychosis and a group of 80 healthy comparison subjects were identified and recruited for research in the Recognition and Prevention Program. At baseline, participants were assessed with a comprehensive neurocognitive battery as well as measures of social and role functioning. Results Relative to healthy comparison subjects, clinical high-risk patients showed significant impairments in the domains of processing speed, verbal memory, executive function, working memory, visuospatial processing, motor speed, sustained attention, and language. Clinical high-risk patients also displayed impaired social and role functioning at baseline. Among patients with attenuated positive symptoms, processing speed was related to social and role functioning at baseline. Conclusions These findings demonstrate that cognitive and functional impairments are detectable in patients at clinical high risk for psychosis before the onset of psychotic illness and that processing speed appears to be an important cognitive predictor of poor functioning. PMID:21536691

  2. Measuring Disability in Population Based Surveys: The Interrelationship between Clinical Impairments and Reported Functional Limitations in Cameroon and India

    PubMed Central

    2016-01-01

    Purpose To investigate the relationship between two distinct measures of disability: self-reported functional limitations and objectively-screened clinical impairments. Methods We undertook an all age population-based survey of disability in two areas: North-West Cameroon (August/October 2013) and Telangana State, India (Feb/April 2014). Participants were selected for inclusion via two-stage cluster randomised sampling (probability proportionate to size cluster selection and compact segment sampling within clusters). Disability was defined as the presence of self-reported functional limitations across eight domains, or presence of moderate or greater clinical impairments. Clinical impairment screening comprised of visual acuity testing for vision impairment, pure tone audiometry for hearing impairment, musculoskeletal functioning assessment for musculoskeletal impairment, reported seizure history for epilepsy and reported symptoms of clinical depression (depression adults only). Information was collected using structured questionnaires, observations and examinations. Results Self-reported disability prevalence was 5.9% (95% CI 4.7–7.4) and 7.5% (5.9–9.4) in Cameroon and India respectively. The prevalence of moderate or greater clinical impairments in the same populations were 8.4% (7.5–9.4) in Cameroon and 10.5% (9.4–11.7) in India. Overall disability prevalence (self-report and/or screened positive to a moderate or greater clinical impairment) was 10.5% in Cameroon and 12.2% in India, with limited overlap between the sub-populations identified using the two types of tools. 33% of participants in Cameroon identified to have a disability, and 45% in India, both reported functional limitations and screened positive to objectively-screened impairments, whilst the remainder were identified via one or other tool only. A large proportion of people with moderate or severe clinical impairments did not self-report functional difficulties despite reporting participation restrictions. Conclusion Tools to assess reported functional limitation alone are insufficient to identify all persons with participation restrictions and moderate or severe clinical impairments. A self-reported functional limitation tool followed by clinical screening of all those who report any level of difficulty would identify 94% of people with disabilities in Cameroon and 95% in India, meeting the study criteria. PMID:27741320

  3. Measuring Disability in Population Based Surveys: The Interrelationship between Clinical Impairments and Reported Functional Limitations in Cameroon and India.

    PubMed

    Mactaggart, Islay; Kuper, Hannah; Murthy, G V S; Oye, Joseph; Polack, Sarah

    2016-01-01

    To investigate the relationship between two distinct measures of disability: self-reported functional limitations and objectively-screened clinical impairments. We undertook an all age population-based survey of disability in two areas: North-West Cameroon (August/October 2013) and Telangana State, India (Feb/April 2014). Participants were selected for inclusion via two-stage cluster randomised sampling (probability proportionate to size cluster selection and compact segment sampling within clusters). Disability was defined as the presence of self-reported functional limitations across eight domains, or presence of moderate or greater clinical impairments. Clinical impairment screening comprised of visual acuity testing for vision impairment, pure tone audiometry for hearing impairment, musculoskeletal functioning assessment for musculoskeletal impairment, reported seizure history for epilepsy and reported symptoms of clinical depression (depression adults only). Information was collected using structured questionnaires, observations and examinations. Self-reported disability prevalence was 5.9% (95% CI 4.7-7.4) and 7.5% (5.9-9.4) in Cameroon and India respectively. The prevalence of moderate or greater clinical impairments in the same populations were 8.4% (7.5-9.4) in Cameroon and 10.5% (9.4-11.7) in India. Overall disability prevalence (self-report and/or screened positive to a moderate or greater clinical impairment) was 10.5% in Cameroon and 12.2% in India, with limited overlap between the sub-populations identified using the two types of tools. 33% of participants in Cameroon identified to have a disability, and 45% in India, both reported functional limitations and screened positive to objectively-screened impairments, whilst the remainder were identified via one or other tool only. A large proportion of people with moderate or severe clinical impairments did not self-report functional difficulties despite reporting participation restrictions. Tools to assess reported functional limitation alone are insufficient to identify all persons with participation restrictions and moderate or severe clinical impairments. A self-reported functional limitation tool followed by clinical screening of all those who report any level of difficulty would identify 94% of people with disabilities in Cameroon and 95% in India, meeting the study criteria.

  4. Pharmacokinetics and Tolerability of Lorcaserin in Special Populations: Elderly Patients and Patients with Renal or Hepatic Impairment.

    PubMed

    Christopher, Ronald J; Morgan, Michael E; Tang, Yong; Anderson, Christen; Sanchez, Matilde; Shanahan, William

    2017-04-01

    To determine whether dosage adjustment is likely to be necessary for effective and well-tolerated use of a pharmaceutical agent, guidance documents from the US Food and Drug Administration recommend pharmacokinetics studies in patients with impaired renal or impaired hepatic function and in the elderly population. Three studies were conducted to evaluate the pharmacokinetic properties and tolerability of lorcaserin in these populations. Lorcaserin was evaluated in single-dose pharmacokinetics studies of 3 overweight/obese populations: (1) elderly (aged >65 years) patients; (2) patients with impaired renal function; and (3) those with impaired hepatic function. In elderly patients, C max was lower (geometric mean ratio [GMR], 0.83; 90% CI, 0.71-0.97), but AUC was unchanged versus adult patients. In patients with renal impairment, C max was reduced versus that in patients with normal renal function (GMR: mild impairment, 0.99 [90% CI, 0.76-1.29]; moderate, 0.70 [90% CI, 0.54-0.90]; and severe, 0.69 [90% CI, 0.53-0.89]); no trend in AUC was observed in this group versus renal impairment. In patients with hepatic impairment, C max was decreased (GMR: mild impairment, 0.92 [90% CI, 0.76-1.11]; moderate, 0.86 [90% CI, 0.71-1.04]), and AUC was increased versus patients with normal hepatic function. Based on these findings, no lorcaserin dose adjustments are necessary in elderly patients with normal renal function or in patients with mild/moderate renal or hepatic impairment. ClinicalTrials.gov identifiers: NCT00828581, NCT00828438, and NCT00828932. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  5. 38 CFR 4.75 - General considerations for evaluating visual impairment.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... refraction), visual field, and muscle function. (b) Examination for visual impairment. The examination must.... Examinations of visual fields or muscle function will be conducted only when there is a medical indication of disease or injury that may be associated with visual field defect or impaired muscle function. Unless...

  6. 38 CFR 4.75 - General considerations for evaluating visual impairment.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... refraction), visual field, and muscle function. (b) Examination for visual impairment. The examination must.... Examinations of visual fields or muscle function will be conducted only when there is a medical indication of disease or injury that may be associated with visual field defect or impaired muscle function. Unless...

  7. 38 CFR 4.75 - General considerations for evaluating visual impairment.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... refraction), visual field, and muscle function. (b) Examination for visual impairment. The examination must.... Examinations of visual fields or muscle function will be conducted only when there is a medical indication of disease or injury that may be associated with visual field defect or impaired muscle function. Unless...

  8. Marital Conflict, Depressive Symptoms, and Functional Impairment

    ERIC Educational Resources Information Center

    Choi, Heejeong; Marks, Nadine F

    2008-01-01

    Guided by a stress process perspective, we investigated (a) whether marital conflict might directly lead to changes in depression and functional impairment, (b) whether marital conflict might indirectly lead to changes in functional impairment via depression, and (c) whether marital conflict might indirectly lead to changes in depression via…

  9. Effect of Visual Impairment on Physical and Cognitive Function in Old Age: Findings of a Population-Based Prospective Cohort Study in Germany.

    PubMed

    Hajek, André; Brettschneider, Christian; Lühmann, Dagmar; Eisele, Marion; Mamone, Silke; Wiese, Birgitt; Weyerer, Siegfried; Werle, Jochen; Pentzek, Michael; Fuchs, Angela; Riedel-Heller, Steffi G; Luck, Tobias; Bickel, Horst; Weeg, Dagmar; Koppara, Alexander; Wagner, Michael; Scherer, Martin; Maier, Wolfgang; König, Hans-Helmut

    2016-11-01

    To examine how visual impairment affects physical and cognitive function in old age. A longitudinal population-based prospective cohort study. General practitioner offices at six study centers in Germany. They were observed every 1.5 years over four waves. Individuals aged 77-101 at follow-up Wave 2 (N = 2,394). Physical and cognitive function were assessed using an adapted scale that had been previously developed, and visual impairment was rated on a Likert scale (none, mild, severe or profound). Adjusting for sociodemographic factors and comorbidity, linear fixed-effects regression showed that the onset of severe visual impairment was associated with a decline in physical function score in the total sample (β = -0.15, P = .01) and in women (β = -.15, P = .03). Moreover, the onset of severe visual impairment was associated with decline in cognitive function score in the total sample (β = -0.38, P < .001) and in women (β = -0.38, P < .001) and men (β = -0.37, P = .001). Visual impairment affects physical and cognitive function in old age. Interventional strategies to postpone visual impairment may contribute to maintaining physical and cognitive function. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  10. The Compensatory ADHD Behaviors Scale (CABS): Development and Initial Validation.

    PubMed

    Castagna, Peter J; Roye, Scott; Calamia, Matthew

    2018-05-01

    Several measures are available that assess inattention, hyperactivity/impulsivity, and executive functioning deficits. Treatments for adults with attention-deficit/hyperactivity disorder (ADHD) and skill-based academic interventions focus on improving compensatory strategies to ameliorate functional impairment; however, no measure exists that examines the compensatory behaviors adults utilize to compensate for the functional deficits associated with inattention and hyperactivity/impulsivity. The current study aimed to determine the psychometric properties of the Compensatory ADHD Behaviors Scale (CABS). Five-hundred participants ( M age = 36.83, SD = 11.57) completed measures of ADHD symptomatology, executive functioning, functional impairment, mood disorder symptoms, and the CABS. Analyses revealed that scales assessing both use and effectiveness of compensatory behaviors subscales had similar factor structures, reflecting present- and future-oriented behaviors. The present-, but not future-oriented, behaviors significantly related to ADHD symptomatology, executive dysfunction, and functional impairment; effectiveness of present-oriented compensatory behaviors demonstrated incremental validity in predicting impairment. Compensatory strategies may be a useful variable to measure when examining functional impairment associated with inattention and hyperactivity/impulsivity. The current study provides preliminary evidence of the ability of CABS to validly measure various strategies associated with (clinical and subclinical) ADHD symptomatology, executive functioning, and overall impairment.

  11. 20 CFR 404.1527 - Evaluating opinion evidence.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... impairment(s) in the Listing of Impairments in appendix 1 to this subpart, your residual functional capacity... your residual functional capacity. These administrative findings of fact are based on the evidence in...

  12. Body Dysmorphic Symptoms, Functional Impairment, and Depression: The Role of Appearance-Based Teasing.

    PubMed

    Weingarden, Hilary; Renshaw, Keith D

    2016-01-01

    Body dysmorphic disorder is associated with elevated social and occupational impairment and comorbid depression, but research on risk factors for body dysmorphic symptoms and associated outcomes is limited. Appearance-based teasing may be a potential risk factor. To examine the specificity of this factor, the authors assessed self-reported appearance-based teasing, body dysmorphic, and obsessive-compulsive symptom severity, functional impairment (i.e., social, occupational, family impairment), and depression in a nonclinical sample of undergraduates. As hypothesized, appearance-based teasing was positively correlated with body dysmorphic symptoms. The correlation between teasing and body dysmorphic symptoms was stronger than that between teasing and obsessive-compulsive symptom severity. Last, body dysmorphic symptom severity and appearance-based teasing interacted in predicting functional impairment and depression. Specifically, appearance-based teasing was positively associated with depression and functional impairment only in those with elevated body dysmorphic symptoms. When a similar moderation was tested with obsessive-compulsive, in place of body dysmorphic, symptom severity, the interaction was nonsignificant. Findings support theory that appearance-based teasing is a specific risk factor for body dysmorphic symptoms and associated functional impairment.

  13. Functional impairment and the economic consequences of female breast cancer.

    PubMed

    Chirikos, Thomas N; Russell-Jacobs, Anita; Jacobsen, Paul B

    2002-01-01

    Recent trends in breast cancer diagnosis and mortality suggest that long-term survivors are now more likely to be functionally impaired and, hence, more likely to experience adverse economic outcomes. This study tests whether women who have survived breast cancer for at least five years exhibit more, or more severe, functional impairments than otherwise similar women without breast cancer. It also tests whether women with more severe impairments experience poorer economic outcomes attributable to their functional status. A group of 105 breast cancer survivors was interviewed to obtain data on health and economic changes in the five-year period since diagnosis and initial treatment. An age- and work-matched group of 105 women without cancer was also interviewed to obtain the same data over the same time period. Key changes in the functional status of the subjects as well as economic outcomes such as changes in market earnings, household income, and insurance coverage were measured. Whether impairment is more severe in the breast cancer group than the comparison group was then tested statistically; whether economic outcomes are more adverse in more impaired than less impaired women regardless of their breast cancer status was also tested. The analysis turned up statistically significant evidence in regard to each of these relationships. Breast cancer survivors were more likely than controls to be functionally impaired at the five-year benchmark. Impaired women, in turn, were more likely to reduce work effort and experience downturns in market earnings, among other things. Policy and research implications are discussed.

  14. Parallel functional category deficits in clauses and nominal phrases: The case of English agrammatism

    PubMed Central

    Wang, Honglei; Yoshida, Masaya; Thompson, Cynthia K.

    2015-01-01

    Individuals with agrammatic aphasia exhibit restricted patterns of impairment of functional morphemes, however, syntactic characterization of the impairment is controversial. Previous studies have focused on functional morphology in clauses only. This study extends the empirical domain by testing functional morphemes in English nominal phrases in aphasia and comparing patients’ impairment to their impairment of functional morphemes in English clauses. In the linguistics literature, it is assumed that clauses and nominal phrases are structurally parallel but exhibit inflectional differences. The results of the present study indicated that aphasic speakers evinced similar impairment patterns in clauses and nominal phrases. These findings are consistent with the Distributed Morphology Hypothesis (DMH), suggesting that the source of functional morphology deficits among agrammatics relates to difficulty implementing rules that convert inflectional features into morphemes. Our findings, however, are inconsistent with the Tree Pruning Hypothesis (TPH), which suggests that patients have difficulty building complex hierarchical structures. PMID:26379370

  15. The Association of Domestic Violence and Social Resources With Functioning in an Adult Trauma-Affected Sample Living in Kurdistan, Northern Iraq.

    PubMed

    Kane, Jeremy C; Hall, Brian J; Bolton, Paul; Murray, Laura K; Mohammed Amin Ahmed, Ahmed; Bass, Judith K

    2016-03-27

    Domestic violence (DV) and other experienced trauma types increase the risk for impaired functioning. Access to social resources may provide a buffer to existing risks and allow individuals to continue and build functioning. This cross-sectional study investigated the direct effects of DV and access to social resources (perceived social support, social integration, and frequency of social contact), as well as their potential interactive effects, on daily functioning among 894 male and female trauma survivors who attended primary care clinics in Kurdistan, Iraq in 2009 and 2010. Experiencing DV was not associated with functioning for males (p=.15) or females (p=.60), suggesting that in the context of a trauma-affected sample, the experience of DV may not significantly increase the risk for functional impairment. Greater amounts of social integration were associated with less functional impairment among males (p<.01) and females (p<.05); social integration was associated with less functional impairment among males only (p<.01); and frequency of social contact was associated with less functional impairment among females only (p<.05), indicating that the association between social resource type and functioning differed by gender. Social resources had a stronger effect on functioning among men compared to women. Among males who experienced DV, social integration was the only social resource associated with less functional impairment (p<.01); among male trauma survivors who did not experience DV, social support was the only resource associated with less functional impairment (p<.01). Further investigation into these associations is warranted to inform intervention strategies for survivors of DV and other traumas in post-conflict settings. © The Author(s) 2016.

  16. What explains health in persons with visual impairment?

    PubMed Central

    2014-01-01

    Background Visual impairment is associated with important limitations in functioning. The International Classification of Functioning, Disability and Health (ICF) adopted by the World Health Organisation (WHO) relies on a globally accepted framework for classifying problems in functioning and the influence of contextual factors. Its comprehensive perspective, including biological, individual and social aspects of health, enables the ICF to describe the whole health experience of persons with visual impairment. The objectives of this study are (1) to analyze whether the ICF can be used to comprehensively describe the problems in functioning of persons with visual impairment and the environmental factors that influence their lives and (2) to select the ICF categories that best capture self-perceived health of persons with visual impairment. Methods Data from 105 persons with visual impairment were collected, including socio-demographic data, vision-related data, the Extended ICF Checklist and the visual analogue scale of the EuroQoL-5D, to assess self-perceived health. Descriptive statistics and a Group Lasso regression were performed. The main outcome measures were functioning defined as impairments in Body functions and Body structures, limitations in Activities and restrictions in Participation, influencing Environmental factors and self-perceived health. Results In total, 120 ICF categories covering a broad range of Body functions, Body structures, aspects of Activities and Participation and Environmental factors were identified. Thirteen ICF categories that best capture self-perceived health were selected based on the Group Lasso regression. While Activities-and-Participation categories were selected most frequently, the greatest impact on self-perceived health was found in Body-functions categories. The ICF can be used as a framework to comprehensively describe the problems of persons with visual impairment and the Environmental factors which influence their lives. Conclusions There are plenty of ICF categories, Environmental-factors categories in particular, which are relevant to persons with visual impairment, but have hardly ever been taken into consideration in literature and visual impairment-specific patient-reported outcome measures. PMID:24886326

  17. Comparison of Spontaneously Elicited Language Patterns in Specific Language Impairment and High-Functioning Autism.

    PubMed

    Craig, Megan; Trauner, Doris

    2018-02-01

    We aimed to characterize differences in the use of language in children with specific language impairment and high-functioning autism by analyzing verbal responses on standardized tests. The overall goal was to provide clinicians with additional tools with which to aid in distinguishing the two neurodevelopmental disorders. This study included 16 children with specific language impairment, 28 children with high-functioning autism, and 52 typically developing participants between the ages of six and 14. Groups were matched for age, and specific language impairment and high-functioning autism groups were matched on verbal and performance IQ. Responses from standardized tests were examined for response length, grammatical errors, filler words, perseverations, revisions (repeated attempts to begin or continue a sentence), off-topic attention shifts (lapses in attention to the task), and rambling. Data were analyzed using parametric and nonparametric methods. Specific language impairment responses were longer and contained more filler words than did those of the other two groups, whereas high-functioning autism responses exhibited more grammatical errors, off-topic attention shifts, and rambling. Specific language impairment and high-functioning autism responses showed higher rates of perseveration compared with controls. There were no significant differences in revisions among the three groups. Differences in language patterns of participants with specific language impairment and high-functioning autism may be useful to the clinician in helping to differentiate isolated language impairment from high-functioning autism. The results also support the conclusion that the two conditions are separable, and each exhibits a different pattern of language dysfunction. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Annual Research Review: Conceptualising Functional Impairment in Children and Adolescents

    ERIC Educational Resources Information Center

    Rapee, Ronald M.; Bogels, Susan M.; van der Sluis, Cathy M.; Craske, Michelle G.; Ollendick, Thomas

    2012-01-01

    Functional impairment is a key factor in the clinical importance of mental health problems in children. Yet, the nature of impairment and criteria for defining and assessing impairment in childhood disorders has been surprisingly overlooked in much of the literature. The current article examines the extant literature on the conceptualisation,…

  19. Executive Functions in Children with Communication Impairments, in Relation to Autistic Symptomatology. 2: Response Inhibition

    ERIC Educational Resources Information Center

    Bishop, Dorothy V. M.; Norbury, Courtenay Frazier

    2005-01-01

    Although impairment in executive functions has been described in autism, there has been debate as to whether response inhibition is specifically affected. We compared four groups: highfunctioning autism; pragmatic language impairment; specific language impairment; and control. Inhibition was assessed using two subtests from the Test of Everyday…

  20. Research the mobile phone operation interfaces for vision-impairment.

    PubMed

    Yao, Yen-Ting; Leung, Cherng-Yee

    2012-01-01

    Due to the vision-impaired users commonly having difficulty with mobile-phone function operations and adaption any manufacturer's user interface design, the goals for this research are established for evaluating how to improve for them the function operation convenience and user interfaces of either mobile phones or electronic appliances in the market currently. After applying collecting back 30 effective questionnaires from 30 vision-impairment, the comments have been concluded from this research include: (1) All mobile phone manufactures commonly ignorant of the vision-impairment difficulty with operating mobile phone user interfaces; (2) The vision-impairment preferential with audio alert signals; (3) The vision-impairment incapable of mobile-phone procurement independently unless with assistance from others; (4) Preferential with adding touch-usage interface design by the vision-impairment; in contrast with the least requirement for such functions as braille, enlarging keystroke size and diversifying-function control panel. With exploring the vision-impairment's necessary improvements and obstacles for mobile phone interface operation, this research is established with goals for offering reference possibly applied in electronic appliance design and . Hopefully, the analysis results of this research could be used as data references for designing electronic and high-tech products and promoting more usage convenience for those vision-impaired.

  1. Leptin concentration and risk of impaired physical function in older adults: the Seniors-ENRICA cohort.

    PubMed

    Lana, Alberto; Struijk, Ellen; Guallar-Castillón, Pilar; Martín-Moreno, Jose María; Rodríguez Artalejo, Fernando; Lopez-Garcia, Esther

    2016-11-01

    leptin resistance, which may develop during the ageing process, stimulates the production of pro-inflammatory cytokines and insulin resistance that could impair the muscle function. However, the role of leptin on physical functioning among older adults has not yet been elucidated. to examine the association between serum leptin levels and physical function impairment in older adults. prospective study of 1,556 individuals 60 years and older from the Seniors-ENRICA cohort, who were free of physical function limitation at baseline. serum leptin was measured in 2008-10, and incident functional limitation was assessed through 2012. Self-reported limitations in agility and mobility were assessed with the Rosow and Breslau scale, limitation in the lower extremity function was measured with the Short Physical Performance Battery, and impairment in the overall physical performance with the physical component summary of the SF-12. after adjustment for potential confounders and compared to individuals in the lowest quartile of leptin concentration, those in the highest quartile showed increased risk of impaired physical function; the odds ratio (95% confidence interval) and P-trend was: 1.95 (1.11-3.43), P = 0.006 for self-reported impaired mobility; 1.76 (1.08-2.87), P = 0.02 for self-reported impaired agility; 1.48 (1.02-2.15), P = 0.04 for limitation in the lower extremity function; and 1.97 (1.20-3.22), P = 0.01, for decreased overall physical performance. These associations were only modestly explained by C-reactive protein and insulin resistance. Moreover, the associations held across groups with varying health status and were independent of estimated total body fat. higher leptin concentration was associated with increased risk of impaired physical function. Preserving metabolic function during the old age could help delaying physical function decline. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Differential impairments underlying decision making in anorexia nervosa and bulimia nervosa: a cognitive modeling analysis.

    PubMed

    Chan, Trista Wai Sze; Ahn, Woo-Young; Bates, John E; Busemeyer, Jerome R; Guillaume, Sebastien; Redgrave, Graham W; Danner, Unna N; Courtet, Philippe

    2014-03-01

    This study examined the underlying processes of decision-making impairments in individuals with anorexia nervosa (AN) and bulimia nervosa (BN). We deconstructed their performance on the widely used decision task, the Iowa Gambling Task (IGT) into cognitive, motivational, and response processes using cognitive modeling analysis. We hypothesized that IGT performance would be characterized by impaired memory functions and heightened punishment sensitivity in AN, and by elevated sensitivity to reward as opposed to punishment in BN. We analyzed trial-by-trial data of IGT obtained from 224 individuals: 94 individuals with AN, 63 with BN, and 67 healthy comparison individuals (HC). The prospect valence learning model was used to assess cognitive, motivational, and response processes underlying IGT performance. Individuals with AN showed marginally impaired IGT performance compared to HC. Their performance was characterized by impairments in memory functions. Individuals with BN showed significantly impaired IGT performance compared to HC. They showed greater relative sensitivity to gains as opposed to losses than HC. Memory functions in AN were positively correlated with body mass index. This study identified differential impairments underlying IGT performance in AN and BN. Findings suggest that impaired decision making in AN might involve impaired memory functions. Impaired decision making in BN might involve altered reward and punishment sensitivity. Copyright © 2013 Wiley Periodicals, Inc.

  3. The 20-Year Longitudinal Trajectories of Social Functioning in Individuals With Psychotic Disorders.

    PubMed

    Velthorst, Eva; Fett, Anne-Kathrin J; Reichenberg, Avraham; Perlman, Greg; van Os, Jim; Bromet, Evelyn J; Kotov, Roman

    2017-11-01

    Social impairment is a long-recognized core feature of schizophrenia and is common in other psychotic disorders. Still, to date the long-term trajectories of social impairment in psychotic disorders have rarely been studied systematically. Data came from the Suffolk County Mental Health Project, a 20-year prospective study of first-admission patients with psychotic disorders. A never-psychotic comparison group was also assessed. Latent class growth analysis was applied to longitudinal data on social functioning from 485 respondents with schizophrenia spectrum disorders and psychotic mood disorders, and associations of the empirically derived trajectories with premorbid social adjustment, diagnosis, and 20-year outcomes were examined. Four mostly stable trajectories of preserved (N=82; 59th percentile of comparison group sample distribution), moderately impaired (N=148; 17th percentile), severely impaired (N=181; 3rd percentile), and profoundly impaired (N=74; 1st percentile) functioning best described the 20-year course of social functioning across diagnoses. The outcome in the group with preserved functioning did not differ from that of never-psychotic individuals at 20 years, but the other groups functioned significantly worse. Differences among trajectories were already evident in childhood. The two most impaired trajectories started to diverge in early adolescence. Poorer social functioning trajectories were strongly associated with other real-world outcomes at 20 years. Multiple trajectories were represented within each disorder. However, more participants with schizophrenia spectrum disorders had impaired trajectories, and more with mood disorders had better functioning trajectories. The results highlight substantial variability of social outcomes within diagnoses-albeit overall worse social outcomes in schizophrenia spectrum disorders-and show remarkably stable long-term impairments in social functioning after illness onset across all diagnoses.

  4. Visual impairment, visual functioning, and quality of life assessments in patients with glaucoma.

    PubMed Central

    Parrish, R K

    1996-01-01

    BACKGROUND/PURPOSE: To determine the relation between visual impairment, visual functioning, and the global quality of life in patients with glaucoma. METHODS: Visual impairment, defined with the American Medical Association Guides to the Evaluation of Permanent Impairment; visual functioning, measured with the VF-14 and the Field Test Version of the National Eye Institute-Visual Functioning Questionnaire (NEI-VFQ); and the global quality of life, assessed with the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), were determined in 147 consecutive patients with glaucoma. RESULTS: None of the SF-36 domains demonstrated more than a weak correlation with visual impairment. The VF-14 scores were moderately correlated with visual impairment. Of the twelve NEI-VFQ scales, distance activities and vision specific dependency were moderately correlated with visual impairment. Of the twelve NEI-VFQ scales, distance activities and vision specific dependency were moderately correlated with visual field impairment; vision specific social functioning, near activities, vision specific role difficulties, general vision, vision specific mental health, color vision, and driving were modestly correlated; visual pain was weakly correlated; and two were not significantly correlated. Correcting for visual actuity weakened the strength of the correlation coefficients. CONCLUSIONS: The SF-36 is unlikely to be useful in determining visual impairment in patients with glaucoma. Based on the moderate correlation between visual field impairment and the VF-14 score, this questionnaire may be generalizable to patients with glaucoma. Several of the NEI-VFQ scales correlate with visual field impairment scores in patients with a wide range of glaucomatous damage. PMID:8981717

  5. Functional Impairment in Latino Children with ADHD: Implications for Culturally Appropriate Conceptualization and Measurement

    ERIC Educational Resources Information Center

    Haack, Lauren Marie; Gerdes, Alyson C.

    2011-01-01

    Conceptualizing and measuring functional impairment related to childhood ADHD, particularly within the rapidly growing, yet underserved, Latino population, is an important area of research that is in its infancy in the field of psychology. The functional impairments related to academic achievement, social competence, and familial relations…

  6. Displacement as a predictor of functional impairment in tsunami-exposed children.

    PubMed

    Lee, Christopher; Du, Ye Beverly; Christina, Desy; Palfrey, Judith; O'Rourke, Edward; Belfer, Myron

    2015-01-01

    Thirty months after the Indian Ocean tsunami of 26 December 2004, thousands of families in Aceh Province, Indonesia, remained in temporary barracks while sanitation conditions and non-governmental organisation support deteriorated. This study sought to determine the factors associated with functional impairment in a sample of 138 displaced and non-displaced Acehnese children. Using multivariate linear regression models, it was found that displacement distance was a consistent predictor of impairment using the Brief Impairment Scale. Exposure to tsunami-related trauma markers was not significantly linked with impairment in the model. Paternal employment was a consistent protective factor for child functioning. These findings suggest that post-disaster displacement and the subsequent familial economic disruption are significant predictors of impaired functioning in children's daily activities. Post-disaster interventions should consider the disruption of familiar environments for families and children when relocating vulnerable populations to avoid deleterious impacts on children's functioning. © 2014 The Author(s). Disasters © Overseas Development Institute, 2014.

  7. High Prolactin Excretion in Patients with Diabetes Mellitus and Impaired Renal Function.

    PubMed

    Triebel, Jakob; Moreno-Vega, Aura Ileana; Vázquez-Membrillo, Miguel; Nava, Gabriel; García-Franco, Renata; López-Star, Ellery; Baldivieso-Hurtado, Olivia; Ochoa, Daniel; Macotela, Yazmín; Bertsch, Thomas; Martinez de la Escalera, Gonzalo; Clapp, Carmen

    2015-01-01

    The metabolic clearance of prolactin (PRL) is partially executed by the kidney. Here, we investigate the urine excretion of PRL in patients with Diabetes Mellitus and renal impairment. Serum and urine samples were collected from male, mestizo patients in central Mexico employing a cross-sectional study design. Ninety-eight individuals had either no diabetes and normal renal function (control), diabetes and normal renal function, or diabetes with impaired renal function. PRL was determined by a chemiluminescent immunometric assay; protein, albumin, and creatinine were evaluated using quantitative colorimetric assays. The results were analyzed using ANOVA-testing. Patients with Diabetes Mellitus and renal impairment had significantly higher urine PRL levels than patients with Diabetes Mellitus and normal renal function and control patients. Higher urine PRL levels were associated with lower glomerular filtration rates, higher serum creatinine, and higher urinary albumin-to-creatinine ratios (UACR). Urine PRL levels correlated positively with UACR. Serum PRL levels were similar among groups. Patients with Diabetes Mellitus and impaired renal function demonstrate a high urinary PRL excretion. Urinary PRL excretion in the context of proteinuria could contribute to PRL dysregulation in renal impairment.

  8. Cognitive functioning in dyskinetic cerebral palsy: Its relation to motor function, communication and epilepsy.

    PubMed

    Ballester-Plané, Júlia; Laporta-Hoyos, Olga; Macaya, Alfons; Póo, Pilar; Meléndez-Plumed, Mar; Toro-Tamargo, Esther; Gimeno, Francisca; Narberhaus, Ana; Segarra, Dolors; Pueyo, Roser

    2018-01-01

    Cerebral palsy (CP) is a disorder of motor function often accompanied by cognitive impairment. There is a paucity of research focused on cognition in dyskinetic CP and on the potential effect of related factors. To describe the cognitive profile in dyskinetic CP and to assess its relationship with motor function and associated impairments. Fifty-two subjects with dyskinetic CP (28 males, mean age 24 y 10 mo, SD 13 y) and 52 typically-developing controls (age- and gender-matched) completed a comprehensive neuropsychological assessment. Gross Motor Function Classification System (GMFCS), Communication Function Classification System (CFCS) and epilepsy were recorded. Cognitive performance was compared between control and CP groups, also according different levels of GMFCS. The relationship between cognition, CFCS and epilepsy was examined through partial correlation coefficients, controlling for GMFCS. Dyskinetic CP participants performed worse than controls on all cognitive functions except for verbal memory. Milder cases (GMFCS I) only showed impairment in attention, visuoperception and visual memory. Participants with GMFCS II-III also showed impairment in language-related functions. Severe cases (GMFCS IV-V) showed impairment in intelligence and all specific cognitive functions but verbal memory. CFCS was associated with performance in receptive language functions. Epilepsy was related to performance in intelligence, visuospatial abilities, visual memory, grammar comprehension and learning. Cognitive performance in dyskinetic CP varies with the different levels of motor impairment, with more cognitive functions impaired as motor severity increases. This study also demonstrates the relationship between communication and epilepsy and cognitive functioning, even controlling for the effect of motor severity. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  9. Functional assessment of the elderly. A comparison of standard instruments with clinical judgment.

    PubMed

    Pinholt, E M; Kroenke, K; Hanley, J F; Kussman, M J; Twyman, P L; Carpenter, J L

    1987-03-01

    Using specific instruments and scales to measure mental status, nutritional state, visual acuity, gait, and activities of daily living, we studied 79 medical inpatients aged 70 years or older. We then interviewed the patients' primary physicians and nurses and asked them to rate their patients. The prevalence of functional impairment was high: 25 (32%) of the 79 patients were mentally impaired, 31 (39%) were malnourished, 18 (23%) were visually impaired, 31 (39%) had impaired gait, and 23 (29%) had problems with continence. Although clinicians recognized severe impairments, the sensitivity of their clinical judgment was poor in detecting moderate impairment in four categories: mental status sensitivity was 28% (5/18); nutrition, 54% (14/26); vision, 27% (4/15); and continence, 42% (5/12). With clinical judgment alone, physicians and nurses correctly identify severe impairment, but the more prevalent moderate impairments in mental status, nutrition, vision, and continence are poorly recognized. Comprehensive functional assessment instruments can detect these moderate impairments, which may be remediable through early intervention.

  10. The neuropsychological function of children with achondroplasia.

    PubMed

    Wigg, Kimberley; Tofts, Louise; Benson, Suzanne; Porter, Melanie

    2016-11-01

    The current observational study had three specific objectives: (i) to document any neuropsychological impairment in a sample of children with achondroplasia; (ii) to explore individual variability; and (iii) to determine the functional impact of any impairments. Fourteen children aged between 6 and 15 years with a medically confirmed diagnosis of achondroplasia (FGFR 3 mutation positive) underwent a comprehensive standardized neuropsychological evaluation. On average, while generally still within normal limits, significantly lower scores compared to standardized means were identified on: Full-scale IQ, verbal IQ, working memory, arithmetic, attention, executive functioning and aspects of day-to-day emotional, social, and behavioral functioning. Clinically significant levels of impairment at a group level were identified on measures of: arithmetic, attention, and executive functioning. There was variability among the group and for most measures scores ranged from impaired to within normal limits. A high percentage of children were impaired on measures of: verbal IQ, attention and executive functioning. Results of this study suggest a need for individual neuropsychological evaluation and monitoring of children with achondroplasia and suggest verbal IQ, arithmetic, attention, and executive functioning are particularly common areas of impairment. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. 20 CFR 220.120 - The claimant's residual functional capacity.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... medically determinable impairment(s), such as skin impairment(s), epilepsy, impairment(s) of vision, hearing... with a low back disorder may be fully capable of the physical demands consistent with those of...

  12. 20 CFR 220.120 - The claimant's residual functional capacity.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... medically determinable impairment(s), such as skin impairment(s), epilepsy, impairment(s) of vision, hearing... with a low back disorder may be fully capable of the physical demands consistent with those of...

  13. 20 CFR 220.120 - The claimant's residual functional capacity.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... medically determinable impairment(s), such as skin impairment(s), epilepsy, impairment(s) of vision, hearing... with a low back disorder may be fully capable of the physical demands consistent with those of...

  14. 20 CFR 220.120 - The claimant's residual functional capacity.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... medically determinable impairment(s), such as skin impairment(s), epilepsy, impairment(s) of vision, hearing... with a low back disorder may be fully capable of the physical demands consistent with those of...

  15. Potential mechanisms for chemotherapy-induced impairments in cognitive function.

    PubMed

    Jansen, Catherine; Miaskowski, Christine; Dodd, Marilyn; Dowling, Glenna; Kramer, Joel

    2005-11-03

    To review the domains of cognitive function and their corresponding neuroanatomic structures as well as present current evidence for neurotoxicity associated with specific chemotherapeutic agents and potential mechanisms for chemotherapy-induced cognitive impairments. Published research articles, review articles, and textbooks. Chemotherapy does not appear to cross the blood-brain barrier when given in standard doses; however, many chemotherapy drugs have the potential to cause cognitive impairments through more than one mechanism. In addition, patient factors may be protective or place individuals at higher risk for cognitive impairments. Although evidence of chemotherapy-induced impairments in cognitive function exists, no clinical studies have attempted to elucidate the mechanisms for chemotherapy-induced impairments in cognitive function. In addition, further studies are needed to determine predictive factors, potential biomarkers, and relevant assessment parameters. The ability to identify high-risk patients has important implications for practice in regard to informed consent, patient education about the effects of treatment, and preventive strategies.

  16. Usefulness of the University of California San Diego Performance-Based Skills Assessment for the evaluation of cognitive function and activities of daily living function in patients with cognitive impairment.

    PubMed

    Jeon, Dong-Wook; Ju, Hyun-Bin; Jung, Do-Un; Kim, Sung-Jin; Shim, Joo-Cheol; Moon, Jung-Joon; Kim, You-Na

    2017-10-25

    To assess the usefulness of the University of California San Diego Performance-Based Skills Assessment (UPSA) as a new diagnostic method and tool for the assessment of cognitive function and activities of daily living function in patients with cognitive impairment. In total, 35 patients with cognitive impairment and 35 healthy controls were recruited for this study. The Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Global Deterioration Scale (GDS) were used for the evaluation of cognitive function, while the Barthel Activities of Daily Living Index (BADL), Instrumental Activities of Daily Living Index (IADL), and UPSA were used for the evaluation of activities of daily living function. UPSA scores were significantly lower in patients with cognitive impairment than in controls. The UPSA total score was significantly correlated with MMSE, CDR, GDS, and IADL scores. With regard to the detection of cognitive impairment, UPSA exhibited a greater determination power (R 2 = 0.593) compared with BADL (R 2 = 0.149) and IADL (R 2 = 0.423) and higher sensitivity and specificity compared with IADL. Our results suggest that UPSA is a useful tool for the evaluation of cognitive function and activities of daily living function in patients with cognitive impairment.

  17. Impaired renal function modifies the risk of severe hypoglycaemia among users of insulin but not glyburide: a population-based nested case-control study.

    PubMed

    Weir, Matthew A; Gomes, Tara; Mamdani, Muhammad; Juurlink, David N; Hackam, Daniel G; Mahon, Jeffrey L; Jain, Arsh K; Garg, Amit X

    2011-06-01

    Little evidence justifies the avoidance of glyburide in patients with impaired renal function. We aimed to determine if renal function modifies the risk of hypoglycaemia among patients using glyburide. We conducted a nested case-control study using administrative records and laboratory data from Ontario, Canada. We included outpatients 66 years of age and older with diabetes mellitus and prescriptions for glyburide, insulin or metformin. We ascertained hypoglycaemic events using administrative records and estimated glomerular filtration rates (eGFR) using serum creatinine concentrations. From a cohort of 19,620 patients, we identified 204 cases whose eGFR was ≥ 60 mL/min/1.73 m(2) (normal renal function) and 354 cases whose eGFR was < 60 mL/min/1.73 m(2) (impaired renal function). Compared to metformin, glyburide is associated with a greater risk of hypoglycaemia in patients with both normal [adjusted odds ratio (OR) 9.0, 95% confidence interval (95% CI) 4.9-16.4] and impaired renal function (adjusted OR 6.0, 95% CI 3.8-9.5). We observed a similar relationship when comparing insulin to metformin; the risk was greater in patients with normal renal function (adjusted OR 18.7, 95% CI 10.5-33.5) compared to those with impaired renal function (adjusted OR 7.9, 95% CI 5.0-12.4). Tests of interaction showed that among glyburide users, renal function did not significantly modify the risk of hypoglycaemia, but among insulin users, impaired renal function is associated with a lower risk. In this population-based study, impaired renal function did not augment the risk of hypoglycaemia associated with glyburide use.

  18. Frontal lobe connectivity and cognitive impairment in pediatric frontal lobe epilepsy.

    PubMed

    Braakman, Hilde M H; Vaessen, Maarten J; Jansen, Jacobus F A; Debeij-van Hall, Mariette H J A; de Louw, Anton; Hofman, Paul A M; Vles, Johan S H; Aldenkamp, Albert P; Backes, Walter H

    2013-03-01

    Cognitive impairment is frequent in children with frontal lobe epilepsy (FLE), but its etiology is unknown. With functional magnetic resonance imaging (fMRI), we have explored the relationship between brain activation, functional connectivity, and cognitive functioning in a cohort of pediatric patients with FLE and healthy controls. Thirty-two children aged 8-13 years with FLE of unknown cause and 41 healthy age-matched controls underwent neuropsychological assessment and structural and functional brain MRI. We investigated to which extent brain regions activated in response to a working memory task and assessed functional connectivity between distant brain regions. Data of patients were compared to controls, and patients were grouped as cognitively impaired or unimpaired. Children with FLE showed a global decrease in functional brain connectivity compared to healthy controls, whereas brain activation patterns in children with FLE remained relatively intact. Children with FLE complicated by cognitive impairment typically showed a decrease in frontal lobe connectivity. This decreased frontal lobe connectivity comprised both connections within the frontal lobe as well as connections from the frontal lobe to the parietal lobe, temporal lobe, cerebellum, and basal ganglia. Decreased functional frontal lobe connectivity is associated with cognitive impairment in pediatric FLE. The importance of impairment of functional integrity within the frontal lobe network, as well as its connections to distant areas, provides new insights in the etiology of the broad-range cognitive impairments in children with FLE. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  19. Osteogenesis imperfecta in childhood: impairment and disability--a follow-up study.

    PubMed

    Engelbert, R H; Beemer, F A; van der Graaf, Y; Helders, P J

    1999-08-01

    To evaluate differences over time (mean follow-up, 14 months) on impairment parameters (range of joint motion and muscle strength), functional limitation parameters (functional ability), and disability parameters (caregiver assistance in achieving functional skills) in osteogenesis imperfecta (OI), related to the different types of the disease. A prospective, descriptive study. Fifty-four children with OI and their parents participated at the start of the study. At the end, 44 children participated in the assessment of functional skills and 42 of them participated in clinical assessment (OI type I, n = 19; OI type III, n = 13; OI type IV, n = 10). Range of joint motion was measured by means of goniometry. Generalized hypermobility was scored according to Bulbena. Manual muscle strength was scored by means of the MRC grading system. The level of ambulation was scored according to Bleck, and functional skills and caregiver assistance were scored with the Pediatric Evaluation of Disability Inventory. The different types of OI have impact on impairment, functional limitation, and disability. Almost all impairment parameters did not change significantly over time, whereas some disability parameters seemed to improve significantly. Impairment parameters in OI are presumably not always preconditions for functional limitation and disability. A 1-year follow-up revealed no significant changes in impairment parameters, whereas some disability parameters improved. Treatment strategies in OI should, therefore, focus primarily on improving functional ability, with respect to the natural course of the disease, and not only on impairment parameters.

  20. Obesity's Effects on the Onset of Functional Impairment among Older Adults

    ERIC Educational Resources Information Center

    Jenkins, Kristi Rahrig

    2004-01-01

    Purpose: This study has two purposes. First, it determines if there is a relationship between body weight and the onset of functional impairment across time among this sample of older adults. More specifically, it examines if obese older adults are more likely to experience the onset of functional impairment. Second, it explores how health…

  1. The Brief Impairment Scale (Bis): A Multidimensional Scale of Functional Impairment for Children and Adolescents.

    ERIC Educational Resources Information Center

    Bird, Hector R.; Canino, Glorisa J.; Davies, Mark; Ramirez, Rafael; Chavez, Ligia; Duarte, Cristiane; Shen, Sa

    2005-01-01

    Objective: This article provides the results of the psychometric testing of the Brief Impairment Scale (BIS). The BIS is a 23-item instrument that evaluates three domains of functioning: interpersonal relations, school/work functioning, and self-care/self-fulfilment. It capitalizes on the strengths of existing global measures while addressing some…

  2. Executive Function and Behavioral Problems in Students with Visual Impairments at Mainstream and Special Schools

    ERIC Educational Resources Information Center

    Heyl, Vera; Hintermair, Manfred

    2015-01-01

    Introduction: In this study, executive function of school-aged children with visual impairments (that is, those who are blind or have low vision) is examined in the context of behavioral problems and communicative competence. Methods: Teachers assessed the executive function of a sample of 226 visually impaired students from mainstream schools and…

  3. Examining the Disability Model From the International Classification of Functioning, Disability, and Health Using a Large Data Set of Community-Dwelling Malaysian Older Adults

    PubMed Central

    Loke, Seng Cheong; Lim, Wee Shiong; Someya, Yoshiko; Hamid, Tengku A.; Nudin, Siti S. H.

    2015-01-01

    Objective: This study examines the International Classification of Functioning, Disability, and Health model (ICF) using a data set of 2,563 community-dwelling elderly with disease-independent measures of mobility, physical activity, and social networking, to represent ICF constructs. Method: The relationship between chronic disease and disability (independent and dependent variables) was examined using logistic regression. To demonstrate variability in activity performance with functional impairment, graphing was used. The relationship between functional impairment, activity performance, and social participation was examined graphically and using ANOVA. The impact of cognitive deficits was quantified through stratifying by dementia. Results: Disability is strongly related to chronic disease (Wald 25.5, p < .001), functional impairment with activity performance (F = 34.2, p < .001), and social participation (F= 43.6, p < .001). With good function, there is considerable variability in activity performance (inter-quartile range [IQR] = 2.00), but diminishes with high impairment (IQR = 0.00) especially with cognitive deficits. Discussion: Environment modification benefits those with moderate functional impairment, but not with higher grades of functional loss. PMID:26472747

  4. The association of domestic violence and social resources with functioning in an adult trauma-affected sample living in Kurdistan, Northern Iraq

    PubMed Central

    Kane, Jeremy C.; Hall, Brian J.; Bolton, Paul; Murray, Laura K.; Ahmed, Ahmed Mohammed Amin; Bass, Judith K.

    2016-01-01

    Ability to function in tasks and activities is an important aspect of daily living. There are factors that increase the risk for impaired functioning, such as experiences of domestic violence (DV) and other trauma types, and factors that provide a buffer to existing risks and allow the individual to continue and build functioning, such as access to social resources. This cross-sectional study investigated the direct effects of DV and access to social resources (perceived social support, social integration, and frequency of social contact), as well as their potential interactive effects, on daily functioning among 894 male and female trauma survivors who attended primary care clinics in Kurdistan, Iraq in 2009 and 2010. Experiencing DV was not associated with functioning for males (p=.15) or females (p=.60), suggesting that in the context of a trauma-affected sample, the experience of DV may not significantly increase the risk for functional impairment. Greater amounts of social integration were associated with less functional impairment among males (p<.01) and females (p<.05); social integration was associated with less functional impairment among males only (p<.01); and frequency of social contact was associated with less functional impairment among females only (p<.05), indicating that the association between social resource type and functioning differed by gender. Standardized beta coefficients indicated that social resources had a stronger effect on functioning among men compared to women. Among males who experienced DV, social integration was the only social resource associated with less functional impairment (p<.01); among male trauma survivors who did not experience DV, social support was the only resource associated with less functional impairment (p<.01). Further investigation into the association of social resources with functioning and how these differ by gender and DV exposure is warranted to inform intervention strategies for survivors of DV and other traumas in post-conflict settings. PMID:27021741

  5. Symptoms of problematic cellular phone use, functional impairment and its association with depression among adolescents in Southern Taiwan.

    PubMed

    Yen, Cheng-Fang; Tang, Tze-Chun; Yen, Ju-Yu; Lin, Huang-Chi; Huang, Chi-Fen; Liu, Shu-Chun; Ko, Chih-Hung

    2009-08-01

    The aims of this study were: (1) to examine the prevalence of symptoms of problematic cellular phone use (CPU); (2) to examine the associations between the symptoms of problematic CPU, functional impairment caused by CPU and the characteristics of CPU; (3) to establish the optimal cut-off point of the number of symptoms for functional impairment caused by CPU; and (4) to examine the association between problematic CPU and depression in adolescents. A total of 10,191 adolescent students in Southern Taiwan were recruited into this study. Participants' self-reported symptoms of problematic CPU and functional impairments caused by CPU were collected. The associations of symptoms of problematic CPU with functional impairments and with the characteristics of CPU were examined. The cut-off point of the number of symptoms for functional impairment was also determined. The association between problematic CPU and depression was examined by logistic regression analysis. The results indicated that the symptoms of problematic CPU were prevalent in adolescents. The adolescents who had any one of the symptoms of problematic CPU were more likely to report at least one dimension of functional impairment caused by CPU, called more on cellular phones, sent more text messages, or spent more time and higher fees on CPU. Having four or more symptoms of problematic CPU had the highest potential to differentiate between the adolescents with and without functional impairment caused by CPU. Adolescents who had significant depression were more likely to have four or more symptoms of problematic CPU. The results of this study may provide a basis for detecting symptoms of problematic CPU in adolescents.

  6. Effects of renal function on pharmacokinetics and pharmacodynamics of lesinurad in adult volunteers.

    PubMed

    Gillen, Michael; Valdez, Shakti; Zhou, Dongmei; Kerr, Bradley; Lee, Caroline A; Shen, Zancong

    2016-01-01

    Lesinurad is a selective uric acid reabsorption inhibitor approved for the treatment of gout in combination with a xanthine oxidase inhibitor (XOI) in patients who have not achieved target serum uric acid (sUA) levels with an XOI alone. Most people with gout have chronic kidney disease. The pharmacokinetics, pharmacodynamics, and safety of lesinurad were assessed in subjects with impaired renal function. Two Phase I, multicenter, open-label, single-dose studies enrolled subjects with normal renal function (estimated creatinine clearance [eCrCl] >90 mL/min; N=12) or mild (eCrCl 60-89 mL/min; N=8), moderate (eCrCl 30-59 mL/min; N=16), or severe (eCrCl <30 mL/min; N=6) renal impairment. Subjects were given a single oral lesinurad dose of 200 mg (N=24) or 400 mg (N=18). Blood and urine samples were analyzed for plasma lesinurad concentrations and serum and urine uric acid concentrations. Safety was assessed by adverse events and laboratory data. Mild, moderate, and severe renal impairment increased lesinurad plasma area under the plasma concentration-time curve by 34%, 54%-65%, and 102%, respectively. Lesinurad plasma C max was unaffected by renal function status. Lower renal clearance and urinary excretion of lesinurad were associated with the degree of renal impairment. The sUA-lowering effect of a single dose of lesinurad was similar between mild renal impairment and normal function, reduced in moderate impairment, and greatly diminished in severe impairment. Lesinurad increased urinary urate excretion in normal function and mild renal impairment; the increase was less with moderate or severe renal impairment. Lesinurad was well tolerated by all subjects. Lesinurad exposure increased with decreasing renal function; however, the effects of lesinurad on sUA were attenuated in moderate to severe renal impairment.

  7. Chemosensory interaction: acquired olfactory impairment is associated with decreased taste function.

    PubMed

    Landis, Basile N; Scheibe, Mandy; Weber, Cornelia; Berger, Robert; Brämerson, Annika; Bende, Mats; Nordin, Steven; Hummel, Thomas

    2010-08-01

    Olfaction, taste and trigeminal function are three distinct modalities. However, in daily life they are often activated concomitantly. In health and disease, it has been shown that in two of these senses, the trigeminal and olfactory senses, modification of one sense leads to changes in the other sense and vice versa. The objective of the study was to investigate whether and (if so) how, the third modality, taste, is influenced by olfactory impairment. We tested 210 subjects with normal (n = 107) or impaired (n = 103) olfactory function for their taste identification capacities. Validated tests were used for olfactory and gustatory testing (Sniffin' Sticks, Taste Strips). In an additional experiment, healthy volunteers underwent reversible olfactory cleft obstruction to investigate short-time changes of gustatory function after olfactory alteration. Mean gustatory identification (taste strip score) for the subjects with impaired olfaction was 19.4 +/- 0.6 points and 22.9 +/- 0.5 points for those with normal olfactory function (t = 4.6, p < 0.001). The frequencies of both, smell and taste impairments interacted significantly (Chi(2), F = 16.4, p < 0.001), and olfactory and gustatory function correlated (r (210) = 0.30, p < 0.001). Neither age nor olfactory impairment cause effects interfered with this olfactory-gustatory interaction. In contrast, after short-lasting induced olfactory decrease, gustatory function remained unchanged. The present study suggests that longstanding impaired olfactory function is associated with decreased gustatory function. These findings seem to extend previously described mutual chemosensory interactions also to smell and taste. It further raises the question whether chemical senses in general decrease mutually after acquired damage.

  8. Heterogeneity in ADHD: Neurocognitive predictors of peer, family, and academic functioning.

    PubMed

    Kofler, Michael J; Sarver, Dustin E; Spiegel, Jamie A; Day, Taylor N; Harmon, Sherelle L; Wells, Erica L

    2017-08-01

    Childhood attention-deficit/hyperactivity disorder (ADHD) is associated with impairments in peer, family, and academic functioning. Although impairment is required for diagnosis, children with ADHD vary significantly in the areas in which they demonstrate clinically significant impairment. However, relatively little is known about the mechanisms and processes underlying these individual differences. The current study examined neurocognitive predictors of heterogeneity in peer, family, and academic functioning in a well-defined sample of 44 children with ADHD aged 8-13 years (M = 10.31, SD = 1.42; 31 boys, 13 girls; 81% Caucasian). Reliable change analysis indicated that 98% of the sample demonstrated objectively-defined impairment on at least one assessed outcome measure; 65% were impaired in two or all three areas of functioning. ADHD children with quantifiable deficits in academic success and family functioning performed worse on tests of working memory (d = 0.68 to 1.09), whereas children with impaired parent-reported social functioning demonstrated slower processing speed (d = 0.53). Dimensional analyses identified additional predictors of peer, family, and academic functioning. Working memory abilities were associated with individual differences in all three functional domains, processing speed predicted social functioning, and inhibitory control predicted family functioning. These results add to a growing literature implicating neurocognitive abilities not only in explaining behavioral differences between ADHD and non-ADHD groups, but also in the substantial heterogeneity in ecologically-valid functional outcomes associated with the disorder.

  9. Airway somatosensory deficits and dysphagia in Parkinson's disease.

    PubMed

    Hammer, Michael J; Murphy, Caitlin A; Abrams, Trisha M

    2013-01-01

    Individuals with Parkinson's disease (PD) often experience substantial impairment of swallow control, and are typically unaware of the presence or severity of their impairments suggesting that these individuals may also experience airway sensory deficits. However, the degree to which impaired swallow function in PD may relate to airway sensory deficits has yet to be formally tested. The purpose of this study was to examine whether airway sensory function is associated with swallow impairment in PD. Eighteen PD participants and 18 healthy controls participated in this study and underwent endoscopic assessment of airway somatosensory function, endoscopic assessment of swallow function, and clinical ratings of swallow and disease severity. PD participants exhibited abnormal airway somatosensory function and greater swallow impairment compared with healthy controls. Swallow and sensory deficits in PD were correlated with disease severity. Moreover, PD participants reported similar self-rated swallow function as healthy controls, and swallow deficits were correlated with sensory function suggesting an association between impaired sensory function and poor self-awareness of swallow deficits in PD. These results suggest that control of swallow is influenced by airway somatosensory function, that swallow-related deficits in PD are related to abnormal somatosensation, and that swallow and airway sensory function may degrade as a function of disease severity. Therefore, the basal ganglia and related neural networks may play an important role to integrate airway sensory input for swallow-related motor control. Furthermore, the airway deficits observed in PD suggest a disintegration of swallow-related sensory and motor control.

  10. Psychosocial functioning in offspring of parents with bipolar disorder.

    PubMed

    Bella, Tolulope; Goldstein, Tina; Axelson, David; Obreja, Mihaela; Monk, Kelly; Hickey, Mary Beth; Goldstein, Benjamin; Brent, David; Diler, Rasim Somer; Kupfer, David; Sakolsky, Dara; Birmaher, Boris

    2011-09-01

    Offspring of parents with bipolar disorder are at increased risk for a range of psychopathology, including bipolar disorder. It is not clear if they also have impairments in their psychosocial functioning. We compared the psychosocial functioning of three groups of children enrolled in the Pittsburgh Bipolar Offspring Study (BIOS): offspring of probands with bipolar disorder (n=388), offspring of probands with other types of psychopathology (n=132), and offspring of healthy probands (n=118). Psychosocial functioning was assessed at study intake using the schedule of the Adolescent Longitudinal Interval Follow-Up Evaluation (A-LIFE), the Child Behavior Check List (CBCL) and the Children's Global Assessment Scale (CGAS). Offspring of probands with bipolar disorder exhibited impairments in various aspects of psychosocial functioning. On all measures, they had worse functioning in comparison with offspring of healthy probands. Offspring of probands with bipolar disorder generally exhibited more impairment than offspring of probands with nonbipolar psychopathology. After adjusting for proband parent functioning and the child's Axis I psychopathology, functioning of offspring of probands with bipolar disorder was similar to that of offspring of healthy probands. Data are cross-sectional and therefore do not allow for causal conclusions about the association between parental psychopathology, child psychopathology and offspring psychosocial functioning. Offspring of parents with bipolar disorder exhibit impairments in psychosocial functioning which appear largely attributable to proband parent functional impairment and the child's own psychopathology. As such, interventions to improve parental functioning, as well as early interventions to treat the child's psychopathology may help reduce the risk for long-term functional impairment in offspring. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. The Ways of the Hand: A Study of Hand Function among Blind, Visually Impaired and Visually Impaired Multi-Handicapped Children and Adolescents.

    ERIC Educational Resources Information Center

    Rogow, Sally M.

    1987-01-01

    The manual development of 148 blind, visually impaired, and visually impaired multi-handicapped students, aged 3-19, was studied. Results indicated a significant relationship between object manipulation and speech, and an inverse relationship between object manipulation and stereotypic hand mannerisms. Optimal development of manual functions and…

  12. Major Depressive Disorder Is Associated with Broad Impairments on Neuropsychological Measures of Executive Function: A Meta-Analysis and Review

    ERIC Educational Resources Information Center

    Snyder, Hannah R.

    2013-01-01

    Cognitive impairments are now widely acknowledged as an important aspect of major depressive disorder (MDD), and it has been proposed that executive function (EF) may be particularly impaired in patients with MDD. However, the existence and nature of EF impairments associated with depression remain strongly debated. Although many studies have…

  13. Differential Item Functioning Comparisons on a Performance-Based Alternate Assessment for Students with Severe Cognitive Impairments, Autism and Orthopedic Impairments

    ERIC Educational Resources Information Center

    Laitusis, Cara Cahalan; Maneckshana, Behroz; Monfils, Lora; Ahlgrim-Delzell, Lynn

    2009-01-01

    The purpose of this study was to examine Differential Item Functioning (DIF) by disability groups on an on-demand performance assessment for students with severe cognitive impairments. Researchers examined the presence of DIF for two comparisons. One comparison involved students with severe cognitive impairments who served as the reference group…

  14. Assessing physical function and physical activity in patients with CKD.

    PubMed

    Painter, Patricia; Marcus, Robin L

    2013-05-01

    Patients with CKD are characterized by low levels of physical functioning, which, along with low physical activity, predict poor outcomes in those treated with dialysis. The hallmark of clinical care in geriatric practice and geriatric research is the orientation to and assessment of physical function and functional limitations. Although there is increasing interest in physical function and physical activity in patients with CKD, the nephrology field has not focused on this aspect of care. This paper provides an in-depth review of the measurement of physical function and physical activity. It focuses on physiologic impairments and physical performance limitations (impaired mobility and functional limitations). The review is based on established frameworks of physical impairment and functional limitations that have guided research in physical function in the aging population. Definitions and measures for physiologic impairments, physical performance limitations, self-reported function, and physical activity are presented. On the basis of the information presented, recommendations for incorporating routine assessment of physical function and encouragement for physical activity in clinical care are provided.

  15. Cognitive Ability as a Resource for Everyday Functioning among Older Adults Who Are Visually Impaired

    ERIC Educational Resources Information Center

    Heyl, Vera; Wahl, Hans-Werner

    2010-01-01

    This article reports on a study that investigated the role of cognitive resources in the everyday functioning of 121 older adults who were visually impaired and 150 sighted older adults, with a mean age of 82 years. Cognitive performance and everyday functioning were most strongly related in the group who were visually impaired. The authors…

  16. Reduced global brain metabolism but maintained vascular function in amnestic mild cognitive impairment.

    PubMed

    Thomas, Binu P; Sheng, Min; Tseng, Benjamin Y; Tarumi, Takashi; Martin-Cook, Kristen; Womack, Kyle B; Cullum, Munro C; Levine, Benjamin D; Zhang, Rong; Lu, Hanzhang

    2017-04-01

    Amnestic mild cognitive impairment represents an early stage of Alzheimer's disease, and characterization of physiological alterations in mild cognitive impairment is an important step toward accurate diagnosis and intervention of this condition. To investigate the extent of neurodegeneration in patients with mild cognitive impairment, whole-brain cerebral metabolic rate of oxygen in absolute units of µmol O 2 /min/100 g was quantified in 44 amnestic mild cognitive impairment and 28 elderly controls using a novel, non-invasive magnetic resonance imaging method. We found a 12.9% reduction ( p = 0.004) in cerebral metabolic rate of oxygen in mild cognitive impairment, which was primarily attributed to a reduction in the oxygen extraction fraction, by 10% ( p = 0.016). Global cerebral blood flow was not found to be different between groups. Another aspect of vascular function, cerebrovascular reactivity, was measured by CO 2 -inhalation magnetic resonance imaging and was found to be equivalent between groups. Therefore, there seems to be a global, diffuse diminishment in neural function in mild cognitive impairment, while their vascular function did not show a significant reduction.

  17. Individual and Area Level Socioeconomic Status and Its Association with Cognitive Function and Cognitive Impairment (Low MMSE) among Community-Dwelling Elderly in Singapore.

    PubMed

    Wee, Liang En; Yeo, Wei Xin; Yang, Gui Rong; Hannan, Nazirul; Lim, Kenny; Chua, Christopher; Tan, Mae Yue; Fong, Nikki; Yeap, Amelia; Chen, Lionel; Koh, Gerald Choon-Huat; Shen, Han Ming

    2012-01-01

    Neighborhood socioeconomic status (SES) can affect cognitive function. We assessed cognitive function and cognitive impairment among community-dwelling elderly in a multi-ethnic urban low-SES Asian neighborhood and compared them with a higher-SES neighborhood. The study population involved all residents aged ≥60 years in two housing estates comprising owner-occupied housing (higher SES) and rental flats (low SES) in Singapore in 2012. Cognitive impairment was defined as <24 on the Mini Mental State Examination. Demographic/clinical details were collected via questionnaire. Multilevel linear regression was used to evaluate factors associated with cognitive function, while multilevel logistic regression determined predictors of cognitive impairment. Participation was 61.4% (558/909). Cognitive impairment was found in 26.2% (104/397) of residents in the low-SES community and in 16.1% (26/161) of residents in the higher-SES community. After adjusting for other sociodemographic variables, living in a low-SES community was independently associated with poorer cognitive function (β = -1.41, SD = 0.58, p < 0.01) and cognitive impairment (adjusted odds ratio 5.13, 95% CI 1.98-13.34). Among cognitively impaired elderly in the low-SES community, 96.2% (100/104) were newly detected. Living in a low-SES community is independently associated with cognitive impairment in an urban Asian society.

  18. Subjective daytime functioning assessment in people with insomnia.

    PubMed

    Grabowski, Karol; Nowicka-Sauer, Katarzyna; Zdrojewski, Tomasz; Rutkowski, Marcin; Bandosz, Piotr; Nowicki, Zbigniew

    2017-10-29

    The aim of this study was to assess the prevalence and severity of subjective daytime functioning impairment among people with insomnia complaints. Another goal was to establish its relationships with age, gender, type and duration of subjective insomnia. Study group consisted of NATPOL study participants - 2,413 people (1,245 women and 1,168 men) aged 18-79. We extracted group with declared insomnia complaints, consisting of 1,221 people (736 women and 485 men) aged 18-79. Data on insomnia symptoms characteristics, their duration and subjective functioning impairment were further analyzed. Functioning impairment was declared by 825 people (67.7% of those who declared subjective insomnia) and it was more common in women. It was most common among people with insomnia complaints lasting over two weeks - 72.4%. In people with symptoms lasting less than two weeks or for a few days it was 70.7% and 64.9% respectively. People with insomnia symptoms lasting over two weeks accounted for 20% of group with severe functioning impairment. For shorter duration of symptoms it was 8.6% and 6.9% respectively. Among people with mild functioning impairment, persons with symptoms lasting for a few days and less than two weeks were predominant - 32.5% and 35.3% respectively. In people aged 18-24 years mild functioning impairment was predominant (66.66%). Subjective daytime functioning impairment is common in people declaring insomnia symptoms. It is more common in women and its prevalence and intensity are greater in people with longer duration of sleep problems. Its prevalence is not correlated with age and it is the mildest in people aged 18-24.

  19. Changes in Neuropsychological Status during the Initial Phase of Abstinence in Alcohol Use Disorder: Neurocognitive Impairment and Implications for Clinical Care.

    PubMed

    Mulhauser, Kyler; Weinstock, Jeremiah; Ruppert, Phillip; Benware, Jeffrey

    2018-05-12

    Neuropsychological deficits are common in individuals with alcohol use disorder (AUD) and impact daily functioning and AUD treatment outcomes. Longitudinal studies demonstrate that extended abstinence improves neuropsychological functioning. The effects of short-term abstinence are less clear. This study examined changes in neuropsychological functioning after acute detoxification over a 10-day period at the beginning of residential AUD treatment. Notably, this study evaluated cognitive functioning according to diagnostic classifications for neurocognitive disorder according to DSM-5. Using a within-subjects design, neuropsychological functioning of participants (N = 28) undergoing a 14-day residential AUD treatment program was assessed at two time points over 10 days (i.e., treatment entry, prior to treatment discharge). Tests of immediate memory, visuospatial abilities, attention, language abilities, delayed memory, and executive functioning were administered. After completing acute detoxification, almost all participants (93%) were clinically impaired in at least one of the five cognitive domains at residential treatment entry, with one third of the sample impaired on ≥3 domains. Ten days later, 71% remained clinically impaired in at least one of five cognitive domains, with 29% of the sample impaired on ≥3 domains. Significant improvement over the 10-day period was observed for immediate memory, visuospatial abilities, and overall cognitive functioning. Clinical significance of these changes is also reported. Conclusions/Importance: The results from this study help to characterize cognitive functioning in terms of neurocognitive impairment. A brief period of abstinence begins to ameliorate neuropsychological deficits, but many individuals remain cognitively impaired throughout treatment. Implications for treatment are discussed.

  20. Contrasting olfaction, vision, and audition as predictors of cognitive change and impairment in non-demented older adults.

    PubMed

    MacDonald, Stuart W S; Keller, Connor J C; Brewster, Paul W H; Dixon, Roger A

    2018-05-01

    This study examines the relative utility of a particular class of noninvasive functional biomarkers-sensory functions-for detecting those at risk of cognitive decline and impairment. Three central research objectives were examined including whether (a) olfactory function, vision, and audition exhibited significant longitudinal declines in nondemented older adults; (b) multiwave change for these sensory function indicators predicted risk of mild cognitive impairment (MCI); and (c) change within persons for each sensory measure shared dynamic time-varying associations with within-person change in cognitive functioning. A longitudinal sample (n = 408) from the Victoria Longitudinal Study was assembled. Three cognitive status subgroups were identified: not impaired cognitively, single-assessment MCI, and multiple-assessment MCI. We tested independent predictive associations, contrasting change in sensory function as predictors of cognitive decline and impairment, utilizing both linear mixed models and logistic regression analysis. Olfaction and, to a lesser extent, vision were identified as the most robust predictors of cognitive status and decline; audition showed little predictive influence. These findings underscore the potential utility of deficits in olfactory function, in particular, as an early marker of age- and pathology-related cognitive decline. Functional biomarkers may represent potential candidates for use in the early stages of a multistep screening approach for detecting those at risk of cognitive impairment, as well as for targeted intervention. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  1. Managing daily life with age-related sensory loss: cognitive resources gain in importance.

    PubMed

    Heyl, Vera; Wahl, Hans-Werner

    2012-06-01

    This paper investigates the role of cognitive resources in everyday functioning, comparing visually impaired, hearing impaired, and sensory unimpaired older adults. According to arguments that cognitive resources are of increased importance and a greater awareness of cognitive restrictions exists among sensory impaired individuals, in particular among visually impaired individuals, we hypothesized differential relationships between resources and outcomes when comparing sensory impaired and sensory unimpaired older adults. Findings are based on samples of 121 visually impaired, 116 hearing impaired, and 150 sensory unimpaired older adults (M = 82 years). Results from a sample of 43 dual sensory impaired older adults are reported for comparison. Assessment relied on established instruments (e.g., WAIS-R, ADL/IADL). Structural equation modeling showed that cognitive resources and behavior-related everyday functioning were more strongly related in the sensory impaired groups as compared to the sensory unimpaired group. Cognitive resources and evaluation of everyday functioning were significantly linked only among the sensory impaired groups. When medical condition was controlled for, these effects persisted. It is concluded that both cognitive training as well as psychosocial support may serve as important additions to classic vision and hearing loss rehabilitation. PsycINFO Database Record (c) 2012 APA, all rights reserved

  2. Executive Functioning Heterogeneity in Pediatric ADHD.

    PubMed

    Kofler, Michael J; Irwin, Lauren N; Soto, Elia F; Groves, Nicole B; Harmon, Sherelle L; Sarver, Dustin E

    2018-04-28

    Neurocognitive heterogeneity is increasingly recognized as a valid phenomenon in ADHD, with most estimates suggesting that executive dysfunction is present in only about 33%-50% of these children. However, recent critiques question the veracity of these estimates because our understanding of executive functioning in ADHD is based, in large part, on data from single tasks developed to detect gross neurological impairment rather than the specific executive processes hypothesized to underlie the ADHD phenotype. The current study is the first to comprehensively assess heterogeneity in all three primary executive functions in ADHD using a criterion battery that includes multiple tests per construct (working memory, inhibitory control, set shifting). Children ages 8-13 (M = 10.37, SD = 1.39) with and without ADHD (N = 136; 64 girls; 62% Caucasian/Non-Hispanic) completed a counterbalanced series of executive function tests. Accounting for task unreliability, results indicated significantly improved sensitivity and specificity relative to prior estimates, with 89% of children with ADHD demonstrating objectively-defined impairment on at least one executive function (62% impaired working memory, 27% impaired inhibitory control, 38% impaired set shifting; 54% impaired on one executive function, 35% impaired on two or all three executive functions). Children with working memory deficits showed higher parent- and teacher-reported ADHD inattentive and hyperactive/impulsive symptoms (BF 10  = 5.23 × 10 4 ), and were slightly younger (BF 10  = 11.35) than children without working memory deficits. Children with vs. without set shifting or inhibitory control deficits did not differ on ADHD symptoms, age, gender, IQ, SES, or medication status. Taken together, these findings confirm that ADHD is characterized by neurocognitive heterogeneity, while suggesting that contemporary, cognitively-informed criteria may provide improved precision for identifying a smaller number of neuropsychologically-impaired subtypes than previously described.

  3. Post-tuberculous lung function impairment in a tuberculosis reference clinic in Cameroon.

    PubMed

    Mbatchou Ngahane, Bertrand Hugo; Nouyep, Junior; Nganda Motto, Malea; Mapoure Njankouo, Yacouba; Wandji, Adeline; Endale, Mireille; Afane Ze, Emmanuel

    2016-05-01

    After completion of treatment, a proportion of pulmonary TB (pTB) patients experience lung function impairment which can influence their quality of life. This study aimed to determine the prevalence of lung function impairment in patients treated for pTB and investigate its associated factors. A cross-sectional study was conducted in TB clinic of the Douala Laquintinie Hospital in Cameroon. Patients aged 15 and above who were treated for pTB between 2008 and 2012 were included in the study. Demographic data, respiratory symptoms prior TB diagnosis, comorbidities and chest radiography findings prior to TB treatment were collected. All participants underwent spirometric measurements. Airflow obstruction was defined as a post-bronchodilation FEV1/FVC <70% with FVC >80%, restrictive defects as an FEV1/FVC ratio of ≥70% with an FVC <80% predicted, and mixed defects as FVC of <80% predicted and an FEV1/FVC ratio of <70%. Lung function impairment was defined by the presence of at least one of these three abnormalities. Logistic regression analysis was employed to investigate risk factors of lung function impairment. Of a total of 269 participants included in the study, 146 (54.3%) were male. The median age of participants was 33 years. The median duration of symptoms before diagnosis of TB was 4 weeks [interquartile range (IQR) 3-8]. The prevalence of lung function impairment was 45.4% (95% CI 39-51). The multivariate analysis identified duration of symptoms [OR 1.08; 95% CI (1.01-1.15)] and fibrotic pattern [OR 3.54; 95% CI (1.40-8.95)] as independent risk factors for lung function impairment. Post-tuberculous pulmonary function impairment is frequent in Douala. Sensitization of patient with symptoms of pulmonary TB for an earlier visit to healthcare facilities could reduce the impact of pTB on lung function of patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. ASSESSMENT OF UPPER EXTREMITY IMPAIRMENT, FUNCTION, AND ACTIVITY FOLLOWING STROKE: FOUNDATIONS FOR CLINICAL DECISION MAKING

    PubMed Central

    Lang, Catherine E.; Bland, Marghuretta D.; Bailey, Ryan R.; Schaefer, Sydney Y.; Birkenmeier, Rebecca L.

    2012-01-01

    The purpose of this review is to provide a comprehensive approach for assessing the upper extremity (UE) after stroke. First, common upper extremity impairments and how to assess them are briefly discussed. While multiple UE impairments are typically present after stroke, the severity of one impairment, paresis, is the primary determinant of UE functional loss. Second, UE function is operationally defined and a number of clinical measures are discussed. It is important to consider how impairment and loss of function affect UE activity outside of the clinical environment. Thus, this review also identifies accelerometry as an objective method for assessing UE activity in daily life. Finally, the role that each of these levels of assessment should play in clinical decision making is discussed in order to optimize the provision of stroke rehabilitation services. PMID:22975740

  5. Cognitive profile in Duchenne muscular dystrophy boys without intellectual disability: The role of executive functions.

    PubMed

    Battini, R; Chieffo, D; Bulgheroni, S; Piccini, G; Pecini, C; Lucibello, S; Lenzi, S; Moriconi, F; Pane, M; Astrea, G; Baranello, G; Alfieri, P; Vicari, S; Riva, D; Cioni, G; Mercuri, E

    2018-02-01

    The aim of our prospective observational study was to assess profiles of cognitive function and a possible impairment of executive functions in a cohort of boys with Duchenne muscular dystrophy without intellectual and behavior disability. Forty Duchenne boys (range of age: 6 years to 11 years and 6 months) were assessed by Wechsler Intelligence scale and battery of tests including tasks assessing working memory and executive functions (inhibition and switching, problem solving and planning). In our cohort some aspects of cognitive function were often impaired. These included multitasking, problem solving, inhibition and working memory necessary to plan and direct goal oriented behavior. Our results support the suggestion that aspects of cognitive function could be impaired even in boys without intellectual disability and support the hypothesis that executive functions may play an important role in specific aspects of cognitive impairment in Duchenne muscular dystrophy. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. A network analysis of DSM-5 posttraumatic stress disorder and functional impairment in UK treatment-seeking veterans.

    PubMed

    Ross, Jana; Murphy, Dominic; Armour, Cherie

    2018-05-28

    Network analysis is a relatively new methodology for studying psychological disorders. It focuses on the associations between individual symptoms which are hypothesized to mutually interact with each other. The current study represents the first network analysis conducted with treatment-seeking military veterans in UK. The study aimed to examine the network structure of posttraumatic stress disorder (PTSD) symptoms and four domains of functional impairment by identifying the most central (i.e., important) symptoms of PTSD and by identifying those symptoms of PTSD that are related to functional impairment. Participants were 331 military veterans with probable PTSD. In the first step, a network of PTSD symptoms based on the PTSD Checklist for DSM-5 was estimated. In the second step, functional impairment items were added to the network. The most central symptoms of PTSD were recurrent thoughts, nightmares, negative emotional state, detachment and exaggerated startle response. Functional impairment was related to a number of different PTSD symptoms. Impairments in close relationships were associated primarily with the negative alterations in cognitions and mood symptoms and impairments in home management were associated primarily with the reexperiencing symptoms. The results are discussed in relation to previous PTSD network studies and include implications for clinical practice. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Association of Dynapenia, Sarcopenia, and Cognitive Impairment Among Community-Dwelling Older Taiwanese.

    PubMed

    Huang, Chung-Yu; Hwang, An-Chun; Liu, Li-Kuo; Lee, Wei-Ju; Chen, Liang-Yu; Peng, Li-Ning; Lin, Ming-Hsien; Chen, Liang-Kung

    2016-02-01

    A decline in physical and/or cognitive function is a common feature of aging, and frailty has been shown to be associated with cognitive impairment and dementia. This study aimed to evaluate the association between dynapenia, sarcopenia, and cognitive impairment among community-dwelling older people in Taiwan. Data from the I-Lan Longitudinal Aging Study (ILAS) were retrieved for study. Global cognitive function was assessed by Mini-Mental State Examination (MMSE), whereas the Chinese Version Verbal Learning Test, Boston Naming Test, Verbal Fluency Test, Taylor Complex Figure Test, Digits Backward Test, and Clock Drawing Test were used to assess different domains of cognitive function. Association between sarcopenia and global cognitive function as well as all different dimensions of cognitive function were evaluated. Data from 731 elderly participants (mean age 73.4 ± 5.4 years, 53.8% males) were used for study analysis. The overall prevalence of sarcopenia was 6.8%, which was significantly higher in men (9.3% versus 4.1%, p < 0.05). The mean MMSE score was 23.4 ± 4.4 for all participants, and 10.3% of the study participants were cognitively impaired. Sarcopenia was not significantly associated with global cognitive function (odds ratio [OR] = 1.55, p = 0.317), but global cognitive impairment was significantly associated with low physical performance (OR = 2.31, p = 0.003) and low muscle strength (OR = 2.59, p = 0.011). Nonetheless, sarcopenia was significantly associated with impairment in the verbal fluency test (OR = 3.96, p = 0.006) after adjustment for potential confounders. Dynapenia was significantly associated with cognitive impairment in multiple dimensions and global cognitive function, but sarcopenia was only associated with an impaired verbal fluency test. Reduced muscle strength and/or physical performance related to non-muscle etiology were strongly associated with cognitive impairment. More longitudinal studies are needed.

  8. Safety, Tolerability, and Pharmacokinetics of Ribavirin in Hepatitis C Virus-Infected Patients with Various Degrees of Renal Impairment

    PubMed Central

    Wang, K.; Blotner, S.; Magnusson, M. O.; Wilkins, J. J.; Martin, P.; Solsky, J.; Nieforth, K.; Wat, C.; Grippo, J. F.

    2013-01-01

    Ribavirin (RBV) is an integral part of standard-of-care hepatitis C virus (HCV) treatments and many future regimens under investigation. The pharmacokinetics (PK), safety, and tolerability of RBV in chronically HCV-infected patients with renal impairment are not well defined and were the focus of an open-label PK study in HCV-infected patients receiving RBV plus pegylated interferon. Serial RBV plasma samples were collected over 12 h on day 1 of weeks 1 and 12 from patients with moderate renal impairment (creatinine clearance [CLCR], 30 to 50 ml/min; RBV, 600 mg daily), severe renal impairment (CLCR, <30 ml/min; RBV, 400 mg daily), end-stage renal disease (ESRD) (RBV, 200 mg daily), or normal renal function (CLCR, >80 ml/min; RBV, 800 to 1,200 mg daily). Of the 44 patients, 9 had moderately impaired renal function, 10 had severely impaired renal function, 13 had ESRD, and 12 had normal renal function. The RBV dose was reduced because of adverse events (AEs) in 71% and 53% of severe and moderate renal impairment groups, respectively. Despite this modification, patients with moderate and severe impairment had 12-hour (area under the concentration-time curve from 0 to 12 h [AUC0–12]) values 36% (38,452 ng · h/ml) and 25% (35,101 ng · h/ml) higher, respectively, than those with normal renal function (28,192 ng · h/ml). Patients with ESRD tolerated a 200-mg daily dose, and AUC0–12 was 20% lower (22,629 ng · h/ml) than in patients with normal renal function. PK modeling and simulation (M&S) indicated that doses of 200 mg or 400 mg alternating daily for patients with moderate renal impairment and 200 mg daily for patients with severe renal impairment were the most appropriate dose regimens in these patients. PMID:24080649

  9. Body representation disorders predict left right orientation impairments after stroke: A voxel-based lesion symptom mapping study.

    PubMed

    van Stralen, Haike E; Dijkerman, H Chris; Biesbroek, J Matthijs; Kuijf, Hugo J; van Gemert, H Maarten A; Sluiter, David; Kappelle, L Jaap; van Zandvoort, Martine J E

    2017-06-07

    Deficits in the ability to distinguish between the left and right side of the body can severely impair daily life functioning. The current study examined the relation between left right orientation (LRO) impairments and somatosensory related deficits, ranging from primary somatosensory impairments to body representation impairments, in patients who suffered a recent stroke. We also examined which areas in the brain are associated with LRO impairments using a Voxel-based Lesion Symptom Mapping (VLSM) analysis. We tested 47 first-ever stroke patients and 48 age-matched healthy controls. LRO was assessed with the Bergen Right Left Discrimination Test (BRLD). Impairments on primary somatosensory function (touch perception, proprioception), higher order somatosensory function (finger gnosis, subjective sense of body ownership) and other cognitive functions (language, attention & working memory, visuospatial neglect) were entered as predictors in a logistic regression analyses. Outcome measures consisted of the BRLD-total performance which was further subdivided in performance for 1) first person perspective stimuli, 2) third person perspective stimuli, 3) alternating between first- and third person perspective. Impairments on BRLD-total performance was predicted by impairments in finger gnosis and visuospatial neglect. For items placed in third person perspective, performance was predicted by body representation impairments; finger agnosia and the subjective sense of body ownership. VLSM analysis showed a significant association between LRO impairments and damage to the right insula. The current study suggests that the somatosensory system is important for LRO. Furthermore, the results indicate that an affected body representation may hinder adopting a third person perspective that may subsequently also lead to LRO impairments. The right insular cortex appeared crucially involved in these processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. A continuum of executive function deficits in early subcortical vascular cognitive impairment: A systematic review and meta-analysis.

    PubMed

    Sudo, Felipe Kenji; Amado, Patricia; Alves, Gilberto Sousa; Laks, Jerson; Engelhardt, Eliasz

    2017-01-01

    Subcortical Vascular Cognitive Impairment (SVCI) is a clinical continuum of vascular-related cognitive impairment, including Vascular Mild Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive Function (EF) are hallmarks of the disorder, but the best methods to assess this function have yet to be determined. The insidious and almost predictable course of SVCI and the multidimensional concept of EF suggest that a temporal dissociation of impairments in EF domains exists early in the disorder. This study aims to review and analyze data from the literature about performance of VaMCI patients on the most used EF tests through a meta-analytic approach. Medline, Web of Knowledge and PsycINFO were searched, using the terms: "vascular mild cognitive impairment" OR "vascular cognitive impairment no dementia" OR "vascular mild neurocognitive disorder" AND "dysexecutive" OR "executive function". Meta-analyses were conducted for each of the selected tests, using random-effect models. Systematic review showed major discrepancies among the results of the studies included. Meta-analyses evidenced poorer performance on the Trail-Making Test part B and the Stroop color test by VaMCI patients compared to controls. A continuum of EF impairments has been proposed in SVCI. Early deficits appear to occur in cognitive flexibility and inhibitory control.

  11. Pharmacokinetic Properties of Fostamatinib in Patients With Renal or Hepatic Impairment: Results From 2 Phase I Clinical Studies.

    PubMed

    Martin, Paul; Oliver, Stuart; Gillen, Michael; Marbury, Thomas; Millson, David

    2015-12-01

    Phase III trials of fostamatinib, an oral spleen tyrosine kinase inhibitor, in the treatment of rheumatoid arthritis have been completed. Herein, we report the effects of renal and hepatic impairment on the pharmacokinetic (PK) properties of the active metabolite of fostamatinib, R406, in plasma, and on the urinary excretion of R406 and its metabolite N-glucuronide. Two Phase I, single-center, open-label clinical trials determined the PK properties and tolerability of fostamatinib in subjects with normal or impaired renal or hepatic function. Twenty-four subjects in the study in renal impairment (8 per group: normal renal function, moderate renal dysfunction, or end-stage renal disease [ESRD]), and 32 subjects in the study in hepatic impairment (8 per group: normal hepatic function or mild, moderate, or severe hepatic impairment) received a single 150-mg dose of fostamatinib. Patients with ESRD in the study in renal impairment participated in 2 treatment periods separated by a ≥1-week washout. In these patients, fostamatinib was administered after dialysis or 2 hours before dialysis. Geometric mean R406 Cmax and AUC values were less in the combined renally impaired group than in the group with normal renal function; Tmax was similar across groups. However, renal impairment had no apparent effect considered clinically relevant on unbound R406. In patients with ESRD, R406 exposure was less when fostamatinib was administered after compared with before dialysis. Urinary excretion of R406 N-glucuronide was decreased with increasing severity of renal impairment. Renal elimination of R406 was negligible in all groups. Varying degrees of hepatic impairment had no consistent effects on the PK properties of R406. R406 Cmax values were 10% to 15% less in all hepatically impaired groups than in the group with normal hepatic function. AUC and Tmax values were similar between the groups with normal and severely impaired hepatic function; in the groups with mild or moderate hepatic impairment, AUC was less and Tmax was greater. The geometric mean percentage of unbound R406 ranged from 0.64% to 1.95% and was greatest in the group with severe hepatic impairment. The urinary excretion of R406 was minimal. The amount of R406 N-glucuronide excreted in urine was greater in severely hepatically impaired patients. Fostamatinib 150 mg was generally well tolerated. In these patients, renal or hepatic impairment did not affect exposure to the active metabolite of fostamatinib, R406, to a clinically relevant extent. ClinicalTrials.gov identifiers: NCT01245790 (renal) and NCT01222455 (hepatic). Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

  12. Pain, Bullying Involvement, and Mental Health Problems Among Children and Adolescents With ADHD in Taiwan.

    PubMed

    Yeh, Yi-Chun; Huang, Mei-Feng; Wu, Yu-Yu; Hu, Huei-Fan; Yen, Cheng-Fang

    2017-08-01

    The aim of this study was to examine the relationships of pain and pain-induced functional impairment with bullying involvement, as well as the relationships between pain and mental health problems among 474 children and adolescents with ADHD. The levels of pain, pain-induced functional impairment, involvement in bullying, depression, anxiety, ADHD symptoms, and sleep quality were assessed. Both victims of verbal and relational bullying and victims of physical bullying were more likely to have pain and pain-induced functional impairment than nonvictims. The perpetrators of verbal and relational bullying were more likely to have pain than the nonperpetrators. Participants with pain and pain-induced functional impairment experienced more severe depression and anxiety and worse sleep quality than did those without pain or pain-induced functional impairment. Clinical and educational professionals should consider the possibility of involvement in bullying and comorbid depression, anxiety, and poor sleep quality among ADHD children and adolescents with pain problems.

  13. Different Functional and Microstructural Changes Depending on Duration of Mild Cognitive Impairment in Parkinson Disease.

    PubMed

    Shin, N-Y; Shin, Y S; Lee, P H; Yoon, U; Han, S; Kim, D J; Lee, S-K

    2016-05-01

    The higher cortical burden of Lewy body and Alzheimer disease-type pathology has been reported to be associated with a faster onset of cognitive impairment of Parkinson disease. So far, there has been a few studies only about the changes of gray matter volume depending on duration of cognitive impairment in Parkinson disease. Therefore, our aim was to evaluate the different patterns of structural and functional changes in Parkinson disease with mild cognitive impairment according to the duration of parkinsonism before mild cognitive impairment. Fifty-nine patients with Parkinson disease with mild cognitive impairment were classified into 2 groups on the basis of shorter (<1 year, n = 16) and longer (≥1 year, n = 43) durations of parkinsonism before mild cognitive impairment. Fifteen drug-naïve patients with de novo Parkinson disease with intact cognition were included for comparison. Cortical thickness, Tract-Based Spatial Statistics, and seed-based resting-state functional connectivity analyses were performed. Age, sex, years of education, age at onset of parkinsonism, and levodopa-equivalent dose were included as covariates. The group with shorter duration of parkinsonism before mild cognitive impairment showed decreased fractional anisotropy and increased mean and radial diffusivity values in the frontal areas compared with the group with longer duration of parkinsonism before mild cognitive impairment (corrected P < .05). The group with shorter duration of parkinsonism before mild cognitive impairment showed decreased resting-state functional connectivity in the default mode network area when the left or right posterior cingulate was used as a seed, and in the dorsolateral prefrontal areas when the left or right caudate was used as a seed (corrected P < .05). The group with longer duration of parkinsonism before mild cognitive impairment showed decreased resting-state functional connectivity mainly in the medial prefrontal cortex when the left or right posterior cingulate was used as a seed, and in the parieto-occipital areas when the left or right caudate was used as a seed (corrected P < .05). No differences in cortical thickness were found in all group contrasts. Resting-state functional connectivity and WM alterations might be useful imaging biomarkers for identifying changes in patients with Parkinson disease with mild cognitive impairment according to the duration of parkinsonism before mild cognitive impairment. The functional and microstructural substrates may topographically differ depending on the rate of cognitive decline in these patients. © 2016 by American Journal of Neuroradiology.

  14. Understanding Pervasive Language Impairment in Young Children: Exploring Patterns in Narrative Language and Functional Communication

    ERIC Educational Resources Information Center

    Waters, Anna Jeddeloh

    2013-01-01

    Research has identified language impairment as a pervasive disability (Bishop & Edmundson, 1987; Greenhalgh & Strong, 2001). Classroom communication behaviors have a role in the maintenance of special education eligibility and functional communication difficulties for young children with language impairment. This paper reviews the…

  15. Israeli adolescents with ongoing exposure to terrorism: suicidal ideation, posttraumatic stress disorder, and functional impairment.

    PubMed

    Chemtob, Claude M; Pat-Horenczyk, Ruth; Madan, Anita; Pitman, Seth R; Wang, Yanping; Doppelt, Osnat; Burns, Kelly Dugan; Abramovitz, Robert; Brom, Daniel

    2011-12-01

    In this study, we examined the relationships among terrorism exposure, functional impairment, suicidal ideation, and probable partial or full posttraumatic stress disorder (PTSD) from exposure to terrorism in adolescents continuously exposed to this threat in Israel. A convenience sample of 2,094 students, aged 12 to 18, was drawn from 10 Israeli secondary schools. In terms of demographic factors, older age was associated with increased risk for suicidal ideation, OR = 1.33, 95% CI [1.09, 1.62], p < .01, but was protective against probable partial or full PTSD, OR = 0.72, 95% CI [0.54, 0.95], p < .05; female gender was associated with greater likelihood of probable partial or full PTSD, OR = 1.57, 95% CI [1.02, 2.40], p < .05. Exposure to trauma due to terrorism was associated with increased risk for each of the measured outcomes including probable partial or full PTSD, functional impairment, and suicidal ideation. When age, gender, level of exposure to terrorism, probable partial or full PTSD, and functional impairment were examined together, only terrorism exposure and functional impairment were associated with suicidal ideation. This study underscores the importance and feasibility of examining exposure to terrorism and functional impairment as risk factors for suicidal ideation. Copyright © 2011 International Society for Traumatic Stress Studies.

  16. Impairment in Occupational Functioning and Adult ADHD: The Predictive Utility of Executive Function (EF) Ratings Versus EF Tests

    PubMed Central

    Barkley, Russell A.; Murphy, Kevin R.

    2010-01-01

    Attention deficit hyperactivity disorder (ADHD) is associated with deficits in executive functioning (EF). ADHD in adults is also associated with impairments in major life activities, particularly occupational functioning. We investigated the extent to which EF deficits assessed by both tests and self-ratings contributed to the degree of impairment in 11 measures involving self-reported occupational problems, employer reported workplace adjustment, and clinician rated occupational adjustment. Three groups of adults were recruited as a function of their severity of ADHD: ADHD diagnosis (n = 146), clinical controls self-referring for ADHD but not diagnosed with it (n = 97), and community controls (n = 109). Groups were combined and regression analyses revealed that self-ratings of EF were significantly predictive of impairments in all 11 measures of occupational adjustment. Although several tests of EF also did so, they contributed substantially less than did the EF ratings, particularly when analyzed jointly with the ratings. We conclude that EF deficits contribute to the impairments in occupational functioning that occur in conjunction with adult ADHD. Ratings of EF in daily life contribute more to such impairments than do EF tests, perhaps because, as we hypothesize, each assesses a different level in the hierarchical organization of EF as a meta-construct. PMID:20197297

  17. Depression, anxiety and somatization in primary care: syndrome overlap and functional impairment.

    PubMed

    Löwe, Bernd; Spitzer, Robert L; Williams, Janet B W; Mussell, Monika; Schellberg, Dieter; Kroenke, Kurt

    2008-01-01

    To determine diagnostic overlap of depression, anxiety and somatization as well as their unique and overlapping contribution to functional impairment. Two thousand ninety-one consecutive primary care clinic patients participated in a multicenter cross-sectional survey in 15 primary care clinics in the United States (participation rate, 92%). Depression, anxiety, somatization and functional impairment were assessed using validated scales from the Patient Health Questionnaire (PHQ) (PHQ-8, eight-item depression module; GAD-7, seven-item Generalized Anxiety Disorder Scale; and PHQ-15, 15-item somatic symptom scale) and the Short-Form General Health Survey (SF-20). Multiple linear regression analyses were used to investigate unique and overlapping associations of depression, anxiety and somatization with functional impairment. In over 50% of cases, comorbidities existed between depression, anxiety and somatization. The contribution of the commonalities of depression, anxiety and somatization to functional impairment substantially exceeded the contribution of their independent parts. Nevertheless, depression, anxiety and somatization did have important and individual effects (i.e., separate from their overlap effect) on certain areas of functional impairment. Given the large syndrome overlap, a potential consideration for future diagnostic classification would be to describe basic diagnostic criteria for a single overarching disorder and to optionally code additional diagnostic features that allow a more detailed classification into specific depressive, anxiety and somatoform subtypes.

  18. Myocardial Perfusion and Function Are Distinctly Altered by Sevoflurane Anesthesia in Diet-Induced Prediabetic Rats.

    PubMed

    van den Brom, Charissa E; Boly, Chantal A; Bulte, Carolien S E; van den Akker, Rob F P; Kwekkeboom, Rick F J; Loer, Stephan A; Boer, Christa; Bouwman, R Arthur

    2016-01-01

    Preservation of myocardial perfusion during surgery is particularly important in patients with increased risk for perioperative complications, such as diabetes. Volatile anesthetics, like sevoflurane, have cardiodepressive effects and may aggravate cardiovascular complications. We investigated the effect of sevoflurane on myocardial perfusion and function in prediabetic rats. Rats were fed a western diet (WD; n = 18) or control diet (CD; n = 18) for 8 weeks and underwent (contrast) echocardiography to determine perfusion and function during baseline and sevoflurane exposure. Myocardial perfusion was estimated based on the product of microvascular filling velocity and blood volume. WD-feeding resulted in a prediabetic phenotype characterized by obesity, hyperinsulinemia, hyperlipidemia, glucose intolerance, and hyperglycemia. At baseline, WD-feeding impaired myocardial perfusion and systolic function compared to CD-feeding. Exposure of healthy rats to sevoflurane increased the microvascular filling velocity without altering myocardial perfusion but impaired systolic function. In prediabetic rats, sevoflurane did also not affect myocardial perfusion; however, it further impaired systolic function. Diet-induced prediabetes is associated with impaired myocardial perfusion and function in rats. While sevoflurane further impaired systolic function, it did not affect myocardial perfusion in prediabetic rats. Our findings suggest that sevoflurane anesthesia leads to uncoupling of myocardial perfusion and function, irrespective of the metabolic state.

  19. Oral status, cognitive function and dependency among New Zealand nursing home residents.

    PubMed

    Thomson, William M; Smith, Moira B; Ferguson, Catherine Anna; Kerse, Ngaire M; Peri, Kathryn; Gribben, Barry

    2018-04-23

    To investigate clinical oral disease and its association with cognitive function and dependency among older New Zealanders in residential aged care. National survey of oral health in aged residential care throughout New Zealand. We classified residents into 1 of 3 levels of care: "low dependency care (or assisted living)"; "high dependency care"; or "specialist dementia care/psychogeriatric care." The Abbreviated Mental Test characterised cognitive function as "unimpaired" (scores of 7-10), "moderately impaired" (4-6) or "severely impaired" (0-3). Intra-oral examinations were conducted, along with a computer-assisted personal interview. Most of the 987 clinically examined participants were either at low or high dependency care level, with another 1 in 6 in psychogeriatric care. Almost half overall had severely impaired cognitive function. Just under half of the sample had 1 or more natural teeth remaining. Negative binomial regression modelling showed that the number of carious teeth was lower among women and higher among those who were older, those with more teeth and in those with severely impaired cognitive function. Oral debris scores (representing plaque biofilm and other soft deposits on teeth) were higher in men, those with more teeth, and in those with severely impaired cognitive function. Impaired cognitive function is a risk indicator for both dental caries and oral debris in aged residential care. © 2018 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

  20. Restoring function in major depressive disorder: A systematic review.

    PubMed

    Sheehan, David V; Nakagome, Kazuyuki; Asami, Yuko; Pappadopulos, Elizabeth A; Boucher, Matthieu

    2017-06-01

    Functional impairment contributes to significant disability and economic burden in major depressive disorder (MDD). Treatment response is measured by improvement in depressive symptoms, but functional improvement often lags behind symptomatic improvement. Residual deficits are associated with relapse of depressive symptoms. A literature search was conducted using the following terms: "major depressive disorder," "functional impairment," "functional outcomes," "recovery of function," "treatment outcome," "outcome assessment," "social functioning," "presenteeism," "absenteeism," "psychiatric status rating scales," and "quality of life." Search limits included publication date (January 1, 1995 to August 31, 2016), English language, and human clinical trials. Controlled, acute-phase, nonrecurrent MDD treatment studies in adults were included if a functional outcome was measured at baseline and endpoint. The qualitative analysis included 35 controlled studies. The Sheehan Disability Scale was the most commonly used functional assessment. Antidepressant treatments significantly improved functional outcomes. Early treatment response predicted functional improvement, while baseline disease severity did not. Clinical studies utilized various methodologies and assessments for functional impairment, and were not standardized or adequately powered. The lack of synchronicity between symptomatic and functional improvement highlights an unmet need for MDD. Treatment guided by routine monitoring of symptoms and functionality may minimize residual functional impairments. Copyright © 2017. Published by Elsevier B.V.

  1. [Functional impairment associated with cognitive impairment in hospitalised elderly].

    PubMed

    Ocampo-Chaparro, José Mauricio; Mosquera-Jiménez, José Ignacio; Davis, Annabelle S; Reyes-Ortiz, Carlos A

    The aim of this study was to analyse the effect of cognitive impairment on functional decline in hospitalised patients aged ≥60 years. Measurements at admission included demographic data, Charlson's comorbidity index, and cognitive impairment (according to education level). Data were also collected on hospital length of stay, depression, and delirium developed during hospitalisation. The outcome, Barthel Index (BI), was measured at admission, discharge, and 1-month post-discharge. Patients with BI≤75 at admission (n=54) or with a missing BI value were excluded (n=1). Multivariate logistic regression analyses were conducted to explore predictive factors with functional decline (BI≤75) from admission to discharge, and 1-month later. Of the 133 patients included, 24.8% and 19.6% had a BI≤75 at discharge and at 1-month, respectively. Compared with men, women had more than double risk for functional decline at discharge and 1-month (P<.05). Compared with those without delirium and without cognitive impairment, those with delirium and cognitive impairment had an increased risk for functional decline (BI≤75) at discharge (OR 5.15, 95% CI; 1.94-13.67), and at 1-month (OR 6.26, 95% CI; 2.30-17.03). Similarly, those with comorbidity (≥2) had increased functional decline at discharge (OR 2.36, 95% CI; 1.14-4.87), and at 1-month after discharge (OR 2.71, 95% CI; 1.25-5.89). Delirium during hospitalisation, together with cognitive impairment on admission, was a strong predictor of functional decline. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Mirror therapy in chronic stroke survivors with severely impaired upper limb function: a randomized controlled trial.

    PubMed

    Colomer, Carolina; NOé, Enrique; Llorens, Roberto

    2016-06-01

    Mirror therapy (MT) has been proposed to improve the motor function of chronic individuals with stroke with mild to moderate impairment. With regards to severe upper limb paresis, MT has shown to provide limited motor improvement in the acute or sub-acute phase. However, no previous research has described the effects of MT in chronic individuals with stroke with severely impaired upper limb function. The aim of this study was to determine the effectiveness of MT on chronic stroke survivors with severe upper-limb impairment in comparison with passive mobilization. A randomized controlled trial. Rehabilitative outpatient unit. A total of 31 chronic subjects poststroke with severely impaired upper limb function were randomly assigned to either an experimental group (N.=15), or a control group (N.=16). Twenty-four intervention sessions were performed for both groups. Each session included 45-minute period of MT (experimental group) or passive mobilization (control group), administered three days a week. Participants were assessed before and after the intervention with the Wolf Motor Function Test, the Fugl-Meyer Assessment, and the Nottingham Sensory Assessment. Improvement in motor function was observed in both groups on the time (P=0.002) and ability (P=0.001) subscales of the Wolf Motor Function Test. No differences were detected in kinesthesis or stereognosis. However, the experimental group showed a significant improvement in tactile sensation that was mainly observed as an increased sensitivity to light touches. In comparison with passive mobilization, MT in chronic stroke survivors with severely impaired upper-limb function may provide a limited but positive effect on light touch sensitivity while providing similar motor improvement. MT is a therapeutic approach that can be used in the rehabilitation of severely impaired upper limb in chronic stroke survivors, specifically to address light touch sensitivity deficits.

  3. Validation of Self-Report Impairment Measures for Section III Obsessive-Compulsive and Avoidant Personality Disorders.

    PubMed

    Liggett, Jacqueline; Carmichael, Kieran L C; Smith, Alexander; Sellbom, Martin

    2017-01-01

    This study examined the validity of newly developed disorder-specific impairment scales (IS), modeled on the Level of Personality Functioning Scale, for obsessive-compulsive (OCPD) and avoidant (AvPD) personality disorders. The IS focused on content validity (items directly reflected the disorder-specific impairments listed in DSM-5 Section III) and severity of impairment. A community sample of 313 adults completed personality inventories indexing the DSM-5 Sections II and III diagnostic criteria for OCPD and AvPD, as well as measures of impairment in the domains of self- and interpersonal functioning. Results indicated that both impairment measures (for AvPD in particular) showed promise in their ability to measure disorder-specific impairment, demonstrating convergent validity with their respective Section II counterparts and discriminant validity with their noncorresponding Section II disorder and with each other. The pattern of relationships between scores on the IS and scores on external measures of personality functioning, however, did not indicate that it is useful to maintain a distinction between impairment in the self- and interpersonal domains, at least for AvPD and OCPD.

  4. Vocal function after transoral videolaryngoscopic surgery (TOVS) for hypopharyngeal and supraglottic cancer.

    PubMed

    Tanaka, Shingo; Tomifuji, Masayuki; Araki, Koji; Uno, Kosuke; Tanaka, Yuya; Mizokami, Daisuke; Suzuki, Hiroshi; Miyagawa, Yoshihiro; Taniai, Shinichi; Shiotani, Akihiro

    2017-04-01

    The resection of the medial and lateral pyriform sinus was associated with post-operative voice impairment after TOVS. Scar contracture around the cricoarytenoid joint lead to arytenoid fixation toward lateral position, and this wound healing process caused insufficient glottis closure. Although oncological and functional outcomes of TOVS was satisfactory, surgeons should mention the risk of post-operative voice impairment in pre-operative counseling. Transoral surgery is a minimally invasive treatment option for hypopharyngeal and supraglottic cancer. Post-operative vocal function was satisfactory in most cases, but in some cases vocal cord was fixed and occasionally voice impairment persists. Vocal function of 55 patients who underwent transoral videolaryngoscopic surgery (TOVS) for hypopharyngeal and supraglottic cancers was evaluated by the GRBAS perceptive scale, aerodynamic tests and acoustic analyses, and the Voice Handicap Index questionnaire. The risk factors for voice impairment were identified. Voice impairment (G score ≧2) was found in 16 cases (29.1%). Univariate analysis revealed that the resection of medial and lateral pyriform sinus (p = .0018) and neck dissection (p = .0421) were associated with post-operative voice impairment. Multivariate analysis revealed that the resection of medial and lateral pyriform sinus (p = .0021) was associated with post-operative voice impairment.

  5. Impaired Voluntary Movement Control and Its Rehabilitation in Cerebral Palsy.

    PubMed

    Gordon, Andrew M

    2016-01-01

    Cerebral palsy is caused by early damage to the developing brain, as the most common pediatric neurological disorder. Hemiplegia (unilateral spastic cerebral palsy) is the most common subtype, and the resulting impairments, lateralized to one body side, especially affect the upper extremity, limiting daily function. This chapter first describes the pathophysiology and mechanisms underlying impaired upper extremity control of cerebral palsy. It will be shown that the severity of impaired hand function closely relates to the integrity of the corticospinal tract innervating the affected hand. It will also shown that the developing corticospinal tract can reorganize its connectivity depending on the timing and location of CNS injury, which also has implications for the severity of hand impairments and rehabilitation. The mechanisms underlying impaired motor function will be highlighted, including deficits in movement execution and planning and sensorimotor integration. It will be shown that despite having unimanual hand impairments, bimanual movement control deficits and mirror movements also impact function. Evidence for motor learning-based therapies including Constraint-Induced Movement Therapy and Bimanual Training, and the possible pathophysiological predictors of treatment outcome and plasticity will be described. Finally, future directions for rehabilitations will be presented.

  6. Executive functions deficit in mild cognitive impairment.

    PubMed

    Traykov, Latchezar; Raoux, Nadine; Latour, Florence; Gallo, Livia; Hanon, Olivier; Baudic, Sophie; Bayle, Catherine; Wenisch, Emilie; Remy, Philippe; Rigaud, Anne-Sophie

    2007-12-01

    To investigate whether patients diagnosed with amnestic mild cognitive impairment (MCI) have also impairment in attention/executive functions, and therefore to clarify whether all subcomponents of executive control are equally affected in MCI. MCI refers to the transitional state between normal aging and dementia. Amnestic MCI is characterized by impaired episodic memory, although subtle impairment of executive functions has been noted on neuropsychologic tests. We investigated 20 MCI patients and 20 normal controls using episodic memory, attention/executive functions, language, and praxis tests. MCI patients had significantly lower scores on all measures of the Free and Cued Selective Reminding Test (P<0.05 to 0.01) than controls. Furthermore, MCI had a greater number of perseverations (P<0.01) on Modified Card Sorting Test and the lowest performance on the Stroop Test (P<0.02). Our findings showed impairment in episodic memory performance in MCI as compared with that of controls. In addition, MCI patients had problems with response inhibition, switching, and cognitive flexibility, which encompass various aspects of executive functions. This suggests that MCI may be identified by using a more detailed procedure for the assessment of cognitive decline than the evaluation of memory alone.

  7. Testing a Model of Functional Impairment in Telephone Crisis Support Workers.

    PubMed

    Kitchingman, Taneile A; Wilson, Coralie J; Caputi, Peter; Wilson, Ian; Woodward, Alan

    2017-11-01

    It is well known that helping professionals experience functional impairment related to elevated symptoms of psychological distress as a result of frequent empathic engagement with distressed others. Whether telephone crisis support workers are impacted in a similar way is not currently reported in the literature. The purpose of this study was to test a hypothesized model of factors contributing to functional impairment in telephone crisis support workers. A national sample of 210 telephone crisis support workers completed an online survey including measures of emotion regulation, symptoms of general psychological distress and suicidal ideation, intentions to seek help for symptoms, and functional impairment. Structural equation modeling was used to test the fit of the data to the hypothesized model. Goodness-of-fit indices were adequate and supported the interactive effects of emotion regulation, general psychological distress, suicidal ideation, and intentions to seek help for ideation on functional impairment. These results warrant the deliberate management of telephone crisis support workers' impairment through service selection, training, supervision, and professional development strategies. Future research replicating and extending this model will further inform the modification and/or development of strategies to optimize telephone crisis support workers' well-being and delivery of support to callers.

  8. Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in Japanese patients with type 2 diabetes mellitus.

    PubMed

    Sarashina, Akiko; Ueki, Kohjiro; Sasaki, Tomohiro; Tanaka, Yuko; Koiwai, Kazuki; Sakamoto, Wataru; Woerle, Hans J; Salsali, Afshin; Broedl, Uli C; Macha, Sreeraj

    2014-11-01

    The purpose of this study was to assess the effect of renal impairment on the pharmacokinetic, pharmacodynamic, and safety profiles of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in Japanese patients with type 2 diabetes mellitus (T2DM). In an open-label, parallel-group study, 32 Japanese patients with T2DM and different degrees of renal function (n = 8 per renal function category: normal renal function, estimated glomerular filtration rate [eGFR; Japanese equation] ≥90 mL/min/1.73 m(2); mild renal impairment, eGFR of 60-<90 mL/min/1.73 m(2); moderate renal impairment, eGFR of 30-<60 mL/min/1.73 m(2); and severe renal impairment, eGFR of 15-<30 mL/min/1.73 m(2)) received a single 25 mg dose of empagliflozin. Empagliflozin exposure increased with increasing renal impairment. Maximum empagliflozin plasma concentrations were similar among all renal function groups. Adjusted geometric mean ratios for extent of exposure (AUC0-∞) to empagliflozin versus normal renal function were 128.8% (95% CI, 106.0-156.6%), 143.8% (95% CI, 118.3-174.8%), and 152.3% (95% CI, 125.3-185.2%) for patients with mild, moderate, and severe renal impairment, respectively. Decreases in renal clearance of empagliflozin correlated with eGFR. Urinary glucose excretion decreased with increasing renal impairment and correlated with eGFR (adjusted mean [SE] change from baseline: 75.0 [4.84] g, 62.6 [5.75] g, 57.9 [4.86] g, and 23.7 [5.24] g for patients with normal renal function and mild, moderate, and severe renal impairment, respectively). Only 2 patients (6%) had adverse events; both were mild. Pharmacokinetic data suggest that no dose adjustment of empagliflozin is necessary in Japanese patients with T2DM and renal impairment because increases in exposure were <2-fold. Urinary glucose excretion decreased with increasing renal impairment. ClinicalTrials.gov identifier: NCT01581658. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

  9. Does impaired socioemotional functioning account for behavioral dysexecutive disorders? Evidence from a transnosological study.

    PubMed

    Narme, Pauline; Roussel, Martine; Mouras, Harold; Krystkowiak, Pierre; Godefroy, Olivier

    2017-01-01

    Behavioral dysexecutive disorders are highly prevalent in patients with neurological diseases but cannot be explained by cognitive dysexecutive impairments. In fact, the underlying mechanisms are poorly understood. Given that socioemotional functioning underlies appropriate behavior, socioemotional impairments may contribute to the appearance of behavioral disorders. To investigate this issue, we performed a transnosological study. Seventy-five patients suffering from various neurological diseases (Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal lobar degeneration, and stroke) were included in the study. The patients were comprehensively assessed in terms of cognitive and behavioral dysexecutive disorders and socioemotional processes (facial emotion recognition and theory of mind). As was seen for cognitive and behavioral dysexecutive impairments, the prevalence of socioemotional impairments varied according to the diagnosis. Stepwise logistic regressions showed that (i) only cognitive executive indices predicted hypoactivity with apathy/abulia, (ii) theory of mind impairments predicted hyperactivity-distractibility-impulsivity and stereotyped/perseverative behaviors, and (iii) impaired facial emotion recognition predicted social behavior disorders. Several dysexecutive behavioral disorders are associated with an underlying impairment in socioemotional processes but not with cognitive indices of executive functioning (except for apathy). These results strongly suggest that some dysexecutive behavioral disorders are the outward signs of an underlying impairment in socioemotional processes.

  10. Intrinsic motivation as a mediator between metacognition deficits and impaired functioning in psychosis.

    PubMed

    Luther, Lauren; Firmin, Ruth L; Vohs, Jenifer L; Buck, Kelly D; Rand, Kevin L; Lysaker, Paul H

    2016-09-01

    Poor functioning has long been observed in individuals with psychosis. Recent studies have identified metacognition - one's ability to form complex ideas about oneself and others and to use that information to respond to psychological and social challenges-as being an important determinant of functioning. However, the exact process by which deficits in metacognition lead to impaired functioning remains unclear. This study first examined whether low intrinsic motivation, or the tendency to pursue novel experiences and to engage in self-improvement, mediates the relationship between deficits in metacognition and impaired functioning. We then examined whether intrinsic motivation significantly mediated the relationship when controlling for age, education, symptoms, executive functioning, and social cognition. Mediation models were examined in a cross-sectional data set. One hundred and seventy-five individuals with a psychotic disorder completed interview-based measures of metacognition, intrinsic motivation, symptoms, and functioning and performance-based measures of executive functioning and social cognition. Analyses revealed that intrinsic motivation mediated the relationship between metacognition deficits and impaired functioning (95% CI of indirect effect [0.12-0.43]), even after controlling for the aforesaid variables (95% CI of indirect effect [0.04-0.29]). Results suggest that intrinsic motivation may be a mechanism that underlies the link between deficits in metacognition and impaired functioning and indicate that metacognition and intrinsic motivation may be important treatment targets to improve functioning in individuals with psychosis. The findings of this study suggest that deficits in metacognition may indirectly lead to impaired functioning through their effect on intrinsic motivation in individuals with psychosis. Psychological treatments that target deficits in both metacognition and intrinsic motivation may help to alleviate impaired functioning in individuals with psychosis. The cross-sectional design of this study is a limitation, and additional longitudinal studies are needed to confirm the direction of the findings and rule out rival hypotheses. Generalization of the findings may be limited by the sample composition. It may be that different relationships exist between metacognition, intrinsic motivation, and functioning in those with early psychosis or among those in an acute phase or who decline treatment. © 2016 The British Psychological Society.

  11. An experimental evaluation of a new designed apparatus (NDA) for the rapid measurement of impaired motor function in rats.

    PubMed

    Jarrahi, M; Sedighi Moghadam, B; Torkmandi, H

    2015-08-15

    Assessment of the ability of rat to balance by rotarod apparatus (ROTA) is frequently used as a measure of impaired motor system function. Most of these methods have some disadvantages, such as failing to sense motor coordination rather than endurance and as the sensitivity of the method is low, more animals are needed to obtain statistically significant results. We have designed and tested a new designed apparatus (NDA) to measure motor system function in rats. Our system consists of a glass box containing 4 beams which placed with 1cm distance between them, two electrical motors for rotating the beams, and a camera to record the movements of the rats. The RPM of the beams is adjustable digitally between 0 and 50 rounds per minute. We evaluated experimentally the capability of the NDA for the rapid measurement of impaired motor function in rats. Also we demonstrated that the sensitivity of the NDA increases by faster rotation speeds and may be more sensitive than ROTA for evaluating of impaired motor system function. Compared to a previous version of this task, our NDA provides a more efficient method to test rodents for studies of motor system function after impaired motor nervous system. In summary, our NDA will allow high efficient monitoring of rat motor system function and may be more sensitive than ROTA for evaluating of impaired motor system function in rats. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Working memory and social functioning in children.

    PubMed

    McQuade, Julia D; Murray-Close, Dianna; Shoulberg, Erin K; Hoza, Betsy

    2013-07-01

    This study extends previous research and examines whether working memory (WM) is associated with multiple measures of concurrent social functioning (peer rejection, overall social competence, relational aggression, physical aggression, and conflict resolutions skills) in typically developing fourth- and fifth-grade children (N=116). Poor central executive WM was associated with both broad social impairments (peer rejection and poor overall social competence) and specific social impairments (physical aggression, relational aggression, and impaired conflict resolution skills); poor verbal storage was associated only with greater peer rejection, and spatial storage was not associated with any measures of social impairment. Analyses also examined whether specific impairments in aggressive behavior and conflict resolution skills mediated the association between central executive and broad measures of social functioning. Greater physical aggression and impaired conflict resolution skills were both significant mediators; relational aggression was not. Implications for theory and future research are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Impaired Kidney Function and Associated Factors Among Rural Adults With Disabilities in Taiwan.

    PubMed

    Chen, Chu-Yeh; Chiu, Wen-Nan; Lin, Yu-Chen; Jane, Sui-Hwi; Chiang, Hsin-Hung; Chen, Mei-Yen

    2017-04-01

    The results of numerous studies indicate that people with disabilities seek more healthcare than those who are not disabled, particularly for conditions such as chronic kidney disease, cardiovascular disease, and obesity. However, little is known about the incidence of impaired kidney function and its associated factors among adults with disabilities in Taiwan. The aim of this study was to explore the prevalence and factors associated with impaired kidney function among adults with disabilities. This descriptive study was nurse led and was conducted as part of a health promotion program for disadvantaged rural adults with disabilities in Chiayi County, Taiwan. Health screening and a health needs survey were conducted between July and December 2013. Kidney function, physiological biomarkers, health-related behaviors, and demographic characteristics were examined. Eight hundred ten rural adults with disabilities were enrolled. The most common disabilities included physical-related disability (33.1%), intellectual-related disability (26.7%), and hearing and vision impairment (18.6%). The prevalence of impaired kidney function in this population was 85%. According to classification for chronic kidney disease, 68.6% were in Stages 1-2, and 16.8% were in Stages 3-4. Univariate analysis showed that impaired kidney function was significantly associated with lower educational level (p < .001), hearing or vision impairment (p < .001), being overweight or obese (p < .05), high systolic blood pressure (p < .01), fasting blood glucose (p < .001), total cholesterol (p < .001), total triglyceride (p < .05), older age (p < .001), smoking (p < .05), chewing betel nuts (p = .001), and low levels of participation in social activities (p < .05). The final logistic regression model showed that residents with disabilities who were older or had less education, high fasting blood glucose, and high total cholesterol tended to have impaired kidney function after adjustment for other potential confounding variables. Most participants showed impaired kidney function. The factors that were found to relate significantly to this impairment include being overweight, having hyperlipidemia, having hypertension, having high fasting blood glucose, and having an unhealthy lifestyle. Because of the lack of symptoms during the early stages of chronic kidney disease, a community-based health promotion program for these factors is an important element in health advocacy for this vulnerable population.

  14. 20 CFR 220.13 - Establishment of permanent disability for work in regular railroad occupation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... functional capacity test or other consultative examinations; (B) Step 2. If the employee's impairment(s) has... differences in opinions concerning the residual functional capacity evaluations among treating physicians, or significant differences between the results of functional capacity evaluations and residual functional...

  15. 20 CFR 220.120 - The claimant's residual functional capacity.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false The claimant's residual functional capacity... RETIREMENT ACT DETERMINING DISABILITY Residual Functional Capacity § 220.120 The claimant's residual functional capacity. (a) General. The claimant's impairment(s), and any related symptoms, such as pain, may...

  16. Acute hypoglycemia impairs executive cognitive function in adults with and without type 1 diabetes.

    PubMed

    Graveling, Alex J; Deary, Ian J; Frier, Brian M

    2013-10-01

    Acute hypoglycemia impairs cognitive function in several domains. Executive cognitive function governs organization of thoughts, prioritization of tasks, and time management. This study examined the effect of acute hypoglycemia on executive function in adults with and without diabetes. Thirty-two adults with and without type 1 diabetes with no vascular complications or impaired awareness of hypoglycemia were studied. Two hyperinsulinemic glucose clamps were performed at least 2 weeks apart in a single-blind, counterbalanced order, maintaining blood glucose at 4.5 mmol/L (euglycemia) or 2.5 mmol/L (hypoglycemia). Executive functions were assessed with a validated test suite (Delis-Kaplan Executive Function). A general linear model (repeated-measures ANOVA) was used. Glycemic condition (euglycemia or hypoglycemia) was the within-participant factor. Between-participant factors were order of session (euglycemia-hypoglycemia or hypoglycemia-euglycemia), test battery used, and diabetes status (with or without diabetes). Compared with euglycemia, executive functions (with one exception) were significantly impaired during hypoglycemia; lower test scores were recorded with more time required for completion. Large Cohen d values (>0.8) suggest that hypoglycemia induces decrements in aspects of executive function with large effect sizes. In some tests, the performance of participants with diabetes was more impaired than those without diabetes. Executive cognitive function, which is necessary to carry out many everyday activities, is impaired during hypoglycemia in adults with and without type 1 diabetes. This important aspect of cognition has not received previous systematic study with respect to hypoglycemia. The effect size is large in terms of both accuracy and speed.

  17. Quality of life and functional impairment in obsessive-compulsive disorder: a comparison of patients with and without comorbidity, patients in remission, and healthy controls.

    PubMed

    Huppert, Jonathan D; Simpson, H Blair; Nissenson, Kore J; Liebowitz, Michael R; Foa, Edna B

    2009-01-01

    Several studies have demonstrated that obsessive-compulsive disorder (OCD) is associated with interference in quality of life (QOL) and functional impairment. However, these studies did not compare individuals in remission to individuals who continue to have the disorder, predominantly used comparisons with norms and not with a matched normal sample, and did not always consider the impact of comorbidity. We administered multiple measures that assess QOL and functional impairment to 66 OCD patients who had previously consented for a clinical trial and to 36 age and sex matched individuals who denied any psychiatric history. Results confirm that OCD was associated with significantly lower QOL and functional impairment compared to healthy controls (HCs) in areas of work, social life, and family life. Individuals with OCD and other comorbid psychiatric diagnoses showed the poorest QOL and functioning, with comorbid depression accounting for much of the variance. The levels of QOL and functioning in individuals in remission tended to lie in between HCs and individuals with current OCD: their QOL or functioning did not differ significantly from HCs nor did they consistently differ significantly from those who had current OCD. These results suggest that individuals who are in remission have improved levels of QOL and functioning, whereas individuals with OCD are significantly impaired, and individuals with OCD and comorbid disorders are the most impaired. Treatment strategies should be focused on achieving remission of all symptoms to have the greatest impact on functioning and QOL. Published 2008 Wiley-Liss, Inc.

  18. Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C.

    Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon,more » 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions.« less

  19. Cognitive Rehabilitation for Bipolar Disorder: An Open Trial for Employed Patients with Residual Depressive Symptoms

    PubMed Central

    Deckersbach, Thilo; Nierenberg, Andrew A.; Kessler, Ronald; Lund, Hannah G.; Ametrano, Rebecca M.; Sachs, Gary; Rauch, Scott L.; Dougherty, Darin

    2009-01-01

    Introduction Bipolar Disorder is characterized by recurrent episodes of depression and/or mania along with interepisodic mood symptoms that interfere with psychosocial functioning. Despite periods of symptomatic recovery, individuals with bipolar disorder often continue to experience impairments in psychosocial functioning, particularly occupational functioning. Two determinants of psychosocial functioning of euthymic (neither fully depressed nor manic) individuals with bipolar disorder are residual depressive symptoms and cognitive impairment (i.e. difficulties with executive functioning, attention and memory). Aims The present study explored whether a new cognitive remediation (CR) treatment designed to treat residual depressive symptoms and, for the first time to the best of our knowledge, address cognitive impairment would be associated with improvement in psychosocial functioning in individuals with bipolar disorder. Following a neuropsychological and clinical assessment 18 individuals with DSM-IV bipolar disorder were treated with 14 individual sessions of CR. Results Results indicated that at the end of treatment, as well as at the 3-months follow-up, patients showed lower residual depressive symptoms, and increased occupational, as well as overall psychosocial functioning. Pre-treatment neuropsychological impairment predicted treatment response. Improvements in executive functioning were associated with improvements in occupational functioning. Conclusions These findings suggest that treating residual depressive symptoms and cognitive impairment may be an avenue to improving occupational and overall functioning in individuals with bipolar disorder. PMID:19895584

  20. Sleep and its associations with perceived and objective cognitive impairment in individuals with multiple sclerosis.

    PubMed

    Hughes, Abbey J; Parmenter, Brett A; Haselkorn, Jodie K; Lovera, Jesus F; Bourdette, Dennis; Boudreau, Eilis; Cameron, Michelle H; Turner, Aaron P

    2017-08-01

    Problems with sleep and cognitive impairment are common among people with multiple sclerosis (MS). The present study examined the relationship between self-reported sleep and both objective and perceived cognitive impairment in MS. Data were obtained from the baseline assessment of a multi-centre intervention trial (NCT00841321). Participants were 121 individuals with MS. Nearly half (49%) of participants met the criteria for objective cognitive impairment; however, cognitively impaired and unimpaired participants did not differ on any self-reported sleep measures. Nearly two-thirds (65%) of participants met the criteria for 'poor' sleep, and poorer sleep was significantly associated with greater levels of perceived cognitive impairment. Moreover, the relationships between self-reported sleep and perceived cognitive impairment were significant beyond the influence of clinical and demographic factors known to influence sleep and cognitive functioning (e.g. age, sex, education level, disability severity, type of MS, disease duration, depression and fatigue). However, self-reported sleep was not associated with any measures of objective cognitive impairment. Among different types of perceived cognitive impairment, poor self-reported sleep was most commonly related to worse perceived executive function (e.g. planning/organization) and prospective memory. Results from the present study emphasize that self-reported sleep is significantly and independently related to perceived cognitive impairment in MS. In terms of clinical implications, interventions focused on improving sleep may help improve perceived cognitive function and quality of life in this population; however, the impact of improved sleep on objective cognitive function requires further investigation. © 2017 European Sleep Research Society.

  1. Delineating the trajectories of social and occupational functioning of young people attending early intervention mental health services in Australia: a longitudinal study.

    PubMed

    Iorfino, Frank; Hermens, Daniel F; Cross, Shane Pm; Zmicerevska, Natalia; Nichles, Alissa; Badcock, Caro-Anne; Groot, Josine; Scott, Elizabeth M; Hickie, Ian B

    2018-03-27

    Mental disorders typically emerge during adolescence and young adulthood and put young people at risk for prolonged socioeconomic difficulties. This study describes the longitudinal course of social and occupational functioning of young people attending primary care-based, early intervention services. A longitudinal study of young people receiving mental healthcare. Data were collected between January 2005 and August 2017 from a designated primary care-based mental health service. 554 young people (54% women) aged 12-32 years. A systematic medical file audit collected clinical and functional information at predetermined time intervals (ie, 3 months to 5+ years) using a clinical pro forma. Group-based trajectory modelling (GBTM) was used to identify distinct trajectories of social and occupational functioning over time (median number of observations per person=4; median follow-up time=23 months). Between first clinical contact and time last seen, 15% of young people had reliably deteriorated, 23% improved and 62% did not demonstrate substantive change in function. Of the whole cohort, 69% had functional scores less than 70 at time last seen, indicative of ongoing and substantive impairment. GBTM identified six distinct functional trajectories whereby over 60% had moderate-to-serious functional impairment at entry and remained chronically impaired over time; 7% entered with serious impairment and deteriorated further; a quarter were mildly impaired at entry and functionally recovered and only a small minority (4%) presented with serious impairments and functionally improved over time. Not being in education, employment or training, previous hospitalisation and a younger age at baseline emerged as significant predictors of these functional trajectories. Young people with emerging mental disorders have significant functional impairment at presentation for care, and for the majority, it persists over the course of clinical care. In addition to providing clinical care earlier in the course of illness, these data suggest that more sophisticated and more intensive individual-level and organisational strategies may be required to achieve significant and sustained functional improvements. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Parent and Self-Ratings of Executive Function in Adolescents with Specific Language Impairment

    ERIC Educational Resources Information Center

    Hughes, Deanna M.; Turkstra, Lyn S.; Wulfeck, Beverly B.

    2009-01-01

    Background: There is accumulating evidence that adolescents with specific language impairment (SLI) have impairments in domains beyond formal language that may affect academic and social outcomes. The findings of previous studies as well as parent reports of behavioural concerns suggest that they lag behind peers in functions such as…

  3. Abnormal Functional Lateralization and Activity of Language Brain Areas in Typical Specific Language Impairment (Developmental Dysphasia)

    ERIC Educational Resources Information Center

    de Guibert, Clement; Maumet, Camille; Jannin, Pierre; Ferre, Jean-Christophe; Treguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

    2011-01-01

    Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting…

  4. Disagreement between Parent and Adolescent Reports of Functional Impairment

    ERIC Educational Resources Information Center

    Kramer, Teresa L.; Phillips, Susan D.; Hargis, Michael B.; Miller, Terri L.; Burns, Barbara J.; Robbins, James M.

    2004-01-01

    Objective: Adolescents' functional impairment has become increasingly important as a criterion for diagnosis and service eligibility as well as a target of therapeutic intervention in mental health settings. This study examines three critical issues in measuring functioning: 1) agreement between parent and adolescent reports of functioning, 2)…

  5. Visual impairment in children and adolescents in Norway.

    PubMed

    Haugen, Olav H; Bredrup, Cecilie; Rødahl, Eyvind

    2016-06-01

    BACKGROUND Due to failures in reporting and poor data security, the Norwegian Registry of Blindness was closed down in 1995. Since that time, no registration of visual impairment has taken place in Norway. All the other Nordic countries have registries for children and adolescents with visual impairment. The purpose of this study was to survey visual impairments and their causes in children and adolescents, and to assess the need for an ophthalmic registry.MATERIAL AND METHOD Data were collected via the county teaching centres for the visually impaired in the period from 2005 - 2010 on children and adolescents aged less than 20 years with impaired vision (n = 628). This was conducted as a point prevalence study as of 1 January 2004. Visual function, ophthalmological diagnosis, systemic diagnosis and additional functional impairments were recorded.RESULTS Approximately two-thirds of children and adolescents with visual impairment had reduced vision, while one-third were blind. The three largest diagnostic groups were neuro-ophthalmic diseases (37 %), retinal diseases (19 %) and conditions affecting the eyeball in general (14 %). The prevalence of additional functional impairments was high, at 53 %, most often in the form of motor problems or cognitive impairments.INTERPRETATION The results of the study correspond well with similar investigations in the other Nordic countries. Our study shows that the registries associated with teaching for the visually impaired are inadequate in terms of medical data, and this underlines the need for an ophthalmic registry of children and adolescents with visual impairment.

  6. Impairment in proverb interpretation as an executive function deficit in patients with amnestic mild cognitive impairment and early Alzheimer's disease.

    PubMed

    Leyhe, Thomas; Saur, Ralf; Eschweiler, Gerhard W; Milian, Monika

    2011-01-01

    Proverb interpretation is assumed to reflect executive functions. We hypothesized that proverb interpretation is impaired in patients with amnestic mild cognitive impairment (aMCI) diagnosed as single-domain impairment by common neuropsychological testing. We compared performance in a proverb interpretation test in single-domain aMCI patients and patients with early Alzheimer's disease (EAD). The groups with aMCI and EAD performed significantly worse than healthy controls. Both patient groups gave concrete answers with a similar frequency. However, patients with EAD tended to give senseless answers more frequently. Our data suggest that in patients diagnosed as single-domain aMCI, deterioration of executive functions is detectable with subtle and appropriate neuropsychological testing. Implementation of these procedures may improve the early prediction of AD.

  7. Psychological distress as a mediator of the association between disease severity and occupational functioning among employed spouses of women recently diagnosed with breast cancer.

    PubMed

    Manne, Sharon L; Siegel, Scott; Heckman, Carolyn J; Kashy, Deborah A

    2015-11-01

    The purpose was to evaluate whether patient and spouse cancer-specific distress mediated the association between cancer severity and occupational functioning among employed spouses of women diagnosed with breast cancer. We examined whether sociodemographic characteristics, lower spouse-reported marital quality, and lower spouse self-rated health were associated with poorer spouse occupational functioning. One hundred forty-three currently employed spouses of women diagnosed with breast cancer were administered measures of socioeconomic status, occupational functioning (work absenteeism, low productivity, and poor performance), cancer-specific distress, marital quality, and self-rated health. Patients completed measures of cancer-related distress and functional impairment and cancer stage were collected from medical charts. In the model evaluating work absenteeism, greater patient functional impairment was associated with more absenteeism, but there was no evidence of a mediating effect for either partners' cancer-specific distress. Higher cancer stage and more functional impairment were associated with higher spouse cancer-specific distress, which in turn predicted poorer work productivity. Patient cancer-specific distress did not mediate the association between patient functional impairment or cancer stage and spouse work productivity. Finally, higher cancer stage was associated with more spouse cancer-specific distress, which in turn predicted poorer work performance. There were no direct or indirect effects of the patient's functional impairment on spouse work performance. Distressed spouses are more likely to have poorer work productivity after their partners' breast cancer diagnosis. These spouses may need assistance in managing their distress and the patient's functional impairment to ensure that their work productivity is not adversely affected. Copyright © 2015 John Wiley & Sons, Ltd.

  8. Medication and finance management among HIV-infected adults: the impact of age and cognition.

    PubMed

    Thames, April D; Kim, Michelle S; Becker, Brian W; Foley, Jessica M; Hines, Lindsay J; Singer, Elyse J; Heaton, Robert K; Castellon, Steven A; Hinkin, Charles H

    2011-02-01

    This study examined the effects of aging and cognitive impairment on medication and finance management in an HIV sample. We observed main effects of age (older < younger) and neuropsychological impairment on functional task performance. Interactions between age and cognition demonstrated that older impaired individuals performed significantly more poorly than all other comparison groups. There were no relationships between laboratory performance and self-reported medication and finance management. The interaction of advancing age and cognitive impairment may confer significant functional limitations for HIV individuals that may be better detected by performance-based measures of functional abilities rather than patient self-report.

  9. Medication and finance management among HIV-infected adults: The impact of age and cognition

    PubMed Central

    Thames, April D.; Kim, Michelle S.; Becker, Brian W.; Foley, Jessica M.; Hines, Lindsay J.; Singer, Elyse J.; Heaton, Robert K.; Castellon, Steven A.; Hinkin, Charles H.

    2013-01-01

    This study examined the effects of aging and cognitive impairment on medication and finance management in an HIV sample. We observed main effects of age (older < younger) and neuropsychological impairment on functional task performance. Interactions between age and cognition demonstrated that older impaired individuals performed significantly more poorly than all other comparison groups. There were no relationships between laboratory performance and self-reported medication and finance management. The interaction of advancing age and cognitive impairment may confer significant functional limitations for HIV individuals that may be better detected by performance-based measures of functional abilities rather than patient self-report. PMID:20694873

  10. Development of disability in chronic obstructive pulmonary disease: beyond lung function.

    PubMed

    Eisner, Mark D; Iribarren, Carlos; Blanc, Paul D; Yelin, Edward H; Ackerson, Lynn; Byl, Nancy; Omachi, Theodore A; Sidney, Stephen; Katz, Patricia P

    2011-02-01

    COPD is a major cause of disability, but little is known about how disability develops in this condition. The authors analysed data from the Function, Living, Outcomes and Work (FLOW) Study which enrolled 1202 Kaiser Permanente Northern California members with COPD at baseline and re-evaluated 1051 subjects at 2-year follow-up. The authors tested the specific hypothesis that the development of specific non-respiratory impairments (abnormal body composition and muscle strength) and functional limitations (decreased lower extremity function, poor balance, mobility-related dyspnoea, reduced exercise performance and decreased cognitive function) will determine the risk of disability in COPD, after controlling for respiratory impairment (FEV(1) and oxygen saturation). The Valued Life Activities Scale was used to assess disability in terms of a broad range of daily activities. The primary disability outcome measure was defined as an increase in the proportion of activities that cannot be performed of 3.3% or greater from baseline to 2-year follow-up (the estimated minimal important difference). Multivariable logistic regression was used for analysis. Respiratory impairment measures were related to an increased prospective risk of disability (multivariate OR 1.75; 95% CI 1.26 to 2.44 for 1 litre decrement of FEV(1) and OR 1.57 per 5% decrement in oxygen saturation; 95% CI 1.13 to 2.18). Non-respiratory impairment (body composition and lower extremity muscle strength) and functional limitations (lower extremity function, exercise performance, and mobility-related dyspnoea) were all associated with an increased longitudinal risk of disability after controlling for respiratory impairment (p<0.05 in all cases). Non-respiratory impairment and functional limitations were predictive of prospective disability, above-and-beyond sociodemographic characteristics, smoking status and respiratory impairment (area under the receiver operating characteristic curve increased from 0.65 to 0.75; p<0.001). Development of non-respiratory impairment and functional limitations, which reflect the systemic nature of COPD, appear to be critical determinants of disablement. Prevention and treatment of disability require a comprehensive approach to the COPD patient.

  11. Clinical progression and outcome of dysphagia following paediatric traumatic brain injury: a prospective study.

    PubMed

    Morgan, Angela; Ward, Elizabeth; Murdoch, Bruce

    2004-04-01

    To provide a preliminary clinical profile of the resolution and outcomes of oral-motor impairment and swallowing function in a group of paediatric dysphagia patients post-traumatic brain injury (TBI). To document the level of cognitive impairment parallel to the return to oral intake, and to investigate the correlation between the resolution of impaired swallow function versus the resolution of oral-motor impairment and cognitive impairment. Thirteen children admitted to an acute care setting for TBI. A series of oral-motor (Verbal Motor Production Assessment for Children, Frenchay Dysarthria Assessment, Schedule for Oral Motor Assessment) and swallowing (Paramatta Hospital's Assessment for Dysphagia) assessments, an outcome measure for swallowing (Royal Brisbane Hospital's Outcome Measure for Swallowing), and a cognitive rating scale (Rancho Level of Cognitive Functioning Scale). Across the patient group, oral-motor deficits resolved to normal status between 3 and 11 weeks post-referral (and at an average of 12 weeks post-injury) and swallowing function and resolution to normal diet status were achieved by 3-11 weeks post-referral (and at an average of 12 weeks post-injury). The resolution of dysphagia and the resolution of oral-motor impairment and cognitive impairment were all highly correlated. The provision of a preliminary profile of oral-motor functioning and dysphagia resolution, and data on the linear relationship between swallowing impairment and cognition, will provide baseline information on the course of rehabilitation of dysphagia in the paediatric population post-TBI. Such data will contribute to more informed service provision and rehabilitation planning for paediatric patients post-TBI.

  12. Individuals with knee impairments identify items in need of clarification in the Patient Reported Outcomes Measurement Information System (PROMIS®) pain interference and physical function item banks - a qualitative study.

    PubMed

    Lynch, Andrew D; Dodds, Nathan E; Yu, Lan; Pilkonis, Paul A; Irrgang, James J

    2016-05-11

    The content and wording of the Patient Reported Outcome Measurement Information System (PROMIS) Physical Function and Pain Interference item banks have not been qualitatively assessed by individuals with knee joint impairments. The purpose of this investigation was to identify items in the PROMIS Physical Function and Pain Interference Item Banks that are irrelevant, unclear, or otherwise difficult to respond to for individuals with impairment of the knee and to suggest modifications based on cognitive interviews. Twenty-nine individuals with knee joint impairments qualitatively assessed items in the Pain Interference and Physical Function Item Banks in a mixed-methods cognitive interview. Field notes were analyzed to identify themes and frequency counts were calculated to identify items not relevant to individuals with knee joint impairments. Issues with clarity were identified in 23 items in the Physical Function Item Bank, resulting in the creation of 43 new or modified items, typically changing words within the item to be clearer. Interpretation issues included whether or not the knee joint played a significant role in overall health and age/gender differences in items. One quarter of the original items (31 of 124) in the Physical Function Item Bank were identified as irrelevant to the knee joint. All 41 items in the Pain Interference Item Bank were identified as clear, although individuals without significant pain substituted other symptoms which interfered with their life. The Physical Function Item Bank would benefit from additional items that are relevant to individuals with knee joint impairments and, by extension, to other lower extremity impairments. Several issues in clarity were identified that are likely to be present in other patient cohorts as well.

  13. Obesity and functional impairment: influence of comorbidity, joint pain, and mental health.

    PubMed

    Heo, Moonseong; Pietrobelli, Angelo; Wang, Dan; Heymsfield, Steven B; Faith, Myles S

    2010-10-01

    To examine the relationship between obesity and functional impairment and the influence of comorbidity, joint pain, and mental health on this association, we used US adult respondents (N = 430,912) to the 2007 Behavioral Risk Factor Surveillance Survey (BRFSS-07). Functional impairment was indicated if a respondent was either (i) limited in any way or in any activities because of physical, mental, or emotional problems, or (ii) had any health problem that required using special equipment such as a cane, wheelchair, special bed, or special telephone. Approximately 62.8% of respondents were overweight or obese and 20.3% were functionally impaired. The unadjusted relationship between obesity and functional impairment revealed a classical J-shaped pattern with odds ratios (95% confidence interval) compared to the normal weight group: 1.63 (1.54-1.73), 1.22 (1.20-1.25), 1.77 (1.73-1.81), 2.43 (2.36-2.51), and 4.12 (3.97-4.27) for underweight, overweight, obesity class I, II, and III, respectively. Although inclusion of different combinations of sociodemographic and medical covariates substantially attenuated the unadjusted association, the collective inclusion of all covariates in a single model did not eliminate the significant J-shaped association resulting in the following corresponding adjusted odds ratios: 1.19 (1.13-1.25), 1.01 (0.99-1.04), 1.23 (1.19-1.27), 1.38 (1.32-1.44), and 1.92 (1.82-2.02). The attenuation was mostly influenced by medical comorbidity. In conclusion, functional impairment is associated with obesity, primarily due to medical comorbidity conditions. The significant residual association highlights the importance of sustainable obesity prevention and treatment at both the individual and public level as functional impairment can create burdens at individual, familial, and societal levels.

  14. Functional and cognitive impairment, social environment, frailty and adverse health outcomes in older patients with head and neck cancer, a systematic review.

    PubMed

    van Deudekom, Floor J; Schimberg, Anouk S; Kallenberg, Marije H; Slingerland, Marije; van der Velden, Lily-Ann; Mooijaart, Simon P

    2017-01-01

    Older head and neck cancer patients are at increased risk for adverse health outcomes, but little is known about which geriatric assessment associates with poor outcome. The aim is to study the association of functional or cognitive impairment, social environment and frailty with adverse health outcomes in patients with head and neck cancer. Four libraries were searched for studies reporting on an association of functional or cognitive impairment, social environment and frailty with adverse outcomes in head and neck cancer patients. Of 4158 identified citations, 31 articles were included. The mean age was ⩾60years in twelve studies (39%). Geriatric conditions were prevalent: between 40 and 50% of the included participants were functional impaired, around 50% had depressive symptoms, and around 40% did not have a partner. Functional impairment was assessed in 18 studies, two studies reported on a cognitive test, eight studies examined mood and social status was depicted by 14 studies. None of the included studies addressed frailty or objectively measured physical capacity such as hand grip strength, gait speed or balance tests. In 64% of the reported associations, a decline in functional or cognitive impairment, mood or social environment was associated with adverse outcomes. Functional and cognitive impairment, depressive symptoms and social isolation are highly prevalent in head and neck cancer patients and associate with high risk of adverse health outcomes. In the future, these measurements may guide decision-making and customize treatments, but more research is needed to further improve and firmly establish clinical usability. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  15. Screening for malnutrition in nursing home residents: comparison of different risk markers and their association to functional impairment.

    PubMed

    Stange, I; Poeschl, K; Stehle, P; Sieber, C C; Volkert, D

    2013-04-01

    To identify nursing home residents with malnutrition or at risk of malnutrition by using different markers, determine if the Mini Nutritional Assessment (MNA®) is able to identify all residents at risk according to single risk markers and explore the relation between risk markers and functional impairment. Cross-sectional study. Six German nursing homes. 286 residents (86±7y, 89% female). Screening for malnutrition or its risk included low BMI (≤22 kg/m²), recent weight loss (WL), low food intake (LI) as single risk markers and MNA (<24 points, p.) as composite marker. Prevalence of single nutritional risk markers in different MNA categories was compared by cross-tables. Mental (cognition, mood) and physical function (mobility) were assessed by interviewing nursing staff and association of impaired status to nutritional risk markers determined by Chi² test. 32.9% of residents had a low BMI, 11.9% WL and 21.3% LI. 60.2% were categorized malnourished (18.2%) or at risk of malnutrition (42.0%) by MNA. 64% presented at least one of these nutritional risk markers. Of those classified malnourished by MNA, 96.2% also showed low BMI, WL or LI. In contrast, eleven residents (9.6%) considered well-nourished by MNA presented single risk markers (9 low BMI, 2 WL). Cognitive impairment, depressive symptoms and immobility was present in 59.0%, 20.8% and 25.5%, respectively. Functional impairment, and in particular severe impairment, was to a higher proportion present in residents at nutritional risk independent of the chosen marker (MNA<24 p., low BMI, WL, LI). The high prevalence of nutritional risk highlights the importance of regular screening of nursing home residents. The MNA identified nearly all residents with low BMI, WL and LI. The close association between nutritional risk and functional impairment requires increased awareness for nutritional problems especially in functionally impaired residents, to early initiate nutritional measures and thus, prevent further nutritional and functional deterioration.

  16. Cognitive syndromes after the first stroke.

    PubMed

    Salihović, Denisa; Smajlović, Dževdet; Mijajlović, Milija; Zoletić, Emina; Ibrahimagić, Omer Ć

    2018-05-19

    The aim of this study is to determine impairments of certain cognitive functions in certain vascular cognitive syndromes and to identify predictors of dementia. One-year prospective study included 275 patients, who were hospitalized at the Department of Neurology Tuzla and therefore fulfilled certain criteria. Patients were divided into following subgroups of vascular cognitive impairment (VCI): dementia of strategic infarct (DSI), cortical dementia (CD), sub cortical dementia (SCD), hemorrhagic dementia (HD), and patients without dementia. Each of the patients underwent the clinical examination and scoring with appropriate measurement scales. Some of the types of VCI were verified in 190 (69%) patients, and the most common was SCD (58%). There was statistically significant connection between the level of intelligence and occurrence of VCI in patients after stroke (p < 0.001). We found significant connection between occurrence of dementia and impairment in narrative memory, numerical memory, visual perceptive, and visual constructive functions in patients with dementia compared with non-demented (p = 0.0001). The executive functions were statistically impaired in patients with CD (p = 0.004) and SCD (p < 0.001). Patients without dementia have significantly better quality of life than the demented ones (p < 0.0001). The algorithm "tree of decision" can help us in the prediction of dementia based on the impairment of certain cognitive functions. Vascular cognitive syndromes are common after stroke. Some of the cognitive functions are significantly impaired in patients with dementia. Impairment of the certain cognitive functions can help in predicting the onset of dementia. Patients without dementia have better quality of life.

  17. Perspective on Physical Therapist Management of Functional Constipation.

    PubMed

    George, Susan E; Borello-France, Diane F

    2017-04-01

    Functional constipation is a common bowel disorder leading to activity restrictions and reduced health-related quality of life. Typically, this condition is initially managed with prescription of laxatives or fiber supplementation, or both. However, these interventions are often ineffective and fail to address the underlying pathophysiology and impairments contributing to this condition. Physical therapists possess the knowledge and skills to diagnose and manage a wide range of musculoskeletal and motor coordination impairments that may contribute to functional constipation. Relevant anatomic, physiologic, and behavioral contributors to functional constipation are discussed with regard to specific constipation diagnoses. A framework for physical therapist examination of impairments that can affect gastrointestinal function, including postural, respiratory, musculoskeletal, neuromuscular, and behavioral impairments, is offered. Within the context of diagnosis-specific patient cases, multifaceted interventions are described as they relate to impairments underlying functional constipation type. The current state of evidence to support these interventions and patient recommendations is summarized. This perspective article aims not only to heighten physical therapists' awareness and management of this condition, but also to stimulate clinical questioning that will open avenues for future research to improve patient care. © 2016 American Physical Therapy Association.

  18. Prevalence and patterns of cognitive impairment in adult hemodialysis patients: the COGNITIVE-HD study.

    PubMed

    van Zwieten, Anita; Wong, Germaine; Ruospo, Marinella; Palmer, Suetonia C; Barulli, Maria Rosaria; Iurillo, Annalisa; Saglimbene, Valeria; Natale, Patrizia; Gargano, Letizia; Murgo, Marco; Loy, Clement T; Tortelli, Rosanna; Craig, Jonathan C; Johnson, David W; Tonelli, Marcello; Hegbrant, Jörgen; Wollheim, Charlotta; Logroscino, Giancarlo; Strippoli, Giovanni F M

    2017-11-22

    Mounting evidence indicates an increased risk of cognitive impairment in adults with end-stage kidney disease on dialysis, but the extent and pattern of deficits across the spectrum of cognitive domains are uncertain. We conducted a cross-sectional study of 676 adult hemodialysis patients from 20 centers in Italy, aiming to evaluate the prevalence and patterns of cognitive impairment across five domains of learning and memory, complex attention, executive function, language and perceptual-motor function. We assessed cognitive function using a neuropsychological battery of 10 tests and calculated test and domain z-scores using population norms (age or age/education). We defined cognitive impairment as a z-score  ≤ -1.5. Participants' median age was 70.9 years (range 21.6-94.1) and 262 (38.8%) were women. Proportions of impairment on each domain were as follows: perceptual-motor function 31.5% (150/476), language 41.2% (273/662), executive function 41.7% (281/674), learning and memory 42.2% (269/638), complex attention 48.8% (329/674). Among 474 participants with data for all domains, only 28.9% (n  =  137) were not impaired on any domain, with 25.9% impaired on a single domain (n  =  123), 17.3% on two (n  =  82), 13.9% on three (n  =  66), 9.1% on four (n  =  43) and 4.9% (n  =  23) on all five. Across patients, patterns of impairment combinations were diverse. In conclusion, cognitive impairment is extremely common in hemodialysis patients, across numerous domains, and patients often experience multiple deficits simultaneously. Clinical care should be tailored to meet the needs of patients with different types of cognitive impairment and future research should focus on identifying risk factors for cognitive decline. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  19. Ecological validity of virtual reality daily living activities screening for early dementia: longitudinal study.

    PubMed

    Tarnanas, Ioannis; Schlee, Winfried; Tsolaki, Magda; Müri, René; Mosimann, Urs; Nef, Tobias

    2013-08-06

    Dementia is a multifaceted disorder that impairs cognitive functions, such as memory, language, and executive functions necessary to plan, organize, and prioritize tasks required for goal-directed behaviors. In most cases, individuals with dementia experience difficulties interacting with physical and social environments. The purpose of this study was to establish ecological validity and initial construct validity of a fire evacuation Virtual Reality Day-Out Task (VR-DOT) environment based on performance profiles as a screening tool for early dementia. The objectives were (1) to examine the relationships among the performances of 3 groups of participants in the VR-DOT and traditional neuropsychological tests employed to assess executive functions, and (2) to compare the performance of participants with mild Alzheimer's-type dementia (AD) to those with amnestic single-domain mild cognitive impairment (MCI) and healthy controls in the VR-DOT and traditional neuropsychological tests used to assess executive functions. We hypothesized that the 2 cognitively impaired groups would have distinct performance profiles and show significantly impaired independent functioning in ADL compared to the healthy controls. The study population included 3 groups: 72 healthy control elderly participants, 65 amnestic MCI participants, and 68 mild AD participants. A natural user interface framework based on a fire evacuation VR-DOT environment was used for assessing physical and cognitive abilities of seniors over 3 years. VR-DOT focuses on the subtle errors and patterns in performing everyday activities and has the advantage of not depending on a subjective rating of an individual person. We further assessed functional capacity by both neuropsychological tests (including measures of attention, memory, working memory, executive functions, language, and depression). We also evaluated performance in finger tapping, grip strength, stride length, gait speed, and chair stands separately and while performing VR-DOTs in order to correlate performance in these measures with VR-DOTs because performance while navigating a virtual environment is a valid and reliable indicator of cognitive decline in elderly persons. The mild AD group was more impaired than the amnestic MCI group, and both were more impaired than healthy controls. The novel VR-DOT functional index correlated strongly with standard cognitive and functional measurements, such as mini-mental state examination (MMSE; rho=0.26, P=.01) and Bristol Activities of Daily Living (ADL) scale scores (rho=0.32, P=.001). Functional impairment is a defining characteristic of predementia and is partly dependent on the degree of cognitive impairment. The novel virtual reality measures of functional ability seem more sensitive to functional impairment than qualitative measures in predementia, thus accurately differentiating from healthy controls. We conclude that VR-DOT is an effective tool for discriminating predementia and mild AD from controls by detecting differences in terms of errors, omissions, and perseverations while measuring ADL functional ability.

  20. Association of Nondisease-Specific Problems with Mortality, Long-Term Care, and Functional Impairment among Older Adults Who Require Skilled Nursing Care after Dialysis Initiation

    PubMed Central

    Plantinga, Laura; Hall, Rasheeda K.; Mirk, Anna; Zhang, Rebecca; Kutner, Nancy

    2016-01-01

    Background and objectives The majority of older adults who initiate dialysis do so during a hospitalization, and these patients may require post-acute skilled nursing facility (SNF) care. For these patients, a focus on nondisease-specific problems, including cognitive impairment, depressive symptoms, exhaustion, falls, impaired mobility, and polypharmacy, may be more relevant to outcomes than the traditional disease-oriented approach. However, the association of the burden of nondisease-specific problems with mortality, transition to long-term care (LTC), and functional impairment among older adults receiving SNF care after dialysis initiation has not been studied. Design, setting, participants, & measurements We identified 40,615 Medicare beneficiaries ≥65 years old who received SNF care after dialysis initiation between 2000 and 2006 by linking renal disease registry data with the Minimum Data Set. Nondisease-specific problems were ascertained from the Minimum Data Set. We defined LTC as ≥100 SNF days and functional impairment as dependence in all four essential activities of daily living at SNF discharge. Associations of the number of nondisease-specific problems (≤1, 2, 3, and 4–6) with 6-month mortality, LTC, and functional impairment were examined. Results Overall, 39.2% of patients who received SNF care after dialysis initiation died within 6 months. Compared with those with ≤1 nondisease-specific problems, multivariable adjusted hazard ratios (95% confidence interval) for mortality were 1.26 (1.19 to 1.32), 1.40 (1.33 to 1.48), and 1.66 (1.57 to 1.76) for 2, 3, and 4–6 nondisease-specific problems, respectively. Among those who survived, 37.1% required LTC; of those remaining who did not require LTC, 74.7% had functional impairment. A higher likelihood of transition to LTC (among those who survived 6 months) and functional impairment (among those who survived and did not require LTC) was seen with a higher number of problems. Conclusions Identifying nondisease-specific problems may help patients and families anticipate LTC needs and functional impairment after dialysis initiation. PMID:27733436

  1. Association of Nondisease-Specific Problems with Mortality, Long-Term Care, and Functional Impairment among Older Adults Who Require Skilled Nursing Care after Dialysis Initiation.

    PubMed

    Bowling, C Barrett; Plantinga, Laura; Hall, Rasheeda K; Mirk, Anna; Zhang, Rebecca; Kutner, Nancy

    2016-12-07

    The majority of older adults who initiate dialysis do so during a hospitalization, and these patients may require post-acute skilled nursing facility (SNF) care. For these patients, a focus on nondisease-specific problems, including cognitive impairment, depressive symptoms, exhaustion, falls, impaired mobility, and polypharmacy, may be more relevant to outcomes than the traditional disease-oriented approach. However, the association of the burden of nondisease-specific problems with mortality, transition to long-term care (LTC), and functional impairment among older adults receiving SNF care after dialysis initiation has not been studied. We identified 40,615 Medicare beneficiaries ≥65 years old who received SNF care after dialysis initiation between 2000 and 2006 by linking renal disease registry data with the Minimum Data Set. Nondisease-specific problems were ascertained from the Minimum Data Set. We defined LTC as ≥100 SNF days and functional impairment as dependence in all four essential activities of daily living at SNF discharge. Associations of the number of nondisease-specific problems (≤1, 2, 3, and 4-6) with 6-month mortality, LTC, and functional impairment were examined. Overall, 39.2% of patients who received SNF care after dialysis initiation died within 6 months. Compared with those with ≤1 nondisease-specific problems, multivariable adjusted hazard ratios (95% confidence interval) for mortality were 1.26 (1.19 to 1.32), 1.40 (1.33 to 1.48), and 1.66 (1.57 to 1.76) for 2, 3, and 4-6 nondisease-specific problems, respectively. Among those who survived, 37.1% required LTC; of those remaining who did not require LTC, 74.7% had functional impairment. A higher likelihood of transition to LTC (among those who survived 6 months) and functional impairment (among those who survived and did not require LTC) was seen with a higher number of problems. Identifying nondisease-specific problems may help patients and families anticipate LTC needs and functional impairment after dialysis initiation. Copyright © 2016 by the American Society of Nephrology.

  2. A Single-Dose, Open-Label Study of the Pharmacokinetics, Safety, and Tolerability of Lisdexamfetamine Dimesylate in Individuals With Normal and Impaired Renal Function

    PubMed Central

    Ermer, James; Corcoran, Mary; Lasseter, Kenneth; Marbury, Thomas; Yan, Brian

    2016-01-01

    Background: Lisdexamfetamine (LDX) and d-amphetamine pharmacokinetics were assessed in individuals with normal and impaired renal function after a single LDX dose; LDX and d-amphetamine dialyzability was also examined. Methods: Adults (N = 40; 8/group) were enrolled in 1 of 5 renal function groups [normal function, mild impairment, moderate impairment, severe impairment/end-stage renal disease (ESRD) not requiring hemodialysis, and ESRD requiring hemodialysis] as estimated by glomerular filtration rate (GFR). Participants with normal and mild to severe renal impairment received 30 mg LDX; blood samples were collected predose and serially for 96 hours. Participants with ESRD requiring hemodialysis received 30 mg LDX predialysis and postdialysis separated by a washout period of 7–14 days. Predialysis blood samples were collected predose, serially for 72 hours, and from the dialyzer during hemodialysis; postdialysis blood samples were collected predose and serially for 48 hours. Pharmacokinetic end points included maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve from time 0 to infinity (AUC0–∞) or to last assessment (AUClast). Results: Mean LDX Cmax, AUClast, and AUC0–∞ in participants with mild to severe renal impairment did not differ from those with normal renal function; participants with ESRD had higher mean Cmax and AUClast than those with normal renal function. d-amphetamine exposure (AUClast and AUC0–∞) increased and Cmax decreased as renal impairment increased. Almost no LDX and little d-amphetamine were recovered in the dialyzate. Conclusions: There seems to be prolonged d-amphetamine exposure after 30 mg LDX as renal impairment increases. In individuals with severe renal impairment (GFR: 15 ≤ 30 mL·min−1·1.73 m−2), the maximum LDX dose is 50 mg/d; in patients with ESRD (GFR: <15 mL·min−1·1.73 m−2), the maximum LDX dose is 30 mg/d. Neither LDX nor d-amphetamine is dialyzable. PMID:26926668

  3. Impaired Executive Functions in Subjects with Frequent Nightmares as Reflected by Performance in Different Neuropsychological Tasks

    ERIC Educational Resources Information Center

    Simor, Peter; Pajkossy, Peter; Horvath, Klara; Bodizs, Robert

    2012-01-01

    Nightmare disorder is a prevalent parasomnia characterized by vivid and highly unpleasant dream experiences during night time sleep. The neural background of disturbed dreaming was proposed to be associated with impaired prefrontal and fronto-limbic functioning during REM sleep. We hypothesized that the impaired prefrontal and fronto-limbic…

  4. Procedures and Tools Used by Teachers When Completing Functional Vision Assessments with Children with Visual Impairments

    ERIC Educational Resources Information Center

    Kaiser, Justin T.; Herzberg, Tina S.

    2017-01-01

    Introduction: This study analyzed survey responses from 314 teachers of students with visual impairments regarding the tools and procedures used in completing functional vision assessments (FVAs). Methods: Teachers of students with visual impairments in the United States and Canada completed an online survey during spring 2016. Results: The…

  5. The Effectiveness of a Multidisciplinary Group Rehabilitation Program on the Psychosocial Functioning of Elderly People Who Are Visually Impaired

    ERIC Educational Resources Information Center

    Alma, Manna A.; Groothoff, Johan W.; Melis-Dankers, Bart J. M.; Suurmeijer, Theo P. B. M.; van der Mei, Sijrike F.

    2013-01-01

    Introduction: The pilot study reported here determined the effectiveness of a multidisciplinary group rehabilitation program, Visually Impaired Elderly Persons Participating (VIPP), on psychosocial functioning. Methods: The single-group pretest-posttest pilot study included 29 persons with visual impairments (aged 55 and older) who were referred…

  6. Attention profiles in autism spectrum disorder and subtypes of attention-deficit/hyperactivity disorder.

    PubMed

    Boxhoorn, Sara; Lopez, Eva; Schmidt, Catharina; Schulze, Diana; Hänig, Susann; Freitag, Christine M

    2018-03-06

    Attention problems are observed in attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Most neuropsychological studies that compared both disorders focused on complex executive functions (EF), but missed to contrast basic attention functions, as well as ASD- and ADHD subtypes. The present study compared EF as well as basic attention functioning of children with the combined subtype (ADHD-C), the predominantly inattentive subtype (ADHD-I), and autism spectrum disorder without ADHD (ASD-) with typically developing controls (TD). Basic attention functions and EF profiles were analysed by testing the comprehensive attention function model of van Zomeren and Brouwer using profile analysis. Additionally, neurocognitive impairments in ASD- and ADHD were regressed on dimensional measures of attention- and hyperactive-impulsive symptoms across and within groups. ADHD-C revealed a strong impairment across measures of EF compared to ASD- and TD. The ADHD-C profile furthermore showed disorder specific impairments in interference control, whereas the ASD- profile showed a disorder specific impairment in basic attention component divided attention. Attention- and hyperactive-impulsive symptom severity did not predict neurocognitive impairments across- or within groups. Study findings thus support disorder and subtype specific attention/EF profiles, which refute the idea of a continuum of ADHD-I, ADHD-C, and ASD with increasing neurocognitive impairments.

  7. Family functioning in two treatments for adolescent anorexia nervosa.

    PubMed

    Ciao, Anna C; Accurso, Erin C; Fitzsimmons-Craft, Ellen E; Lock, James; Le Grange, Daniel

    2015-01-01

    Family functioning impairment is widely reported in the eating disorders literature, yet few studies have examined the role of family functioning in treatment for adolescent anorexia nervosa (AN). This study examined family functioning in two treatments for adolescent AN from multiple family members' perspectives. Participants were 121 adolescents with AN ages 12-18 from a randomized-controlled trial comparing family-based treatment (FBT) to individual adolescent-focused therapy (AFT). Multiple clinical characteristics were assessed at baseline. Family functioning from the perspective of the adolescent and both parents was assessed at baseline and after 1 year of treatment. Full remission from AN was defined as achieving both weight restoration and normalized eating disorder psychopathology. In general, families dealing with AN reported some baseline impairment in family functioning, but average ratings were only slightly elevated compared to published impaired functioning cutoffs. Adolescents' perspectives on family functioning were the most impaired and were generally associated with poorer psychosocial functioning and greater clinical severity. Regardless of initial level of family functioning, improvements in several family functioning domains were uniquely related to full remission at the end of treatment in both FBT and AFT. However, FBT had a more positive impact on several specific aspects of family functioning compared to AFT. Families seeking treatment for adolescent AN report some difficulties in family functioning, with adolescents reporting the greatest impairment. Although FBT may be effective in improving some specific aspects of family dynamics, remission from AN was associated with improved family dynamics, regardless of treatment type. © 2014 Wiley Periodicals, Inc.

  8. Atypicalities in cortical structure, handedness, and functional lateralization for language in autism spectrum disorders.

    PubMed

    Lindell, Annukka K; Hudry, Kristelle

    2013-09-01

    Language is typically a highly lateralized function, with atypically reduced or reversed lateralization linked to language impairments. Given the diagnostic and prognostic role of impaired language for autism spectrum disorders (ASDs), this paper reviews the growing body of literature that examines patterns of lateralization in individuals with ASDs. Including research from structural and functional imaging paradigms, and behavioral evidence from investigations of handedness, the review confirms that atypical lateralization is common in people with ASDs. The evidence indicates reduced structural asymmetry in fronto-temporal language regions, attenuated functional activation in response to language and pre-linguistic stimuli, and more ambiguous (mixed) hand preferences, in individuals with ASDs. Critically, the evidence emphasizes an intimate relationship between atypical lateralization and language impairment, with more atypical asymmetries linked to more substantive language impairment. Such evidence highlights opportunities for the identification of structural and functional biomarkers of ASDs, affording the potential for earlier diagnosis and intervention implementation.

  9. Similar verbal memory impairments in schizophrenia and healthy aging. Implications for understanding of neural mechanisms.

    PubMed

    Silver, Henry; Bilker, Warren B

    2015-03-30

    Memory is impaired in schizophrenia patients but it is not clear whether this is specific to the illness and whether different types of memory (verbal and nonverbal) or memories in different cognitive domains (executive, object recognition) are similarly affected. To study relationships between memory impairments and schizophrenia we compared memory functions in 77 schizophrenia patients, 58 elderly healthy individuals and 41 young healthy individuals. Tests included verbal associative and logical memory and memory in executive and object recognition domains. We compared relationships of memory functions to each other and to other cognitive functions including psychomotor speed and verbal and spatial working memory. Compared to the young healthy group, schizophrenia patients and elderly healthy individuals showed similar severe impairment in logical memory and in the ability to learn new associations (NAL), and similar but less severe impairment in spatial working memory and executive and object memory. Verbal working memory was significantly more impaired in schizophrenia patients than in the healthy elderly. Verbal episodic memory impairment in schizophrenia may share common mechanisms with similar impairment in healthy aging. Impairment in verbal working memory in contrast may reflect mechanisms specific to schizophrenia. Study of verbal explicit memory impairment tapped by the NAL index may advance understanding of abnormal hippocampus dependent mechanisms common to schizophrenia and aging. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. The Potential Utility of Eye Movements in the Detection and Characterization of Everyday Functional Difficulties in Mild Cognitive Impairment.

    PubMed

    Seligman, Sarah C; Giovannetti, Tania

    2015-06-01

    Mild cognitive impairment (MCI) refers to the intermediate period between the typical cognitive decline of normal aging and more severe decline associated with dementia, and it is associated with greater risk for progression to dementia. Research has suggested that functional abilities are compromised in MCI, but the degree of impairment and underlying mechanisms remain poorly understood. The development of sensitive measures to assess subtle functional decline poses a major challenge for characterizing functional limitations in MCI. Eye-tracking methodology has been used to describe visual processes in everyday, naturalistic action among healthy older adults as well as several case studies of severely impaired individuals, and it has successfully differentiated healthy older adults from those with MCI on specific visual tasks. These studies highlight the promise of eye-tracking technology as a method to characterize subtle functional decline in MCI. However, to date no studies have examined visual behaviors during completion of naturalistic tasks in MCI. This review describes the current understanding of functional ability in MCI, summarizes findings of eye-tracking studies in healthy individuals, severe impairment, and MCI, and presents future research directions to aid with early identification and prevention of functional decline in disorders of aging.

  11. 'Executive' functions and normal aging: selective impairment in conditional exclusion compared to abstraction and inhibition.

    PubMed

    Silver, Henry; Goodman, Craig; Gur, Ruben C; Gur, Raquel E; Bilker, Warren B

    2011-01-01

    Some executive functions may be selectively impaired in normal aging over and above the general cognitive decline. We examined the performance of healthy high functioning young (n = 77) and older (n = 57) individuals on three 'executive' tests: conditional exclusion, abstraction, and inhibition of prepotent responses. We compared their relationships to each other and to other cognitive functions including attention, psychomotor speed and working memory. Conditional exclusion was significantly more impaired than abstraction or inhibition in the elderly compared to the younger group and unlike them, showed a nonlinear relationship with age. These findings were independent of other cognitive functions. Analysis of PCET performance characteristics showed that older individuals were particularly impaired in attaining the last of the three achievable categories, were slower, and had fewer error monitoring resources compared to the younger group. Conditional exclusion shows an age-related pattern of impairment distinct from inhibition and abstraction. We propose that in healthy well-functioning individuals, it taps processes integrating task set establishment and shifting in context of accumulating information. It may thus be useful as a specific marker of complex cognitive functions in studies of normal cognitive aging and in early detection of cognitive dysfunction. Copyright © 2010 S. Karger AG, Basel.

  12. A preliminary investigation of sleep quality in functional neurological disorders: Poor sleep appears common, and is associated with functional impairment.

    PubMed

    Graham, Christopher D; Kyle, Simon D

    2017-07-15

    Functional neurological disorders (FND) are disabling conditions for which there are few empirically-supported treatments. Disturbed sleep appears to be part of the FND context; however, the clinical importance of sleep disturbance (extent, characteristics and impact) remains largely unknown. We described sleep quality in two samples, and investigated the relationship between sleep and FND-related functional impairment. We included a sample recruited online via patient charities (N=205) and a consecutive clinical sample (N=20). Participants completed validated measures of sleep quality and sleep characteristics (e.g. total sleep time, sleep efficiency), mood, and FND-related functional impairment. Poor sleep was common in both samples (89% in the clinical range), which was characterised by low sleep efficiency (M=65.40%) and low total sleep time (M=6.05h). In regression analysis, sleep quality was negatively associated with FND-related functional impairment, accounting for 16% of the variance and remaining significant after the introduction of mood variables. These preliminary analyses suggest that subjective sleep disturbance (low efficiency, short sleep) is common in FND. Sleep quality was negatively associated with the functional impairment attributed to FND, independent of depression. Therefore, sleep disturbance may be a clinically important feature of FND. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Working Memory and Executive Function Profiles of Individuals with Borderline Intellectual Functioning

    ERIC Educational Resources Information Center

    Alloway, T. P.

    2010-01-01

    Background: The aim of the present study was to investigate the following issues: (1) Do students with borderline intellectual functioning have a pervasive pattern of impaired working memory skills across both verbal and visuo-spatial domains? (2) Is there evidence for impairment in executive function skills, and which tasks indicate greater…

  14. Why is impaired sexual function distressing to women? The primacy of pleasure in female sexual dysfunction.

    PubMed

    Stephenson, Kyle R; Meston, Cindy M

    2015-03-01

    Recent research has highlighted a complex association between female sexual function and subjective distress regarding sexual activity. These findings are difficult to explain given limited knowledge as to the mechanisms through which impaired sexual function causes distress. The current study assessed whether a number of specific consequences of impaired sexual function, including decreased physical pleasure, disruption of sexual activity, and negative partner responses, mediated the association between sexual function and distress. Eighty-seven women in sexually active relationships reporting impairments in sexual function completed validated self-report measures and daily online assessments of sexual experiences. Participants completed the Sexual Satisfaction Scale for Women, the Female Sexual Function Index, and the Measure of Sexual Consequences. Results suggested that decreased physical pleasure and disruption of sexual activity, but not partner responses, statistically mediated the association between sexual function and distress. Sexual consequences represent potential maintaining factors of sexual dysfunction that are highly distressing to women. Results are discussed in the context of theoretical models of sexual dysfunction and related treatments. © 2014 International Society for Sexual Medicine.

  15. Why is impaired sexual function distressing to women? The primacy of pleasure in female sexual dysfunction

    PubMed Central

    Stephenson, Kyle R.; Meston, Cindy M.

    2015-01-01

    Introduction Recent research has highlighted a complex association between female sexual function and subjective distress regarding sexual activity. These findings are difficult to explain given limited knowledge as to the mechanisms through which impaired sexual function causes distress. Aim The current study assessed whether a number of specific consequences of impaired sexual function, including decreased physical pleasure, disruption of sexual activity, and negative partner responses, mediated the association between sexual function and distress. Methods Eighty seven women in sexually active relationships reporting impairments in sexual function completed validated self-report measures and daily online assessments of sexual experiences. Main Outcome Measures Participants completed the Sexual Satisfaction Scale for Women (SSS-W), the Female Sexual Function Index (FSFI), and the Measure of Sexual Consequences (MSC). Results Results suggested that decreased physical pleasure and disruption of sexual activity, but not partner responses, statistically mediated the association between sexual function and distress. Conclusion Sexual consequences represent potential maintaining factors of sexual dysfunction that are highly distressing to women. Results are discussed in the context of theoretical models of sexual dysfunction and related treatments. PMID:25556719

  16. Associations between cognitive impairment and patient-reported measures of physical/mental functioning in older people living with HIV.

    PubMed

    Underwood, J; De Francesco, D; Post, F A; Vera, J H; Williams, I; Boffito, M; Mallon, P W; Anderson, J; Sachikonye, M; Sabin, C; Winston, A

    2017-05-01

    While cognitive impairment is frequently reported in HIV-positive individuals and has historically been associated with poorer functional outcomes, the associations between cognitive impairment and patient-reported outcome measures (PROMs) in contemporary cohorts are unclear. We tested cognitive function using a computerized battery (CogState ™ ) in 290 HIV-positive and 97 HIV-negative individuals aged ≥ 50 years participating in the Pharmacokinetic and Clinical Observations in People Over Fifty (POPPY) study. Participants completed questionnaires detailing physical and mental health [Short Form Health Survey (SF-36)], cognitive function [European AIDS Clinical Society (EACS) questions], activities of daily living [Lawton Instrumental Activities of Daily Living (IADL)], depression [Patient Depression Questionnaire (PHQ-9) and Centres for Epidemiologic Studies Depression scale (CES-D)], falls and sexual desire. Cognitive impairment was defined using the Frascati criteria, global deficit score (GDS) and multivariate normative comparison (MNC). In the HIV-positive group, the classification performances of the different definitions of cognitive impairment and dichotomized questionnaire results were calculated. The prevalence of cognitive impairment in the HIV-positive group was 34.5% (GDS), 30.0% (Frascati) and 22.1% (MNC), with only 2% diagnosed with HIV-associated dementia. In general, the associations between cognitive impairment and PROMs were weak regardless of the definition used: mean c-statistics were 0.543 (GDS), 0.530 (MNC) and 0.519 (Frascati). Associations were similar using the global T-score to define cognitive impairment. Summary health scores (SF-36) were lower, but only significantly so for those with cognitive impairment identified using MNC, for both mental health (61.4 vs. 75.8; P = 0.03) and physical health (60.9 vs. 75.0; P = 0.03). The associations between cognitive impairment and PROMs were weak, possibly because impairment was mild and therefore largely asymptomatic. Further work is needed to elucidate the clinical implications of cognitive impairment in HIV-disease. © 2016 British HIV Association.

  17. Incidence of cognitively defined late-onset Alzheimer's dementia subgroups from a prospective cohort study.

    PubMed

    Crane, Paul K; Trittschuh, Emily; Mukherjee, Shubhabrata; Saykin, Andrew J; Sanders, R Elizabeth; Larson, Eric B; McCurry, Susan M; McCormick, Wayne; Bowen, James D; Grabowski, Thomas; Moore, Mackenzie; Bauman, Julianna; Gross, Alden L; Keene, C Dirk; Bird, Thomas D; Gibbons, Laura E; Mez, Jesse

    2017-12-01

    There may be biologically relevant heterogeneity within typical late-onset Alzheimer's dementia. We analyzed cognitive data from people with incident late-onset Alzheimer's dementia from a prospective cohort study. We determined individual averages across memory, visuospatial functioning, language, and executive functioning. We identified domains with substantial impairments relative to that average. We compared demographic, neuropathology, and genetic findings across groups defined by relative impairments. During 32,286 person-years of follow-up, 869 people developed Alzheimer's dementia. There were 393 (48%) with no domain with substantial relative impairments. Some participants had isolated relative impairments in memory (148, 18%), visuospatial functioning (117, 14%), language (71, 9%), and executive functioning (66, 8%). The group with isolated relative memory impairments had higher proportions with ≥ APOE ε4 allele, more extensive Alzheimer's-related neuropathology, and higher proportions with other Alzheimer's dementia genetic risk variants. A cognitive subgrouping strategy may identify biologically distinct subsets of people with Alzheimer's dementia. Copyright © 2017 the Alzheimer's Association. All rights reserved.

  18. Daily activity level improvement with antidepressant medications predicts long-term clinical outcomes in outpatients with major depressive disorder.

    PubMed

    Jha, Manish K; Teer, Raymond B; Minhajuddin, Abu; Greer, Tracy L; Rush, A John; Trivedi, Madhukar H

    2017-01-01

    Major depressive disorder (MDD) significantly impacts performance of both work- and nonwork-related routine daily activities. We have shown that work productivity is significantly impaired in employed MDD patients, but the extent of impairments in nonwork-related routine activities and its association with antidepressant treatment outcomes has not been established. Activity impairment was measured using the sixth item of Work Productivity and Activity Impairment Scale in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial (n=665). Published norms were used to define activity impairment levels. The relationship between activity impairment and baseline sociodemographic and clinical characteristics was evaluated along with changes in activity impairment and its relationship with other clinical outcomes such as symptom severity, function, and side effect burden. Remission status at 3 and 7 months was predicted based on week 6 activity impairment level. Higher psychosocial and cognitive impairments and greater number of comorbid medical conditions were associated with greater activity impairment at baseline. Proportion of participants with severe activity impairment declined from 47.6% at baseline to 18.7% at 3 months, while mean activity impairment decreased from 57.1 at baseline to 32.8 at 3 months. During course of treatment, levels of activity impairment correlated most strongly with psychosocial function among measures of symptom severity, function, quality of life, and side effect burden. No or minimal activity impairment at week 6 was associated with two to three times higher rates of remission at 3 and 7 months as compared to moderate or severe activity impairment levels even after controlling for remission status at week 6 and select baseline variables. Depressed patients have high levels of nonwork-related activity impairment at baseline that improves significantly with treatment and independently predicts long-term clinical outcomes. Brief systematic assessment of activity impairment during the course of antidepressant treatment can help inform clinical decision-making.

  19. [Apolipoprotein e polymorphism and cognitive function change of the elderly in a rural area, Korea].

    PubMed

    Kim, Sang Kyu; Hwang, Tae Yoon; Lee, Kyeong Soo; Kang, Pock Soo; Cho, Hee Soon; Bae, Young Kyung

    2009-07-01

    The aim of this study is to examine the cognitive function change related to aging, the incidence of cognitive impairment, and the association between apolipoprotein E polymorphism and cognitive impairment through a follow-up of the elderly with normal cognitive ability at baseline. Two hundred and fifteen subjects aged 65 and over were surveyed in February, 1998 (baseline survey), and their cognitive function was assessed again in 2003 (1st follow-up) and the once again in 2006 (2nd follow-up). Ninety one subjects completed all surveys up through the 2nd follow-up and their cognitive function scores using MMSE-K (Korean Version of the Mini-Mental State Examination) and the distribution of apolipoprotein E allele were analyzed. The cognitive function scores decreased with aging and the difference between baseline and the 2nd follow-up scores of the study increased with the age group. The incidence rate of cognitive impairment through an 8-year follow-up was 38.5% and higher in older age groups. Age was the only significant factor for incidence of cognitive impairment, but there was no significant association between apolipoprotein E genotype and incidence of cognitive impairment. The cognition of the elderly decreased with aging and the association of apolipoprotein E genotype with incidence of cognitive impairment was not significant in this study. To confirm the association between apolipoprotein E polymorphism and incidence of cognitive impairment further studies will be needed.

  20. Early Morning Functional Impairments in Stimulant-Treated Children with Attention-Deficit/Hyperactivity Disorder Versus Controls: Impact on the Family.

    PubMed

    Faraone, Stephen V; Schachar, Russell J; Barkley, Russell A; Nullmeier, Rick; Sallee, F Randy

    2017-10-01

    Children with attention-deficit/hyperactivity disorder (ADHD) frequently manifest early morning functional (EMF) impairments before school. We conducted a quantitative research survey to assess the impact of these EMF impairments on the family unit (caregiver, spouse/partner, and siblings). We developed an online survey questionnaire to collect data from 300 primary caregivers of children with ADHD and 50 primary caregivers of children who did not have ADHD. Although the ADHD children we surveyed were currently treated with stable doses of stimulants as their primary ADHD medication for at least 3 months, their parents reported high levels of EMF impairments in the child, which had a substantial negative effect on the emotional well-being of parents, on parents' functioning during the early morning routine, and on the level of conflict with siblings. The impact of EMF impairments on family functioning was mediated by the severity of the index child's impairments. EMF impairments exert a pervasive and significantly negative emotional and functional burden on not only the primary caregiver but also on the spouse/partner and siblings. This work suggests that adequate ADHD symptom control during the early morning period may be an unmet need for school-age children with ADHD being treated with stimulants. More work is needed to confirm this finding and determine the degree to which symptom control at other times of day is also an unmet need.

  1. Early Morning Functional Impairments in Stimulant-Treated Children with Attention-Deficit/Hyperactivity Disorder Versus Controls: Impact on the Family

    PubMed Central

    Schachar, Russell J.; Barkley, Russell A.; Nullmeier, Rick; Sallee, F. Randy

    2017-01-01

    Abstract Objective: Children with attention-deficit/hyperactivity disorder (ADHD) frequently manifest early morning functional (EMF) impairments before school. We conducted a quantitative research survey to assess the impact of these EMF impairments on the family unit (caregiver, spouse/partner, and siblings). Study Design: We developed an online survey questionnaire to collect data from 300 primary caregivers of children with ADHD and 50 primary caregivers of children who did not have ADHD. Results: Although the ADHD children we surveyed were currently treated with stable doses of stimulants as their primary ADHD medication for at least 3 months, their parents reported high levels of EMF impairments in the child, which had a substantial negative effect on the emotional well-being of parents, on parents' functioning during the early morning routine, and on the level of conflict with siblings. The impact of EMF impairments on family functioning was mediated by the severity of the index child's impairments. Conclusions: EMF impairments exert a pervasive and significantly negative emotional and functional burden on not only the primary caregiver but also on the spouse/partner and siblings. This work suggests that adequate ADHD symptom control during the early morning period may be an unmet need for school-age children with ADHD being treated with stimulants. More work is needed to confirm this finding and determine the degree to which symptom control at other times of day is also an unmet need. PMID:28394175

  2. Gamma Radiation (5-10 Gy) Impairs Neuronal Function in the Guinea Pig Hippocampus

    DTIC Science & Technology

    1993-01-01

    Radiation (5-10 Gy) Impairs Neuronal Function in the Guinea Pig Hippocampus TERRY C. PELLMAR AND DENNIS L. LEPINSKI Ph.vsiology Department..Irmned Forces...L. Gamma Radiation ioral effects. Within hours of irradiation with 10 Gy and (5- 10 Gy) Impairs Neuronal Function in the Guinea Pig Hippo- less...acti v- Guinea pigs were exposed to 5 and 10 Gy ’y radiation. Hippo- ity (9) are evident. campal brain slices were isolated 30 min, I day, 3 days and 5

  3. Impairment in Proverb Interpretation as an Executive Function Deficit in Patients with Amnestic Mild Cognitive Impairment and Early Alzheimer's Disease

    PubMed Central

    Leyhe, Thomas; Saur, Ralf; Eschweiler, Gerhard W.; Milian, Monika

    2011-01-01

    Background/Aims Proverb interpretation is assumed to reflect executive functions. We hypothesized that proverb interpretation is impaired in patients with amnestic mild cognitive impairment (aMCI) diagnosed as single-domain impairment by common neuropsychological testing. Methods We compared performance in a proverb interpretation test in single-domain aMCI patients and patients with early Alzheimer's disease (EAD). Results The groups with aMCI and EAD performed significantly worse than healthy controls. Both patient groups gave concrete answers with a similar frequency. However, patients with EAD tended to give senseless answers more frequently. Conclusions Our data suggest that in patients diagnosed as single-domain aMCI, deterioration of executive functions is detectable with subtle and appropriate neuropsychological testing. Implementation of these procedures may improve the early prediction of AD. PMID:22163233

  4. Impairment of cognitive abilities and decision making after chronic use of alcohol: the impact of multiple detoxifications.

    PubMed

    Loeber, Sabine; Duka, Theodora; Welzel, Helga; Nakovics, Helmut; Heinz, Andreas; Flor, Herta; Mann, Karl

    2009-01-01

    In the present study, the effect of previous detoxifications on prefrontal function and decision making was examined in alcohol-dependent patients. Further, we examined whether the length of abstinence affects cognitive function. Forty-eight alcohol-dependent patients were recruited from an inpatient detoxification treatment facility and cognitive function was compared to a control group of 36 healthy controls. The patient population was then divided into a group of patients with less than two previous detoxifications (LO-detox group, n = 27) and a group of patients with two or more previous detoxifications (HI-detox group, n = 21) and cognitive function was compared. In addition, cognitive function of recently (i.e. less than 16 days; median split) and longer abstinent patients was compared. We assessed prefrontal function, memory function and intelligence. Alcoholics, when compared to healthy controls, performed worse with regard to the performance index Attention/Executive function. Cognitive impairment in these tasks was pronounced in recently abstinent patients. We found no significant differences between HI-detox and LO-detox patients with regard to the Attention/Executive function. However, in the IOWA gambling Task, the HI-detox group seemed to be less able to learn to choose cards from the more advantageous decks over time. Our results provide additional evidence for cognitive impairment of alcohol-dependent patients with regard to tasks sensitive to frontal lobe function and underline the importance of abstinence for these impairments to recover. We found only little evidence for the impairing effects of repeated withdrawal on prefrontal function and we suggest that executive function is affected earlier in dependence.

  5. Respiratory symptoms and pulmonary function impairment among detergent plant workers in Jos, Northern Nigeria.

    PubMed

    Babashani, M; Iliyasu, Z; Ukoli, C O

    2008-01-01

    The industrial process of detergent production could be deleterious to lung function. This study describes respiratory symptoms and ventilatory function impairment among detergent workers in Jos, Northern Nigeria. Two hundred detergent plant workers and controls were studied for the presence of respiratory symptoms and ventilatory function impairment using the MRC questionnaire and Spirometry. A significantly higher proportion of exposed detergent workers 178 (87.0%) reported respiratory symptoms compared to 52 (26.0%) controls [OR=23; 95% CI=12.9-41.3] (P<0.001). Commonest symptoms include rhinitis (57.5% versus 11.0%) and cough (48.5% versus 15%). Symptoms were most prevalent in the packaging section. FEV1, FVC and PEFR were significantly reduced among exposed detergent workers. Similarly, the predicted values of PEFR, FVC and FEV1, were significantly reduced among smokers (P<0. 001). Respiratory symptoms are highly prevalent among detergent workers. This was associated with impaired pulmonary function. Protective equipment and periodic lung function tests could reduce these effects.

  6. [Self-consciousness in elderly persons with cognitive impairment and vascular dementia].

    PubMed

    Dubinina, E A; Novikova, Yu G; Kalitskaya, A V; Finagentova, N V

    2016-01-01

    Self-consciousness was compared in 17 elderly (aged 65-89 years old) persons with cognitive impairment without dementia and 17 patients with vascular dementia. Neurocognitive functions and mental health complaints were evaluated. Neuropsychological assessment included evaluation of higher psychological functions, such as attention, memory, conceptualization, gnosis (optic, acoustic), manual skill, speech. Older persons with cognitive impairment assessed their neurocognitive functions adequately. Patients with vascular dementia usually denied cognitive deficit or explained it as a result of aging. Regardless of physical health, older persons with cognitive impairment have active attitude to aging. They could find ways of compensation of cognitive deficits without assistance. Patients with vascular dementia could not compensate their cognitive deficit even with support.

  7. Association between socioeconomic deprivation and functional impairment after stroke: the South London Stroke Register.

    PubMed

    Chen, Ruoling; Crichton, Siobhan; McKevitt, Christopher; Rudd, Anthony G; Sheldenkar, Anita; Wolfe, Charles D A

    2015-03-01

    Previous findings of the association between socioeconomic deprivation and functional impairment after stroke are inconsistent. There is a lack of data on long-term association. We assessed the association and differences by age, sex, prestroke comorbidities, and stroke phenotypes. We examined data from the South London Stroke Register cohort of 1995 to 2011, recording all first-ever strokes in patients of all ages in South London. A total of 2104 patients were alive at 3 months after stroke. Socioeconomic deprivation was measured using the index of multiple deprivation based on patient postcodes, and functional impairment after stroke was defined as a Barthel index of <15. At 3 months after stroke, 643 patients had functional impairment (30.6%; 95% confidence interval, 28.6%-32.5%). Compared with the first quartile of index of multiple deprivation (the least deprived), multivariate-adjusted odds ratios for functional impairment in patients with the second, third, and fourth quartiles were 1.29 (95% confidence interval, 0.94-1.76), 1.33 (0.97-1.82), and 1.78 (1.31-2.43), overall P=0.004. The association was significant in patients aged ≥65 years (corresponding odds ratios were 1.49 [1.02-2.17], 1.21 [0.83-1.75], and 1.94 [1.34-2.81]; P=0.003); in women, P=0.008, in patients who do not have prestroke comorbidities, P=0.009, and in patients with ischemic stroke, P<0.001, but not significant in their counterpart patients. There were similar patterns of the associations of socioeconomic deprivation with impairment at 3 years after stroke. There are significant inequalities in short- and long-term functional recovery after stroke. General socioeconomic improvement, targeting groups at high risk of functional impairment is likely to reduce inequality in functional recovery after stroke. © 2015 American Heart Association, Inc.

  8. The Weiss Functional Impairment Rating Scale-Parent Form for assessing ADHD: evaluating diagnostic accuracy and determining optimal thresholds using ROC analysis.

    PubMed

    Thompson, Trevor; Lloyd, Andrew; Joseph, Alain; Weiss, Margaret

    2017-07-01

    The Weiss Functional Impairment Rating Scale-Parent Form (WFIRS-P) is a 50-item scale that assesses functional impairment on six clinically relevant domains typically affected in attention-deficit/hyperactivity disorder (ADHD). As functional impairment is central to ADHD, the WFIRS-P offers potential as a tool for assessing functional impairment in ADHD. These analyses were designed to examine the overall performance of WFIRS-P in differentiating ADHD and non-ADHD cases using receiver operating characteristics (ROC) analysis. This is the first attempt to empirically determine the level of functional impairment that differentiates ADHD children from normal controls. This observational study comprised 5-19-year-olds with physician-diagnosed ADHD (n = 476) and non-ADHD controls (n = 202). ROC analysis evaluated the ability of WFIRS-P to discriminate between ADHD and non-ADHD, and identified a WFIRS-P cut-off score that optimises correct classification. Data were analysed for the complete sample, for males versus females and for participants in two age groups (5-12 versus 13-19 years). Area under the curve (AUC) was 0.91 (95% confidence interval 0.88-0.93) for the overall WFIRS-P score, suggesting highly accurate classification of ADHD distinct from non-ADHD. Sensitivity (0.83) and specificity (0.85) were maximal for a mean overall WFIRS-P score of 0.65, suggesting that this is an appropriate threshold for differentiation. DeLong's test found no significant differences in AUCs for males versus females or 5-12 versus 13-19 years, suggesting that WFIRS-P is an accurate classifier of ADHD across gender and age. When assessing function, WFIRS-P appears to provide a simple and effective basis for differentiating between individuals with/without ADHD in terms of functional impairment. Disease-specific applications of QOL research.

  9. Impairment in immuno-modulatory function of Flk1(+)CD31(-)CD34(-) MSCs from MDS-RA patients.

    PubMed

    Han, Qin; Sun, Zhao; Liu, Lihui; Chen, Bin; Cao, Ying; Li, Kanghua; Zhao, Robert Chunhua

    2007-11-01

    Myelodysplastic syndromes are a group of hematopoietic disorders characterized by hematopoietic stem cell dysregulation and abnormalities in the immune system. Mesenchymal stem cells (MSCs) and their derived stromal cells constitute a bone marrow microenvironment, which is the niche for hematopoiesis and a key compartment for immune development and regulation. Existing evidence has shown that MSCs from MDS patients have impaired capacity in supporting hematopoiesis. Here, we conducted an investigation to determine whether the immuno-modulatory function of MSCs is also impaired in MDS-RA (refractory anemia) patients. Flk1(+)CD31(-)CD34(-) MSCs were isolated from 15 MDS-RA patients and cultured for testing biological and immunological characteristics. MDS-RA patient-derived Flk1(+)CD31(-)CD34(-) MSCs showed normal morphology, phenotype and karyotype but appeared impaired in immuno-modulatory function. The capacity of patient Flk1(+)CD31(-)CD34(-) MSCs to inhibit T lymphocyte activation and proliferation was impaired in vitro. In conclusion, MDS-RA patient-derived MSCs have impaired immuno-modulatory functions, suggesting that the dysregulation of hematopoiesis and immune response may originate from MSCs rather than HSCs. MSCs might be a potential target for developing efficacious cures for MDS.

  10. Developmental dyscalculia is related to visuo-spatial memory and inhibition impairment.

    PubMed

    Szucs, Denes; Devine, Amy; Soltesz, Fruzsina; Nobes, Alison; Gabriel, Florence

    2013-01-01

    Developmental dyscalculia is thought to be a specific impairment of mathematics ability. Currently dominant cognitive neuroscience theories of developmental dyscalculia suggest that it originates from the impairment of the magnitude representation of the human brain, residing in the intraparietal sulcus, or from impaired connections between number symbols and the magnitude representation. However, behavioral research offers several alternative theories for developmental dyscalculia and neuro-imaging also suggests that impairments in developmental dyscalculia may be linked to disruptions of other functions of the intraparietal sulcus than the magnitude representation. Strikingly, the magnitude representation theory has never been explicitly contrasted with a range of alternatives in a systematic fashion. Here we have filled this gap by directly contrasting five alternative theories (magnitude representation, working memory, inhibition, attention and spatial processing) of developmental dyscalculia in 9-10-year-old primary school children. Participants were selected from a pool of 1004 children and took part in 16 tests and nine experiments. The dominant features of developmental dyscalculia are visuo-spatial working memory, visuo-spatial short-term memory and inhibitory function (interference suppression) impairment. We hypothesize that inhibition impairment is related to the disruption of central executive memory function. Potential problems of visuo-spatial processing and attentional function in developmental dyscalculia probably depend on short-term memory/working memory and inhibition impairments. The magnitude representation theory of developmental dyscalculia was not supported. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Safety and efficacy of repaglinide in type 2 diabetic patients with and without impaired renal function.

    PubMed

    Hasslacher, Christoph

    2003-03-01

    To evaluate the influence of renal impairment on the safety and efficacy of repaglinide in type 2 diabetic patients. This multinational, open-label study comprised a 6-week run-in period, continuing prestudy antidiabetic medication, followed by a titration period (1-4 weeks) and a 3-month maintenance period. Patients with normal renal function (n = 151) and various degrees of renal impairment (n = 130) were treated with repaglinide (maximal dose of 4 mg, three times daily). Safety and efficacy assessments were performed at baseline (end of run-in) and at the end of study treatment. The type and severity of adverse events during repaglinide treatment were similar to the run-in period. The number of patients with adverse events was not significantly related to renal function during run-in or repaglinide treatment. Percentage of patients with hypoglycemic episodes increased significantly (P = 0.007) with increasing severity of renal impairment during run-in but not during repaglinide treatment (P = 0.074). Metabolic control (HbA(1c) and fasting blood glucose) with repaglinide was unchanged from that on previous antidiabetic medication. Final repaglinide dose tended to be lower for patients with severe and extreme renal impairment than for patients with less severe renal impairment or normal renal function (P = 0.032). Repaglinide has a good safety and efficacy profile in type 2 diabetic patients complicated by renal impairment and is an appropriate treatment choice, even for individuals with more severe degrees of renal impairment.

  12. Inferential functioning in visually impaired children.

    PubMed

    Puche-Navarro, Rebeca; Millán, Rafael

    2007-01-01

    The current study explores the inferential abilities of visually impaired children in a task presented in two formats, manipulative and verbal. The results showed that in the group of visually impaired children, just as with children with normal sight, there was a wide range of inference types. It was found that the visually impaired children perform slightly better in the use of inductive and relational inferences in the verbal format, while in the manipulative format children with normal sight perform better. These results suggest that in inferential functioning of young children, and especially visually impaired children, the format of the task influences performance more than the child's visual ability.

  13. Common and specific impairments in attention functioning in girls with chromosome 22q11.2 deletion, fragile X or Turner syndromes

    PubMed Central

    2014-01-01

    Background Chromosome 22q11.2 deletion syndrome (22q11.2DS), fragile X syndrome (FXS), and Turner syndrome (TS) are complex and variable developmental syndromes caused by different genetic abnormalities; yet, they share similar cognitive impairments in the domains of numbers, space, and time. The atypical development of foundational neural networks that underpin the attentional system is thought to result in further impairments in higher-order cognitive functions. The current study investigates whether children with similar higher-order cognitive impairments but different genetic disorders also show similar impairments in alerting, orienting, and executive control of attention. Methods Girls with 22q11.2DS, FXS, or TS and typically developing (TD) girls, aged 7 to 15 years, completed an attention network test, a flanker task with alerting and orienting cues. Exploration of reaction times and accuracy allowed us to test for potential commonalities in attentional functioning in alerting, orienting, and executive control. Linear regression models were used to test whether the predictors of group and chronological age were able to predict differences in attention indices. Results Girls with 22q11.2DS, FXS, or TS demonstrated unimpaired function of the alerting system and impaired function of the executive control system. Diagnosis-specific impairments were found such that girls with FXS made more errors and had a reduced orienting index, while girls with 22q11.2DS showed specific age-related deficits in the executive control system. Conclusions These results suggest that the control but not the implementation of attention is selectively impaired in girls with 22q11.2DS, TS or FXS. Additionally, the age effect on executive control in girls with 22q11.2DS implies a possible altered developmental trajectory. PMID:24628892

  14. Measuring impairment when diagnosing adolescent ADHD: Differentiating problems due to ADHD versus other sources.

    PubMed

    Vazquez, Alejandro L; H Sibley, Margaret; Campez, Mileini

    2018-06-01

    The DSM-5 requires clinicians to link ADHD symptoms to clinically meaningful impairments in daily life functioning. Measuring impairment during ADHD assessments may be particularly challenging in adolescence, when ADHD is often not the sole source of a youth's difficulties. Existing impairment rating scales are criticized for not specifying ADHD as the source of impairment in their instructions, leading to potential problems with rating scale specificity. The current study utilized a within subjects design (N = 107) to compare parent report of impairment on two versions of a global impairment measure: one that specified ADHD as the source of impairment (Impairment Rating Scale-ADHD) and a standard version that did not (Impairment Rating Scale). On the standard family impairment item, parents endorsed greater impairment as compared to the IRS-ADHD. This finding was particularly pronounced when parents reported high levels of parenting stress. More severe ADHD symptoms were associated with greater concordance between the two versions. Findings indicate that adolescent family related impairments reported during ADHD assessments may be due to sources other than ADHD symptoms, such as developmental maladjustment. To prevent false positive diagnoses, symptom-specific wording may optimize impairment measures when assessing family functioning in diagnostic assessments for adolescents with ADHD. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Moderators of noise-induced cognitive change in healthy adults.

    PubMed

    Wright, Bernice Al; Peters, Emmanuelle R; Ettinger, Ulrich; Kuipers, Elizabeth; Kumari, Veena

    2016-01-01

    Environmental noise causes cognitive impairment, particularly in executive function and episodic memory domains, in healthy populations. However, the possible moderating influences on this relationship are less clear. This study assessed 54 healthy participants (24 men) on a cognitive battery (measuring psychomotor speed, attention, executive function, working memory, and verbal learning and memory) under three (quiet, urban, and social) noise conditions. IQ, subjective noise sensitivity, sleep, personality, paranoia, depression, anxiety, stress, and schizotypy were assessed on a single occasion. We found significantly slower psychomotor speed (urban), reduced working memory and episodic memory (urban and social), and more cautious decision-making (executive function, urban) under noise conditions. There was no effect of sex. Variance in urban noise-induced changes in psychomotor speed, attention, Trail Making B-A (executive function), and immediate recall and social noise-induced changes in verbal fluency (executive function) and immediate recall were explained by a combination of baseline cognition and paranoia, noise sensitivity, sleep, or cognitive disorganization. Higher baseline cognition (but not IQ) predicted greater impairment under urban and social noise for most cognitive variables. Paranoia predicted psychomotor speed, attention, and executive function impairment. Subjective noise sensitivity predicted executive function and memory impairment. Poor sleep quality predicted less memory impairment. Finally, lower levels of cognitive disorganization predicted slower psychomotor speed and greater memory impairment. The identified moderators should be considered in studies aiming to reduce the detrimental effects of occupational and residential noise. These results highlight the importance of studying noise effects in clinical populations characterized by high levels of the paranoia, sleep disturbances, noise sensitivity, and cognitive disorganization.

  16. Moderators of noise-induced cognitive change in healthy adults

    PubMed Central

    Wright, Bernice AL; Peters, Emmanuelle R; Ettinger, Ulrich; Kuipers, Elizabeth; Kumari, Veena

    2016-01-01

    Environmental noise causes cognitive impairment, particularly in executive function and episodic memory domains, in healthy populations. However, the possible moderating influences on this relationship are less clear. This study assessed 54 healthy participants (24 men) on a cognitive battery (measuring psychomotor speed, attention, executive function, working memory, and verbal learning and memory) under three (quiet, urban, and social) noise conditions. IQ, subjective noise sensitivity, sleep, personality, paranoia, depression, anxiety, stress, and schizotypy were assessed on a single occasion. We found significantly slower psychomotor speed (urban), reduced working memory and episodic memory (urban and social), and more cautious decision-making (executive function, urban) under noise conditions. There was no effect of sex. Variance in urban noise-induced changes in psychomotor speed, attention, Trail Making B-A (executive function), and immediate recall and social noise-induced changes in verbal fluency (executive function) and immediate recall were explained by a combination of baseline cognition and paranoia, noise sensitivity, sleep, or cognitive disorganization. Higher baseline cognition (but not IQ) predicted greater impairment under urban and social noise for most cognitive variables. Paranoia predicted psychomotor speed, attention, and executive function impairment. Subjective noise sensitivity predicted executive function and memory impairment. Poor sleep quality predicted less memory impairment. Finally, lower levels of cognitive disorganization predicted slower psychomotor speed and greater memory impairment. The identified moderators should be considered in studies aiming to reduce the detrimental effects of occupational and residential noise. These results highlight the importance of studying noise effects in clinical populations characterized by high levels of the paranoia, sleep disturbances, noise sensitivity, and cognitive disorganization. PMID:27157685

  17. Assessing Functional Impairment in Siblings Living With Children With Disability

    PubMed Central

    Havercamp, Susan; Jamieson, Barry; Sahr, Timothy

    2013-01-01

    OBJECTIVE: The purpose of this study was to empirically test if siblings of children with disability had higher levels of parent-reported behavioral and emotional functional impairment compared with a peer group of siblings residing with only typically developing children. METHODS: This was a retrospective secondary analysis of data from the Medical Expenditure Panel Survey. We included only households with at least 2 children to ensure sibling relationships. Two groups of siblings were formed: 245 siblings resided in households with a child with disability and 6564 siblings resided in households with typically developing children. Parents responded to questions from the Columbia Impairment Scale to identify functional impairment in their children. RESULTS: On the basis of parent reports and after adjusting for sibling demographic characteristics and household background, siblings of children with disability were more likely than siblings residing with typically developing children to have problems with interpersonal relationships, psychopathological functioning, functioning at school, and use of leisure time (P < .05). The percentage of siblings of children with disability classified with significant functional impairment was 16.0% at the first measurement period and 24.2% at the second (P < .001). For siblings of typically developing children there was a smaller percentage increase from 9.5% to 10.3% (P < .001). CONCLUSIONS: Functional impairment is a key indicator for the need of mental health services and, as such, early assessment and interventions to limit increasing severity and short- to long-term consequences need to be addressed. Health care professionals need to consider a family-based health care approach for families raising children with disability. PMID:23897909

  18. Assessing functional impairment in siblings living with children with disability.

    PubMed

    Goudie, Anthony; Havercamp, Susan; Jamieson, Barry; Sahr, Timothy

    2013-08-01

    The purpose of this study was to empirically test if siblings of children with disability had higher levels of parent-reported behavioral and emotional functional impairment compared with a peer group of siblings residing with only typically developing children. This was a retrospective secondary analysis of data from the Medical Expenditure Panel Survey. We included only households with at least 2 children to ensure sibling relationships. Two groups of siblings were formed: 245 siblings resided in households with a child with disability and 6564 siblings resided in households with typically developing children. Parents responded to questions from the Columbia Impairment Scale to identify functional impairment in their children. On the basis of parent reports and after adjusting for sibling demographic characteristics and household background, siblings of children with disability were more likely than siblings residing with typically developing children to have problems with interpersonal relationships, psychopathological functioning, functioning at school, and use of leisure time (P < .05). The percentage of siblings of children with disability classified with significant functional impairment was 16.0% at the first measurement period and 24.2% at the second (P < .001). For siblings of typically developing children there was a smaller percentage increase from 9.5% to 10.3% (P < .001). Functional impairment is a key indicator for the need of mental health services and, as such, early assessment and interventions to limit increasing severity and short- to long-term consequences need to be addressed. Health care professionals need to consider a family-based health care approach for families raising children with disability.

  19. Exercise training in Tgαq*44 mice during the progression of chronic heart failure: cardiac vs. peripheral (soleus muscle) impairments to oxidative metabolism.

    PubMed

    Grassi, Bruno; Majerczak, Joanna; Bardi, Eleonora; Buso, Alessia; Comelli, Marina; Chlopicki, Stefan; Guzik, Magdalena; Mavelli, Irene; Nieckarz, Zenon; Salvadego, Desy; Tyrankiewicz, Urszula; Skórka, Tomasz; Bottinelli, Roberto; Zoladz, Jerzy A; Pellegrino, Maria Antonietta

    2017-08-01

    Cardiac function, skeletal (soleus) muscle oxidative metabolism, and the effects of exercise training were evaluated in a transgenic murine model (Tgα q *44) of chronic heart failure during the critical period between the occurrence of an impairment of cardiac function and the stage at which overt cardiac failure ensues (i.e., from 10 to 12 mo of age). Forty-eight Tgα q *44 mice and 43 wild-type FVB controls were randomly assigned to control groups and to groups undergoing 2 mo of intense exercise training (spontaneous running on an instrumented wheel). In mice evaluated at the beginning and at the end of training we determined: exercise performance (mean distance covered daily on the wheel); cardiac function in vivo (by magnetic resonance imaging); soleus mitochondrial respiration ex vivo (by high-resolution respirometry); muscle phenotype [myosin heavy chain (MHC) isoform content; citrate synthase (CS) activity]; and variables related to the energy status of muscle fibers [ratio of phosphorylated 5'-AMP-activated protein kinase (AMPK) to unphosphorylated AMPK] and mitochondrial biogenesis and function [peroxisome proliferative-activated receptor-γ coactivator-α (PGC-1α)]. In the untrained Tgα q *44 mice functional impairments of exercise performance, cardiac function, and soleus muscle mitochondrial respiration were observed. The impairment of mitochondrial respiration was related to the function of complex I of the respiratory chain, and it was not associated with differences in CS activity, MHC isoforms, p-AMPK/AMPK, and PGC-1α levels. Exercise training improved exercise performance and cardiac function, but it did not affect mitochondrial respiration, even in the presence of an increased percentage of type 1 MHC isoforms. Factors "upstream" of mitochondria were likely mainly responsible for the improved exercise performance. NEW & NOTEWORTHY Functional impairments in exercise performance, cardiac function, and soleus muscle mitochondrial respiration were observed in transgenic chronic heart failure mice, evaluated in the critical period between the occurrence of an impairment of cardiac function and the terminal stage of the disease. Exercise training improved exercise performance and cardiac function, but it did not affect the impaired mitochondrial respiration. Factors "upstream" of mitochondria, including an enhanced cardiovascular O 2 delivery, were mainly responsible for the functional improvement. Copyright © 2017 the American Physiological Society.

  20. Family factors, emotional functioning, and functional impairment in juvenile fibromyalgia syndrome.

    PubMed

    Kashikar-Zuck, Susmita; Lynch, Anne M; Slater, Shalonda; Graham, T Brent; Swain, Nicole F; Noll, Robert B

    2008-10-15

    Family factors and emotional functioning can play an important role in the ability of adolescents with juvenile primary fibromyalgia syndrome (JPFS) to cope with their condition and function in their everyday lives. The primary objectives of this study were to determine 1) whether adolescents with JPFS and their caregivers differed from healthy age-matched comparison peers and their caregivers in terms of emotional distress and functional impairment; 2) whether there were any differences in the family environment of adolescents with JPFS compared with healthy comparison peers; and 3) which individual-, caregiver-, and family-level variables were associated with functional impairment in adolescents with JPFS. Participants were 47 adolescents with JPFS recruited from a pediatric rheumatology clinic and 46 comparison peers without chronic illness matched for age, sex, and race. Participants and their caregivers (all mothers) completed a battery of standardized measures administered in their homes. Adolescents with JPFS had greater internalizing and externalizing symptoms than healthy comparison peers. Mothers of adolescents with JPFS reported twice as many pain conditions and significantly greater depressive symptoms than mothers of comparison peers. The JPFS group also had poorer overall family functioning and more conflicted family relationships. In adolescents with JPFS, maternal pain history was associated with significantly higher functional impairment. Increased distress and chronic pain are evident in families of adolescents with JPFS, and family relationships are also impacted. Implications for child functional impairment and the need for inclusion of caregivers in treatment are discussed.

  1. Systemic lipopolysaccharide administration impairs retrieval of context-object discrimination, but not spatial, memory: Evidence for selective disruption of specific hippocampus-dependent memory functions during acute neuroinflammation

    PubMed Central

    Czerniawski, Jennifer; Miyashita, Teiko; Lewandowski, Gail; Guzowski, John F.

    2014-01-01

    Neuroinflammation is implicated in impairments in neuronal function and cognition that arise with aging, trauma, and/or disease. Therefore, understanding the underlying basis of the effect of immune system activation on neural function could lead to therapies for treating cognitive decline. Although neuroinflammation is widely thought to preferentially impair hippocampus-dependent memory, data on the effects of cytokines on cognition are mixed. One possible explanation for these inconsistent results is that cytokines may disrupt specific neural processes underlying some forms of memory but not others. In an earlier study, we tested the effect of systemic administration of bacterial lipopolysaccharide (LPS) on retrieval of hippocampus-dependent context memory and neural circuit function in CA3 and CA1 (Czerniawski and Guzowski, 2014). Paralleling impairment in context discrimination memory, we observed changes in neural circuit function consistent with disrupted pattern separation function. In the current study we tested the hypothesis that acute neuroinflammation selectively disrupts memory retrieval in tasks requiring hippocampal pattern separation processes. Male Sprague-Dawley rats given LPS systemically prior to testing exhibited intact performance in tasks that do not require hippocampal pattern separation processes: novel object recognition and spatial memory in the water maze. By contrast, memory retrieval in a task thought to require hippocampal pattern separation, context-object discrimination, was strongly impaired in LPS-treated rats in the absence of any gross effects on exploratory activity or motivation. These data show that LPS administration does not impair memory retrieval in all hippocampus-dependent tasks, and support the hypothesis that acute neuroinflammation impairs context discrimination memory via disruption of pattern separation processes in hippocampus. PMID:25451612

  2. Impaired left atrial function predicts inappropriate shocks in primary prevention implantable cardioverter-defibrillator candidates.

    PubMed

    Tao, Susumu; Ashikaga, Hiroshi; Ciuffo, Luisa A; Yoneyama, Kihei; Lima, Joao A C; Frank, Terry F; Weiss, Robert G; Tomaselli, Gordon F; Wu, Katherine C

    2017-07-01

    Inappropriate implantable cardioverter-defibrillator (ICD) shocks, commonly caused by atrial fibrillation (AF), are associated with an increased mortality. Because impaired left atrial (LA) function predicts development of AF, we hypothesized that impaired LA function predicts inappropriate shocks beyond a history of AF. We prospectively analyzed the association between LA function and incident inappropriate shocks in primary prevention ICD candidates. In the Prospective Observational Study of ICD (PROSE-ICD), we assessed LA function using tissue-tracking cardiac magnetic resonance (CMR) prior to ICD implantation. A total of 162 patients (113 males, age 56 ± 15 years) were included. During the mean follow-up of 4.0 ± 2.9 years, 26 patients (16%) experienced inappropriate shocks due to AF (n = 19; 73%), supraventricular tachycardia (n = 5; 19%), and abnormal sensing (n = 2; 8%). In univariable analyses, inappropriate shocks were associated with AF history prior to ICD implantation, age below 70 years, QRS duration less than 120 milliseconds, larger LA minimum volume, lower LA stroke volume, lower LA emptying fraction, impaired LA maximum and preatrial contraction strains (S max and S preA ), and impaired LA strain rate during left ventricular systole and atrial contraction (SR s and SR a ). In multivariable analysis, impaired S max (hazard ratio [HR]: 0.96, P = 0.044), S preA (HR: 0.94, P = 0.030), and SR a (HR: 0.25, P < 0.001) were independently associated with inappropriate shocks. The receiver-operating characteristics curve showed that SR a improved the predictive value beyond the patient demographics including AF history (P = 0.033). Impaired LA function assessed by tissue-tracking CMR is an independent predictor of inappropriate shocks in primary prevention ICD candidates beyond AF history. © 2017 Wiley Periodicals, Inc.

  3. Systemic lipopolysaccharide administration impairs retrieval of context-object discrimination, but not spatial, memory: Evidence for selective disruption of specific hippocampus-dependent memory functions during acute neuroinflammation.

    PubMed

    Czerniawski, Jennifer; Miyashita, Teiko; Lewandowski, Gail; Guzowski, John F

    2015-02-01

    Neuroinflammation is implicated in impairments in neuronal function and cognition that arise with aging, trauma, and/or disease. Therefore, understanding the underlying basis of the effect of immune system activation on neural function could lead to therapies for treating cognitive decline. Although neuroinflammation is widely thought to preferentially impair hippocampus-dependent memory, data on the effects of cytokines on cognition are mixed. One possible explanation for these inconsistent results is that cytokines may disrupt specific neural processes underlying some forms of memory but not others. In an earlier study, we tested the effect of systemic administration of bacterial lipopolysaccharide (LPS) on retrieval of hippocampus-dependent context memory and neural circuit function in CA3 and CA1 (Czerniawski and Guzowski, 2014). Paralleling impairment in context discrimination memory, we observed changes in neural circuit function consistent with disrupted pattern separation function. In the current study we tested the hypothesis that acute neuroinflammation selectively disrupts memory retrieval in tasks requiring hippocampal pattern separation processes. Male Sprague-Dawley rats given LPS systemically prior to testing exhibited intact performance in tasks that do not require hippocampal pattern separation processes: novel object recognition and spatial memory in the water maze. By contrast, memory retrieval in a task thought to require hippocampal pattern separation, context-object discrimination, was strongly impaired in LPS-treated rats in the absence of any gross effects on exploratory activity or motivation. These data show that LPS administration does not impair memory retrieval in all hippocampus-dependent tasks, and support the hypothesis that acute neuroinflammation impairs context discrimination memory via disruption of pattern separation processes in hippocampus. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Prospective Cohort Study of Work Functioning Impairment and Subsequent Absenteeism Among Japanese Workers.

    PubMed

    Fujino, Yoshihisa; Shazuki, Shuichiro; Izumi, Hiroyuki; Uehara, Masamichi; Muramatsu, Keiji; Kubo, Tatsuhiko; Oyama, Ichiro; Matsuda, Shinya

    2016-07-01

    This study examined the association of work functioning impairment as measured by work functioning impairment scale (WFun) and subsequent sick leave. A prospective cohort study was conducted at a manufacturer in Japan, and 1263 employees participated. Information on sick leave was gathered during an 18-month follow-up period. The hazard ratios (HRs) of long-term sick leave were substantially increased for those with a WFun score greater than 25 (HR = 3.99, P = 0.003). The incidence rate ratios (IRRs) of days of short-term absence gradually increased as scores of WFun increased (IRR = 1.18, P < 0.001 in the subjects with WFun of over 25 comparing with those with WFun of 14 or less). Assessing work functioning impairment is a useful way of classifying risk for future sick leave among employees.

  5. Regular voluntary exercise cures stress-induced impairment of cognitive function and cell proliferation accompanied by increases in cerebral IGF-1 and GST activity in mice.

    PubMed

    Nakajima, Sanae; Ohsawa, Ikuroh; Ohta, Shigeo; Ohno, Makoto; Mikami, Toshio

    2010-08-25

    Chronic stress impairs cognitive function and hippocampal neurogenesis. This impairment is attributed to increases in oxidative stress, which result in the accumulation of lipid peroxide. On the other hand, voluntary exercise enhances cognitive function, hippocampal neurogenesis, and antioxidant capacity in normal animals. However, the effects of voluntary exercise on cognitive function, neurogenesis, and antioxidants in stressed mice are unclear. This study was designed to investigate whether voluntary exercise cures stress-induced impairment of cognitive function accompanied by improvement of hippocampal neurogenesis and increases in antioxidant capacity. Stressed mice were exposed to chronic restraint stress (CRS), which consisted of 12h immobilization daily and feeding in a small cage, for 8 weeks. Exercised mice were allowed free access to a running wheel during their exposure to CRS. At the 6th week, cognitive function was examined using the Morris water maze (MWM) test. Daily voluntary exercise restored stress-induced impairment of cognitive function and the hippocampal cell proliferation of newborn cells but not cell survival. Voluntary exercise increased insulin-like growth factor 1 (IGF-1) protein and mRNA expression in the cerebral cortex and liver, respectively. In addition, CRS resulted in a significant increase in the number of 4-hydrosynonenal (4-HNE)-positive cells in the hippocampal dentate gyrus; whereas, voluntary exercise inhibited it and enhanced glutathione s-transferases (GST) activity in the brain. These findings suggest that voluntary exercise attenuated the stress-induced impairment of cognitive function accompanied by improvement of cell proliferation in the dentate gyrus. This exercise-induced improvement was attributed to exercise-induced enhancement of IGF-1 protein and GST activity in the brain. Copyright 2010 Elsevier B.V. All rights reserved.

  6. Gene expression profiles in Parkinson disease prefrontal cortex implicate FOXO1 and genes under its transcriptional regulation.

    PubMed

    Dumitriu, Alexandra; Latourelle, Jeanne C; Hadzi, Tiffany C; Pankratz, Nathan; Garza, Dan; Miller, John P; Vance, Jeffery M; Foroud, Tatiana; Beach, Thomas G; Myers, Richard H

    2012-06-01

    Parkinson disease (PD) is a complex neurodegenerative disorder with largely unknown genetic mechanisms. While the degeneration of dopaminergic neurons in PD mainly takes place in the substantia nigra pars compacta (SN) region, other brain areas, including the prefrontal cortex, develop Lewy bodies, the neuropathological hallmark of PD. We generated and analyzed expression data from the prefrontal cortex Brodmann Area 9 (BA9) of 27 PD and 26 control samples using the 44K One-Color Agilent 60-mer Whole Human Genome Microarray. All samples were male, without significant Alzheimer disease pathology and with extensive pathological annotation available. 507 of the 39,122 analyzed expression probes were different between PD and control samples at false discovery rate (FDR) of 5%. One of the genes with significantly increased expression in PD was the forkhead box O1 (FOXO1) transcription factor. Notably, genes carrying the FoxO1 binding site were significantly enriched in the FDR-significant group of genes (177 genes covered by 189 probes), suggesting a role for FoxO1 upstream of the observed expression changes. Single-nucleotide polymorphisms (SNPs) selected from a recent meta-analysis of PD genome-wide association studies (GWAS) were successfully genotyped in 50 out of the 53 microarray brains, allowing a targeted expression-SNP (eSNP) analysis for 52 SNPs associated with PD affection at genome-wide significance and the 189 probes from FoxO1 regulated genes. A significant association was observed between a SNP in the cyclin G associated kinase (GAK) gene and a probe in the spermine oxidase (SMOX) gene. Further examination of the FOXO1 region in a meta-analysis of six available GWAS showed two SNPs significantly associated with age at onset of PD. These results implicate FOXO1 as a PD-relevant gene and warrant further functional analyses of its transcriptional regulatory mechanisms.

  7. Gene Expression Profiles in Parkinson Disease Prefrontal Cortex Implicate FOXO1 and Genes under Its Transcriptional Regulation

    PubMed Central

    Dumitriu, Alexandra; Latourelle, Jeanne C.; Hadzi, Tiffany C.; Pankratz, Nathan; Garza, Dan; Miller, John P.; Vance, Jeffery M.; Foroud, Tatiana; Beach, Thomas G.; Myers, Richard H.

    2012-01-01

    Parkinson disease (PD) is a complex neurodegenerative disorder with largely unknown genetic mechanisms. While the degeneration of dopaminergic neurons in PD mainly takes place in the substantia nigra pars compacta (SN) region, other brain areas, including the prefrontal cortex, develop Lewy bodies, the neuropathological hallmark of PD. We generated and analyzed expression data from the prefrontal cortex Brodmann Area 9 (BA9) of 27 PD and 26 control samples using the 44K One-Color Agilent 60-mer Whole Human Genome Microarray. All samples were male, without significant Alzheimer disease pathology and with extensive pathological annotation available. 507 of the 39,122 analyzed expression probes were different between PD and control samples at false discovery rate (FDR) of 5%. One of the genes with significantly increased expression in PD was the forkhead box O1 (FOXO1) transcription factor. Notably, genes carrying the FoxO1 binding site were significantly enriched in the FDR–significant group of genes (177 genes covered by 189 probes), suggesting a role for FoxO1 upstream of the observed expression changes. Single-nucleotide polymorphisms (SNPs) selected from a recent meta-analysis of PD genome-wide association studies (GWAS) were successfully genotyped in 50 out of the 53 microarray brains, allowing a targeted expression–SNP (eSNP) analysis for 52 SNPs associated with PD affection at genome-wide significance and the 189 probes from FoxO1 regulated genes. A significant association was observed between a SNP in the cyclin G associated kinase (GAK) gene and a probe in the spermine oxidase (SMOX) gene. Further examination of the FOXO1 region in a meta-analysis of six available GWAS showed two SNPs significantly associated with age at onset of PD. These results implicate FOXO1 as a PD–relevant gene and warrant further functional analyses of its transcriptional regulatory mechanisms. PMID:22761592

  8. Early diagnosis of diabetic vascular complications: impairment of red blood cell deformability

    NASA Astrophysics Data System (ADS)

    Shin, Sehyun; Ku, Yunhee; Park, Cheol-Woo; Suh, Jang-Soo

    2006-02-01

    Reduced deformability of red blood cells (RBCs) may play an important role on the pathogenesis of chronic vascular complications of diabetes mellitus. However, available techniques for measuring RBC deformability often require washing process after each measurement, which is not optimal for day-to-day clinical use at point of care. The objectives of the present study are to develop a device and to delineate the correlation of impaired RBC deformability with diabetic nephropathy. We developed a disposable ektacytometry to measure RBC deformability, which adopted a laser diffraction technique and slit rheometry. The essential features of this design are its simplicity (ease of operation and no moving parts) and a disposable element which is in contact with the blood sample. We studied adult diabetic patients divided into three groups according to diabetic complications. Group I comprised 57 diabetic patients with normal renal function. Group II comprised 26 diabetic patients with chronic renal failure (CRF). Group III consisted of 30 diabetic subjects with end-stage renal disease (ESRD) on hemodialysis. According to the renal function for the diabetic groups, matched non-diabetic groups were served as control. We found substantially impaired red blood cell deformability in those with normal renal function (group I) compared to non-diabetic control (P = 0.0005). As renal function decreases, an increased impairment in RBC deformability was found. Diabetic patients with chronic renal failure (group II) when compared to non-diabetic controls (CRF) had an apparently greater impairment in RBC deformability (P = 0.07). The non-diabetic cohort (CRF), on the other hand, manifested significant impairment in red blood cell deformability compared to healthy control (P = 0.0001). The newly developed slit ektacytometer can measure the RBC deformability with ease and accuracy. In addition, progressive impairment in cell deformability is associated with renal function loss in all patients regardless of the presence or absence of diabetes. In diabetic patients, early impairment in RBC deformability appears in patients with normal renal function.

  9. Endocrine pancreatic function changes after acute pancreatitis.

    PubMed

    Wu, Deqing; Xu, Yaping; Zeng, Yue; Wang, Xingpeng

    2011-10-01

    This study aimed to investigate the impairment of pancreatic endocrine function and the associated risk factors after acute pancreatitis (AP). Fifty-nine patients were subjected to tests of pancreatic function after an attack of pancreatitis. The mean time after the event was 3.5 years. Pancreatic endocrine function was evaluated by fasting blood glucose (FBG), glycosylated hemoglobin, fasting blood insulin, and C-peptide. Homeostasis model assessment was used to evaluate insulin resistance and islet β-cell function. Pancreatic exocrine function was evaluated by fecal elastase 1. Factors that could influence endocrine function were also investigated. Nineteen patients (32%) were found to have elevated FBG, whereas 5 (8%) had abnormal glycosylated hemoglobin levels. The levels of FBG, fasting blood insulin, and C-peptide were higher in patients than in controls (P < 0.01). The islet β-cell function of patients was lower than that of controls (P < 0.01), whereas insulin resistance index was higher among patients (P < 0.01). Obesity, hyperlipidemia, and diabetes-related symptoms were found to be associated with endocrine insufficiency. Pancreatic exocrine functional impairment was found at the same time. Endocrine functional impairment with insulin resistance was found in patients after AP. Obesity, hyperlipidemia, and diabetes-related symptoms increased the likelihood of developing functional impairment after AP.

  10. Specific Language Impairment and Executive Functioning: Parent and Teacher Ratings of Behavior

    ERIC Educational Resources Information Center

    Wittke, Kacie; Spaulding, Tammie J.; Schechtman, Calli J.

    2013-01-01

    Purpose: The current study used the Behavior Rating Inventory of Executive Function--Preschool Version (BRIEF-P; Gioia, Espy, & Isquith, 2003), a rating scale designed to investigate executive behaviors in everyday activities, to examine the executive functioning of preschool children with specific language impairment (SLI) relative to their…

  11. Functional Impairment and Occupational Outcome in Adults with ADHD

    ERIC Educational Resources Information Center

    Gjervan, Bjorn; Torgersen, Terje; Nordahl, Hans M.; Rasmussen, Kirsten

    2012-01-01

    Objective: ADHD is associated with poor functional outcomes. The objectives were to investigate the prevalence of functional impairment and occupational status in a clinically referred sample of adults with ADHD and explore factors predicting occupational outcome. Method: A sample of 149 adults with a confirmed diagnosis of ADHD participated in…

  12. Other drug use does not impact cognitive impairments in chronic ketamine users.

    PubMed

    Zhang, Chenxi; Tang, Wai Kwong; Liang, Hua Jun; Ungvari, Gabor Sandor; Lin, Shih-Ku

    2018-05-01

    Ketamine abuse causes cognitive impairments, which negatively impact on users' abstinence, prognosis, and quality of life. of cognitive impairments in chronic ketamine users have been inconsistent across studies, possibly due to the small sample sizes and the confounding effects of concomitant use of other illicit drugs. This study investigated the cognitive impairment and its related factors in chronic ketamine users with a large sample size and explored the impact of another drug use on cognitive functions. Cognitive functions, including working, verbal and visual memory and executive functions were assessed in ketamine users: 286 non-heavy other drug users and 279 heavy other drug users, and 261 healthy controls. Correlations between cognitive impairment and patterns of ketamine use were analysed. Verbal and visual memory were impaired, but working memory and executive functions were intact for all ketamine users. No significant cognitive differences were found between the two ketamine groups. Greater number of days of ketamine use in the past month was associated with worse visual memory performance in non-heavy other drug users. Higher dose of ketamine use was associated with worse short-term verbal memory in heavy other drug users. Verbal and visual memory are impaired in chronic ketamine users. Other drug use appears to have no impact on ketamine users' cognitive performance. Copyright © 2018. Published by Elsevier B.V.

  13. Developmental dyscalculia is related to visuo-spatial memory and inhibition impairment☆

    PubMed Central

    Szucs, Denes; Devine, Amy; Soltesz, Fruzsina; Nobes, Alison; Gabriel, Florence

    2013-01-01

    Developmental dyscalculia is thought to be a specific impairment of mathematics ability. Currently dominant cognitive neuroscience theories of developmental dyscalculia suggest that it originates from the impairment of the magnitude representation of the human brain, residing in the intraparietal sulcus, or from impaired connections between number symbols and the magnitude representation. However, behavioral research offers several alternative theories for developmental dyscalculia and neuro-imaging also suggests that impairments in developmental dyscalculia may be linked to disruptions of other functions of the intraparietal sulcus than the magnitude representation. Strikingly, the magnitude representation theory has never been explicitly contrasted with a range of alternatives in a systematic fashion. Here we have filled this gap by directly contrasting five alternative theories (magnitude representation, working memory, inhibition, attention and spatial processing) of developmental dyscalculia in 9–10-year-old primary school children. Participants were selected from a pool of 1004 children and took part in 16 tests and nine experiments. The dominant features of developmental dyscalculia are visuo-spatial working memory, visuo-spatial short-term memory and inhibitory function (interference suppression) impairment. We hypothesize that inhibition impairment is related to the disruption of central executive memory function. Potential problems of visuo-spatial processing and attentional function in developmental dyscalculia probably depend on short-term memory/working memory and inhibition impairments. The magnitude representation theory of developmental dyscalculia was not supported. PMID:23890692

  14. Pharmacokinetics of carfilzomib in patients with advanced malignancies and varying degrees of hepatic impairment: an open-label, single-arm, phase 1 study.

    PubMed

    Brown, Jennifer; Plummer, Ruth; Bauer, Todd M; Anthony, Stephen; Sarantopoulos, John; De Vos, Filip; White, Mike; Schupp, Marco; Ou, Ying; Vaishampayan, Ulka

    2017-01-01

    Carfilzomib is approved in the United States and Europe for treatment of relapsed or refractory multiple myeloma (MM). This study evaluated pharmacokinetics (PK) and safety of carfilzomib in patients with relapsed or progressive advanced malignancies and varying degrees of impaired hepatic function. Patients with normal hepatic function (normal) or hepatic impairment (mild, moderate, or severe) received carfilzomib infusion in 28-day cycles. The primary objective was to assess the influence of hepatic impairment on carfilzomib PK following 27 and 56 mg/m 2 doses. The majority of patients enrolled in this study had solid tumors (n = 44) vs. MM (n = 2) since patients with multiple myeloma do not tend to have severe hepatic impairment in the same way as patients with solid tumors. A total of 11 normal and 17 mild, 14 moderate, and 4 severe hepatic impairment patients were enrolled. Compared with patients with normal hepatic function, patients with mild and moderate hepatic impairment had 44 and 26% higher carfilzomib AUC 0-last , respectively (27 mg/m 2 dose); increases at the 56 mg/m 2 dose were 45 and 21%, respectively. Considerable PK variability (% coefficient of variation in AUC ≤100%) was discerned and no consistent trend of increasing exposure resulting from increasing hepatic impairment severity (moderate vs. mild) was seen. The observed adverse event (AE) profile in patients of mostly solid tumors was consistent with the known safety profile of carfilzomib, with the exception of an increased frequency of AEs consistent with hepatic function abnormalities. In this population of primarily advanced solid tumor patients, patients with mild and moderate hepatic impairment had approximately 20-50% higher carfilzomib AUC vs. normal hepatic function patients. These increases are unlikely to be clinically significant, in light of the intrinsic PK variability and exposure-response relationship of carfilzomib. Trial registration http://clinicaltrials.gov NCT01949545; date of registration: September 6, 2013.

  15. Functional impairment and cognitive performance in mood disorders: A community sample of young adults.

    PubMed

    Reyes, Amanda N; Cardoso, Taiane A; Jansen, Karen; Mondin, Thaíse C; Souza, Luciano D M; Magalhães, Pedro V S; Kapczinski, Flavio; Silva, Ricardo A

    2017-05-01

    The aim of this study was to compare the global functioning and cognitive performance in a community sample of young adults with mood disorders versus community controls. This was a cross-sectional study nested in a cohort study with a community sample. Data was collected from February 2012 to June 2014; specifically, at a mean of five years after the first phase, all young adults were invited to participate in a re-evaluation. Mini International Neuropsychiatric Interview - PLUS (MINI-PLUS) was used for the diagnosis of mood disorders. The Functional Assessment Short Test (FAST) and the Montreal Cognitive Assessment (MoCA) were used to assess the global functioning, and cognitive performance, respectively. Were included 1258 subjects. Functional impairment was greater in subjects with bipolar disorder when compared to community controls, and there were no differences between major depressive disorder and community controls. There were no significant differences in cognitive performance between young adults with mood disorders when compared to community controls. Functional impairment is a marker for bipolar disorder in young adults; however, gross cognitive impairment assessed by a screening test is not, possibly because cognition is impaired in more advanced stages of the disorder. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  16. Susceptibility of functional impairment scales to noncredible responses in the clinical evaluation of adult ADHD.

    PubMed

    Fuermaier, Anselm B M; Tucha, Oliver; Koerts, Janneke; Butzbach, Marah; Weisbrod, Matthias; Aschenbrenner, Steffen; Tucha, Lara

    2018-05-01

    A growing body of research questions the reliance of symptom self-reports in the clinical evaluation of attention-deficit/hyperactivity disorder (ADHD) in adulthood. A recent study suggested that also impairment reports are vulnerable to noncredible responses, as derived from a simulation design using a global functional impairment scale. The present study aims to add evidence to this issue, by using an ADHD specific impairment scale in a simulation design on large samples. Impairment ratings on the Weiss Functional Impairment Rating Scale (WFIRS) of 62 patients with ADHD were compared to 142 healthy individuals who were instructed to show normal behavior. Furthermore, impairment ratings of patients with ADHD were compared to ratings of 330 healthy individuals who were randomly assigned to one of four simulation conditions that were instructed to complete the scale as if they had ADHD. Patients with ADHD reported higher levels of impairment than the healthy control group in all domains of life. Furthermore, individuals instructed to feign ADHD indicated higher levels of impairments in most domains of life compared to control participants and genuine patients with ADHD. The group differences between individuals feigning ADHD and individuals with genuine ADHD, however, were only small to moderate. Further analyses revealed that the WFRIS was not useful to successfully differentiate genuine from feigned ADHD. The present study confirms the conclusion that self-reported impairments are susceptible to noncredible responses and should be used with caution in the clinical evaluation of adult ADHD.

  17. Auckland Stroke Outcomes Study. Part 1: Gender, stroke types, ethnicity, and functional outcomes 5 years poststroke.

    PubMed

    Feigin, V L; Barker-Collo, S; Parag, V; Senior, H; Lawes, C M M; Ratnasabapathy, Y; Glen, E

    2010-11-02

    Studying long-term stroke outcomes including body functioning (neurologic and neuropsychological impairments) and activity limitations and participation is essential for long-term evidence-based rehabilitation and service planning, resource allocation, and improving health outcomes in stroke. However, reliable data to address these issues is lacking. This study (February 2007-December 2008) sourced its participants from the population-based incidence study conducted in Auckland in 2002-2003. Participants completed structured self-administered questionnaires, and a face-to-face interview including a battery of neuropsychological tests. Logistic regression analysis was used to analyze associations between and within functional outcomes and their potential predictors. Of 418 5-year stroke survivors, two-thirds had good functional outcome in terms of neurologic impairment and disability (defined as modified Rankin Score <3), 22.5% had cognitive impairment indicative of dementia, 20% had experienced a recurrent stroke, almost 15% were institutionalized, and 29.6% had symptoms suggesting depression. Highly significant correlations were found between and within various measurements of body functioning (especially neuropsychological impairments), activity, and participation. Age, dependency, and depression were independently associated with most outcomes analyzed. The strong associations between neuropsychological impairment and other functional outcomes and across various measurements of body functioning, activity, and participation justify utilizing a multidisciplinary approach to studying and managing long-term stroke outcomes. Observed gender and ethnic differences in some important stroke outcomes warrant further investigations.

  18. Cortisol Excess and the Brain.

    PubMed

    Resmini, Eugenia; Santos, Alicia; Webb, Susan M

    2016-01-01

    Until the last decade, little was known about the effects of chronic hypercortisolism on the brain. In the last few years, new data have arisen thanks to advances in imaging techniques; therefore, it is now possible to investigate brain activity in vivo. Memory impairments are present in patients with Cushing's syndrome (CS) and are related to hippocampal damage; functional dysfunctions would precede structural abnormalities as detected by brain imaging. Earlier diagnosis and rapid normalization of hypercortisolism could stop the progression of hippocampal damage and memory impairments. Impairments of executive functions (including decision-making) and other functions such as visuoconstructive skills, language, motor functions and information processing speed are also present in CS patients. There is controversy concerning the reversibility of brain impairment. It seems that longer disease duration and older age are associated with less recovery of brain functioning. Conversely, earlier diagnosis and rapid normalization of hypercortisolism appear to stop progression of brain damage and functional impairments. Moreover, brain tissue functioning and neuroplasticity can be influenced by many factors. Currently available studies appear to be complementary, evaluating the same phenomenon from different points of view, but are often not directly comparable. Finally, CS patients have a high prevalence of psychopathology, such as depression and anxiety which do not completely revert after cure. Thus, psychological or psychiatric evaluation could be recommended in CS patients, so that treatment may be prescribed if required. © 2016 S. Karger AG, Basel.

  19. An exploration of subgroups of mild cognitive impairment based on cognitive, neuropsychiatric and functional features: analysis of data from the National Alzheimer's Coordinating Center.

    PubMed

    Hanfelt, John J; Wuu, Joanne; Sollinger, Ann B; Greenaway, Melanie C; Lah, James J; Levey, Allan I; Goldstein, Felicia C

    2011-11-01

    To empirically expand the existing subtypes of mild cognitive impairment (MCI) by incorporating information on neuropsychiatric and functional features, and to assess whether cerebrovascular disease (CVD) risk factors are associated with any of these subgroups. Latent class analysis using 1,655 patients with MCI. Participants in the Uniform Data Set (UDS) from 29 National Institutes of Health-supported Alzheimer's Disease Centers. Patients with a consensus diagnosis of MCI from each center and with a Mini-Mental State Examination score of 22 or greater. UDS cognitive battery, Neuropsychiatric Inventory Questionnaire, and Functional Assessment Questionnaire administered at initial visit. Seven empirically based subgroups of MCI were identified: 1) minimally impaired (relative frequency, 12%); 2) amnestic only (16%); 3) amnestic with functional and neuropsychiatric features (16%); 4) amnestic multidomain (12%); 5) amnestic multidomain with functional and neuropsychiatric features (12%); 6) functional and neuropsychiatric features (15%); and 7) executive function and language impairments (18%). Two of these subgroups with functional and neuropsychiatric features were at least 3.8 times more likely than the minimally impaired subgroup to have a Rosen-Hachinski score of 4 or greater, an indicator of probable CVD. Findings suggest that there are several distinct phenotypes of MCI characterized by prominent cognitive features, prominent functional features, and neuropsychiatric features or a combination of all three. Subgroups with functional and neuropsychiatric features are significantly more likely to have CVD, which suggests that there may be distinct differences in disease etiology from the other phenotypes.

  20. In vitro analysis of platelet function in acute aneurysmal subarachnoid haemorrhage.

    PubMed

    von der Brelie, Christian; Subai, Alexander; Limperger, Verena; Rohde, Veit; Dempfle, Astrid; Boström, Azize

    2018-04-01

    Platelet function might play an essential role in the pathogenesis of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (SAH). Thus, impaired platelet function and disturbed primary haemostasis induced by intake of acetylsalicylic acid (ASA) might influence the rate of DCI. Primary haemostasis and platelet function can be measured with in vitro diagnosis (platelet function analyser test, PFA 100). The aim of this study is to evaluate the rate of DCI, haemorrhagic complications and the neurological outcome. Two groups were compared (patients with regular platelet function versus patients with impaired platelet function). This is a retrospective observational study. An initial cohort of 787 patients with SAH has been treated from January 2005 to September 2012. Seventy-nine patients (10%) with aneurysmal SAH, a history of ASA medication and PFA testing within the first 24 h after aneurysm rupture have been included. The overall rate of DCI in the present study was 43%. In vitro platelet function testing showed pathological primary haemostasis in 69.6%. The DCI rate was higher in patients with regular tested primary haemostasis (p = 0.02, OR = 3.16, 95%CI = [1.19; 8.83]). However, outcome assessment by mGOS did not show a significant difference between the groups. Patients with impaired primary haemostasis did not display a higher rate of haemorrhagic complications. Impairment of primary haemostasis resulting from an impairment of platelet function at an early stage after SAH might lead to a lower rate of DCI. In vitro testing of platelet function might be useful to predict the occurrence of DCI in the course.

  1. Evaluating and Stimulating Vision in the Multiply Impaired.

    ERIC Educational Resources Information Center

    Jose, Randall T.; And Others

    1980-01-01

    Techniques for evaluating the multiply impaired child's functional level of vision are described and a sequence of visual stimulation instruction for children with visual impairments is presented. (PHR)

  2. Effect of hepatic impairment on the pharmacokinetics of a single dose of cilostazol.

    PubMed

    Bramer, S L; Forbes, W P

    1999-01-01

    The pharmacokinetic profiles of cilostazol and its metabolites following a single oral dose of cilostazol 100 mg were compared between individuals with impaired and normal liver function. The study was conducted as a single-centre, open-label, single dose pharmacokinetic and tolerability trial. 12 patients with impaired and compensated liver function were compared with 12 volunteers with normal liver function. Participants in each group were matched for gender, age and weight. Of the 12 patients with hepatic impairment examined in this study, 10 had mild impairment (Child-Pugh class A) and 2 had moderate impairment (Child-Pugh class B). Blood and urine were collected up to 144 hours after drug administration. Pharmacokinetics were determined by noncompartmental methods. Protein binding did not differ between the groups (95.2% healthy volunteers, 94.6% hepatically impaired patients). Mean +/- SD unbound oral clearance of cilostazol decreased by 8.6% because of hepatic impairment (3380 +/- 1400 ml/min in healthy volunteers, 3260 +/- 2030 ml/min in hepatically impaired patients). Total urinary excretion of metabolites was significantly higher in healthy volunteers (26 vs 17% of dose). Overall, the pharmacokinetics of cilostazol and its metabolites, OPC-13213 and OPC-13015, were not substantially different in those with mild and moderate hepatic disease compared with values in healthy volunteers. Except for terminal-phase disposition half-life and apparent terminal-phase volume of distribution for cilostazol, the ratios of geometric means of pharmacokinetic parameters for plasma cilostazol, OPC-13213 and OPC-13015 in those with hepatic impairment versus healthy volunteers were close to 100%. Based on the results of the pharmacokinetic analysis, dose adjustment in patients with mild hepatic impairment is not necessary. However, caution should be exercised when cilostazol is administered to patients with moderate or severe hepatic impairment.

  3. Distinct patterns of brain function in children with isolated spelling impairment: new insights.

    PubMed

    Gebauer, Daniela; Enzinger, Christian; Kronbichler, Martin; Schurz, Matthias; Reishofer, Gernot; Koschutnig, Karl; Kargl, Reinhard; Purgstaller, Christian; Fazekas, Franz; Fink, Andreas

    2012-06-01

    Studies investigating reading and spelling difficulties heavily focused on the neural correlates of reading impairments, whereas spelling impairments have been largely neglected so far. Hence, the aim of the present study was to investigate brain structure and function of children with isolated spelling difficulties. Therefore, 31 children, aged ten to 15 years, were investigated by means of functional MRI and DTI. This study revealed that children with isolated spelling impairment exhibit a stronger right hemispheric activation compared to children with reading and spelling difficulties and controls, when engaged in an orthographic decision task, presumably reflecting a highly efficient serial grapheme-phoneme decoding compensation strategy. In addition, children with spelling impairment activated bilateral inferior and middle frontal gyri during processing correctly spelled words and misspelled words, whereas the other two groups showed bilateral activation only in the misspelled condition, suggesting that additional right frontal engagement could be related to generally higher task demand and effort. DTI analyses revealed stronger frontal white matter integrity (fractional anisotropy) in controls (compared to spelling and reading impaired children), whereas no structural differences between controls and spelling impaired children were observed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. The relationship between separation anxiety and impairment

    PubMed Central

    Foley, Debra L; Rowe, Richard; Maes, Hermine; Silberg, Judy; Eaves, Lindon; Pickles, Andrew

    2009-01-01

    The goal of this study was to characterize the contemporaneous and prognostic relationship between symptoms of separation anxiety disorder (SAD) and associated functional impairment. The sample comprised n=2067 8–16 year-old twins from a community-based registry. Juvenile subjects and their parents completed a personal interview on two occasions, separated by an average follow-up period of 18 months, about the subject’s current history of SAD and associated functional impairment. Results showed that SAD symptoms typically caused very little impairment but demonstrated significant continuity over time. Older youth had significantly more persistent symptoms than younger children. Prior symptom level independently predicted future symptom level and diagnostic symptom threshold, with and without impairment. Neither diagnostic threshold nor severity of impairment independently predicted outcomes after taking account of prior symptom levels. The results indicate that impairment may index current treatment need but symptom levels provide the best information about severity and prognosis. PMID:17658718

  5. The functional IME: A linkage of expertise across the disability continuum.

    PubMed

    Clifton, David W

    2006-01-01

    Disability assessment remains a significant challenge especially in welfare systems like workers' compensation and disability insurance. Many of today's managed care strategies do not impact on the seminal issue of return to gainful employment. Employers, insurers, attorneys and case managers routinely request independent medical examinations (IMEs) as a means of determining degree of disability, functional limitations, work restrictions and "estimated" physical capacities. However, this approach is limited because physicians are not trained in the functional model of disability assessment. IMEs address pathology and impairments which represent a portion of the disability continuum described by the World Health Organization, Nagi, Guccione and others [e.g. pathology-impairment-disability-handicap]. Functional capacity evaluations or FCEs are often performed by physical and occupational therapists who are trained in a function-based model of disability assessment. Unlike an IME physician who completes "Estimated Physical Capacities", therapists measure actual physical functioning. The value of both IMEs and FCEs can be enhanced through a "functional IME" that combines both models; medical-based examination and a function-based disability evaluation. This combination enhances the assessment of the relationship of pathology to impairment and impairment to disability status especially, in musculoskeletal disorders which tend to drive costs in workers' compensation.

  6. Strong Association between Plasma Dipeptidyl Peptidase-4 Activity and Impaired Cognitive Function in Elderly Population with Normal Glucose Tolerance.

    PubMed

    Chen, Bo; Zheng, Tianpeng; Qin, Linyuan; Hu, Xueping; Zhang, Xiaoxi; Liu, Yihong; Liu, Hongbo; Qin, Shenghua; Li, Gang; Li, Qinghua

    2017-01-01

    Objective: Inflammation, oxidative stress, and decreased glucagon-like peptide-1 (GLP-1) are risk factors for cognitive impairment. Dipeptidyl peptidase-4 (DPP4) was identified as a novel adipokine capable of enhancing these risk factors. Hence, we investigated the relationship between plasma DPP4 activity and impaired cognitive function in elderly Chinese population with normal glucose tolerance (NGT). Methods: We performed a cross-sectional study using data from 1229 elderly participants (60 years or older) in Guilin. Plasma DPP4 activity, oxidative stress parameters, fasting active GLP-1, and inflammatory markers were measured in all participants. Impaired cognitive function was diagnosed according to the National Institute on Aging-Alzheimer's Association workgroups criteria. Results: Participants in the upper quartile of plasma DPP4 activity had higher C-reactive protein (CRP), interleukin-6 (IL-6), 8-iso-PGF2a, nitrotyrosine, and lower GLP-1 and Montreal Cognitive Assessment (MoCA) scores compared with those in the lowest quartile ( P < 0.001). The odds ratios (ORs) for increased CRP, IL-6, 8-iso-PGF2a, nitrotyrosine, and decreased active GLP-1 were higher with increasing DPP4 quartiles after adjustment for confounders (all P < 0.001). In the highest DPP4 quartile, impaired cognitive function risk was higher (OR, 2.26; 95% confidence interval, 1.36-3.76) than in the lowest quartile after adjustment for potential confounders. The risk for impaired cognitive function increased more with higher levels of DPP4 activity, nitrotyrosine and 8-iso-PGF2a ( P < 0.05), but not with higher IL-6, CRP or lower GLP-1. Conclusion: Plasma DPP4 activity is significantly and independently associated with impaired cognitive function, mainly executive, in elderly Chinese population with NGT. The underlying mechanisms for this association may be partly attributed to the effect of DPP4 on oxidative stress. Plasma DPP4 activity might serve as a risk biomarker or therapeutic target for the prevention and treatment of impaired cognitive function.

  7. Subjective cognitive impairment and brain structural networks in Chinese gynaecological cancer survivors compared with age-matched controls: a cross-sectional study.

    PubMed

    Zeng, Yingchun; Cheng, Andy S K; Song, Ting; Sheng, Xiujie; Zhang, Yang; Liu, Xiangyu; Chan, Chetwyn C H

    2017-11-28

    Subjective cognitive impairment can be a significant and prevalent problem for gynaecological cancer survivors. The aims of this study were to assess subjective cognitive functioning in gynaecological cancer survivors after primary cancer treatment, and to investigate the impact of cancer treatment on brain structural networks and its association with subjective cognitive impairment. This was a cross-sectional survey using a self-reported questionnaire by the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) to assess subjective cognitive functioning, and applying DTI (diffusion tensor imaging) and graph theoretical analyses to investigate brain structural networks after primary cancer treatment. A total of 158 patients with gynaecological cancer (mean age, 45.86 years) and 130 age-matched non-cancer controls (mean age, 44.55 years) were assessed. Patients reported significantly greater subjective cognitive functioning on the FACT-Cog total score and two subscales of perceived cognitive impairment and perceived cognitive ability (all p values <0.001). Compared with patients who had received surgery only and non-cancer controls, patients treated with chemotherapy indicated the most altered global brain structural networks, especially in one of properties of small-worldness (p = 0.004). Reduced small-worldness was significantly associated with a lower FACT-Cog total score (r = 0.412, p = 0.024). Increased characteristic path length was also significantly associated with more subjective cognitive impairment (r = -0.388, p = 0.034). When compared with non-cancer controls, a considerable proportion of gynaecological cancer survivors may exhibit subjective cognitive impairment. This study provides the first evidence of brain structural network alteration in gynaecological cancer patients at post-treatment, and offers novel insights regarding the possible neurobiological mechanism of cancer-related cognitive impairment (CRCI) in gynaecological cancer patients. As primary cancer treatment can result in a more random organisation of structural brain networks, this may reduce brain functional specificity and segregation, and have implications for cognitive impairment. Future prospective and longitudinal studies are needed to build upon the study findings in order to assess potentially relevant clinical and psychosocial variables and brain network measures, so as to more accurately understand the specific risk factors related to subjective cognitive impairment in the gynaecological cancer population. Such knowledge could inform the development of appropriate treatment and rehabilitation efforts to ameliorate cognitive impairment in gynaecological cancer survivors.

  8. The impact of visual impairment on self-reported visual functioning in Latinos: The Los Angeles Latino Eye Study.

    PubMed

    Globe, Denise R; Wu, Joanne; Azen, Stanley P; Varma, Rohit

    2004-06-01

    To assess the association between presenting binocular visual acuity (VA) and self-reported visual function as measured by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). A population-based, prevalence study of eye disease in Latinos 40 years and older residing in La Puente, California (Los Angeles Latino Eye Study [LALES]). Six thousand three hundred fifty-seven Latinos 40 years and older from 6 census tracts in La Puente. All participants completed a standardized interview, including the NEI-VFQ-25 to measure visual functioning, and a detailed eye examination. Two definitions of visual impairment were used: (1) presenting binocular distance VA of 20/40 or worse and (2) presenting binocular distance VA worse than 20/40. Analysis of variance was used to determine any systematic differences in mean NEI-VFQ-25 scores by visual impairment. Regression analyses were completed (1) to determine the association of age, gender, number of systemic comorbidities, depression, and VA with self-reported visual function and (2) to estimate a visual impairment-related difference for each subscale based on differences in VA. The NEI-VFQ-25 scores in persons with visual impairment. Of the 5287 LALES participants with complete NEI-VFQ-25 data, 6.3% (including 20/40) and 4.2% (excluding 20/40) were visually impaired. In the visually impaired participants, the NEI-VFQ-25 subscale scores ranged from 46.2 (General Health) to 93.8 (Color Vision). In the regression model, only VA, depression, and number of comorbidities were significantly associated with all subscale scores (R(2) ranged from 0.09 for Ocular Pain to 0.33 for the composite score). For 9 of 11 subscales, a 5-point change was equivalent to a 1- or 2-line difference in VA. Relationships were similar regardless of the definition of visual impairment. In this population-based study of Latinos, the NEI-VFQ-25 was sensitive to differences in VA. A 5-point difference on the NEI-VFQ-25 seems to be a minimal criterion for a visual impairment-related difference. Self-reported visual function is essentially unchanged if the definition of visual impairment includes or excludes a VA of 20/40.

  9. Gene Network Construction from Microarray Data Identifies a Key Network Module and Several Candidate Hub Genes in Age-Associated Spatial Learning Impairment

    PubMed Central

    Uddin, Raihan; Singh, Shiva M.

    2017-01-01

    As humans age many suffer from a decrease in normal brain functions including spatial learning impairments. This study aimed to better understand the molecular mechanisms in age-associated spatial learning impairment (ASLI). We used a mathematical modeling approach implemented in Weighted Gene Co-expression Network Analysis (WGCNA) to create and compare gene network models of young (learning unimpaired) and aged (predominantly learning impaired) brains from a set of exploratory datasets in rats in the context of ASLI. The major goal was to overcome some of the limitations previously observed in the traditional meta- and pathway analysis using these data, and identify novel ASLI related genes and their networks based on co-expression relationship of genes. This analysis identified a set of network modules in the young, each of which is highly enriched with genes functioning in broad but distinct GO functional categories or biological pathways. Interestingly, the analysis pointed to a single module that was highly enriched with genes functioning in “learning and memory” related functions and pathways. Subsequent differential network analysis of this “learning and memory” module in the aged (predominantly learning impaired) rats compared to the young learning unimpaired rats allowed us to identify a set of novel ASLI candidate hub genes. Some of these genes show significant repeatability in networks generated from independent young and aged validation datasets. These hub genes are highly co-expressed with other genes in the network, which not only show differential expression but also differential co-expression and differential connectivity across age and learning impairment. The known function of these hub genes indicate that they play key roles in critical pathways, including kinase and phosphatase signaling, in functions related to various ion channels, and in maintaining neuronal integrity relating to synaptic plasticity and memory formation. Taken together, they provide a new insight and generate new hypotheses into the molecular mechanisms responsible for age associated learning impairment, including spatial learning. PMID:29066959

  10. Gene Network Construction from Microarray Data Identifies a Key Network Module and Several Candidate Hub Genes in Age-Associated Spatial Learning Impairment.

    PubMed

    Uddin, Raihan; Singh, Shiva M

    2017-01-01

    As humans age many suffer from a decrease in normal brain functions including spatial learning impairments. This study aimed to better understand the molecular mechanisms in age-associated spatial learning impairment (ASLI). We used a mathematical modeling approach implemented in Weighted Gene Co-expression Network Analysis (WGCNA) to create and compare gene network models of young (learning unimpaired) and aged (predominantly learning impaired) brains from a set of exploratory datasets in rats in the context of ASLI. The major goal was to overcome some of the limitations previously observed in the traditional meta- and pathway analysis using these data, and identify novel ASLI related genes and their networks based on co-expression relationship of genes. This analysis identified a set of network modules in the young, each of which is highly enriched with genes functioning in broad but distinct GO functional categories or biological pathways. Interestingly, the analysis pointed to a single module that was highly enriched with genes functioning in "learning and memory" related functions and pathways. Subsequent differential network analysis of this "learning and memory" module in the aged (predominantly learning impaired) rats compared to the young learning unimpaired rats allowed us to identify a set of novel ASLI candidate hub genes. Some of these genes show significant repeatability in networks generated from independent young and aged validation datasets. These hub genes are highly co-expressed with other genes in the network, which not only show differential expression but also differential co-expression and differential connectivity across age and learning impairment. The known function of these hub genes indicate that they play key roles in critical pathways, including kinase and phosphatase signaling, in functions related to various ion channels, and in maintaining neuronal integrity relating to synaptic plasticity and memory formation. Taken together, they provide a new insight and generate new hypotheses into the molecular mechanisms responsible for age associated learning impairment, including spatial learning.

  11. Oropharyngeal dysphagia in preschool children with cerebral palsy: oral phase impairments.

    PubMed

    Benfer, Katherine A; Weir, Kelly A; Bell, Kristie L; Ware, Robert S; Davies, Peter S W; Boyd, Roslyn N

    2014-12-01

    This study aimed to document the prevalence and patterns of oral phase oropharyngeal dysphagia (OPD) in preschool children with cerebral palsy (CP), and its association with mealtime duration, frequency and efficiency. Cross-sectional population-based cohort study of 130 children diagnosed with CP at 18-36 months ca (mean = 27.4 months, 81 males) and 40 children with typical development (mean = 26.2, 18 males). Functional abilities of children with CP were representative of a population sample (GMFCS I = 57, II = 15, III = 23, IV = 12, V = 23). Oral phase impairment was rated from video using the Dyspahgia Disorders Survey, Schedule for Oral Motor Impairment, and Pre-Speech Assessment Scale. Parent-report was collected on a feeding questionnaire. Mealtime frequency, duration and efficiency were calculated from a three day weighed food record completed by parents. Gross motor function was classified using the Gross Motor Function Classification System (GMFCS). Overall, 93.8% of children had directly assessed oral phase impairments during eating or drinking, or in controlling saliva (78.5% with modified cut-points). Directly assessed oral phase impairments were associated with declining gross motor function, with children from GMFCS I having a 2-fold increased likelihood of oral phase impairment compared to the children with TD (OR = 2.0, p = 0.18), and all children from GMFCS II-V having oral phase impairments. Difficulty biting (70%), cleaning behaviours (70%) and chewing (65%) were the most common impairments on solids, and difficulty sipping from a cup (60%) for fluids. OPD severity and GMFCS were not related to mealtime frequency, duration or efficiency, although children on partial tube feeds had significantly reduced mealtime efficiency. Oral phase impairments were common in preschool children with CP, with severity increasing stepwise with declining gross motor function. The prevalence and severity of oral phase impairments were significantly greater for most tasks when compared to children with typical development, even for those with mild CP. Children who were partially tube fed had significantly lower feeding efficiency, so this could be a useful early indicator of children needing supplementation to their nutrition (through increasing energy density of foods/fluids, or tube feeds). Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Treatment Concerns and Functional Impairment in Pediatric Anxiety.

    PubMed

    Wu, Monica S; Salloum, Alison; Lewin, Adam B; Selles, Robert R; McBride, Nicole M; Crawford, Erika A; Storch, Eric A

    2016-08-01

    Although there are efficacious, evidence-based treatments for anxiety disorders, youth often experience delays in seeking therapy. Myriad reasons may contribute to this lag in treatment initiation, with some youth possessing concerns about therapy. Treatment concerns are broadly characterized by worries/ambivalence about seeking treatment, including concerns about the negative reactions, consequences, and inconvenience of treatment. As no studies exist for youth with anxiety disorders, this study examined the phenomenology of treatment concerns in 119 treatment-seeking, anxious youth and utilized a structural equation model to examine the relationship between child anxiety, depressive symptoms, treatment concerns, and anxiety-related functional impairment. Over 90 % of the children positively endorsed some type of treatment-related fear, with the most frequently expressed concern being that therapy would take too much time (50.4 %). Based on the model, both child anxiety and depressive symptoms predicted functional impairment, and treatment concerns mediated the relationship between child anxiety and functional impairment.

  13. Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders

    PubMed Central

    Negrón-Oyarzo, Ignacio; Aboitiz, Francisco; Fuentealba, Pablo

    2016-01-01

    Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC) is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders. PMID:26904302

  14. Prevalence, predictors and covariates of functional status impairment among Finnish Second World War veterans during 1992-2004.

    PubMed

    Leskinen, Riitta; Laatikainen, Tiina; Peltonen, Markku; Levälahti, Esko; Antikainen, Riitta

    2013-07-01

    the functional status is one of the most important health measurements in the elderly. This study aimed to investigate the prevalence of self-reported physical and mental conditions among Finnish Second World War veterans during 1992-2004. We also aimed to study the ability of these conditions in 1992 to predict the functional status impairment in 2004 and to determine whether the worsening of symptoms or the onset of new diseases during 1992-2004 was associated with impaired basic activities of daily living (BADL) and instrumental activities of daily living (IADL) in 2004. the study population was 4,999 veterans living in Finland participating in both the Veteran Project 1992 and 2004. Logistic regression models were employed to identify predictors for impaired BADL and IADL. Analyses were conducted separately for men with and without disability and for women. the highest risk estimate for impaired BADL in 2004 was in men without disability who had a neurological disease in 1992 [odds ratios (OR): 5.78, 95% CI: 2.49-13.43], in men with disability with walking difficulties in 1992 (OR: 2.41, 95% CI: 1.79-3.25) and in women with a musculoskeletal disease in 1992 (OR: 2.39, 95% CI: 1.58-3.62). For impaired IADL, walking difficulties had the highest risk estimate in all veteran groups. mental and physical conditions, especially walking difficulties, can predict veterans' future functional impairment even 12 years in advance, and worsening of these conditions is associated with impaired ADL.

  15. Direct and indirect effects of attention and visual function on gait impairment in Parkinson's disease: influence of task and turning.

    PubMed

    Stuart, Samuel; Galna, Brook; Delicato, Louise S; Lord, Sue; Rochester, Lynn

    2017-07-01

    Gait impairment is a core feature of Parkinson's disease (PD) which has been linked to cognitive and visual deficits, but interactions between these features are poorly understood. Monitoring saccades allows investigation of real-time cognitive and visual processes and their impact on gait when walking. This study explored: (i) saccade frequency when walking under different attentional manipulations of turning and dual-task; and (ii) direct and indirect relationships between saccades, gait impairment, vision and attention. Saccade frequency (number of fast eye movements per-second) was measured during gait in 60 PD and 40 age-matched control participants using a mobile eye-tracker. Saccade frequency was significantly reduced in PD compared to controls during all conditions. However, saccade frequency increased with a turn and decreased under dual-task for both groups. Poorer attention directly related to saccade frequency, visual function and gait impairment in PD, but not controls. Saccade frequency did not directly relate to gait in PD, but did in controls. Instead, saccade frequency and visual function deficit indirectly impacted gait impairment in PD, which was underpinned by their relationship with attention. In conclusion, our results suggest a vital role for attention with direct and indirect influences on gait impairment in PD. Attention directly impacted saccade frequency, visual function and gait impairment in PD, with connotations for falls. It also underpinned indirect impact of visual and saccadic impairment on gait. Attention therefore represents a key therapeutic target that should be considered in future research. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  16. Depressive Symptoms and Impaired Physical Function after Acute Lung Injury

    PubMed Central

    Colantuoni, Elizabeth; Mendez-Tellez, Pedro A.; Dinglas, Victor D.; Shanholtz, Carl; Husain, Nadia; Dennison, Cheryl R.; Herridge, Margaret S.; Pronovost, Peter J.; Needham, Dale M.

    2012-01-01

    Rationale: Survivors of acute lung injury (ALI) frequently have substantial depressive symptoms and physical impairment, but the longitudinal epidemiology of these conditions remains unclear. Objectives: To evaluate the 2-year incidence and duration of depressive symptoms and physical impairment after ALI, as well as risk factors for these conditions. Methods: This prospective, longitudinal cohort study recruited patients from 13 intensive care units (ICUs) in four hospitals, with follow-up 3, 6, 12, and 24 months after ALI. The outcomes were Hospital Anxiety and Depression Scale depression score greater than or equal to 8 (“depressive symptoms”) in patients without a history of depression before ALI, and two or more dependencies in instrumental activities of daily living (“impaired physical function”) in patients without baseline impairment. Measurements and Main Results: During 2-year follow-up of 186 ALI survivors, the cumulative incidences of depressive symptoms and impaired physical function were 40 and 66%, respectively, with greatest incidence by 3-month follow-up; modal durations were greater than 21 months for each outcome. Risk factors for incident depressive symptoms were education 12 years or less, baseline disability or unemployment, higher baseline medical comorbidity, and lower blood glucose in the ICU. Risk factors for incident impaired physical function were longer ICU stay and prior depressive symptoms. Conclusions: Incident depressive symptoms and impaired physical function are common and long-lasting during the first 2 years after ALI. Interventions targeting potentially modifiable risk factors (e.g., substantial depressive symptoms in early recovery) should be evaluated to improve ALI survivors’ long-term outcomes. PMID:22161158

  17. Empirical Derivation and Validation of a Clinical Case Definition for Neuropsychological Impairment in Children and Adolescents.

    PubMed

    Beauchamp, Miriam H; Brooks, Brian L; Barrowman, Nick; Aglipay, Mary; Keightley, Michelle; Anderson, Peter; Yeates, Keith O; Osmond, Martin H; Zemek, Roger

    2015-09-01

    Neuropsychological assessment aims to identify individual performance profiles in multiple domains of cognitive functioning; however, substantial variation exists in how deficits are defined and what cutoffs are used, and there is no universally accepted definition of neuropsychological impairment. The aim of this study was to derive and validate a clinical case definition rule to identify neuropsychological impairment in children and adolescents. An existing normative pediatric sample was used to calculate base rates of abnormal functioning on eight measures covering six domains of neuropsychological functioning. The dataset was analyzed by varying the range of cutoff levels [1, 1.5, and 2 standard deviations (SDs) below the mean] and number of indicators of impairment. The derived rule was evaluated by bootstrap, internal and external clinical validation (orthopedic and traumatic brain injury). Our neuropsychological impairment (NPI) rule was defined as "two or more test scores that fall 1.5 SDs below the mean." The rule identifies 5.1% of the total sample as impaired in the assessment battery and consistently targets between 3 and 7% of the population as impaired even when age, domains, and number of tests are varied. The NPI rate increases in groups known to exhibit cognitive deficits. The NPI rule provides a psychometrically derived method for interpreting performance across multiple tests and may be used in children 6-18 years. The rule may be useful to clinicians and scientists who wish to establish whether specific individuals or clinical populations present within expected norms versus impaired function across a battery of neuropsychological tests.

  18. Are Non-Intellectually Disabled Black Youth with ASD Less Impaired on Parent Report than Their White Peers?

    ERIC Educational Resources Information Center

    Ratto, Allison B.; Anthony, Bruno J.; Kenworthy, Lauren; Armour, Anna Chelsea; Dudley, Katerina; Anthony, Laura Gutermuth

    2016-01-01

    There is a lack of research examining differences in functioning in autism spectrum disorder (ASD) across ethnicity, particularly among those without intellectual disability (ID). This study investigated ethnic differences in parent-reported impairment in executive function, adaptive behavior, and social-emotional functioning. White and Black…

  19. Maternal Positive Parenting Style Is Associated with Better Functioning in Hyperactive/Inattentive Preschool Children

    ERIC Educational Resources Information Center

    Healey, Dione M.; Flory, Janine D.; Miller, Carlin J.; Halperin, Jeffrey M.

    2011-01-01

    Many preschoolers are highly inattentive, impulsive, and hyperactive; but only some are impaired in their functioning. Yet factors leading to functional impairment, above and beyond the severity of inattentive and hyperactive symptoms, have not been systematically examined. This study examined a model suggesting that after controlling for…

  20. Nephrotoxicity of ibandronate and zoledronate in Wistar rats with normal renal function and after unilateral nephrectomy.

    PubMed

    Bergner, R; Siegrist, B; Gretz, N; Pohlmeyer-Esch, G; Kränzlin, B

    2015-09-01

    A previous animal study compared the nephrotoxic effect of ibandronate (IBN) and zoledronate (ZOL), but interpretation of these study results was limited because of the model of minimal nephrotoxic dosage with a dosage ratio of 1:3. The present study investigated the nephrotoxicity of ibandronate and zoledronate in a 1.5:1 dose ratio, as used in clinical practice and compared the nephrotoxicity in rats with normal and with mildly to moderately impaired renal function. We compared rats with normal renal function (SHAM) and with impaired renal function after unilateral nephrectomy (UNX), treated either with ibandronate 1.5mg/kg, zoledronate 1mg/kg or placebo once (1×) or nine (9×) times. Renal function and markers of tubular toxicity were measured over a 27 week period. After last bisphosphonate treatment the rats were sacrificed and kidneys examined histologically. All bisphosphonate treated animals showed a significant tubular toxicity, which was temporary except in the ZOL-UNX-9×-group. Also the renal function was only transiently reduced except in the ZOL-UNX-9×-group. Histologically, bisphosphonate treatment led to cortical tubuloepithelial degeneration/necrosis and medullary tubuloepithelial swelling which were slightly more pronounced in ibandronate treated animals, when compared to zoledronate treated animals, especially with impaired renal function. In contrast to the previous study we found a similar nephrotoxicity of ibandronate and zoledronate in rats with normal renal function. In rats with impaired renal function the peak of toxicity had not even been fully reached until end of experiment in the zoledronate treated animals. The peak of toxicity seems to be more severe and delayed in rats with impaired renal function compared with rats with normal renal function. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Interrelations Between Mitochondrial DNA Copy Number and Inflammation in Older Adults.

    PubMed

    Wu, I-Chien; Lin, Cheng-Chieh; Liu, Chin-San; Hsu, Chih-Cheng; Chen, Ching-Yu; Hsiung, Chao A

    2017-07-01

    Interplays between inflammation and mitochondrial biology are reported. Here, we examined the cross-sectional interrelationships of mitochondrial DNA copy number (mtDNACN) and inflammation and their interaction with physical functioning. A total of 1990 community-dwelling adults aged 65 years and older who were participating in the Healthy Aging Longitudinal Study in Taiwan underwent measurements of peripheral-blood leukocytes MtDNACN, multiple inflammatory markers, grip strength, and gait speed. Principal components analysis revealed two inflammatory factors: factor 1 (high-sensitivity C-reactive protein [hs-CRP], white blood cell count, fibrinogen and interleukin-6 [IL-6]); factor 2 (tumor necrosis factor receptor 1, D-dimer and soluble interleukin-6 receptor). Participants with severe physical functioning impairment (low grip strength and gait speed) had higher (p < .05) levels of factor 1 and 2, but not mtDNACN, than did those with moderately impaired (low grip strength or gait speed) and normal physical functioning. MtDNACN was negatively related to factor 1 (r = -.221, p < .001) but not factor 2 (r = -.002, p = .938). Increased factor 1 was strongly associated with higher odds of physical functioning impairment in those with a low mtDNACN (adjusted odds ratios [OR] of moderate physical function impairment 1.21, 95% CI 1.01-1.44; adjusted OR of severe physical function impairment 1.52, 95% CI 1.25-1.85) but not in those with a high mtDNACN (p for interaction = .016). A low mtDNACN was associated with an inflammation exhibiting elevated hs-CRP, IL-6, fibrinogen, and white blood cell count, and strengthened the association of this inflammation with physical functioning impairment. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Long-Term Cognitive Functioning in Testicular Germ-Cell Tumor Survivors.

    PubMed

    Chovanec, Michal; Vasilkova, Lucia; Setteyova, Lucia; Obertova, Jana; Palacka, Patrik; Rejlekova, Katarina; Sycova-Mila, Zuzana; Kalavska, Katarina; Svetlovska, Daniela; Cingelova, Silvia; Mladosievicova, Beata; Mardiak, Jozef; Mego, Michal

    2018-05-01

    Treatment for cancer may lead to development of cognitive difficulties in cancer survivors. This study aimed to evaluate long-term cognitive functioning (CogF) in germ-cell tumor (GCT) survivors. GCT survivors ( n  = 155) from the National Cancer Institute of Slovakia completed the Functional Assessment of Cancer Therapy Cognitive Function at a median of 10 years of follow-up (range: 5-32). The study group consisted of survivors receiving a cisplatin-based chemotherapy, radiotherapy to the retroperitoneal lymph nodes, or both, whereas the control group included survivors treated with orchiectomy only. Of the total survivors, 138 received treatment beyond orchiectomy and 17 controls had orchiectomy alone. Any treatment resulted in significantly greater cognitive difficulties on the overall cognitive function score. Treatment with radiotherapy was associated with cognitive declines in overall cognitive functioning and in subscales for perceived cognitive impairment and cognitive impairment perceived by others (both p  < .05). The burden of chemotherapy plus radiotherapy or radiotherapy versus controls resulted in the impairment in all cognitive functioning domains (all p  < .05). Overall long-term cognitive impairment was independent of age in the multivariable analysis. This prospective study shows that GCT survivors suffer from a long-term CogF impairment. These results may help guide clinicians' decisions in treatment and follow-up of GCTs. In this study, long-term survivors of germ-cell tumors have reported cognitive impairment after curative treatment with radiotherapy and chemotherapy compared with controls who had treatment with orchiectomy only. These data provide an argument against the use of adjuvant radiotherapy for stage I seminoma. Unnecessary overtreatment with chemotherapy and additional radiotherapy after chemotherapy should be avoided. © AlphaMed Press 2018.

  3. Concordance of Barthel Index, ECOG-PS, and Palliative Performance Scale in the assessment of functional status in patients with advanced medical diseases.

    PubMed

    Hernández-Quiles, C; Bernabeu-Wittel, M; Pérez-Belmonte, L M; Macías-Mir, P; Camacho-González, D; Massa, B; Maiz-Jiménez, M; Ollero-Baturone, M

    2017-09-01

    Analysing most relevant clinical features and concordance between different functional scales in patients with advanced medical diseases (PAMD). Cross-sectional multicentre study that included PAMD (heart, lung, kidney, liver, and neurological diseases) in hospital settings from February 2009 to October 2010. We analysed clinical, biological and functional features in performing activities of daily living (ADL) by medians of Barthel Index (BI); additionally we assessed their performance status by medians of Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) and Palliative Performance Scale (PPS) scores. We evaluated the concordance of these instruments in assessing functional impairment by κ and intraclass correlation coefficient tests. 1847 patients were included (average age 79 years, 50.1% men). Most common symptoms were dyspnoea (62.31%), asthenia (23%) and delirium (20.14%). Functional assessment showed a high prevalence of severe or total impairment in performing basic ADL by medians of used instruments (BI median=35 (IQR=70), and 52.1% of patients with severe-total impairment; ECOG-PS median=2 (IQR 30), and 44% of patients with severe-total impairment; and PPS median=50 (IQR 30), and 32% of patients with severe-total impairment). Concordance among these instruments was acceptably good ( κ indexes ranging from 0.653 to 0.745 (p<0.0001)). PAMD represent a population with severe functional impairment, which requires a multidisciplinary approach for proper management. Assessment of functional ability in this population by BI, ECOG-PS, and PPS showed good concordance. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. Efficacy and safety of lipid lowering by alirocumab in chronic kidney disease.

    PubMed

    Toth, Peter P; Dwyer, Jamie P; Cannon, Christopher P; Colhoun, Helen M; Rader, Daniel J; Upadhyay, Ashish; Louie, Michael J; Koren, Andrew; Letierce, Alexia; Mandel, Jonas; Banach, Maciej

    2018-06-01

    Individuals with chronic kidney disease are at increased risk of premature cardiovascular disease. Among them, many with elevated low-density lipoprotein cholesterol (LDL-C) are unable to achieve optimal LDL-C on statins and require additional lipid-lowering therapy. To study this, we compared the LDL-C-lowering efficacy and safety of alirocumab in individuals with hypercholesterolemia with impaired renal function, defined as eGFR 30-59 ml/min/1.73 m 2 , to those without impaired renal function eGFR ≥60 ml/min/1.73 m 2 . A total of 4629 hypercholesterolemic individuals without or with impaired renal function, pooled from eight phase 3 ODYSSEY trials (double-blind treatments of 24-104 weeks), were on alirocumab 150 mg or 75/150 mg every two weeks vs. placebo or ezetimibe. Overall, 10.1% had impaired renal function and over 99% were receiving statin treatment. Baseline LDL-C in alirocumab and control groups was comparable in subgroups analyzed. LDL-C reductions at week 24 ranged from 46.1 to 62.2% or 48.3 to 60.1% with alirocumab among individuals with or without impaired renal function, respectively. Similar reductions were observed for lipoprotein (a), non-high-density lipoprotein cholesterol, apolipoprotein B, and triglycerides. Safety data were similar in both treatment subgroups, regardless of the degree of CKD. Renal function did not change over time in response to alirocumab. This post hoc efficacy analysis is limited by evaluation of alirocumab treatment effects on renal and lipid parameters by serum biochemistry. Thus, alirocumab consistently lowered LDL-C regardless of impaired renal function, with safety comparable to control, among individuals with hypercholesterolemia who nearly all were on statin treatment. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  5. Impairments in Component Processes of Executive Function and Episodic Memory in Alcoholism, HIV Infection, and HIV Infection with Alcoholism Comorbidity.

    PubMed

    Fama, Rosemary; Sullivan, Edith V; Sassoon, Stephanie A; Pfefferbaum, Adolf; Zahr, Natalie M

    2016-12-01

    Executive functioning and episodic memory impairment occur in HIV infection (HIV) and chronic alcoholism (ALC). Comorbidity of these conditions (HIV + ALC) is prevalent and heightens risk of vulnerability to separate and compounded deficits. Age and disease-related variables can also serve as mediators of cognitive impairment and should be considered, given the extended longevity of HIV-infected individuals in this era of improved pharmacological therapy. HIV, ALC, HIV + ALC, and normal controls (NC) were administered traditional and computerized tests of executive function and episodic memory. Test scores were expressed as age- and education-corrected Z-scores; selective tests were averaged to compute Executive Function and Episodic Memory Composite scores. Efficiency scores were calculated for tests with accuracy and response times. HIV, ALC, and HIV + ALC had lower scores than NC on Executive Function and Episodic Memory Composites, with HIV + ALC even lower than ALC and HIV on the Episodic Memory Composite. Impairments in planning and free recall of visuospatial material were observed in ALC, whereas impairments in psychomotor speed, sequencing, narrative free recall, and pattern recognition were observed in HIV. Lower decision-making efficiency scores than NC occurred in all 3 clinical groups. In ALC, age and lifetime alcohol consumption were each unique predictors of Executive Function and Episodic Memory Composite scores. In HIV + ALC, age was a unique predictor of Episodic Memory Composite score. Disease-specific and disease-overlapping patterns of impairment in HIV, ALC, and HIV + ALC have implications regarding brain systems disrupted by each disease and clinical ramifications regarding the complexities and compounded damping of cognitive functioning associated with dual diagnosis that may be exacerbated with aging. Copyright © 2016 by the Research Society on Alcoholism.

  6. Identification of mild cognitive impairment in ACTIVE: algorithmic classification and stability.

    PubMed

    Cook, Sarah E; Marsiske, Michael; Thomas, Kelsey R; Unverzagt, Frederick W; Wadley, Virginia G; Langbaum, Jessica B S; Crowe, Michael

    2013-01-01

    Rates of mild cognitive impairment (MCI) have varied substantially, depending on the criteria used and the samples surveyed. The present investigation used a psychometric algorithm for identifying MCI and its stability to determine if low cognitive functioning was related to poorer longitudinal outcomes. The Advanced Cognitive Training of Independent and Vital Elders (ACTIVE) study is a multi-site longitudinal investigation of long-term effects of cognitive training with older adults. ACTIVE exclusion criteria eliminated participants at highest risk for dementia (i.e., Mini-Mental State Examination < 23). Using composite normative for sample- and training-corrected psychometric data, 8.07% of the sample had amnestic impairment, while 25.09% had a non-amnestic impairment at baseline. Poorer baseline functional scores were observed in those with impairment at the first visit, including a higher rate of attrition, depressive symptoms, and self-reported physical functioning. Participants were then classified based upon the stability of their classification. Those who were stably impaired over the 5-year interval had the worst functional outcomes (e.g., Instrumental Activities of Daily Living performance), and inconsistency in classification over time also appeared to be associated increased risk. These findings suggest that there is prognostic value in assessing and tracking cognition to assist in identifying the critical baseline features associated with poorer outcomes.

  7. The Relationship Between Neurocognitive Functioning and Occupational Functioning in Bipolar Disorder: A Literature Review

    PubMed Central

    Duarte, Walace; Becerra, Rodrigo; Cruise, Kate

    2016-01-01

    Neurocognitive impairment in Bipolar Disorder (BD) has been widely reported, even during remission. Neurocognitive impairment has been identified as a contributing factor towards unfavourable psychosocial functioning within this population. The objective of this review was to investigate the association between neurocognitive impairment and occupational functioning in BD. A literature review of English-language journal articles from January 1990 to November 2013 was undertaken utilising the PsychINFO, Scopus and Web of Knowledge databases. Studies that made specific reference to occupational outcomes were included, and those that reported on global psychosocial measures were excluded. Majority of the papers reviewed (20 out of 23) identified an association between neurocognitive impairment (particularly in executive functioning, verbal learning and memory, processing speed and attention) and occupational functioning. Several methodological issues were identified. There was a discrepancy in the measures used to assess neurocognitive function across studies and also the definition and measurement of occupational functioning. The clinical features of the samples varied across studies, and confounding variables were intermittently controlled. The review focused on English-language papers only and hence there is a bias toward the Western labour market. These limitations therefore influence the generalizability of the interpreted findings and the reliability of comparisons across studies. Neurocognitive impairment in BD appears to play a role in occupational outcomes. The findings of this review highlight the challenges for future research in this area, particularly in the measurement of neurocognitive and occupational functioning. Incorporating neurocognitive interventions in the treatment of BD, which has traditionally focussed solely on symptomatic recovery, may advance the vocational rehabilitation of these patients. PMID:27872673

  8. Impaired work functioning due to common mental disorders in nurses and allied health professionals: the Nurses Work Functioning Questionnaire.

    PubMed

    Gärtner, F R; Nieuwenhuijsen, K; van Dijk, F J H; Sluiter, J K

    2012-02-01

    Common mental disorders (CMD) negatively affect work functioning. In the health service sector not only the prevalence of CMDs is high, but work functioning problems are associated with a risk of serious consequences for patients and healthcare providers. If work functioning problems due to CMDs are detected early, timely help can be provided. Therefore, the aim of this study is to develop a detection questionnaire for impaired work functioning due to CMDs in nurses and allied health professionals working in hospitals. First, an item pool was developed by a systematic literature study and five focus group interviews with employees and experts. To evaluate the content validity, additional interviews were held. Second, a cross-sectional assessment of the item pool in 314 nurses and allied health professionals was used for item selection and for identification and corroboration of subscales by explorative and confirmatory factor analysis. The study results in the Nurses Work Functioning Questionnaire (NWFQ), a 50-item self-report questionnaire consisting of seven subscales: cognitive aspects of task execution, impaired decision making, causing incidents at work, avoidance behavior, conflicts and irritations with colleagues, impaired contact with patients and their family, and lack of energy and motivation. The questionnaire has a proven high content validity. All subscales have good or acceptable internal consistency. The Nurses Work Functioning Questionnaire gives insight into precise and concrete aspects of impaired work functioning of nurses and allied health professionals. The scores can be used as a starting point for purposeful interventions.

  9. Predictors of impaired work functioning in employees with major depression in remission.

    PubMed

    de Vries, Gabe; Koeter, Maarten W J; Nieuwenhuijsen, Karen; Hees, Hiske L; Schene, Aart H

    2015-10-01

    This study aims to (i) assess work functioning in employees returning to work with a major depression in remission, (ii) study the predictors of impaired work functioning. Participants diagnosed with major depressive disorder (MDD), on long term sick leave (mean 27 weeks) and treated in a specialized mental healthcare setting, were selected from an intervention study sample. They were eligible for this study if they were remitted from their depression and had returned to work for at least 50% of their contract hours at 18 month follow-up. Work functioning was assessed with the Work Limitations Questionnaire (WLQ) and the Need For Recovery scale (NFR). Potential predictors of impaired work functioning were demographic characteristics (assessed at baseline), health characteristics (assessed at baseline, six and twelve month follow-up), and personality- and work characteristics (assessed at 18 month follow-up). After their return to work with MDD in remission, employees were on average still impaired in their work functioning. Personality characteristics were the strongest predictor of this impaired work functioning, followed by health and work characteristics. In the final prediction model, only a passive reaction coping style remained as predictor. We used self-report data with respect to work functioning and work characteristics and not an assessment by a supervisor. Personality trait, coping style, and ability to manage the work environment should be addressed in mental health and return-to-work interventions. Subsequent improved work functioning may be beneficial for mental health and may reduce societal costs. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. High-functioning autism patients share similar but more severe impairments in verbal theory of mind than schizophrenia patients.

    PubMed

    Tin, L N W; Lui, S S Y; Ho, K K Y; Hung, K S Y; Wang, Y; Yeung, H K H; Wong, T Y; Lam, S M; Chan, R C K; Cheung, E F C

    2018-06-01

    Evidence suggests that autism and schizophrenia share similarities in genetic, neuropsychological and behavioural aspects. Although both disorders are associated with theory of mind (ToM) impairments, a few studies have directly compared ToM between autism patients and schizophrenia patients. This study aimed to investigate to what extent high-functioning autism patients and schizophrenia patients share and differ in ToM performance. Thirty high-functioning autism patients, 30 schizophrenia patients and 30 healthy individuals were recruited. Participants were matched in age, gender and estimated intelligence quotient. The verbal-based Faux Pas Task and the visual-based Yoni Task were utilised to examine first- and higher-order, affective and cognitive ToM. The task/item difficulty of two paradigms was examined using mixed model analyses of variance (ANOVAs). Multiple ANOVAs and mixed model ANOVAs were used to examine group differences in ToM. The Faux Pas Task was more difficult than the Yoni Task. High-functioning autism patients showed more severely impaired verbal-based ToM in the Faux Pas Task, but shared similar visual-based ToM impairments in the Yoni Task with schizophrenia patients. The findings that individuals with high-functioning autism shared similar but more severe impairments in verbal ToM than individuals with schizophrenia support the autism-schizophrenia continuum. The finding that verbal-based but not visual-based ToM was more impaired in high-functioning autism patients than schizophrenia patients could be attributable to the varied task/item difficulty between the two paradigms.

  11. Cognitive Impairment and Structural Abnormalities in Late Life Depression with Olfactory Identification Impairment: an Alzheimer's Disease-Like Pattern.

    PubMed

    Chen, Ben; Zhong, Xiaomei; Mai, Naikeng; Peng, Qi; Wu, Zhangying; Ouyang, Cong; Zhang, Weiru; Liang, Wanyuan; Wu, Yujie; Liu, Sha; Chen, Lijian; Ning, Yuping

    2018-03-15

    Late-life depression patients are at a high risk of developing Alzheimer's disease, and diminished olfactory identification is an indicator in early screening for Alzheimer's disease in the elderly. However, whether diminished olfactory identification is associated with risk of developing Alzheimer's disease in late-life depression patients remains unclear. One hundred and twenty-five late-life depression patients, 50 Alzheimer's disease patients, and 60 normal controls were continuously recruited. The participants underwent a clinical evaluation, olfactory test, neuropsychological assessment, and neuroimaging assessment. The olfactory identification impairment in late-life depression patients was milder than that in Alzheimer's disease patients. Diminished olfactory identification was significantly correlated with worse cognitive performance (global function, memory language, executive function, and attention) and reduced grey matter volume (olfactory bulb and hippocampus) in the late-life depression patients. According to a multiple linear regression analysis, olfactory identification was significantly associated with the memory scores in late-life depression group (B=1.623, P<.001). The late-life depression with olfactory identification impairment group had worse cognitive performance (global, memory, language, and executive function) and more structural abnormalities in Alzheimer's disease-related regions than the late-life depression without olfactory identification impairment group, and global cognitive function and logical memory in the late-life depression without olfactory identification impairment group was intact. Reduced volume observed in many areas (hippocampus, precuneus, etc.) in the Alzheimer's disease group was also observed in late-life depression with olfactory identification impairment group but not in the late-life depression without olfactory identification impairment group. The patterns of cognitive impairment and structural abnormalities in late-life depression with olfactory identification impairment patients were similar to those in Alzheimer's disease; olfactory identification may help identify late-life depression patients who are at a high risk of developing Alzheimer's disease.

  12. A New Version of the Impairment and Functioning Inventory for Patients With Chronic Pain (IFI-R).

    PubMed

    Ramírez-Maestre, Carmen; Esteve, Rosa

    2015-05-01

    Few instruments are available that have adequate psychometric properties for assessing daily functioning in patients with musculoskeletal pain. In addition, none of these instruments assesses the perceived decrease in levels of daily activities after the onset of pain. To review the psychometric qualities of the Impairment and Functioning Inventory (IFI) for patients with chronic pain. Cross-sectional study. Four public primary care centers and a public pain clinic. A total of 483 patients with back pain who were treated at primary care centers and 137 patients with various pain conditions who were treated at a pain clinic. To analyze factorial validity, a confirmatory factor analysis was performed via structural equation modeling. To measure internal consistency, Cronbach's α coefficients were calculated. To assess convergent validity, Pearson correlation coefficients were computed between the 2 scales of the IFI and the measures of the Roland Morris Questionnaire. Criterion validity and generalizability were analyzed by regression analysis via structural equation modeling using the LISREL 8.30 software package. The IFI for patients with chronic pain. A revised version of the IFI (IFI-R) is presented that consists of 30 items with 2 related subscales: Daily Functioning and Impairment (perceived current level of functioning compared with the level of functioning before pain onset). Both subscales were significantly correlated with disability. Depression, pain intensity, and pain anxiety had a negative association with functioning and a positive association with impairment. On the other hand, pain catastrophizing had a negative association with functioning and pain hypervigilance had a positive association with impairment due to pain. The IFI-R appears to be a valid and reliable measurement tool for the assessment of perceived daily functioning and impairment in people with chronic pain. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  13. Sex differences in the association of physical function and cognitive function with life satisfaction in older age: The Rancho Bernardo Study.

    PubMed

    Ratigan, Amanda; Kritz-Silverstein, Donna; Barrett-Connor, Elizabeth

    2016-07-01

    This study examines the cross-sectional associations of cognitive and physical function with life satisfaction in middle-class, community-dwelling adults aged 60 and older. Participants were 632 women and 410 men who had cognitive function tests (CFT) and physical function tasks (PFT) assessed at a clinic visit between 1988 and 1992, and who responded in 1992 to a mailed survey that included life satisfaction measures. Cognitive impairment was defined as ≤24 on MMSE, ≥132 on Trails B, ≤12 on Category Fluency, ≤13 on Buschke long-term recall, and ≤7 on Heaton immediate recall. Physical impairment was defined as participants' self-reported difficulty (yes/no) in performing 10 physical functions. Multiple linear regression examined associations between life satisfaction and impairment on ≥1 CFT or difficulty with ≥1 PFT. The Satisfaction with Life Scale (SWLS; range:0-26) and Life Satisfaction Index-Z (LSI-Z; range:5-35). Participants' average age was 73.4 years (range=60-94). Categorically defined cognitive impairment was present in 40% of men and 47% of women. Additionally, 30% of men and 43% of women reported difficulty performing any PFT. Adjusting for age and impairment on ≥1 CFT, difficulty performing ≥1 PFT was associated with lower LSI-Z and SWLS scores in men (β=-1.73, -1.26, respectively, p<0.05) and women (β=-1.79, -1.93, respectively, p<0.01). However, impairment on ≥ 1 CFT was not associated with LSI-Z or SWLS score after adjusting for age and difficulty with ≥1 PFT. Limited cognitive function was more common than limited physical function; however, limited physical function was more predictive of lower life satisfaction. Interventions to increase or maintain mobility among older adults may improve overall life satisfaction. Copyright © 2016. Published by Elsevier Ireland Ltd.

  14. Emotional intelligence and social functioning in persons with schizotypy.

    PubMed

    Aguirre, Fabian; Sergi, Mark J; Levy, Cynthia A

    2008-09-01

    The present study is the first to examine emotional intelligence in persons with schizotypy. Over 2100 undergraduates were screened for schizotypy with the Schizotypal Personality Questionnaire-Brief Version. Forty participants identified as persons with high schizotypy and 56 participants identified as persons with low schizotypy completed assessments of emotional intelligence (Mayer-Salovey-Caruso Emotional Intelligence Test), social functioning (Social Adjustment Scale-Self Report), verbal episodic (secondary) memory (California Verbal Learning Test), and executive functioning (Wisconsin Card Sorting Test). Persons high in schizotypy were impaired in overall emotional intelligence and two aspects of emotional intelligence, the ability to perceive emotions and the ability to manage emotions. Persons high in schizotypy were also impaired in three aspects of social functioning: peer relationships, family relationships, and academic functioning. Group differences in verbal episodic (secondary) memory and executive functioning were not observed. For persons with high schizotypy, overall emotional intelligence and two aspects of emotional intelligence, the ability to perceive emotions and the ability to manage emotions, were associated with peer relationship functioning. Overall emotional intelligence was associated with verbal episodic (secondary) memory, but not executive functioning, in persons with high schizotypy. The current findings suggest that emotional intelligence is impaired in persons with schizotypy and that these impairments affect their social functioning.

  15. Burden of impaired sleep quality on work productivity in functional dyspepsia.

    PubMed

    Matsuzaki, Juntaro; Suzuki, Hidekazu; Togawa, Koji; Yamane, Tsuyoshi; Mori, Hideki; Komori, Takahiro; Masaoka, Tatsuhiro; Kanai, Takanori

    2018-04-01

    Impaired sleep quality is common, and can reduce work productivity in patients with functional dyspepsia (FD). The objective of this article is to evaluate whether there is a direct association between the presence of FD and the severity of impaired sleep quality, and to calculate the economic loss due to the decreased work productivity associated with sleep quality. In Study 1, using a web-based survey completed by workers with and without FD, we evaluated impaired sleep quality, work and daily productivity, and the severity of reflux and bowel symptoms. In Study 2, the association between the presence of FD and the severity of impaired sleep quality was validated in a hospital-based cohort. In both Study 1 and 2, although impaired sleep quality was more frequent in participants with FD than in those without FD, the independent association between the presence of FD and the severity of impaired sleep quality was not observed after adjustment for the severity of reflux and bowel symptoms. FD participants with impaired sleep quality reported additional economic loss of 53,500 Japanese yen/month. Although the association between impaired sleep quality and FD was indirect, concomitant impaired sleep quality could worsen economic loss.

  16. Prevalence and Treatment Patterns of Physical Impairments in Patients With Metastatic Breast Cancer

    PubMed Central

    Cheville, Andrea L.; Troxel, Andrea B.; Basford, Jeffrey R.; Kornblith, Alice B.

    2014-01-01

    Purpose Physical impairments cause profound functional declines in patients with cancer. Although common rehabilitation measures can address many impairments, the extent of their delivery is unknown. We studied these issues by quantifying physical impairments in patients with metastatic breast cancer and by assessing how they are addressed. Patients and Methods A consecutive sample of 163 community-dwelling patients with metastatic breast cancer was stratified by Karnofsky performance score and administered the Medical Outcomes Study Physical Function Subscale and the Older Americans Resource Study Activities of Daily Living subscales. Cancer-related physical impairments were identified through a physical examination, the 6-Minute Walk Test, and the Functional Independence Measure Mobility Subscale. Patients were questioned regarding the nature, type, and setting of treatments for impairments. Physical rehabilitation needs were determined through a consensus process involving physiatrists and physical/occupational therapists specializing in cancer. Results Ninety-two percent of patients (150 of 163) had at least one physical impairment. Among 530 identified impairments, 484 (92%) required a physical rehabilitation intervention and 469 (88%) required physical therapy (PT) and/or occupational therapy (OT). Only 30% of impairments requiring rehabilitation services and 21% of those requiring PT/OT received treatment. Impairments detected during hospitalization were overwhelmingly more likely to receive a rehabilitation intervention (odds ratio [OR] = 87.9; 95% CI, 28.5 to 271.4), and PT/OT (OR = 558.8; 95% CI, 187.0 to 1,669.6). Low socioeconomic and minority status were significantly associated with nontreatment. Conclusion Remediable physical impairments were prevalent and poorly addressed among patients with metastatic breast cancer, drastically so in the outpatient setting. Undertreatment was particularly prominent among minority and socioeconomically disadvantaged groups. PMID:18509174

  17. Consciousness as a useful concept in epilepsy classification

    PubMed Central

    Blumenfeld, Hal; Meador, Kimford J.

    2014-01-01

    Summary Impaired consciousness has important practical consequences for people living with epilepsy. Recent pathophysiologic studies show that seizures with impaired level of consciousness always affect widespread cortical networks and subcortical arousal systems. In light of these findings and their clinical significance, efforts are underway to revise the International League Against Epilepsy (ILAE) 2010 report to include impaired consciousness in the classification of seizures. Lüders and colleagues have presented one such effort, which we discuss here. We then propose an alternative classification of impaired consciousness in epilepsy based on functional neuroanatomy. Some seizures involve focal cortical regions and cause selective deficits in the content of consciousness but without impaired overall level of consciousness or awareness. These include focal aware conscious seizures (FACS) with lower order cortical deficits such as somatosensory or visual impairment as well as FACS with higher cognitive deficits including ictal aphasia or isolated epileptic amnesia. Another category applies to seizures with impaired level of consciousness leading to deficits in multiple cognitive domains. For this category, we believe the terms “dyscognitive” or “dialeptic” should be avoided because they may create confusion. Instead we propose that seizures with impaired level of consciousness be described based on underlying pathophysiology. Widespread moderately severe deficits in corticothalamic function are seen in absence seizures and in focal impaired consciousness seizures (FICS), including many temporal lobe seizures and other focal seizures with impaired consciousness. Some simple responses or automatisms may be preserved in these seizures. In contrast, generalized tonic–clonic seizures usually produce widespread severe deficits in corticothalamic function causing loss of all meaningful responses. Further work is needed to understand and prevent impaired consciousness in epilepsy, but the first step is to keep this crucial practical and physiologic aspect of seizures front-and-center in our discussions. PMID:24981294

  18. Depression and Cognitive Impairment in Peritoneal Dialysis: A Multicenter Cross-sectional Study.

    PubMed

    Dong, Jie; Pi, Hai-Chen; Xiong, Zu-Ying; Liao, Jin-Lan; Hao, Li; Liu, Gui-Ling; Ren, Ye-Ping; Wang, Qin; Duan, Li-Ping; Zheng, Zhao-Xia

    2016-01-01

    Depression and cognitive impairment have been identified as independent risk factors for mortality in peritoneal dialysis (PD) patients. The relationship between depression and global and specific cognitive functions in PD patients was investigated in this study. Multicenter cross-sectional study. 458 clinically stable patients, drawn from 5 PD units, who performed PD for at least 3 months were enrolled. Depression, defined as depression severity index score > 0.5 using the Zung Self-rating Depression Scale. Global and specific cognitive impairment. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), Trail-Making Test forms A and B for executive function, and subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skills, and language ability. Prevalences of depression and cognitive impairment evaluated by the 3MS were 52% and 28.4%, respectively. Patients with mild or moderate/severe depression had higher prevalences of general cognitive impairment, executive dysfunction, and impaired immediate and delayed memory. After adjusting for demographics, comorbid conditions, and clinical parameters, depression scores were independently associated with lower 3MS scores, lower immediate and delayed memory and language ability scores, and longer completion times of Trails A and B. Even mild depression was independently associated with higher risk for cognitive impairment, executive dysfunction, and impaired immediate and delayed memory after multivariable adjustments. The causal relationship between depression and cognitive impairment could not be determined, and the potential copathogenesis behind depression and cognitive impairment was not fully investigated. Even mild depression is closely associated with global and specific cognitive impairment in PD patients. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  19. Consciousness as a useful concept in epilepsy classification.

    PubMed

    Blumenfeld, Hal; Meador, Kimford J

    2014-08-01

    Impaired consciousness has important practical consequences for people living with epilepsy. Recent pathophysiologic studies show that seizures with impaired level of consciousness always affect widespread cortical networks and subcortical arousal systems. In light of these findings and their clinical significance, efforts are underway to revise the International League Against Epilepsy (ILAE) 2010 report to include impaired consciousness in the classification of seizures. Lüders and colleagues have presented one such effort, which we discuss here. We then propose an alternative classification of impaired consciousness in epilepsy based on functional neuroanatomy. Some seizures involve focal cortical regions and cause selective deficits in the content of consciousness but without impaired overall level of consciousness or awareness. These include focal aware conscious seizures (FACS) with lower order cortical deficits such as somatosensory or visual impairment as well as FACS with higher cognitive deficits including ictal aphasia or isolated epileptic amnesia. Another category applies to seizures with impaired level of consciousness leading to deficits in multiple cognitive domains. For this category, we believe the terms "dyscognitive" or "dialeptic" should be avoided because they may create confusion. Instead we propose that seizures with impaired level of consciousness be described based on underlying pathophysiology. Widespread moderately severe deficits in corticothalamic function are seen in absence seizures and in focal impaired consciousness seizures (FICS), including many temporal lobe seizures and other focal seizures with impaired consciousness. Some simple responses or automatisms may be preserved in these seizures. In contrast, generalized tonic-clonic seizures usually produce widespread severe deficits in corticothalamic function causing loss of all meaningful responses. Further work is needed to understand and prevent impaired consciousness in epilepsy, but the first step is to keep this crucial practical and physiologic aspect of seizures front-and-center in our discussions. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

  20. Childhood adversities and adult psychopathology in the National Comorbidity Survey Replication (NCS-R) III: associations with functional impairment related to DSM-IV disorders.

    PubMed

    McLaughlin, K A; Green, J G; Gruber, M J; Sampson, N A; Zaslavsky, A M; Kessler, R C

    2010-05-01

    Despite evidence that childhood adversities (CAs) are associated with increased risk of mental disorders, little is known about their associations with disorder-related impairment. We report the associations between CAs and functional impairment associated with 12-month DSM-IV disorders in a national sample. We used data from the US National Comorbidity Survey Replication (NCS-R). Respondents completed diagnostic interviews that assessed 12-month DSM-IV disorder prevalence and impairment. Associations of 12 retrospectively reported CAs with impairment among cases (n=2242) were assessed using multiple regression analysis. Impairment measures included a dichotomous measure of classification in the severe range of impairment on the Sheehan Disability Scale (SDS) and a measure of self-reported number of days out of role due to emotional problems in the past 12 months. CAs were positively and significantly associated with impairment. Predictive effects of CAs on the SDS were particularly pronounced for anxiety disorders and were significant in predicting increased days out of role associated with mood, anxiety and disruptive behavior disorders. Predictive effects persisted throughout the life course and were not accounted for by disorder co-morbidity. CAs associated with maladaptive family functioning (MFF; parental mental illness, substance disorder, criminality, family violence, abuse, neglect) were more consistently associated with impairment than other CAs. The joint effects of co-morbid MFF CAs were significantly subadditive. Simulations suggest that CAs account for 19.6% of severely impairing disorders and 17.4% of days out of role. CAs predict greater disorder-related impairment, highlighting the ongoing clinical significance of CAs at every stage of the life course.

  1. The Economics of Cognitive Impairment: Volunteering and Cognitive Function in the HILDA Survey.

    PubMed

    Hosking, Diane E; Anstey, Kaarin J

    2016-01-01

    The economic impact of older-age cognitive impairment has been estimated primarily by the direct and indirect costs associated with dementia care. Other potential costs associated with milder cognitive impairment in the community have received little attention. To quantify the cost of nonclinical cognitive impairment in a large population-based sample in order to more fully inform cost-effectiveness evaluations of interventions to maintain cognitive health. Volunteering by seniors has economic value but those with lower cognitive function may contribute fewer hours. Relations between hours volunteering and cognitive impairment were assessed using the Household, Income and Labour Dynamics in Australia (HILDA) survey data. These findings were extrapolated to the Australian population to estimate one potential cost attributable to nonclinical cognitive impairment. In those aged ≥60 years in HILDA (n = 3,127), conservatively defined cognitive impairment was present in 3.8% of the sample. Impairment was defined by performance ≥1 standard deviation below the age- and education-adjusted mean on both the Symbol Digit Modalities Test and Backwards Digit Span test. In fully adjusted binomial regression models, impairment was associated with the probability of undertaking 1 h 9 min less volunteering a week compared to being nonimpaired (β = -1.15, 95% confidence interval -1.82 to -0.47, p = 0.001). In the population, 3.8% impairment equated to probable loss of AUD 302,307,969 per annum estimated by hours of volunteering valued by replacement cost. Nonclinical cognitive impairment in older age impacts upon on the nonmonetary economy via probable loss of volunteering contribution. Valuing loss of contribution provides additional information for cost-effectiveness evaluations of research and action directed toward maintaining older-age cognitive functioning. © 2016 S. Karger AG, Basel.

  2. The effects of cognitive intervention on cognitive impairments after intensive care unit admission.

    PubMed

    Zhao, Jingjing; Yao, Li; Wang, Changqing; Sun, Yun; Sun, Zhongwu

    2017-04-01

    Patients who survive critical illness commonly suffer cognitive impairments. We aimed to study the effects of cognitive intervention to treat the long-term impairments observed among different populations of intensive care unit (ICU) survivors. The results showed that the intervention significantly suppressed the deterioration of cognitive function in these patients. Medical and neurological ICU survivors were more susceptible than post-anaesthesia ICU patients to severe cognitive damage. In the former, the deterioration of impairments can be slowed by cognitive intervention. In comparison, intervention exerted significantly positive effects on the recovery of the cognitive functions of post-anaesthesia care unit patients. Furthermore, young populations were more likely than older populations to recover from acute cognitive impairments, and the impairment observed among the older population seemed to be multi-factorial and irreversible.

  3. Cognitive Remediation and Bias Modification Strategies in Mood and Anxiety Disorders

    PubMed Central

    Gold, Alexandra K.; Montana, Rebecca E.; Sylvia, Louisa G.; Nierenberg, Andrew A.; Deckersbach, Thilo

    2016-01-01

    Purpose of review Cognitive impairments and biases, which are prevalent in patients with mood and anxiety disorders, can affect quality of life and functioning. Traditional treatments are only insufficiently addressing these impairments and biases. We review the cognitive impairments and biases present in these disorders as well as treatments targeting these domains. Recent findings Interventions aimed at improving cognitive impairments and biases may help improve cognitive deficits and overall functioning in patients with mood and anxiety disorders. Direct comparisons of treatments for cognitive impairments or biases versus more traditional psychosocial interventions have produced diverse results. Summary Overall, treatments for cognitive impairments and cognitive biases warrant additional study in clinical trials. Future research should explore cognitive remediation and cognitive bias modification adjunctive to psychosocial treatments to optimize patient outcomes in mood and anxiety disorders. PMID:27917364

  4. Pharmacokinetic profile of nifedipine GITS in hypertensive patients with chronic renal impairment.

    PubMed

    Schneider, R; Stolero, D; Griffel, L; Kobelt, R; Brendel, E; Iaina, A

    1994-01-01

    25 hypertensive patients with normal or impaired renal function underwent pharmacokinetic and safety studies after single and multiple dose administration of nifedipine GITS (Gastro-Intestinal Therapeutic System) 60mg tablets. Complete pharmacokinetic data were obtained from 23 of these patients. Blood pressure and heart rate changes were compatible with the known properties of the drug. Impaired renal function did not affect the maximum plasma concentrations or bioavailability of nifedipine after single or multiple dose administration of nifedipine GITS, nor was there any evidence of excessive drug accumulation in the presence of renal impairment.

  5. Selective Attention, Working Memory, and Executive Function as Potential Independent Sources of Cognitive Dysfunction in Schizophrenia.

    PubMed

    Gold, James M; Robinson, Benjamin; Leonard, Carly J; Hahn, Britta; Chen, Shuo; McMahon, Robert P; Luck, Steven J

    2017-11-11

    People with schizophrenia demonstrate impairments in selective attention, working memory, and executive function. Given the overlap in these constructs, it is unclear if these represent distinct impairments or different manifestations of one higher-order impairment. To examine this question, we administered tasks from the basic cognitive neuroscience literature to measure visual selective attention, working memory capacity, and executive function in 126 people with schizophrenia and 122 healthy volunteers. Patients demonstrated deficits on all tasks with the exception of selective attention guided by strong bottom-up inputs. Although the measures of top-down control of selective attention, working memory, and executive function were all intercorrelated, several sources of evidence indicate that working memory and executive function are separate sources of variance. Specifically, both working memory and executive function independently contributed to the discrimination of group status and independently accounted for variance in overall general cognitive ability as assessed by the MATRICS battery. These two cognitive functions appear to be separable features of the cognitive impairments observed in schizophrenia. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  6. Functional behavioral analysis and social scripting for the older patient with schizophrenia: a staff development program.

    PubMed

    Markwick, Laura; Smith, Charlene; Mick, Diane

    2014-11-01

    Executive functioning is the ability to plan, strategize, organize, and focus on details. Impaired executive functioning plays a significant role in behavior disturbances. Lack of inhibition, impaired abstract reasoning, thought perseverance, rigidity in routine, and lack of insight disrupt social skills and daily life. Autism and schizophrenia present some similar behaviors, including impaired executive functioning, often resulting in pharmacological management as many healthcare professionals receive limited training in executive functioning. Non-pharmacological tools used in autism for behavior management include functional behavioral analysis and social scripting, which help to identify causes of behavior and teach more appropriate behavioral responses. Described here is an educational program for healthcare workers in a long-term care skilled nursing facility, to help them understand the basis for behaviors in individuals with impaired executive function, to use these same tools for behavioral modification techniques, and to help patients learn more appropriate social skills. Program evaluation suggested the educational program was successful in increasing the staff's knowledge and comfort level in addressing the behavioral issues that arise with this population and staff also reported less use of medication as first-line treatment for behavioral issues.

  7. The effects of increased testicular temperature on testis-specific isoform of Na+/K+ -ATPase in sperm and its role in spermatogenesis and sperm function.

    PubMed

    Thundathil, J C; Rajamanickam, G D; Kastelic, J P; Newton, L D

    2012-08-01

    Impaired testicular thermoregulation is commonly implicated in abnormal spermatogenesis and impaired sperm function in animals and humans, with outcomes ranging from subclinical infertility to sterility. Bovine testes must be maintained 4-5 °C below body-core temperature for normal spermatogenesis. The effects of elevated testicular temperature have been extensively studied in cattle using a scrotal insulation model, which results in abnormal spermatogenesis and impaired sperm morphology and function. Using this model and proteomic approaches, we compared normal and abnormal sperm (from the same bulls) to elucidate the molecular basis of impaired function. We identified a cohort of sperm functional proteins differentially expressed between normal vs abnormal sperm, including a testis-specific isoform of Na(+) /K(+) -ATPase. In addition to its role as a sodium pump regulating sperm motility, Na(+) /K(+) -ATPase is also involved as a signalling molecule during sperm capacitation. In conclusion, because of its involvement in regulation of sperm function, this protein has potential as a fertility marker. Furthermore, comparing normal vs abnormal sperm (induced by scrotal insulation) is a useful model for identifying proteins regulating sperm function. © 2012 Blackwell Verlag GmbH.

  8. Do tasks make a difference? Accounting for heterogeneity of performance of children with reading difficulties on tasks of executive function: findings from a meta-analysis.

    PubMed

    Booth, Josephine N; Boyle, James M E; Kelly, Steve W

    2010-03-01

    Research studies have implicated executive functions in reading difficulties (RD). But while some studies have found children with RD to be impaired on tasks of executive function other studies report unimpaired performance. A meta-analysis was carried out to determine whether these discrepant findings can be accounted for by differences in the tasks of executive function that are utilized. A total of 48 studies comparing the performance on tasks of executive function of children with RD with their typically developing peers were included in the meta-analysis, yielding 180 effect sizes. An overall effect size of 0.57 (SE .03) was obtained, indicating that children with RD have impairments on tasks of executive function. However, effect sizes varied considerably suggesting that the impairment is not uniform. Moderator analysis revealed that task modality and IQ-achievement discrepancy definitions of RD influenced the magnitude of effect; however, the age and gender of participants and the nature of the RD did not have an influence. While the children's RD were associated with executive function impairments, variation in effect size is a product of the assessment task employed, underlying task demands, and definitional criteria.

  9. Diffusion imaging and transcranial magnetic stimulation assessment of transcallosal pathways in chronic stroke.

    PubMed

    Mang, Cameron S; Borich, Michael R; Brodie, Sonia M; Brown, Katlyn E; Snow, Nicholas J; Wadden, Katie P; Boyd, Lara A

    2015-10-01

    To examine the relationship of transcallosal pathway microstructure and transcallosal inhibition (TCI) with motor function and impairment in chronic stroke. Diffusion-weighted magnetic resonance imaging and transcranial magnetic stimulation (TMS) data were collected from 24 participants with chronic stroke and 11 healthy older individuals. Post-stroke motor function (Wolf Motor Function Test) and level of motor impairment (Fugl-Meyer score) were evaluated. Fractional anisotropy (FA) of transcallosal tracts between prefrontal cortices and the mean amplitude decrease in muscle activity during the ipsilateral silent period evoked by TMS over the non-lesioned hemisphere (termed NL-iSPmean) were significantly associated with level of motor impairment and motor function after stroke (p<0.05). A regression model including age, post-stroke duration, lesion volume, lesioned corticospinal tract FA, transcallosal prefrontal tract FA and NL-iSPmean accounted for 84% of variance in motor impairment (p<0.01). Both transcallosal prefrontal tract FA (ΔR(2)=0.12, p=0.04) and NL-iSPmean (ΔR(2)=0.09, p=0.04) accounted for unique variance in motor impairment level. Prefrontal transcallosal tract microstructure and TCI are each uniquely associated with motor impairment in chronic stroke. Utilizing a multi-modal approach to assess transcallosal pathways may improve our capacity to identify important neural substrates of motor impairment in the chronic phase of stroke. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  10. Mitochondrial impairments contribute to spatial learning and memory dysfunction induced by chronic tramadol administration in rat: Protective effect of physical exercise.

    PubMed

    Mehdizadeh, Hajar; Pourahmad, Jalal; Taghizadeh, Ghorban; Vousooghi, Nasim; Yoonessi, Ali; Naserzadeh, Parvaneh; Behzadfar, Ladan; Rouini, Mohammad Reza; Sharifzadeh, Mohammad

    2017-10-03

    Despite the worldwide use of tramadol, few studies have been conducted about its effects on memory and mitochondrial function, and controversial results have been reported. Recently, there has been an increasing interest in physical exercise as a protective approach to neuronal and cognitive impairments. Therefore, the aim of this study was to investigate the effects of physical exercise on spatial learning and memory and brain mitochondrial function in tramadol-treated rats. After completion of 2-week (short-term) and 4-week (long-term) treadmill exercise regimens, male Wistar rats received tramadol (20, 40, 80mg/kg/day) intraperitoneally for 30days. Then spatial learning and memory was assessed by Morris water maze test (MWM). Moreover, brain mitochondrial function was evaluated by determination of mitochondrial reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), mitochondrial swelling and cytochrome c release from mitochondria. Chronic administration of tramadol impaired spatial learning and memory as well as brain mitochondrial function as indicated by increased ROS level, MMP collapse, increased mitochondrial swelling and cytochrome c release from mitochondria. Conversely, treadmill exercise significantly attenuated the impairments of spatial learning and memory and brain mitochondrial dysfunction induced by tramadol. The results revealed that chronic tramadol treatment caused memory impairments through induction of brain mitochondrial dysfunction. Furthermore, pre-exposure to physical exercise markedly mitigated these impairments through its positive effects on brain mitochondrial function. Copyright © 2017. Published by Elsevier Inc.

  11. Associations Between Emotion Regulation and Social Impairment in Children and Adolescents with Autism Spectrum Disorder.

    PubMed

    Goldsmith, Samantha F; Kelley, Elizabeth

    2018-06-01

    In typically-developing (TD) individuals, effective emotion regulation strategies have been associated with positive outcomes in various areas, including social functioning. Although impaired social functioning is a core criterion of Autism Spectrum Disorder (ASD), the role of emotion regulation ability in ASD has been largely ignored. This study investigated the association between emotion regulation and ASD symptomatology, with a specific emphasis on social impairment. We used parent-report questionnaires to assess the regulatory strategies and symptom severity of 145 youth with ASD. Results showed that: (1) more effective emotion regulation, defined by greater use of reappraisal, predicted less severe ASD symptomatology, and (2) greater use of reappraisal predicted less severe social impairment. Suppression was not predictive of general symptomatology or social functioning.

  12. Greater Adherence to the Alternative Healthy Eating Index Is Associated with Lower Incidence of Physical Function Impairment in the Nurses' Health Study.

    PubMed

    Hagan, Kaitlin A; Chiuve, Stephanie E; Stampfer, Meir J; Katz, Jeffrey N; Grodstein, Francine

    2016-07-01

    Physical function is integral to healthy aging, in particular as a core component of mobility and independent living in older adults, and is a strong predictor of mortality. Limited research has examined the role of diet, which may be an important strategy to prevent or delay a decline in physical function with aging. We prospectively examined the association between the Alternative Healthy Eating Index-2010 (AHEI-2010), a measure of diet quality, with incident impairment in physical function among 54,762 women from the Nurses' Health Study. Physical function was measured by the Medical Outcomes Short Form-36 (SF-36) physical function scale and was administered every 4 y from 1992 to 2008. Cumulative average diet was assessed using food frequency questionnaires, administered approximately every 4 y. We used multivariable Cox proportional hazards models to estimate the HRs of incident impairment of physical function. Participants in higher quintiles of the AHEI-2010, indicating a healthier diet, were less likely to have incident physical impairment than were participants in lower quintiles (P-trend < 0.001). The multivariable-adjusted HR of physical impairment for those in the top compared with those in the bottom quintile of the AHEI-2010 was 0.87 (95% CI: 0.84, 0.90). For individual AHEI-2010 components, higher intake of vegetables (P-trend = 0.003) and fruits (P-trend = 0.02); lower intake of sugar-sweetened beverages (P-trend < 0.001), trans fats (P-trend = 0.03), and sodium (P-trend < 0.001); and moderate alcohol intake (P-trend < 0.001) were each significantly associated with reduced rates of incident physical impairment. Among top contributors to the food components of the AHEI-2010, the strongest relations were found for increased intake of oranges, orange juice, apples and pears, romaine or leaf lettuce, and walnuts. However, associations with each component and with specific foods were generally weaker than the overall score, indicating that overall diet pattern is more important than individual parts. In this large cohort of older women, a healthier diet was associated with a lower risk of developing impairments in physical function. © 2016 American Society for Nutrition.

  13. Older people experiencing homelessness show marked impairment on tests of frontal lobe function.

    PubMed

    Rogoz, Astrid; Burke, David

    2016-03-01

    Reported rates of mild and moderate cognitive impairment in older people experiencing homelessness range from 5-80%. The objective of this study was to determine the prevalence and characteristics of cognitive impairment in older people experiencing homelessness in the inner city of Sydney, Australia. Men and women experiencing homelessness aged 45 years and over in the inner city were screened for cognitive impairment. Participants who scored 26 or below on the mini-mental state examination and/or were impaired on any one of the clock-drawing test, the verbal fluency test and the trail-making test, part B were then assessed with a semi-structured interview, including the 21-item Depression Anxiety Stress Scale and the 12-item General Health Questionnaire. Screening of 144 men and 27 women aged between 45 years and 93 years identified cognitive impairment in 78%. Subsequently, high rates of mental and physical illness were identified, and 75% of subjects who were cognitively impaired performed poorly on frontal lobe tests. The trail-making test, part B was the most sensitive measure of frontal function. This study demonstrated that a large majority of older people experiencing homelessness, in the inner city of a high-income country, showed impairment on tests of frontal lobe function, a finding that could have significant implications for any medical or psychosocial intervention. Copyright © 2015 John Wiley & Sons, Ltd.

  14. Acute Viral Respiratory Infection Rapidly Induces a CD8+ T Cell Exhaustion-like Phenotype.

    PubMed

    Erickson, John J; Lu, Pengcheng; Wen, Sherry; Hastings, Andrew K; Gilchuk, Pavlo; Joyce, Sebastian; Shyr, Yu; Williams, John V

    2015-11-01

    Acute viral infections typically generate functional effector CD8(+) T cells (TCD8) that aid in pathogen clearance. However, during acute viral lower respiratory infection, lung TCD8 are functionally impaired and do not optimally control viral replication. T cells also become unresponsive to Ag during chronic infections and cancer via signaling by inhibitory receptors such as programmed cell death-1 (PD-1). PD-1 also contributes to TCD8 impairment during viral lower respiratory infection, but how it regulates TCD8 impairment and the connection between this state and T cell exhaustion during chronic infections are unknown. In this study, we show that PD-1 operates in a cell-intrinsic manner to impair lung TCD8. In light of this, we compared global gene expression profiles of impaired epitope-specific lung TCD8 to functional spleen TCD8 in the same human metapneumovirus-infected mice. These two populations differentially regulate hundreds of genes, including the upregulation of numerous inhibitory receptors by lung TCD8. We then compared the gene expression of TCD8 during human metapneumovirus infection to those in acute or chronic lymphocytic choriomeningitis virus infection. We find that the immunophenotype of lung TCD8 more closely resembles T cell exhaustion late into chronic infection than do functional effector T cells arising early in acute infection. Finally, we demonstrate that trafficking to the infected lung alone is insufficient for TCD8 impairment or inhibitory receptor upregulation, but that viral Ag-induced TCR signaling is also required. Our results indicate that viral Ag in infected lungs rapidly induces an exhaustion-like state in lung TCD8 characterized by progressive functional impairment and upregulation of numerous inhibitory receptors. Copyright © 2015 by The American Association of Immunologists, Inc.

  15. CASP-19 special section: how does chronic disease status affect CASP quality of life at older ages? Examining the WHO ICF disability domains as mediators of this relationship.

    PubMed

    Sexton, E; King-Kallimanis, B L; Layte, R; Hickey, A

    2015-07-01

    The effect of chronic disease status on quality of life (QoL) has been well established. However, less is known about how chronic diseases affect QoL. This article examines impairment in three domains of the WHO International Classification of Functioning, Health and Disability (ICF) - body function, activity and participation, as well as affective well-being, - as potential mediators of the relationship between chronic disease and QoL. A cross-sectional sample (n = 4961) of the general Irish community-dwelling population aged 50+ years was obtained from the Irish Longitudinal Study of Ageing (TILDA). The CASP measure of QoL was examined as two dimensions - control/autonomy and self-realisation/pleasure. Structural equation modelling was used to test the direct and indirect effects of chronic disease on QoL, via variables capturing body function, activity, participation and positive affect. A factor analysis showed that indicators of body function and activity loaded onto a single overall physical impairment factor. This physical impairment factor fully mediated the effect of chronic disease on positive affect and QoL. The total effect of chronic disease on control/autonomy (-0.160) was primarily composed of an indirect effect via physical impairment (-0.86), and via physical impairment and positive affect (-0.45). The decomposition of effects on self-realisation/pleasure was similar, although the direct effect of physical impairment was weaker. The model fitted the data well (RMSEA = 0.02, TLI = 0.96, CFI = 0.96). Chronic disease affects QoL through increased deficits in physical body function and activity. This overall physical impairment affects QoL both directly and indirectly via reduced positive affect.

  16. Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function.

    PubMed

    Stockburger, Carola; Miano, Davide; Pallas, Thea; Friedland, Kristina; Müller, Walter E

    2016-01-01

    The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer's disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP) function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function.

  17. Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function

    PubMed Central

    Stockburger, Carola; Miano, Davide; Pallas, Thea; Müller, Walter E.

    2016-01-01

    The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer's disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP) function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function. PMID:27747106

  18. Applying an Integrative Framework of Executive Function to Preschoolers with Specific Language Impairment

    ERIC Educational Resources Information Center

    Kapa, Leah L.; Plante, Elena; Doubleday, Kevin

    2017-01-01

    Purpose: The first goal of this research was to compare verbal and nonverbal executive function abilities between preschoolers with and without specific language impairment (SLI). The second goal was to assess the group differences on 4 executive function components in order to determine if the components may be hierarchically related as suggested…

  19. Plasma BDNF Is Reduced among Middle-Aged and Elderly Women with Impaired Insulin Function: Evidence of a Compensatory Mechanism

    ERIC Educational Resources Information Center

    Arentoft, Alyssa; Sweat, Victoria; Starr, Vanessa; Oliver, Stephen; Hassenstab, Jason; Bruehl, Hannah; Tirsi, Aziz; Javier, Elizabeth; McHugh, Pauline F.; Convit, Antonio

    2009-01-01

    Brain-derived neurotrophic factor (BDNF) plays a regulatory role in neuronal differentiation and synaptic plasticity and has been linked to glucose regulation and cognition. Associations among plasma BDNF, cognition, and insulin function were explored. Forty-one participants with impaired insulin function (IIF), ranging from insulin resistance to…

  20. The Need for a Uniform Method of Recording and Reporting Functional Vision Assessments

    ERIC Educational Resources Information Center

    Shaw, Rona; Russotti, Joanne; Strauss-Schwartz, Judy; Vail, Helen; Kahn, Ronda

    2009-01-01

    The use of functional vision by school-age students who have visual impairments, including those with additional disabilities, is typically reported by teachers of students with visual impairments. Functional vision assessments determine how well a student uses his or her vision to perform tasks throughout the school day. The information that is…

  1. Atypical Lexical/Semantic Processing in High-Functioning Autism Spectrum Disorders without Early Language Delay

    ERIC Educational Resources Information Center

    Kamio, Yoko; Robins, Diana; Kelley, Elizabeth; Swainson, Brook; Fein, Deborah

    2007-01-01

    Although autism is associated with impaired language functions, the nature of semantic processing in high-functioning pervasive developmental disorders (HFPDD) without a history of early language delay has been debated. In this study, we aimed to examine whether the automatic lexical/semantic aspect of language is impaired or intact in these…

  2. Assistive Devices for Children with Functional Impairments: Impact on Child and Caregiver Function

    ERIC Educational Resources Information Center

    Henderson, Stacey; Skelton, Heather; Rosenbaum, Peter

    2008-01-01

    Functional impairments can limit a child's ability to participate in the experiences of childhood. This "deprivation" can, in turn, have a negative effect on such children's development, academic performance, and quality of life, as well as on the lives of their caregivers and families. Many adults use assistive devices to overcome functional…

  3. An Evidence Based Review of Acute and Long-Term Effects of Cannabis Use on Executive Cognitive Functions

    PubMed Central

    Crean, Rebecca D.; Crane, Natania A.; Mason, Barbara J.

    2011-01-01

    Cannabis use has been shown to impair cognitive functions on a number of levels—from basic motor coordination to more complex executive function tasks, such as the ability to plan, organize, solve problems, make decisions, remember, and control emotions and behavior. These deficits differ in severity depending on the quantity, recency, age of onset and duration of marijuana use. Understanding how cannabis use impairs executive function is important. Individuals with cannabis-related impairment in executive functions have been found to have trouble learning and applying the skills required for successful recovery, putting them at increased risk for relapse to cannabis use. Here we review the research on the acute, residual, and long-term effects of cannabis use on executive functions, and discuss the implications for treatment. PMID:21321675

  4. Attention and executive functions in the early course of pediatric epilepsy.

    PubMed

    Reuner, Gitta; Kadish, Navah Esther; Doering, Jan Henje; Balke, Doreen; Schubert-Bast, Susanne

    2016-07-01

    Our prospective study aimed at exploring attention and executive functions in children with new-onset epilepsy prior to and during the early course of antiepileptic treatment. Sociodemographic and epilepsy-related factors were analyzed as potential predictors both of impaired cognitive functions as well as for changes in cognitive functioning in the early course of illness. From a total group of 115 children aged six to 17years without major disabilities, 76 children were assessed longitudinally with a screening tool for attention and executive functions (EpiTrack Junior®). Sociodemographic variables (gender, age at epilepsy onset, need of special education) and epilepsy-related variables (etiology of epilepsy, semiology of seizures, number of seizures) were considered as potential predictors for impaired functions prior to treatment and for deterioration/amelioration in cognitive functions in the early course. Attention and executive functions of children with new-onset epilepsy were significantly more often impaired when compared with a healthy population, but less often when compared with children with chronic epilepsy. The majority of children showed stable cognitive functioning in the early course of treatment. The risk of impaired cognitive functions was significantly heightened when etiology of epilepsy was unknown or not classifiable. The chance for improvement of functioning was lowered by having a genetic epilepsy, or an unknown semiology of seizures. Children with new-onset epilepsy are at high risk for impaired attention and executive functions even prior to antiepileptic treatment, especially when etiology of their epilepsy remains unclear. The high stability of cognitive functioning in the early course can be used in counseling of families who worry about negative side effects of drug treatment. Finally, a systematic assessment of cognitive functions in children with new-onset epilepsy is necessary to detect subtle deficits in the early course and adjust treatment accordingly. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Are disease severity, sleep-related problems, and anxiety associated with work functioning in patients with obstructive sleep apnoea?

    PubMed

    Timkova, Vladimira; Nagyova, Iveta; Reijneveld, Sijmen A; Tkacova, Ruzena; van Dijk, Jitse P; Bültmann, Ute

    2018-04-17

    To examine whether Obstructive Sleep Apnoea severity, sleep-related problems, and anxiety are associated with work functioning in Obstructive Sleep Apnoea patients, when controlled for age, gender and type of occupation. To investigate whether anxiety moderates the associations between sleep-related problems and work functioning. We included 105 Obstructive Sleep Apnoea patients (70% male; mean age 46.62 ± 9.79 years). All patients completed the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, the Beck Anxiety Inventory, and the Work Role Functioning Questionnaire-2.0. Obstructive Sleep Apnoea-severity, poor nighttime sleep quality, and anxiety were univariately associated with impaired work functioning. Multivariate analyzes revealed that poor perceived sleep quality was more strongly associated with work functioning than sleep efficiency and daily disturbances. Anxiety was strongly associated with impaired work functioning. After adding anxiety, the explained variance in work functioning increased from 20% to 25%. Anxiety moderated the association between low and medium levels of nighttime sleep quality problems and work functioning. Poor perceived sleep quality and anxiety were strongly associated with impaired work functioning in Obstructive Sleep Apnoea patients. These findings may help to optimize management, standard treatment, and work functioning in people with Obstructive Sleep Apnoea when confirmed in longitudinal studies. Implications for Rehabilitation Studies show an impairment of functional status, including work functioning, in obstructive sleep apnea patients. Aside from physical disorders, obstructive sleep apnea patients often experience mental problems, such as anxiety. As many people with obstructive sleep apnea are undiagnosed, our results demonstrate to employers and healthcare professionals the need to encourage patients for obstructive sleep apnea screening, especially in the situation of impaired work functioning, increased anxiety, and poor sleep quality. The associations between obstructive sleep apnea, sleep and anxiety might increase the awareness of health professionals towards optimizing diagnostic accuracy and standard treatment.

  6. A possible contributory mechanism for impaired idiom perception in schizophrenia.

    PubMed

    Sela, Tal; Lavidor, Michal; Mitchell, Rachel L C

    2015-09-30

    In this review, we focus on the ability of people with schizophrenia to correctly perceive the meaning of idioms; figurative language expressions in which intended meaning is not derived from the meaning of constituent words. We collate evidence on how idiom perception is impaired, ascertain the clinical relevance of this impairment, and consider possible psychological and neural mechanisms behind the impairment. In reviewing extant literature, we searched the PubMed database, from 1975-2014, focussing on articles that directly concerned schizophrenia and idioms, with follow up searches to explore the viability of possible underlying mechanisms. We learn that there is clear evidence of impairment, with a tendency to err towards literal interpretations unless the figurative meaning is salient, and despite contextual cues to figurative interpretations. Given the importance of idioms in everyday language, the potential impact is significant. Clinically, impaired idiom perception primarily relates to positive symptoms of schizophrenia, but also to negative symptoms. The origins of the impairment remain speculation, with impaired executive function, impaired semantic functions, and impaired context processing all proposed to explain the phenomenon. We conclude that a possible contributory mechanism at the neural level is an impaired dorsolateral prefrontal cortex system for cognitive control over semantic processing. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Association of cognitive impairment with smoking, alcohol consumption, tea consumption, and exercise among Chinese nonagenarians/centenarians.

    PubMed

    Huang, Chang-Quan; Dong, Bi-Rong; Zhang, Yan-Ling; Wu, Hong-Mei; Liu, Qing-Xiu

    2009-09-01

    In the present study, we observed the association of cognitive impairment with current/former habits of smoking, alcohol consumption, tea consumption, and exercise among very old people using a Chinese cohort aged 90 to 108 years. A cross-sectional study. The sample included 681 unrelated Chinese nonagenarians/centenarians (67.25% women). In men, compared with subjects without cognitive impairment, those with cognitive impairment had significantly higher prevalence of habits of smoking (P=0.048 and 0.004, for former/current, respectively) and alcohol consumption (P=0.003 and 0.049, for former/current, respectively) but had significantly lower prevalence of habits of tea consumption (P=0.041 and 0.044, for former/current, respectively) and current exercise (P=0.020). Subjects with habits of smoking had significantly lower cognitive function scores than those without these habits (mean difference=1.78 and 1.69, P=0.029 and 0.035, for former/current, respectively), but subjects with habit of current exercise had significantly higher cognitive function scores than those without this habit (mean difference=1.53, P=0.038). However, in women, there were no significant differences in prevalence of these habits between subjects with and without cognitive impairment and also no significant differences in cognitive function scores between subjects with and without these habits. Only current smoking habits in men had a significant odds ratio for cognitive impairment (odds ratio, 2.125; 95% confidence interval, 1.186-3.998). Among nonagenarians/centenarians, in men, there are associations of cognitive impairment with habits of former/current smoking and current exercise, as well as indefinite associations with habits of alcohol and tea consumption. Smoking may have a significant negative impact on cognitive function, but current exercise significantly improve cognitive function. However, in women, there are no associations of cognitive impairment with all the habits.

  8. Aspects of renal function in patients with colorectal cancer in a gastroenterology clinic of a county hospital in Western Romania.

    PubMed

    Velciov, Silvia; Hoinoiu, B; Hoinoiu, Teodora; Popescu, Alina; Gluhovschi, Cristina; Grădinaru, Oana; Popescu, Mădalină; Moţiu, Flavia; Timar, R; Gluhovschi, G H; Sporea, I

    2013-01-01

    Colorectal cancer represents the third cause of cancer. Since its detection in due time is important resolution, appropriate monitoring is mandatory. The present study deals with the relationship between colorectal cancer and renal function, as well as other associated risk factors. Chronic kidney disease (CKD) represents a risk factor of cancer, both in non-dialysed patients and especially in dialysed patients and in patients with renal transplant. It can get aggravated with cancer in general and particularly with colorectal cancer, partly related to the toxins that cannot be appropriately eliminated because of renal functional disturbances. At the same time, immunosuppressive therapy used for treating glomerular or secondary nephropathies represents an important risk factor of cancer. Some patients with colorectal cancer were found to present also impaired renal function, a fact whose significance is still little known. The object of the present paper is an analysis of the case records of a clinic of gastroenterology on the relationship between colorectal cancer and renal functional impairment. We found in the patients with colorectal cancer under study a glomerular filtration rate (GFR calculated with the EPI formula) of < 60 ml/min/1.73m2 in 31/180 patients, respectively 17.22% of the cases, a value that is similar to that in specialised literature. We also analysed associated risk factors that could be related to renal function impairment in these patients: age, gender, anaemia, diabetes mellitus and hypertension. These could represent, together with the colorectal cancer of the investigated patients, risk factors affecting on the one hand renal function, and on the other hand, potentially increasing the risk of cancer. Correction of these risk factors would have beneficial effects on patients. The relationship between renal functional impairment, respectively CKD, and colorectal cancer is to be regarded from the point of view of complex reciprocity: the impairment of the renal function is a factor of risk of colorectal cancer and colorectal cancer can influence renal function of these patients. This report of reciprocity based on important pathogenic mechanisms also interrelates with factors of risk consecutive to both renal function impairment and colorectal cancer.

  9. [Impact of frailty over the functional state of hospitalized elderly].

    PubMed

    García-Cruz, Juan Carlos; García-Peña, Carmen

    2016-01-01

    Frailty in elderly results from impaired physiological reserve in multiple systems. Establishing if frail elderly inpatients develop more functional impairment at discharge, will allow the development of strategies for preventing or limiting the deterioration in this vulnerable group. Prospective cohort in 133 elderly inpatients. At admission, frailty, functional status, comorbidity and comprehensive geriatric evaluation were determined. The main outcome was functional state at hospital discharge. 64 patients presented frailty (48.1%) and 69 did not present that state (51.9%), with a mean age of 73 and 68 years, respectively. Mean decrement in functional state at discharge was -8.06 % (IC 95 % -10.38 to -5.74), from 97.97 % to 89.91 % (p < 0.001) in patients who did not present frailty, and -21.18 % (IC 95 % -24.97 to -17.38), from 87.52 % to 66.34 % (p < 0.001) in frail patients. The difference between groups at discharge was -14.37 % (IC 95 % -16.80 to -11.94, p < 0.001) to the detriment of the frail. Frailty was associated with functional impairment in the univariated and multivariated analysis, beta -13.11 % (IC 95 % -17.45 to -8.78, p < 0.001) and beta -17.27 (IC 95 % -23.27 to -11.28, p < 0.001), respectively. In the final model, frailty (beta -14.73, IC 95 % -19.39 to -10.07, p < 0.001) and cognitive impairment (beta -8.19, IC 95 % -15.28 to -1.10, p = 0.024) predict functional decrement. Frailty independently predicts functional impairment at hospital discharge.

  10. Social learning pathways in the relation between parental chronic pain and daily pain severity and functional impairment in adolescents with functional abdominal pain.

    PubMed

    Stone, Amanda L; Bruehl, Stephen; Smith, Craig A; Garber, Judy; Walker, Lynn S

    2017-10-06

    Having a parent with chronic pain (CP) may confer greater risk for persistence of CP from childhood into young adulthood. Social learning, such as parental modeling and reinforcement, represents one plausible mechanism for the transmission of risk for CP from parents to offspring. Based on a 7-day pain diary in 154 pediatric patients with functional abdominal CP, we tested a model in which parental CP predicted adolescents' daily average CP severity and functional impairment (distal outcomes) via parental modeling of pain behaviors and parental reinforcement of adolescent's pain behaviors (mediators) and adolescents' cognitive appraisals of pain threat (proximal outcome representing adolescents' encoding of parents' behaviors). Results indicated significant indirect pathways from parental CP status to adolescent average daily pain severity (b = 0.18, SE = 0.08, 95% CI: 0.04, 0.31, p = 0.03) and functional impairment (b = 0.08, SE = 0.04, 95% CI: 0.02, 0.15, p = 0.03) over the 7-day diary period via adolescents' observations of parent pain behaviors and adolescent pain threat appraisal. The indirect pathway through parental reinforcing responses to adolescents' pain did not reach significance for either adolescent pain severity or functional impairment. Identifying mechanisms of increased risk for pain and functional impairment in children of parents with CP ultimately could lead to targeted interventions aimed at improving functioning and quality of life in families with chronic pain. Parental modeling of pain behaviors represents a potentially promising target for family based interventions to ameliorate pediatric chronic pain.

  11. Abnormal lung function in adults with congenital heart disease: prevalence, relation to cardiac anatomy, and association with survival.

    PubMed

    Alonso-Gonzalez, Rafael; Borgia, Francesco; Diller, Gerhard-Paul; Inuzuka, Ryo; Kempny, Aleksander; Martinez-Naharro, Ana; Tutarel, Oktay; Marino, Philip; Wustmann, Kerstin; Charalambides, Menelaos; Silva, Margarida; Swan, Lorna; Dimopoulos, Konstantinos; Gatzoulis, Michael A

    2013-02-26

    Restrictive lung defects are associated with higher mortality in patients with acquired chronic heart failure. We investigated the prevalence of abnormal lung function, its relation to severity of underlying cardiac defect, its surgical history, and its impact on outcome across the spectrum of adult congenital heart disease. A total of 1188 patients with adult congenital heart disease (age, 33.1±13.1 years) undergoing lung function testing between 2000 and 2009 were included. Patients were classified according to the severity of lung dysfunction based on predicted values of forced vital capacity. Lung function was normal in 53% of patients with adult congenital heart disease, mildly impaired in 17%, and moderately to severely impaired in the remainder (30%). Moderate to severe impairment of lung function related to complexity of underlying cardiac defect, enlarged cardiothoracic ratio, previous thoracotomy/ies, body mass index, scoliosis, and diaphragm palsy. Over a median follow-up period of 6.7 years, 106 patients died. Moderate to severe impairment of lung function was an independent predictor of survival in this cohort. Patients with reduced force vital capacity of at least moderate severity had a 1.6-fold increased risk of death compared with patients with normal lung function (P=0.04). A reduced forced vital capacity is prevalent in patients with adult congenital heart disease; its severity relates to the complexity of the underlying heart defect, surgical history, and scoliosis. Moderate to severe impairment of lung function is an independent predictor of mortality in contemporary patients with adult congenital heart disease.

  12. Seizure Control and Memory Impairment Are Related to Disrupted Brain Functional Integration in Temporal Lobe Epilepsy.

    PubMed

    Park, Chang-Hyun; Choi, Yun Seo; Jung, A-Reum; Chung, Hwa-Kyoung; Kim, Hyeon Jin; Yoo, Jeong Hyun; Lee, Hyang Woon

    2017-01-01

    Brain functional integration can be disrupted in patients with temporal lobe epilepsy (TLE), but the clinical relevance of this disruption is not completely understood. The authors hypothesized that disrupted functional integration over brain regions remote from, as well as adjacent to, the seizure focus could be related to clinical severity in terms of seizure control and memory impairment. Using resting-state functional MRI data acquired from 48 TLE patients and 45 healthy controls, the authors mapped functional brain networks and assessed changes in a network parameter of brain functional integration, efficiency, to examine the distribution of disrupted functional integration within and between brain regions. The authors assessed whether the extent of altered efficiency was influenced by seizure control status and whether the degree of altered efficiency was associated with the severity of memory impairment. Alterations in the efficiency were observed primarily near the subcortical region ipsilateral to the seizure focus in TLE patients. The extent of regional involvement was greater in patients with poor seizure control: it reached the frontal, temporal, occipital, and insular cortices in TLE patients with poor seizure control, whereas it was limited to the limbic and parietal cortices in TLE patients with good seizure control. Furthermore, TLE patients with poor seizure control experienced more severe memory impairment, and this was associated with lower efficiency in the brain regions with altered efficiency. These findings indicate that the distribution of disrupted brain functional integration is clinically relevant, as it is associated with seizure control status and comorbid memory impairment.

  13. Combining afferent stimulation and mirror therapy for rehabilitating motor function, motor control, ambulation, and daily functions after stroke.

    PubMed

    Lin, Keh-chung; Huang, Pai-chuan; Chen, Yu-ting; Wu, Ching-yi; Huang, Wen-ling

    2014-02-01

    Mirror therapy (MT) and mesh glove (MG) afferent stimulation may be effective in reducing motor impairment after stroke. A hybrid intervention of MT combined with MG (MT + MG) may broaden aspects of treatment benefits. To demonstrate the comparative effects of MG + MT, MT, and a control treatment (CT) on the outcomes of motor impairments, manual dexterity, ambulation function, motor control, and daily function. Forty-three chronic stroke patients with mild to moderate upper extremity impairment were randomly assigned to receive MT + MG, MT, or CT for 1.5 hours/day, 5 days/week for 4 weeks. Outcome measures were the Fugl-Meyer Assessment (FMA) and muscle tone measured by Myoton-3 for motor impairment and the Box and Block Test (BBT) and 10-Meter Walk Test (10 MWT) for motor function. Secondary outcomes included kinematic parameters for motor control and the Motor Activity Log and ABILHAND Questionnaire for daily function. FMA total scores were significantly higher and synergistic shoulder abduction during reach was less in the MT + MG and MT groups compared with the CT group. Performance on the BBT and the 10 MWT (velocity and stride length in self-paced task and velocity in as-quickly-as-possible task) were improved after MT + MG compared with MT. MT + MG improved manual dexterity and ambulation. MT + MG and MT reduced motor impairment and synergistic shoulder abduction more than CT. Future studies may integrate functional task practice into treatments to enhance functional outcomes in patients with various levels of motor severity. The long-term effects of MG + MT remain to be evaluated.

  14. Longitudinal associations between physical and cognitive performance among community-dwelling older adults.

    PubMed

    Tolea, Magdalena I; Morris, John C; Galvin, James E

    2015-01-01

    To assess the directionality of the association between physical and cognitive decline in later life, we compared patterns of decline in performance across groups defined by baseline presence of cognitive and/or physical impairment [none (n = 217); physical only (n = 169); cognitive only (n = 158), or both (n = 220)] in a large sample of participants in a cognitive aging study at the Knight Alzheimer's Disease Research Center at Washington University in St. Louis who were followed for up to 8 years (3,079 observations). Rates of decline reached 20% for physical performance and varied across cognitive tests (global, memory, speed, executive function, and visuospatial skills). We found that physical decline was better predicted by baseline cognitive impairment (slope = -1.22, p<0.001), with baseline physical impairment not contributing to further decline in physical performance (slope = -0.25, p = 0.294). In turn, baseline physical impairment was only marginally associated with rate of cognitive decline across various cognitive domains. The cognitive-functional association is likely to operate in the direction of cognitive impairment to physical decline although physical impairment may also play a role in cognitive decline/dementia. Interventions to prevent further functional decline and development of disability and complete dependence may benefit if targeted to individuals with cognitive impairment who are at increased risk.

  15. Emotional and cognitive social processes are impaired in Parkinson's disease and are related to behavioral disorders.

    PubMed

    Narme, Pauline; Mouras, Harold; Roussel, Martine; Duru, Cécile; Krystkowiak, Pierre; Godefroy, Olivier

    2013-03-01

    Parkinson's disease (PD) is associated with behavioral disorders that can affect social functioning but are poorly understood. Since emotional and cognitive social processes are known to be crucial in social relationships, impairment of these processes may account for the emergence of behavioral disorders. We used a systematic battery of tests to assess emotional processes and social cognition in PD patients and relate our findings to conventional neuropsychological data (especially behavioral disorders). Twenty-three PD patients and 46 controls (matched for age and educational level) were included in the study and underwent neuropsychological testing, including an assessment of the behavioral and cognitive components of executive function. Emotional and cognitive social processes were assessed with the Interpersonal Reactivity Index caregiver-administered questionnaire (as a measure of empathy), a facial emotion recognition task and two theory of mind (ToM) tasks. When compared with controls, PD patients showed low levels of empathy (p = .006), impaired facial emotion recognition (which persisted after correction for perceptual abilities) (p = .001), poor performance in a second-order ToM task (p = .008) that assessed both cognitive (p = .004) and affective (p = .03) inferences and, lastly, frequent dysexecutive behavioral disorders (in over 40% of the patients). Overall, impaired emotional and cognitive social functioning was observed in 17% of patients and was related to certain cognitive dysexecutive disorders. In terms of behavioral dysexecutive disorders, social behavior disorders were related to impaired emotional and cognitive social functioning (p = .04) but were independent of cognitive impairments. Emotional and cognitive social processes were found to be impaired in Parkinson's disease. This impairment may account for the emergence of social behavioral disorders. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  16. The Adult Respiratory Distress Syndrome Cognitive Outcomes Study

    PubMed Central

    Christie, Jason D.; Lanken, Paul N.; Biester, Rosette C.; Thompson, B. Taylor; Bellamy, Scarlett L.; Localio, A. Russell; Demissie, Ejigayehu; Hopkins, Ramona O.; Angus, Derek C.

    2012-01-01

    Rationale: Cognitive and psychiatric morbidity is common and potentially modifiable after acute lung injury (ALI). However, practical measures of neuropsychological function for use in multicenter trials are lacking. Objectives: To determine whether a validated telephone-based neuropsychological test battery is feasible in a multicenter trial. To determine the frequency and risk factors for long-term neuropsychological impairment. Methods: As an adjunct study to the Acute Respiratory Distress Syndrome Clinical Trials Network Fluid and Catheter Treatment Trial, we assessed neuropsychological function at 2 and 12 months post–hospital discharge. Measurements and Main Results: Of 406 eligible survivors, we approached 261 to participate and 213 consented. We tested 122 subjects at least once, including 102 subjects at 12 months. Memory, verbal fluency, and executive function were impaired in 13% (12 of 92), 16% (15 of 96), and 49% (37 of 76) of long-term survivors. Long-term cognitive impairment was present in 41 of the 75 (55%) survivors who completed cognitive testing. Depression, post-traumatic stress disorder, or anxiety was present in 36% (37 of 102), 39% (40 of 102), and 62% (63 of 102) of long-term survivors. Enrollment in a conservative fluid-management strategy (P = 0.005) was associated with cognitive impairment and lower partial pressure of arterial oxygen during the trial was associated with cognitive (P = 0.02) and psychiatric impairment (P = 0.02). Conclusions: Neuropsychological function can be assessed by telephone in a multicenter trial. Long-term neuropsychological impairment is common in survivors of ALI. Hypoxemia is a risk factor for long-term neuropsychological impairment. Fluid management strategy is a potential risk factor for long-term cognitive impairment; however, given the select population studied and an unclear mechanism, this finding requires confirmation. PMID:22492988

  17. The influence of multiple sensory impairments on functional balance and difficulty with falls among U.S. adults.

    PubMed

    Wilson, Samuel J; Garner, John C; Loprinzi, Paul D

    2016-06-01

    Studies have looked at the individual associations of sensory impairment on balance, but no population-based studies have examined their combined association on balance and difficulty with falls. Thus, the purpose of this study was to examine both the independent associations and combined associations of visual impairment, peripheral neuropathy, and self-reported hearing loss with the odds of reporting difficulty with falls and functional balance. Data from the 2003-2004 National Health and Nutrition Examination Survey were used. Vision and peripheral neuropathy were objectively measured, and hearing was self-reported. Balance testing consisted of a modified Romberg test. After exclusions, 1662 (40-85years of age) participants provided complete data on the study variables. Sensory impairment was associated with perceived difficulty of falls and functional balance. Participants who presented a single sensory impairment had 29% reduced odds of having functional balance (95% CI=0.54-0.93, p=0.01) and increased odds of reporting difficulty with falls by 61% (95% CI=0.99-2.60, p=0.05). Moreover, our multisensory models showed some evidence of a dose-response relationship, in that sensory impairment of multiple sensory systems was associated with worse balance (OR =0.59, CI=0.35-1.00, p=0.05) and perceived difficulty of falls (OR =5.02, 95% CI=1.99-12.66, p=0.002) when compared to those with less sensory impairment. Multiple sensory impairment is associated with significantly higher odds of both reporting difficulty with falls and balance dysfunction, which may lead to a subsequent fall, ultimately compromising the individual's health. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Loss of Mitochondrial Function Impairs Lysosomes.

    PubMed

    Demers-Lamarche, Julie; Guillebaud, Gérald; Tlili, Mouna; Todkar, Kiran; Bélanger, Noémie; Grondin, Martine; Nguyen, Angela P; Michel, Jennifer; Germain, Marc

    2016-05-06

    Alterations in mitochondrial function, as observed in neurodegenerative diseases, lead to disrupted energy metabolism and production of damaging reactive oxygen species. Here, we demonstrate that mitochondrial dysfunction also disrupts the structure and function of lysosomes, the main degradation and recycling organelle. Specifically, inhibition of mitochondrial function, following deletion of the mitochondrial protein AIF, OPA1, or PINK1, as well as chemical inhibition of the electron transport chain, impaired lysosomal activity and caused the appearance of large lysosomal vacuoles. Importantly, our results show that lysosomal impairment is dependent on reactive oxygen species. Given that alterations in both mitochondrial function and lysosomal activity are key features of neurodegenerative diseases, this work provides important insights into the etiology of neurodegenerative diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Are Non-intellectually Disabled Black Youth with ASD Less Impaired on Parent Report than Their White Peers?

    PubMed Central

    Anthony, Bruno J.; Kenworthy, Lauren; Armour, Anna Chelsea; Dudley, Katerina; Anthony, Laura Gutermuth

    2016-01-01

    There is a lack of research examining differences in functioning in autism spectrum disorder (ASD) across ethnicity, particularly among those without intellectual disability (ID). This study investigated ethnic differences in parent-reported impairment in executive function, adaptive behavior, and social–emotional functioning. White and Black youth (n = 64; ages 6–17) with ASD without ID were compared on each of these domains. Black youth had significantly lower levels of impairment on all three domains. Findings may reflect better daily functioning among Black youth with ASD and/or cultural differences in parent response to questionnaires. Regardless, these findings raise concern about the sensitivity of commonly used measures for Black children with ASD and the impact of culture on daily functioning and symptom manifestation. PMID:26439481

  20. Are Non-intellectually Disabled Black Youth with ASD Less Impaired on Parent Report than Their White Peers?

    PubMed

    Ratto, Allison B; Anthony, Bruno J; Kenworthy, Lauren; Armour, Anna Chelsea; Dudley, Katerina; Anthony, Laura Gutermuth

    2016-03-01

    There is a lack of research examining differences in functioning in autism spectrum disorder (ASD) across ethnicity, particularly among those without intellectual disability (ID). This study investigated ethnic differences in parent-reported impairment in executive function, adaptive behavior, and social-emotional functioning. White and Black youth (n = 64; ages 6-17) with ASD without ID were compared on each of these domains. Black youth had significantly lower levels of impairment on all three domains. Findings may reflect better daily functioning among Black youth with ASD and/or cultural differences in parent response to questionnaires. Regardless, these findings raise concern about the sensitivity of commonly used measures for Black children with ASD and the impact of culture on daily functioning and symptom manifestation.

  1. Functional impairment in elderly patients with mild cognitive impairment and mild Alzheimer's disease

    PubMed Central

    Brown, Patrick J.; Devanand, D.P.; Liu, Xinhua; Caccappolo, Elise

    2013-01-01

    CONTEXT The original mild cognitive impairment (MCI) criteria exclude substantial functional deficits, but recent reports suggest otherwise. Identifying the extent, severity, type, and correlates of functional deficits that occur in MCI and mild Alzheimer’s disease (AD) can aid in early detection of incipient dementia and identify potential mechanistic pathways to disrupted instrumental activities of daily living (IADLs). OBJECTIVES To examine the number, type, and severity of functional impairments and identify the clinical characteristics associated with functional impairment across individuals with amnestic MCI (aMCI) and those with mild AD. DESIGN The study uses baseline data from the Alzheimer’s Disease Neuroimaging Initiative. SETTING Data from the Alzheimer’s Disease Neuroimaging Initiative was collected at multiple research sites in the US and Canada. PATIENTS The samples included 229 controls, 394 aMCI, and 193 AD patients. MAIN OUTCOME MEASURE The 10-item Pfeffer Functional Activities Questionnaire (FAQ) assessed function. RESULTS Informant-reported FAQ deficits were common in patients with aMCI (72.3%) and AD (97.4%) but were rarely self-reported by controls (7.9%). The average severity per FAQ deficit did not differ between patients with aMCI and controls; both were less impaired than patients with AD (P < .001). Two FAQ items (remembering appointments, family occasions, holidays, and medications; assembling tax records, business affairs, or other papers) were specific (0.95) in differentiating controls from the combined aMCI and AD groups (only 34.0% of patients with aMCI and 3.6% of patients with AD had no difficulty with these 2 items). The severity of FAQ deficits in the combined aMCI and AD group was associated with worse Trailmaking Test A scores and smaller hippocampal volumes (P < .001). Within the aMCI group, functionally intact individuals had greater hippocampal volumes and better Auditory Verbal Learning Test 30-minute delay and Trailmaking Test A (P < .001) scores compared with those with moderate or severe FAQ deficits. Patients with a high number of deficits were more likely to express the APOE ε4 allele (63.8%) compared with patients with no (46.8%) or few (48.4%) functional deficits. CONCLUSIONS Mild IADL deficits are common in individuals with aMCI and should be considered in MCI criteria. Two IADLs, remembering appointments, family occasions, holidays, and medications and assembling tax records, business affairs, or other papers, appear to be characteristic of clinically significant cognitive impairment. In patients with aMCI, impairment in memory and processing speed and greater medial temporal atrophy were associated with greater IADL deficits PMID:21646578

  2. Functional impairment in elderly patients with mild cognitive impairment and mild Alzheimer disease.

    PubMed

    Brown, Patrick J; Devanand, D P; Liu, Xinhua; Caccappolo, Elise

    2011-06-01

    The original mild cognitive impairment (MCI) criteria exclude substantial functional deficits, but recent reports suggest otherwise. Identifying the extent, severity, type, and correlates of functional deficits that occur in MCI and mild Alzheimer disease (AD) can aid in early detection of incipient dementia and can identify potential mechanistic pathways to disrupted instrumental activities of daily living (IADLs). To examine the number, type, and severity of functional impairments and to identify the clinical characteristics associated with functional impairment across patients with amnestic MCI (aMCI) and those with mild AD. Study using baseline data from the Alzheimer's Disease Neuroimaging Initiative. Multiple research sites in the United States and Canada. Patients Samples included 229 control individuals, 394 patients with aMCI, and 193 patients with AD. The 10-item Pfeffer Functional Activities Questionnaire (FAQ) assessed function. Informant-reported FAQ deficits were common in patients with aMCI (72.3%) and AD (97.4%) but were rarely self-reported by controls (7.9%). The average severity per FAQ deficit did not differ between patients with aMCI and controls; both were less impaired than patients with AD (P < .001). Two FAQ items (remembering appointments, family occasions, holidays, and medications and assembling tax records, business affairs, or other papers) were specific (specificity estimate, 0.95) in differentiating the control group from the combined aMCI and AD groups (only 34.0% of patients with aMCI and 3.6% of patients with AD had no difficulty with these 2 items). The severity of FAQ deficits in the combined aMCI and AD group was associated with worse Trail Making Test, part A scores and smaller hippocampal volumes (P < .001 for both). Within the aMCI group, functionally intact individuals had greater hippocampal volumes and better Auditory Verbal Learning Test 30-minute delay and Trail Making Test, part A (P < .001 for each) scores compared with individuals with moderate or severe FAQ deficits. Patients with a high number of deficits were more likely to express the apolipoprotein ε4 allele (63.8%) compared with patients with no (46.8%) or few (48.4%) functional deficits. Mild IADL deficits are common in individuals with aMCI and should be incorporated into MCI criteria. Two IADLs--remembering appointments, family occasions, holidays, and medications and assembling tax records, business affairs, or other papers--appear to be characteristic of clinically significant cognitive impairment. In patients with aMCI, impairment in memory and processing speed and greater medial temporal atrophy were associated with greater IADL deficits.

  3. Anticholinergic Burden and Functional Status in Older People with Cognitive Impairment: Results from the Regal Project.

    PubMed

    Boccardi, V; Baroni, M; Paolacci, L; Ercolani, S; Longo, A; Giordano, M; Ruggiero, C; Mecocci, P

    2017-01-01

    The use of drugs with intrinsic anticholinergic properties is widespread among old age persons. A growing body of evidences suggest that a high anticholinergic burden is associated with physical and cognitive impairment. However, the association between anticholinergic drug use and functional status is still poorly investigated, particularly among subjects with initial cognitive impairment. Cross-sectional study examining the association between drug-related anticholinergic burden and functional status in cognitively healthy (CH) (n=691), mild cognitive impairment (MCI) (n=541) or mild Alzheimer's diseases (AD) (n=1127) subjects. Data were gathered from the ReGAl project (Rete Geriatrica Alzheimer-Geriatric Network on Alzheimer's disease), a large longitudinal Italian multicentric clinical-based study, promoted by the Italian Society of Gerontology and Geriatrics (SIGG). 2359 outpatients, older than 65 years, admitted to memory clinics. The total sample size, estimated according to a global effect size of 25% with type I error of 0.05 and a power of 95% is 2010 subjects. Functional status was evaluated by the Katz Index of Independence in Activities of Daily Living (ADL) and the Lawton-Brody Instrumental Activities of Daily Living (IADL) scales. The drug-related anticholinergic burden was estimated by the Anticholinergic Risk Scale (ARS). The 15.9 % (n=375) of total population used at least one drug with anticholinergic properties. Such a drug use was associated with partially dependence in ADL (OR:1.42, CI95%: 1.10-1.83; p=0.006), independently of gender, number of drugs, comorbidity index, presence of clinically relevant neuropsychiatric symptoms and adjusted MMSE. Anticholinergic drug use was associated with un-ability at each IADL task only in male MCI subjects, with significant impairment in shopping (p=0.011), and drug management (p=0.05). The use of medications with anticholinergic properties is common among older persons cognitively health as well as with cognitive impairment. Our results suggest that the use of anticholinergic drugs is associated with functional impairment, especially in old age subjects with initial cognitive impairment. Minimizing anticholinergic burden should result in maintaining daily functioning, especially in a vulnerable population, such as MCI and mild AD.

  4. Prospective, longitudinal assessment of quality of life in children from diagnosis to 3 months off treatment for standard risk acute lymphoblastic leukemia: Results of Children's Oncology Group study AALL0331.

    PubMed

    Mitchell, Hannah-Rose; Lu, Xiaomin; Myers, Regina M; Sung, Lillian; Balsamo, Lyn M; Carroll, William L; Raetz, Elizabeth; Loh, Mignon L; Mattano, Leonard A; Winick, Naomi J; Devidas, Meenakshi; Hunger, Stephen P; Maloney, Kelly; Kadan-Lottick, Nina S

    2016-01-15

    Standard risk acute lymphoblastic leukemia (SR-ALL) has high cure rates, but requires 2-3 years of therapy. We aimed to (i) prospectively evaluate health-related quality of life (HRQOL) during and after SR-ALL therapy, and (ii) identify associated predictors. Parents of 160 SR-ALL patients enrolled on Children's Oncology Group (COG) therapeutic trial AALL0331 at 31 sites completed the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales (physical, emotional and social functioning) and Family Assessment Device-General Functioning (FAD-GF) at 1, 6 and 12 months after diagnosis, and 3 months post-therapy. Mean PedsQL scores in physical, emotional and social functioning were impaired 1 month after diagnosis but steadily improved. Three months post-therapy, impaired physical and social functioning was observed in 27.8 and 25.8% of patients, respectively. In repeated-measures analysis, problematic family functioning predicted emotional (OR = 1.85, 95% CI 1.03-3.34) and social (OR = 1.99, 95% CI 1.21-3.27) impairment. Larger household size was associated with social impairment (OR = 1.21, 95% CI 1.02-1.45). Adverse neurological event(s) during therapy predicted post-therapy physical (OR = 5.17, 95% CI 1.61-16.63) and social (OR = 8.17, 95% CI 1.19-56.16) impairment. HRQOL 1 month after diagnosis was not predictive of HRQOL 3 months after therapy completion. In conclusion, children with SR-ALL experience considerable impairment in HRQOL at the end of induction, but rapidly improve. However, many still experience physical and social impairment 3 months post-therapy, suggesting a role for continued family and physical functioning support. Longer follow-up is needed to determine if post-therapy deficits change over time. © 2015 UICC.

  5. The neural basis of impaired self-awareness after traumatic brain injury

    PubMed Central

    Ham, Timothy E.; Bonnelle, Valerie; Hellyer, Peter; Jilka, Sagar; Robertson, Ian H.; Leech, Robert

    2014-01-01

    Self-awareness is commonly impaired after traumatic brain injury. This is an important clinical issue as awareness affects long-term outcome and limits attempts at rehabilitation. It can be investigated by studying how patients respond to their errors and monitor their performance on tasks. As awareness is thought to be an emergent property of network activity, we tested the hypothesis that impaired self-awareness is associated with abnormal brain network function. We investigated a group of subjects with traumatic brain injury (n = 63) split into low and high performance-monitoring groups based on their ability to recognize and correct their own errors. Brain network function was assessed using resting-state and event-related functional magnetic resonance imaging. This allowed us to investigate baseline network function, as well as the evoked response of networks to specific events including errors. The low performance-monitoring group underestimated their disability and showed broad attentional deficits. Neural activity within what has been termed the fronto-parietal control network was abnormal in patients with impaired self-awareness. The dorsal anterior cingulate cortex is a key part of this network that is involved in performance-monitoring. This region showed reduced functional connectivity to the rest of the fronto-parietal control network at ‘rest’. In addition, the anterior insulae, which are normally tightly linked to the dorsal anterior cingulate cortex, showed increased activity following errors in the impaired group. Interestingly, the traumatic brain injury patient group with normal performance-monitoring showed abnormally high activation of the right middle frontal gyrus, putamen and caudate in response to errors. The impairment of self-awareness was not explained either by the location of focal brain injury, or the amount of traumatic axonal injury as demonstrated by diffusion tensor imaging. The results suggest that impairments of self-awareness after traumatic brain injury result from breakdown of functional interactions between nodes within the fronto-parietal control network. PMID:24371217

  6. The neural basis of impaired self-awareness after traumatic brain injury.

    PubMed

    Ham, Timothy E; Bonnelle, Valerie; Hellyer, Peter; Jilka, Sagar; Robertson, Ian H; Leech, Robert; Sharp, David J

    2014-02-01

    Self-awareness is commonly impaired after traumatic brain injury. This is an important clinical issue as awareness affects long-term outcome and limits attempts at rehabilitation. It can be investigated by studying how patients respond to their errors and monitor their performance on tasks. As awareness is thought to be an emergent property of network activity, we tested the hypothesis that impaired self-awareness is associated with abnormal brain network function. We investigated a group of subjects with traumatic brain injury (n = 63) split into low and high performance-monitoring groups based on their ability to recognize and correct their own errors. Brain network function was assessed using resting-state and event-related functional magnetic resonance imaging. This allowed us to investigate baseline network function, as well as the evoked response of networks to specific events including errors. The low performance-monitoring group underestimated their disability and showed broad attentional deficits. Neural activity within what has been termed the fronto-parietal control network was abnormal in patients with impaired self-awareness. The dorsal anterior cingulate cortex is a key part of this network that is involved in performance-monitoring. This region showed reduced functional connectivity to the rest of the fronto-parietal control network at 'rest'. In addition, the anterior insulae, which are normally tightly linked to the dorsal anterior cingulate cortex, showed increased activity following errors in the impaired group. Interestingly, the traumatic brain injury patient group with normal performance-monitoring showed abnormally high activation of the right middle frontal gyrus, putamen and caudate in response to errors. The impairment of self-awareness was not explained either by the location of focal brain injury, or the amount of traumatic axonal injury as demonstrated by diffusion tensor imaging. The results suggest that impairments of self-awareness after traumatic brain injury result from breakdown of functional interactions between nodes within the fronto-parietal control network.

  7. Prevalence of mental health problems and functional impairment among active component and National Guard soldiers 3 and 12 months following combat in Iraq.

    PubMed

    Thomas, Jeffrey L; Wilk, Joshua E; Riviere, Lyndon A; McGurk, Dennis; Castro, Carl A; Hoge, Charles W

    2010-06-01

    A growing body of literature has demonstrated the association of combat in Iraq and Afghanistan with postdeployment mental health problems, particularly posttraumatic stress disorder (PTSD) and depression. However, studies have shown varying prevalence rates of these disorders based on different case definitions and have not assessed functional impairment, alcohol misuse, or aggressive behavior as comorbid factors occurring with PTSD and depression. To (1) examine the prevalence rates of depression and PTSD using several case definitions including functional impairment, (2) determine the comorbidity of alcohol misuse or aggressive behaviors with depression or PTSD, and (3) compare rates between Active Component and National Guard soldiers at the 3- and 12-month time points following their deployment to Iraq. Population-based, cross-sectional study. United States Army posts and National Guard armories. A total of 18 305 US Army soldiers from 4 Active Component and 2 National Guard infantry brigade combat teams. Between 2004 and 2007, anonymous mental health surveys were collected at 3 and 12 months following deployment. Current PTSD, depression, functional impairment, alcohol misuse, and aggressive behavior. Prevalence rates for PTSD or depression with serious functional impairment ranged between 8.5% and 14.0%, with some impairment between 23.2% and 31.1%. Alcohol misuse or aggressive behavior comorbidity was present in approximately half of the cases. Rates remained stable for the Active Component soldiers but increased across all case definitions from the 3- to 12-month time point for National Guard soldiers. The prevalence rates of PTSD and depression after returning from combat ranged from 9% to 31% depending on the level of functional impairment reported. The high comorbidity with alcohol misuse and aggression highlights the need for comprehensive postdeployment screening. Persistent or increased prevalence rates at 12 months compared with 3 months postdeployment illustrate the persistent effects of war zone service and provide important data to guide postdeployment care.

  8. Does age matter? Age and rehabilitation of visual field disorders after brain injury.

    PubMed

    Schuett, Susanne; Zihl, Josef

    2013-04-01

    Homonymous visual field disorders (HVFD) are frequent and disabling consequences of acquired brain injury, particularly in older age. Their rehabilitation is therefore of great importance. Compensatory oculomotor therapy has been found to be effective in improving the associated functional impairments in reading and visual exploration. But older age is commonly considered to adversely affect practice-dependent functional plasticity and, thus, functional and rehabilitation outcome after acquired brain injury. The effect of age in the compensatory treatment of HVFD, however, has never been investigated hitherto. It remains unknown whether age determines not only patients' functional impairments but also the rehabilitation outcome and the required amount of treatment. We therefore present the first study to determine the effect of age in 38 patients with HVFD receiving compensatory oculomotor treatment for their reading and visual exploration impairments. We investigated whether older patients with HVFD (1) show more pronounced impairments and less spontaneous adaptation, (2) show lesser compensatory treatment-related improvement in reading and visual exploration, and (3) require a higher amount of treatment than younger patients. Our main finding is that older patients achieve the same treatment-induced improvements in reading and visual exploration with the same amount of treatment as younger patients; severity of functional impairment also did not differ between older and younger patients, at least in reading. Age does not seem to be a critical factor determining the functional and rehabilitation outcome in the compensatory treatment of HVFD. Older age per se is not necessarily associated with a decline in practice-dependent functional plasticity and adaptation. To the contrary, the effectiveness of compensatory treatment to reduce the functional impairments to a similar extent in younger and older patients with HVFD adds to the growing evidence for a life-long potential for adaptation to the adverse effects of brain injury. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Pulmonary function and the risk of functional limitation in chronic obstructive pulmonary disease.

    PubMed

    Eisner, Mark D; Iribarren, Carlos; Yelin, Edward H; Sidney, Stephen; Katz, Patricia P; Ackerson, Lynn; Lathon, Phenius; Tolstykh, Irina; Omachi, Theodore; Byl, Nancy; Blanc, Paul D

    2008-05-01

    The authors' objective was to analyze the impact of respiratory impairment on the risk of physical functional limitations among adults with chronic obstructive pulmonary disease (COPD). They hypothesized that greater pulmonary function decrement would result in a broad array of physical functional limitations involving organ systems remote from the lung, a key step in the pathway leading to overall disability. The authors used baseline data from the Function, Living, Outcomes, and Work (FLOW) study, a prospective cohort study of adults with COPD recruited from northern California in 2005-2007. They studied the impact of pulmonary function impairment on the risk of functional limitations using validated measures: lower extremity function (Short Physical Performance Battery), submaximal exercise performance (6-Minute Walk Test), standing balance (Functional Reach Test), skeletal muscle strength (manual muscle testing with dynamometry), and self-reported functional limitation (standardized item battery). Multiple variable analysis was used to control for confounding by age, sex, race, height, educational attainment, and cigarette smoking. Greater pulmonary function impairment, as evidenced by lower forced expiratory volume in 1 second (FEV(1)), was associated with poorer Short Physical Performance Battery scores and less distance walked during the 6-Minute Walk Test. Lower forced expiratory volume in 1 second was also associated with weaker muscle strength and with a greater risk of self-reported functional limitation (p < 0.05). In conclusion, pulmonary function impairment is associated with multiple manifestations of physical functional limitation among COPD patients. Longitudinal follow-up can delineate the impact of these functional limitations on the prospective risk of disability, guiding preventive strategies that could attenuate the disablement process.

  10. Impaired limb reaction to displacement of center of gravity in rats with unilateral striatal ischemic injury.

    PubMed

    Nobile, Cameron W; Palmateer, Julie M; Kane, Jackie; Hurn, Patricia D; Schallert, Timothy; Adkins, DeAnna L

    2014-10-01

    Clinical stroke often results in impaired balance and increased vulnerability to severe injuries due to falling. To evaluate potential preclinical treatments that might target these deficits, it will be important to include tests capable of assessing these impairments chronically in animal models. Previously, we developed a postural instability test (PIT) that revealed chronic, unilateral impairments in postural stability in rat models of hemi-Parkinson's disease (PD) and of unilateral cervical spinal cord injury. Here, we investigated whether this test was also capable of revealing long-term stroke-induced impairments in postural support in rats. Additionally, we examined the ability of more common tests of sensorimotor function to detect chronic impairments. We found that the PIT detected chronic deficits in postural stability/balance enduring for up to 6 weeks post-stroke, outlasting impairments detected in other tests of forelimb sensorimotor function, including asymmetries in upright postural support (cylinder test) and vibrissae-evoked forelimb placing.

  11. Declarative and Procedural Memory in Danish Speaking Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Lum, Jarrad A. G.; Bleses, Dorthe

    2012-01-01

    It has been proposed that the language problems in specific language impairment (SLI) arise from basal ganglia abnormalities that lead to impairments with procedural and working memory but not declarative memory. In SLI, this profile of memory functioning has been hypothesized to underlie grammatical impairment but leave lexical knowledge…

  12. Theory of Mind Ability in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Gillott, A.; Furniss, F.; Walter, A.

    2004-01-01

    Whilst evidence of theory of mind impairments in children with autism is well established, possible impairments in children with language disorder have only recently been investigated. Children with specific language impairment aged between eight and 12 years were matched by age and gender to high functioning children with autism and normally…

  13. Stability of functional impairment in patients with schizotypal, borderline, avoidant, or obsessive–compulsive personality disorder over two years

    PubMed Central

    SKODOL, ANDREW E.; PAGANO, MARIA E.; BENDER, DONNA S.; SHEA, M. TRACIE; GUNDERSON, JOHN G.; YEN, SHIRLEY; STOUT, ROBERT L.; MOREY, LESLIE C.; SANISLOW, CHARLES A.; GRILO, CARLOS M.; ZANARINI, MARY C.; McGLASHAN, THOMAS H.

    2012-01-01

    Background A defining feature of personality disorder (PD) is an enduring pattern of inner experience and behavior that is stable over time. Follow-up and follow-along studies have shown considerable diagnostic instability of PDs, however, even over short intervals. What, then, about personality disorder is stable ? The purpose of this study was to determine the stability of impairment in psychosocial functioning in patients with four different PDs, in contrast to patients with major depressive disorder (MDD) and no PD, prospectively over a 2-year period. Method Six hundred treatment-seeking or treated patients were recruited primarily from clinical services in four metropolitan areas of the Northeastern USA. Patients were assigned to one of five diagnostic groups: schizotypal (STPD) (n=81), borderline (BPD) (n=155), avoidant (AVPD) (n=137), or obsessive–compulsive (OCPD) (n=142) personality disorders or MDD and no PD (n=85), based on the results of semi-structured interview assessments and self-report measures. Impairment in psychosocial functioning was measured using the Longitudinal Interval Follow-up Evaluation (LIFE) at baseline and at three follow-up assessments. Results Significant improvement in psychosocial functioning occurred in only three of seven domains of functioning and was largely the result of improvements in the MDD and no PD group. Patients with BPD or OCPD showed no improvement in functioning overall, but patients with BPD who experienced change in personality psychopathology showed some improvement in functioning. Impairment in social relationships appeared most stable in patients with PDs. Conclusion Impairment in functioning, especially social functioning, may be an enduring component of personality disorder. PMID:15841879

  14. Persistent right ventricular dysfunction, functional capacity limitation, exercise intolerance, and quality of life impairment following pulmonary embolism: Systematic review with meta-analysis.

    PubMed

    Sista, Akhilesh K; Miller, Larry E; Kahn, Susan R; Kline, Jeffrey A

    2017-02-01

    Long-term right ventricular (RV) function, functional capacity, exercise capacity, and quality of life following pulmonary embolism (PE), and the impact of thrombolysis, are unclear. A systematic review of studies that evaluated these outcomes with ⩾ 3-month mean follow-up after PE diagnosis was performed. For each outcome, random effects meta-analyses were performed. Twenty-six studies (3671 patients) with 18-month median follow-up were included. The pooled prevalence of RV dysfunction was 18.1%. Patients treated with thrombolysis had a lower, but not statistically significant, risk of RV dysfunction versus those treated with anticoagulation (odds ratio: 0.51, 95% CI: 0.24 to 1.13, p=0.10). Pooled prevalence of at least mild functional impairment (NYHA II-IV) was 33.2%, and at least moderate functional impairment (NYHA III-IV) was 11.3%. Patients treated with thrombolysis had a lower, but not statistically significant, risk of at least moderate functional impairment versus those treated with anticoagulation (odds ratio: 0.48, 95% CI: 0.15 to 1.49, p=0.20). Pooled 6-minute walk distance was 415 m (95% CI: 372 to 458 m), SF-36 Physical Component Score was 44.8 (95% CI: 43 to 46), and Pulmonary Embolism Quality of Life (QoL) Questionnaire total score was 9.1. Main limitations included heterogeneity among studies for many outcomes, variation in the completeness of data reported, and inclusion of data from non-randomized, non-controlled, and retrospective studies. Persistent RV dysfunction, impaired functional status, diminished exercise capacity, and reduced QoL are common in PE survivors. The effect of thrombolysis on RV function and functional status remains unclear.

  15. Cognitive Impairment in Adults with Non-CNS Cancers (PDQ®)—Health Professional Version

    Cancer.gov

    Cognitive impairment in adult cancer survivors may include problems with memory, concentration, information processing, and executive function. Get comprehensive information about assessing and managing cognitive impairment in this summary for clinicians.

  16. Renal impairment as a surgical indication in primary hyperparathyroidism: do the data support this recommendation?

    PubMed

    Hendrickson, Chase D; Castro Pereira, Daniel J; Comi, Richard J

    2014-08-01

    Management of primary hyperparathyroidism has evolved over the past two decades, yet impaired renal function has consistently been a surgical indication. This recommendation has been based upon the historical association between primary hyperparathyroidism and renal impairment, and a review of the literature is needed to determine whether such a recommendation is warranted. PubMed was utilized to identify English-language articles published between January 1990 and February 2014 using keywords related to hyperparathyroidism and renal function. The keywords were "primary hyperparathyroidism," "surgery," "parathyroidectomy," "kidney," "renal," "glomerular filtration rate," and "creatinine." Of the 1926 articles obtained with this search, all articles germane to the topic that quantified the relationship between primary hyperparathyroidism and renal function were included. All references within these articles were investigated for inclusion. When helpful, data tables were constructed to summarize the results succinctly. A secondary elevation of PTH levels has not been consistently shown to occur at the threshold currently indicated for surgical intervention. While renal impairment is seen with more significant disease, mild asymptomatic primary hyperparathyroidism has not been conclusively associated with renal impairment. Furthermore, there is no evidence to suggest that surgically curing primary hyperparathyroidism via a parathyroidectomy has any impact upon renal function.

  17. Cognitive Impairment Associated with Cancer

    PubMed Central

    Pendergrass, J. Cara; Harrison, John E.

    2018-01-01

    This brief review explores the areas of cognitive impairment that have been observed in cancer patients and survivors, the cognitive assessment tools used, and the management of the observed cognitive changes. Cognitive changes and impairment observed in patients with cancer and those in remission can be related to the direct effects of cancer itself, nonspecific factors or comorbid conditions that are independent of the actual disease, and/or the treatments or combination of treatments administered. Attention, memory, and executive functioning are the most frequently identified cognitive domains impacted by cancer. However, the prevalence and extent of impairment remains largely unknown due to marked differences in methodology, definitions of cognitive impairment, and the assessment measures used. Assessment of cognitive functioning is an important and necessary part of a comprehensive oncological care plan. Research is needed to establish a better understanding of cognitive changes and impairments associated with cancer so that optimal patient outcomes can be achieved. PMID:29497579

  18. Combination of behaviorally sub-effective doses of glutamate NMDA and dopamine D1 receptor antagonists impairs executive function.

    PubMed

    Desai, Sagar J; Allman, Brian L; Rajakumar, Nagalingam

    2017-04-14

    Impairment of executive function is a core feature of schizophrenia. Preclinical studies indicate that injections of either N-methyl d-aspartate (NMDA) or dopamine D 1 receptor blockers impair executive function. Despite the prevailing notion based on postmortem findings in schizophrenia that cortical areas have marked suppression of glutamate and dopamine, recent in vivo imaging studies suggest that abnormalities of these neurotransmitters in living patients may be quite subtle. Thus, we hypothesized that modest impairments in both glutamate and dopamine function can act synergistically to cause executive dysfunction. In the present study, we investigated the effect of combined administration of "behaviorally sub-effective" doses of NMDA and dopamine D 1 receptor antagonists on executive function. An operant conditioning-based set-shifting task was used to assess behavioral flexibility in rats that were systemically injected with NMDA and dopamine D 1 receptor antagonists individually or in combination prior to task performance. Separate injections of the NMDA receptor antagonist, MK-801, and the dopamine D 1 receptor antagonist, SCH 23390, at low doses did not impair set-shifting; however, the combined administration of these same behaviorally sub-effective doses of the antagonists significantly impaired the performance during set-shifting without affecting learning, retrieval of the memory of the initial rule, latency of responses or the number of omissions. The combined treatment also produced an increased number of perseverative errors. Our results indicate that NMDA and D 1 receptor blockade act synergistically to cause behavioral inflexibility, and as such, subtle abnormalities in glutamatergic and dopaminergic systems may act cooperatively to cause deficits in executive function. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Association of homocysteine level and vascular burden and cognitive function in middle-aged and older adults with chronic kidney disease.

    PubMed

    Yeh, Yi-Chun; Huang, Mei-Feng; Hwang, Shang-Jyh; Tsai, Jer-Chia; Liu, Tai-Ling; Hsiao, Shih-Ming; Yang, Yi-Hsin; Kuo, Mei-Chuan; Chen, Cheng-Sheng

    2016-07-01

    Patients with chronic kidney disease (CKD) have been found to have cognitive impairment. However, the core features and clinical correlates of cognitive impairment are still unclear. Elevated homocysteine levels are present in CKD, and this is a risk factor for cognitive impairment and vascular diseases in the general population. Thus, this study investigated the core domains of cognitive impairment and investigated the associations of homocysteine level and vascular burden with cognitive function in patients with CKD. Patients with CKD aged ≥ 50 years and age- and sex-matched normal comparisons were enrolled. The total fasting serum homocysteine level was measured. Vascular burden was assessed using the Framingham Cardiovascular Risk Scale. Cognitive function was evaluated using comprehensive neuropsychological tests. A total of 230 patients with CKD and 92 comparisons completed the study. Memory impairment and executive dysfunction were identified as core features of cognitive impairment in the CKD patients. Among the patients with CKD, higher serum homocysteine levels (β = -0.17, p = 0.035) and higher Framingham Cardiovascular Risk Scale scores (β = -0.18, p = 0.013) were correlated with poor executive function independently. However, an association with memory function was not noted. Our results showed that an elevated homocysteine level and an increased vascular burden were independently associated with executive function, but not memory, in CKD patients. This findings suggested the co-existence of vascular and non-vascular hypotheses regarding executive dysfunction in CKD patients. Meanwhile, other risk factors related to CKD itself should be investigated in the future. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  20. Correlates of impaired function in older women.

    PubMed

    Ensrud, K E; Nevitt, M C; Yunis, C; Cauley, J A; Seeley, D G; Fox, K M; Cummings, S R

    1994-05-01

    To determine the factors associated with impaired function in older women. Cross-sectional analysis of baseline data collected for a multicenter, prospective study of risk factors for osteoporotic fractures. Four clinical centers in Portland, Oregon, Minneapolis, Minnesota, Baltimore, Maryland, and the Monongahela Valley, Pennsylvania. A total of 9,704 ambulatory, non-black women, aged 65 years and older, recruited from population-based listings. Independent variables, including demographic and historical information (medical conditions, health habits, and medications) and physiologic measures (anthropometry, blood pressure, mental status, vision, and neuromuscular performance) were obtained from a baseline questionnaire, interview, and examination. Measurement of function was assessed by self-reported ability to perform six physical and instrumental activities of daily living (ADL) and impaired function (dependent variable) was defined as difficulty performing three or more physical and instrumental ADLs. In order of decreasing strength of association, hip fracture, osteoarthritis, parkinsonism, slower walking speed, lower hip abduction force, back pain, greater Quetelet index, osteoporosis, former alcohol use, stroke, never drinking alcohol, lower mental status, use of anxiolytics and/or sleeping medications, inability to hold the tandem position, postural dizziness, cataracts, greater waist to hip ratio, lower physical activity in the past year, greater lifetime cigarette consumption, and lower grip strength were independently associated with impaired function in multivariate analyses. Age, low educational level, diabetes, current heavy alcohol use, postural hypotension, depth perception, and contrast sensitivity were not independent predictors. A combination of neuromuscular performance measures, including decreased muscle strength and impaired balance and gait, appeared to account for the effect of age on disability. A combination of many factors, including medical conditions, health habits such as obesity, smoking, alcohol abstinence, and physical inactivity, and direct measures of neuromuscular performance are associated with impaired function in older women.

  1. Differentiating between Alzheimer's Disease and Vascular Cognitive Impairment: Is the "Memory Versus Executive Function" Contrast Still Relevant?

    PubMed

    Andriuta, Daniela; Roussel, Martine; Barbay, Mélanie; Despretz-Wannepain, Sandrine; Godefroy, Olivier

    2018-01-01

    The contrast between memory versus executive function impairments is commonly used to differentiate between neurocognitive disorders (NCDs) due to Alzheimer's disease (AD) and vascular cognitive impairment (VCI). We reconsidered this question because of the current use of AD biomarkers and the recent revision of the criteria for AD, VCI, and dysexecutive syndrome. To establish and compare the neuropsychological profiles in AD (i.e., with positive CSF biomarkers) and in VCI. We included 62 patients with mild or major NCDs due to pure AD (with positive CSF biomarker assays), and 174 patients (from the GRECogVASC cohort) with pure VCI. The neuropsychological profiles were compared after stratification for disease severity (mild or major NCD). We defined a memory-executive function index (the mean z score for the third free recall and the delayed free recall in the Free and Cued Selective Reminding Test minus the mean z score for category fluency and the completion time in the Trail Making Test part B) and determined its diagnostic accuracy. Compared with VCI patients, patients with AD had significantly greater memory impairments (p = 0.001). Executive function was impaired to a similar extent in the two groups (p = 0.11). Behavioral executive disorders were more prominent in the AD group (p = 0.001). Although the two groups differed significant with regard to the memory-executive function index (p < 0.001), the latter's diagnostic accuracy was only moderate (sensitivity: 63%, specificity: 87%). Although the contrast between memory and executive function impairments was supported at the group level it does not reliably discriminate between AD and VCI at the individual level.

  2. Hand function in workers with hand-arm vibration syndrome.

    PubMed

    Cederlund, R; Isacsson, A; Lundborg, G

    1999-01-01

    Hand-arm vibration syndrome has been specially addressed in the Scandinavian countries in recent years, but the syndrome is still not sufficiently recognized in many countries. The object of this preliminary study was to describe the nature and character of vibration-induced impairment in the hands of exposed workers. Twenty symptomatic male workers (aged 28 to 65 years) subjected to vibration by hand-held tools were interviewed about subjective symptoms and activities of daily living and were assessed with a battery of objective tests for sensibility, dexterity, grip function, and grip strength. The test results were compared with normative data. The majority of patients complained of cold intolerance, numbness, pain, sensory impairment, and difficulties in handling manual tools and in handwriting. The various objective tests showed considerable variation in indications of pathologic outcome, revealing differences in sensitivity to detect impaired hand function. Semmes-Weinstein monofilament testing for perception of light touch-deep pressure sensation, the small-object shape identification test, and moving two-point discrimination testing for functional sensibility provided the most indications of pathologic outcomes. The authors conclude that vibration-exposed patients present considerable impairment in hand function.

  3. Somatization Increases Disability Independent of Comorbidity

    PubMed Central

    Orav, E. John; Bates, David W.; Barsky, Arthur J.

    2008-01-01

    Background Somatoform disorders are an important factor in functional disability and role impairment, though their independent contribution to disability has been unclear because of prevalent medical and psychiatric comorbidity. Objectives To assess the extent of the overlap of somatization with other psychiatric disorders and medical problems, to compare the functional disability and role impairment of somatizing and non-somatizing patients, and to determine the independent contribution of somatization to functional disability and role impairment. Design Patients were surveyed with self-report questionnaires assessing somatization, psychiatric disorder, and role impairment. Medical morbidity was indexed with a computerized medical record audit. Participants Consecutive adults making scheduled visits to their primary care physicians at two hospital-affiliated primary care practices on randomly chosen days. Measurements Intermediate activities of daily living, social activities, and occupational disability. Results Patients with somatization, as well as those with serious medical and psychiatric illnesses, had significantly more impairment of activities of daily life and social activities. When these predictors were considered simultaneously in a multivariable regression, the association with somatization remained highly significant and was comparable to or greater than many major medical conditions. Conclusions Patients with somatization had substantially greater functional disability and role impairment than non-somatizing patients. The degree of disability was equal to or greater than that associated with many major, chronic medical disorders. Adjusting the results for psychiatric and medical co-morbidity had little effect on these findings. PMID:19031038

  4. Late-life deficits in cognitive, physical and emotional functions, childhood intelligence and occupational profile: a life-course examination of the Aberdeen 1936 Birth Cohort (ABC1936).

    PubMed

    Chapko, Dorota; Staff, Roger T; McNeil, Christopher J; Whalley, Lawrence J; Black, Corri; Murray, Alison D

    2016-07-01

    the 'triad of impairment' phenomenon describes the co-occurrence of age-related cognitive, emotional and physical functioning deficits. We investigated how occupational profile and childhood intelligence contribute to the triad of impairment in late life. we analysed data of a subsample of the Aberdeen Birth Cohort of 1936 (n = 346). Data were collected on participants' childhood intelligence, late-life cognitive ability, physical functioning, depressive symptoms and main lifetime occupation. We summarised the various occupational and impairment measures into two latent variables, 'occupational profile' and the 'triad of impairment'. We used a series of data reduction approaches and structural equation models (SEMs) of increasing complexity to test both the validity of the models and to understand causal relationships between the life-course risks for the triad of impairment. occupational profile had a significant effect on the triad of impairment independent of childhood intelligence. Childhood intelligence was the predominant influence on the triad of impairment and exerted its effect directly and indirectly via its influence on occupation. The direct effect of childhood intelligence exceeded the independent influence of the occupational profile on impairment by a factor of 1.7-1.8 and was greater by a factor of ∼4 from the indirect pathway (via occupation). childhood intelligence was the predominant influence on the triad of impairment in late life, independently of the occupational profile. Efforts to reduce impairment in older adults should be informed by a life-course approach with special attention to the early-life environment. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Visual impairment, but not hearing impairment, is independently associated with lower subjective well-being among individuals over 95 years of age: A population-based study.

    PubMed

    Liu, Zuyun; Wu, Di; Huang, Jiapin; Qian, Degui; Chen, Fei; Xu, Jun; Li, Shilin; Jin, Li; Wang, Xiaofeng

    2016-01-01

    Sensory impairment affects an increasing number of elderly adults, with a negative psychological impact. Our objective was to examine the associations of visual and hearing impairment with subjective well-being (SWB), an important psychological concept defined by life satisfaction [LS], positive affect [PA], negative affect [NA], and affect balance [AB] among long-lived individuals (LLIs) over 95 years of age. Data on 442 LLIs from the Rugao longevity cohort, a population-based study in Rugao, China, were analyzed. Graded classifications of visual and hearing impairment (none, mild, moderate, and severe) were constructed from self-reported items. Bivariate correlation and multiple regression analysis were performed to test the associations. Approximately 66.1% and 87.3% of the subjects reported varying degrees of visual and hearing impairment. Following the degree of vision impairment, LS, PA, and AB decreased linearly, whereas NA increased linearly (all p for trend<0.05). Vision was significantly related to LS (r=0.238, p<0.001), PA (r=0.142, p<0.01), NA (r=-0.157, p<0.001), and AB (r=0.206, p<0.001). After adjustment for multiple variables including functional ability, an important factor of SWB, the associations of vision impairment with LS, NA, and AB, while diminished, still existed. Visual impairment, but not hearing impairment, was independently associated with low SWB among LLIs, and functional ability may play a mediating role in the observed relationship. The findings indicate that rehabilitation targeted for those with reduced vision and functioning in long-lived populations may be important for promoting well-being and quality of life. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Long-Term Cognitive Impairment after Hospitalization for Community-Acquired Pneumonia: a Prospective Cohort Study.

    PubMed

    Girard, Timothy D; Self, Wesley H; Edwards, Kathryn M; Grijalva, Carlos G; Zhu, Yuwei; Williams, Derek J; Jain, Seema; Jackson, James C

    2018-06-01

    Recent studies suggest older patients hospitalized for community-acquired pneumonia are at risk for new-onset cognitive impairment. The characteristics of long-term cognitive impairment after pneumonia, however, have not been elucidated. To characterize long-term cognitive impairment among adults of all ages hospitalized for community-acquired pneumonia. Prospective cohort study. Adults without severe preexisting cognitive impairment who were hospitalized with community-acquired pneumonia. At enrollment, we estimated baseline cognitive function with the Short Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). At 2- and 12-month follow-up, we assessed cognition using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and tests of executive function, diagnosing cognitive impairment when results were ≥ 1.5 standard deviations below published age-adjusted means for the general population. We also identified subtypes of mild cognitive impairment using standard definitions. We assessed 58 (73%) of 80 patients who survived to 2-month follow-up and 57 (77%) of 74 who survived to 12-month follow-up. The median [range] age of survivors tested was 57 [19-97] years. Only 8 (12%) had evidence of mild cognitive impairment at baseline according to the Short IQCODE, but 21 (38%) at 2 months and 17 (30%) at 12 months had mild cognitive impairment per the RBANS. Moderate-to-severe cognitive impairment was common among adults ≥ 65 years [4/13 (31%) and 5/13 (38%) at 2 and 12 months, respectively] but also affected many of those < 65 years [10/43 (23%) and 8/43 (19%) at 2 and 12 months, respectively]. Deficits were most often noted in visuospatial function, attention, and memory. A year after hospitalization for community-acquired pneumonia, moderate-to-severe impairment in multiple cognitive domains affected one-third of patients ≥ 65 years old and 20% of younger patients, and another third of survivors had mild cognitive impairment.

  7. Family Functioning, Social Impairment, and Symptoms Among Adolescents with Bipolar Disorder

    ERIC Educational Resources Information Center

    Keenan-Miller, Danielle; Peris, Tara; Axelson, David; Kowatch, Robert A.; Miklowitz, David J.

    2012-01-01

    Objective: Impaired social functioning is common among youth with bipolar disorder (BD), emerges in multiple settings, and persists over time. However, little is known about factors associated with poor peer and family functioning in the early-onset form of BD. Using a sample of adolescents with BD I or II, we examined which symptoms of BD,…

  8. Increased lipolysis, diminished adipose tissue insulin sensitivity and impaired B-cell function relative to adipose tissue insulin sensitivity in obese youth with impaired glucose tolerance (IGT)

    USDA-ARS?s Scientific Manuscript database

    Despite evidence of insulin resistance and B-cell dysfunction in glucose metabolism in youth with prediabetes, the relationship between adipose tissue insulin sensitivity (ATIS) and B-cell function remains unknown. We investigated whole-body lipolysis, ATIS and B-cell function relative to ATIS [adip...

  9. White Matter Integrity Linked To Functional Impairments in Aging and Early Alzheimer’s Disease

    PubMed Central

    Kavcic, Voyko; Ni, Hongyan; Zhu, Tong; Zhong, Jianhui; Duffy, Charles J.

    2008-01-01

    Background Alzheimer’s disease (AD) is associated with changes in cerebral white matter (WM) but the functional significance of such findings is not yet established. We hypothesized that diffusion tensor imaging (DTI) might reveal links between regional WM changes and specific neuropsychologically and psychophysically defined impairments in early AD. Methods Older adult control subjects (OA, n=18) and mildly impaired AD patients (n=14) underwent neuropsychological and visual perceptual testing along with DTI of cerebral WM. DTI yielded factional anisotropy (FA) and mean diffusivity () maps for nine ROIs in three brain regions that were then compared to the performance measures. Results AD patients showed non-significant trends toward lower FAs in the posterior region’s callosal and sub-cortical ROIs. However, posterior callosal FA was significantly correlated with verbal fluency and figural memory impairments, whereas posterior subcortical FA was correlated with delayed verbal memory, figural memory, and optic flow perceptual impairments. Conclusions WM changes in early AD are concentrated in posterior cerebral areas with distributions that correspond to specific functional impairments. DTI can be used to assess regional pathology related to individual’s deficits in early AD. PMID:19012862

  10. Subjective cognitive function in hoarding disorder.

    PubMed

    Tolin, David F; Hallion, Lauren S; Wootton, Bethany M; Levy, Hannah C; Billingsley, Amber L; Das, Akanksha; Katz, Benjamin W; Stevens, Michael C

    2018-07-01

    The aim of the present study was to examine subjective cognitive impairment among adult patients with hoarding disorder (HD). Eighty-three patients with HD and 46 age- and gender-matched healthy control (HC) participants received a diagnostic interview and completed measures of subjective cognitive functioning and motivations for saving behavior, as well as measures of hoarding severity, depression, anxiety, stress, and obsessive-compulsive disorder (OCD) symptoms. The HD group reported more impairment than did the HC group in domains of memory, distractibility, blunders, memory for names, and inattention. These differences generally remained significant when controlling for comorbid symptoms. In the HD group, the degree of cognitive impairment was significantly correlated with severity of saving and acquiring behaviors, although results were attenuated when controlling for comorbid symptoms (overall HD severity, but not saving behavior specifically, remained significantly correlated with cognitive impairment). Subjective cognitive impairment was further associated with a desire to save possessions in order to avoid forgetting, and these results remained significant when controlling for comorbid symptoms. These results comport with current behavioral models of HD that emphasize decision-making deficits, as well as clinician observations suggestive of impaired cognitive function, and complement a growing body of neuropsychological testing studies. Copyright © 2018. Published by Elsevier B.V.

  11. Degree of exposure to domestic violence, psychopathology, and functional impairment in children and adolescents.

    PubMed

    Bayarri Fernàndez, Eduard; Ezpeleta, Lourdes; Granero, Roser; de la Osa, Núria; Domènech, Josep María

    2011-04-01

    There are discrepancies about whether children who witness and suffer domestic violence (DV) have similar outcomes in terms of psychopathology. This work examines the relationship between different types of exposure to DV and child psychopathology and functional impairment. One hundred and forty-four Spanish children aged from 4 to 17 years and exposed to DV were evaluated using a diagnostic interview and other instruments of psychopathology and functional impairment. The participants were classified in three groups according to the degree of exposure: witness (n = 72), involved (n = 52), and victim (n = 20). According to mothers' self-reports and mother-child combined information, DV equally affects psychopathology and functional impairment regardless of the degree of the exposure. Children's self-reports showed a linear trend to present greater psychopathology as a victim than as a witness. The differential effect of exposure to DV measured in this study depended on the informant, which underlines the importance of obtaining information from the children exposed to violence at home.

  12. Converging models of schizophrenia - Network alterations of prefrontal cortex underlying cognitive impairments

    PubMed Central

    Sakurai, Takeshi; Gamo, Nao J; Hikida, Takatoshi; Kim, Sun-Hong; Murai, Toshiya; Tomoda, Toshifumi; Sawa, Akira

    2015-01-01

    The prefrontal cortex (PFC) and its connections with other brain areas are crucial for cognitive function. Cognitive impairments are one of the core symptoms associated with schizophrenia, and manifest even before the onset of the disorder. Altered neural networks involving PFC contribute to cognitive impairments in schizophrenia. Both genetic and environmental risk factors affect the development of the local circuitry within PFC as well as development of broader brain networks, and make the system vulnerable to further insults during adolescence, leading to the onset of the disorder in young adulthood. Since spared cognitive functions correlate with functional outcome and prognosis, a better understanding of the mechanisms underlying cognitive impairments will have important implications for novel therapeutics for schizophrenia focusing on cognitive functions. Multidisciplinary approaches, from basic neuroscience to clinical studies, are required to link molecules, circuitry, networks, and behavioral phenotypes. Close interactions among such fields by sharing a common language on connectomes, behavioral readouts, and other concepts are crucial for this goal. PMID:26408506

  13. Neural correlates of saccadic inhibition in healthy elderly and patients with amnestic mild cognitive impairment

    PubMed Central

    Alichniewicz, K. K.; Brunner, F.; Klünemann, H. H.; Greenlee, M. W.

    2013-01-01

    Performance on tasks that require saccadic inhibition declines with age and altered inhibitory functioning has also been reported in patients with Alzheimer's disease. Although mild cognitive impairment (MCI) is assumed to be a high-risk factor for conversion to AD, little is known about changes in saccadic inhibition and its neural correlates in this condition. Our study determined whether the neural activation associated with saccadic inhibition is altered in persons with amnestic mild cognitive impairment (aMCI). Functional magnetic resonance imaging (fMRI) revealed decreased activation in parietal lobe in healthy elderly persons compared to young persons and decreased activation in frontal eye fields in aMCI patients compared to healthy elderly persons during the execution of anti-saccades. These results illustrate that the decline in inhibitory functions is associated with impaired frontal activation in aMCI. This alteration in function might reflect early manifestations of AD and provide new insights in the neural activation changes that occur in pathological ageing. PMID:23898312

  14. The effect of stress induction on working memory in patients with psychogenic nonepileptic seizures.

    PubMed

    Bakvis, Patricia; Spinhoven, Philip; Putman, Peter; Zitman, Frans G; Roelofs, Karin

    2010-11-01

    Although psychogenic nonepileptic seizures (PNES) are considered a stress-induced paroxysmal disintegration of cognitive functions, it remains unknown whether stress indeed impairs cognitive integrative functions, such as working memory (WM), in patients with PNES. An N-back task with emotional distracters (angry, happy, and neutral faces) was administered at baseline and after stress induction (Cold Pressor Test) to 19 patients with PNES and 20 matched healthy controls. At baseline, patients displayed increased WM interference for the facial distracters. After stress induction, group differences generalized to the no-distracter condition. Within patients, high cortisol stress responses were associated with larger stress-induced WM impairments in the no-distracter condition. These findings demonstrate that patients' cognitive integrative functions are impaired by social distracters and stress induction. Moreover, the stress- and cortisol-related generalization of the relative WM impairments offers a promising experimental model for the characteristic paroxysmal disintegration of attentional and mnemonic functions in patients with PNES associated with stress. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. Recovery-related indicators of motor network plasticity according to impairment severity after stroke.

    PubMed

    Lee, J; Park, E; Lee, A; Chang, W H; Kim, D-S; Kim, Y-H

    2017-10-01

    Brain connectivity analysis has been widely used to investigate brain plasticity and recovery-related indicators of patients with stroke. However, results remain controversial because of interindividual variability of initial impairment and subsequent recovery of function. In this study, we aimed to investigate the differences in network plasticity and motor recovery-related indicators according to initial severity. We divided participants (16 males and 14 females, aged 54.2 ± 12.0 years) into groups of different severity by Fugl-Mayer Assessment score, i.e. moderate (50-84), severe (20-49) and extremely severe (<20) impairment groups. Longitudinal resting-state functional magnetic resonance imaging data were acquired at 2 weeks and 3 months after onset. The differences in network plasticity and recovery-related indicators between groups were investigated using network distance and graph measurements. As the level of impairment increased, the network balance was more disrupted. Network balance, interhemispheric connectivity and network efficiency were recovered at 3 months only in the moderate impairment group. However, this was not the case in the extremely severe impairment group. A single connection strength between the ipsilesional primary motor cortex and ventral premotor cortex was implicated in the recovery of motor function for the extremely severe impairment group. The connections of the ipsilesional primary motor cortex-ventral premotor cortex were positively associated with motor recovery as the patients were more severely impaired. Differences in plasticity and recovery-related indicators of motor networks were noted according to impairment severity. Our results may suggest meaningful implications for recovery prediction and treatment strategies in future stroke research. © 2017 EAN.

  16. Peak oxygen uptake and left ventricular ejection fraction, but not depressive symptoms, are associated with cognitive impairment in patients with chronic heart failure.

    PubMed

    Steinberg, Gerrit; Lossnitzer, Nicole; Schellberg, Dieter; Mueller-Tasch, Thomas; Krueger, Carsten; Haass, Markus; Ladwig, Karl Heinz; Herzog, Wolfgang; Juenger, Jana

    2011-01-01

    The aim of the present study was to assess cognitive impairment in patients with chronic heart failure (CHF) and its associations with depressive symptoms and somatic indicators of illness severity, which is a matter of controversy. Fifty-five patients with CHF (mean age 55.3 ± 7.8 years; 80% male; New York Heart Association functional class I-III) underwent assessment with an expanded neuropsychological test battery (eg, memory, complex attention, mental flexibility, psychomotor speed) to evaluate objective and subjective cognitive impairment. Depressive symptoms were assessed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID) and a self-report inventory (Hospital Anxiety and Depression Scale [HADS]). A comprehensive clinical dataset, including left ventricular ejection fraction, peak oxygen uptake, and a 6-minute walk test, was obtained for all patients. Neuropsychological functioning revealed impairment in 56% of patients in at least one measure of our neuropsychological test battery. However, the Mini Mental State Examination (MMSE) could only detect cognitive impairment in 1.8% of all patients, 24% had HADS scores indicating depressive symptoms, and 11.1% met SCID criteria for a depressive disorder. No significant association was found between depressive symptoms and cognitive impairment. Left ventricular ejection fraction was related to subjective cognitive impairment, and peak oxygen uptake was related to objective cognitive impairment. Cognitive functioning was substantially reduced in patients with CHF and should therefore be diagnosed and treated in routine clinical practice. Caution is advised when the MMSE is used to identify cognitive impairment in patients with CHF.

  17. Trajectories of Nutritional Status and Cognitive Impairment among Older Taiwanese with Hip Fracture.

    PubMed

    Wang, H P; Liang, J; Kuo, L M; Chen, C Y; Shyu, Y I L

    2017-01-01

    This paper describes the trajectories of nutritional status and cognitive impairment and their correlation among older Taiwanese over 1 year after hip-fracture surgery. Secondary analysis of data from a clinical trial evaluating the effects of three types of post-discharge care for 292 older hip-fracture patients (age >60 years). Nutritional status was assessed by the Mini Nutritional Assessment before and 1, 3, 6, 12 months after hospital discharge. Cognitive function was measured by the Mini-Mental State Examination before surgery, at hospital discharge, 6 and 12 months after discharge. Trajectories of nutritional status and cognitive impairment were depicted by latent class growth modeling, whereas linkages between nutritional-status and cognitive-impairment trajectories were assessed by multinomial logistic regression. Nutritional status in general improved significantly, particularly during the first 3 months after discharge. We identified three trajectories of nutritional status: malnourished (15.4%), at risk for malnutrition (38.9%), and well-nourished (45.7%). In contrast, cognitive changes followed four largely linear but distinct trajectories: moderately impaired (12.2%), mildly impaired (27.8%), borderline impaired (21.8%), and cognitively intact (38.2%). Trajectories of nutritional status were significantly associated with cognitive-function trajectories. For instance, relative to malnourished patients, well-nourished patients were 95% less likely (OR=0.05, CI =0.01-0.24) to be moderately cognitively impaired. A good nutritional-status trajectory after hip fracture was associated with better cognitive function. To treat and care for elderly hip-fractured patients, specific interventions need to target those who are malnourished or at risk of malnutrition to decrease their risk for cognitive impairment.

  18. Longitudinal Study of a Novel, Performance-based Measure of Daily Function

    DTIC Science & Technology

    2016-06-01

    have functional impairments, and healthy age matched controls on the UPSA, as well as measures of cognition (e.g., episodic memory , semantic memory ...controls on the UPSA, as well as measures of cognition (e.g., episodic memory , semantic memory , executive function, speed). We found that patients with...diagnosis have functional impairments, and healthy age matched controls on the UPSA, as well as measures of cognition (e.g., episodic memory , semantic

  19. Pharmacokinetics and Safety of Bortezomib in Patients with Advanced Malignancies and Varying Degrees of Liver Dysfunction: Phase 1 NCI Organ Dysfunction Working Group Study NCI-6432

    PubMed Central

    LoRusso, Patricia M; Venkatakrishnan, Karthik; Ramanathan, Ramesh K; Sarantopoulos, John; Mulkerin, Daniel; Shibata, Stephen I; Hamilton, Anne; Dowlati, Afshin; Mani, Sridhar; Rudek, Michelle A; Takimoto, Chris H; Neuwirth, Rachel; Esseltine, Dixie-Lee; Ivy, Percy

    2013-01-01

    Purpose The proteasome inhibitor bortezomib undergoes oxidative hepatic metabolism. This study (NCI-6432; NCT00091117) was conducted to evaluate bortezomib pharmacokinetics and safety in patients with varying degrees of hepatic impairment, to inform dosing recommendations in these special populations. Methods Patients received bortezomib on days 1, 4, 8, and 11 of 21-day cycles. Patients were assigned to four hepatic function groups based on the National Cancer Institute Organ Dysfunction Working Group classification. Those with normal function received bortezomib at the 1.3 mg/m2 standard dose. Patients with severe, moderate, and mild impairment received escalating doses from 0.5, 0.7, and 1.0 mg/m2, respectively, up to a 1.3 mg/m2 maximum. Serial blood samples were collected for 24 hours post-dose on days 1 and 8, cycle 1, for bortezomib plasma concentration measurements. Results Sixty-one patients were treated, including 14 with normal hepatic function and 17, 12, and 18 with mild, moderate, and severe impairment, respectively. Mild hepatic impairment did not alter dose-normalized bortezomib exposure (AUC0-tlast) or Cmax compared with patients with normal function. Mean dose-normalized AUC0-tlast was increased by approximately 60% on day 8 in patients with moderate or severe impairment. Conclusions Patients with mild hepatic impairment do not require a starting dose adjustment of bortezomib. Patients with moderate or severe hepatic impairment should be started at a reduced dose of 0.7 mg/m2. PMID:22394984

  20. Neurocognitive Impairments in Deficit and Non-Deficit Schizophrenia and Their Relationships with Symptom Dimensions and Other Clinical Variables

    PubMed Central

    Zhang, XiangRong; Zhang, XiaoBin; Sha, WeiWei; Yao, ShuQiao; Shu, Ni; Zhang, XiangYang; Zhang, ZhiJun

    2015-01-01

    Background Deficit schizophrenia (DS) has been proposed as a pathophysiologically distinct subgroup within schizophrenia. Earlier studies focusing on neurocognitive function of DS patients have yielded inconsistent findings ranging from substantial deficits to no significant difference relative to non-deficit schizophrenia patients (NDS). The present study investigated the severity and characteristic patterns of neurocognitive impairments in DS and NDS patients and their relationships with clinical variables. Methods Attention, ideation fluency, cognitive flexibility and visuospatial memory function were assessed in 40 DS patients, 57 NDS patients, and 52 healthy controls by a comprehensive neuropsychological battery. Results Both schizophrenia subgroups had overall more severe cognitive impairments than controls while DS performed worse on every neuropsychological measure except the Stroop interference than the NDS patients with age and education as the covariates. Profile analysis found significantly different patterns of cognitive profiles between two patients group mainly due to their differences in attention and cognitive flexibility functions. Age, education, illness duration and negative symptoms were found to have the correlations with cognitive impairments in the NDS group, while only age and the negative symptoms were correlated with the cognitive impairments in the DS group. Multiple regression analyses revealed that sustained attention and cognitive flexibility were the core impaired cognitive domains mediating other cognitive functions in DS and NDS patients respectively. Conclusions DS patients exemplified worse in almost all cognitive domains than NDS patients. Sustained attention and cognitive flexibility might be the key impaired cognitive domains for DS and NDS patients respectively. The present study suggested the DS as a specific subgroup of schizophrenia. PMID:26381645

  1. Acute Stress Symptoms in Children: Results From an International Data Archive

    PubMed Central

    Kassam-Adams, Nancy; Palmieri, Patrick A.; Rork, Kristine; Delahanty, Douglas L.; Kenardy, Justin; Kohser, Kristen L.; Landolt, Markus A.; Le Brocque, Robyne; Marsac, Meghan L.; Meiser-Stedman, Richard; Nixon, Reginald D. V.; Bui, Eric; McGrath, Caitlin

    2012-01-01

    Objective To describe the prevalence of acute stress disorder (ASD) symptoms and examine proposed DSM-5 symptom criteria in relation to concurrent functional impairment in children. Method From an international archive, datasets were identified which included assessment of acute traumatic stress reactions and concurrent impairment in children age 5 to 17. Data came from 15 studies conducted in the US, UK, Australia, and Switzerland with 1645 children. Dichotomized items were created to indicate the presence or absence of each of the 14 proposed ASD symptoms and functional impairment. The performance of a proposed diagnostic criterion (number of ASD symptoms required) was examined as a predictor of concurrent impairment. Results Each ASD symptom was endorsed by 14% to 51% of children; 41% reported clinically-relevant impairment. Children reported from 0 to 13 symptoms (mean = 3.6). Individual ASD symptoms were associated with greater likelihood of functional impairment. The DSM-5 proposed 8-symptom requirement was met by 202 (12.3%) children, and had low sensitivity (.25) in predicting concurrent clinically-relevant impairment. Requiring fewer symptoms (three to four) greatly improved sensitivity while maintaining moderate specificity. Conclusions This group of symptoms appears to capture aspects of traumatic stress reactions that can create distress and interfere with children’s ability to function in the acute post-trauma phase. Results provide a benchmark for comparison with adult samples; a smaller proportion of children met the 8-symptom criterion than reported for adults. Symptom requirements for the ASD diagnosis may need to be lowered to optimally identify children whose acute distress warrants clinical attention. PMID:22840552

  2. The Relationship of Intellectual Functioning and Cognitive Performance to Brain Structure in Schizophrenia

    PubMed Central

    Wang, Lei; Gama, Clarissa S.; Barch, Deanna M.

    2017-01-01

    Abstract Background: Schizophrenia (SZ) is often characterized by cognitive and intellectual impairment. However, there is much heterogeneity across individuals, suggesting different trajectories of the illness. Recent findings have shown brain volume differences across subgroups of individuals with psychosis (SZ and bipolar disorder), such that those with intellectual and cognitive impairments presented evidence of early cerebral disruption, while those with cognitive but not intellectual impairments showed evidence of progressive brain abnormalities. Our aim was to investigate the relations of cognition and intellectual functioning with brain structure abnormalities in a sample of SZ compared to unaffected individuals. Methods: 92 individuals with SZ and 94 healthy controls part of the Northwestern University Schizophrenia Data and Software Tool (NUSDAST) underwent neuropsychological assessment and structural magnetic resonance imaging (MRI). Individuals with SZ were divided into subgroups according their estimated premorbid crystallized intellectual (ePMC-IQ) and cognitive performance. Brain volumes differences were investigated across groups. Results: SZ with ePMC-IQ and cognitive impairments had reduced total brain volume (TBV), intracranial volume (ICV), TBV corrected for ICV, and cortical gray matter volume, as well as reduced cortical thickness, and insula volumes. SZ with cognitive impairment but intact ePMC-IQ showed only reduced cortical gray matter volume and cortical thickness. Conclusions: These data provide additional evidence for heterogeneity in SZ. Impairments in cognition associated with reduced ePMC-IQ were related to evidence of broad brain structural alterations, including suggestion of early cerebral disruption. In contrast, impaired cognitive functioning in the context of more intact intellectual functioning was associated with cortical alterations that may reflect neurodegeneration. PMID:27369471

  3. Neurocognitive Impairments in Deficit and Non-Deficit Schizophrenia and Their Relationships with Symptom Dimensions and Other Clinical Variables.

    PubMed

    Yu, Miao; Tang, XiaoWei; Wang, Xiang; Zhang, XiangRong; Zhang, XiaoBin; Sha, WeiWei; Yao, ShuQiao; Shu, Ni; Zhang, XiangYang; Zhang, ZhiJun

    2015-01-01

    Deficit schizophrenia (DS) has been proposed as a pathophysiologically distinct subgroup within schizophrenia. Earlier studies focusing on neurocognitive function of DS patients have yielded inconsistent findings ranging from substantial deficits to no significant difference relative to non-deficit schizophrenia patients (NDS). The present study investigated the severity and characteristic patterns of neurocognitive impairments in DS and NDS patients and their relationships with clinical variables. Attention, ideation fluency, cognitive flexibility and visuospatial memory function were assessed in 40 DS patients, 57 NDS patients, and 52 healthy controls by a comprehensive neuropsychological battery. Both schizophrenia subgroups had overall more severe cognitive impairments than controls while DS performed worse on every neuropsychological measure except the Stroop interference than the NDS patients with age and education as the covariates. Profile analysis found significantly different patterns of cognitive profiles between two patients group mainly due to their differences in attention and cognitive flexibility functions. Age, education, illness duration and negative symptoms were found to have the correlations with cognitive impairments in the NDS group, while only age and the negative symptoms were correlated with the cognitive impairments in the DS group. Multiple regression analyses revealed that sustained attention and cognitive flexibility were the core impaired cognitive domains mediating other cognitive functions in DS and NDS patients respectively. DS patients exemplified worse in almost all cognitive domains than NDS patients. Sustained attention and cognitive flexibility might be the key impaired cognitive domains for DS and NDS patients respectively. The present study suggested the DS as a specific subgroup of schizophrenia.

  4. Alterations in memory networks in mild cognitive impairment and Alzheimer's disease: an independent component analysis.

    PubMed

    Celone, Kim A; Calhoun, Vince D; Dickerson, Bradford C; Atri, Alireza; Chua, Elizabeth F; Miller, Saul L; DePeau, Kristina; Rentz, Doreen M; Selkoe, Dennis J; Blacker, Deborah; Albert, Marilyn S; Sperling, Reisa A

    2006-10-04

    Memory function is likely subserved by multiple distributed neural networks, which are disrupted by the pathophysiological process of Alzheimer's disease (AD). In this study, we used multivariate analytic techniques to investigate memory-related functional magnetic resonance imaging (fMRI) activity in 52 individuals across the continuum of normal aging, mild cognitive impairment (MCI), and mild AD. Independent component analyses revealed specific memory-related networks that activated or deactivated during an associative memory paradigm. Across all subjects, hippocampal activation and parietal deactivation demonstrated a strong reciprocal relationship. Furthermore, we found evidence of a nonlinear trajectory of fMRI activation across the continuum of impairment. Less impaired MCI subjects showed paradoxical hyperactivation in the hippocampus compared with controls, whereas more impaired MCI subjects demonstrated significant hypoactivation, similar to the levels observed in the mild AD subjects. We found a remarkably parallel curve in the pattern of memory-related deactivation in medial and lateral parietal regions with greater deactivation in less-impaired MCI and loss of deactivation in more impaired MCI and mild AD subjects. Interestingly, the failure of deactivation in these regions was also associated with increased positive activity in a neocortical attentional network in MCI and AD. Our findings suggest that loss of functional integrity of the hippocampal-based memory systems is directly related to alterations of neural activity in parietal regions seen over the course of MCI and AD. These data may also provide functional evidence of the interaction between neocortical and medial temporal lobe pathology in early AD.

  5. Impaired pulmonary function after treatment for tuberculosis: the end of the disease?

    PubMed Central

    Chushkin, Mikhail Ivanovich; Ots, Oleg Nikolayevich

    2017-01-01

    ABSTRACT Objective: To evaluate the prevalence of pulmonary function abnormalities and to investigate the factors affecting lung function in patients treated for pulmonary tuberculosis. Methods: A total of 214 consecutive patients (132 men and 82 women; 20-82 years of age), treated for pulmonary tuberculosis and followed at a local dispensary, underwent spirometry and plethysmography at least one year after treatment. Results: Pulmonary impairment was present in 102 (47.7%) of the 214 patients evaluated. The most common functional alteration was obstructive lung disease (seen in 34.6%). Of the 214 patients, 60 (28.0%) showed reduced pulmonary function (FEV1 below the lower limit of normal). Risk factors for reduced pulmonary function were having had culture-positive pulmonary tuberculosis in the past, being over 50 years of age, having recurrent tuberculosis, and having a lower level of education. Conclusions: Nearly half of all tuberculosis patients evolve to impaired pulmonary function. That underscores the need for pulmonary function testing after the end of treatment. PMID:28380187

  6. Executive functions and Prader-Willi syndrome: global deficit linked with intellectual level and syndrome-specific associations.

    PubMed

    Chevalère, Johann; Postal, Virginie; Jauregui, Joseba; Copet, Pierre; Laurier, Virginie; Thuilleaux, Denise

    2015-05-01

    The aim of this study was to support the growing evidence suggesting that Prader-Willi Syndrome (PWS) might present with an impairment of executive functions (EFs) and to investigate whether this impairment is specific to patients with PWS or due to their intellectual disability (ID). Six tasks were administered to assess EFs (inhibition, switching, updating, cognitive estimation, and planning) to 17 patients with PWS and 17 age-matched healthy individuals. Performance was significantly impaired in the PWS group on all EFs and after controlling for IQ level, intergroup differences remained only for switching and cognitive estimation. In conclusion, PWS seems to be associated with a global impairment of EFs that appears to be closely linked with intellectual impairment but also with the PWS itself.

  7. Longitudinal Modeling of Functional Decline Associated with Pathologic Alzheimer's Disease in Older Persons without Cognitive Impairment.

    PubMed

    Wang, Dai; Schultz, Tim; Novak, Gerald P; Baker, Susan; Bennett, David A; Narayan, Vaibhav A

    2018-01-01

    Therapeutic research on Alzheimer's disease (AD) has moved to intercepting the disease at the preclinical phase. Most drugs in late development have focused on the amyloid hypothesis. To understand the magnitude of amyloid-related functional decline and to identify the functional domains sensitive to decline in a preclinical AD population. Data were from the Religious Orders Study and the Rush Memory and Aging Project. Cognitive decline was measured by a modified version of the Alzheimer's Disease Cooperative Study Preclinical Alzheimer Cognitive Composite. The trajectories of functional decline, as measured by the instrumental and basic activities of daily living, were longitudinally modeled in 484 participants without cognitive impairment at baseline and having both a final clinical and a postmortem neuropathology assessment of AD. Individuals with different final clinical diagnoses had different trajectories of cognitive and functional decline. Individuals with AD dementia, minor cognitive impairment, and no cognitive impairment had the most, intermediate, and least declines. While individuals with pathologic AD had significantly more cognitive decline over time than those without, the magnitude of difference in functional decline between these two groups was small. Functional domains such as handling finance and handling medications were more sensitive to decline. Demonstrating the functional benefit of an amyloid-targeting drug represents a significant challenge as elderly people experience functional decline due to a wide range of reasons with limited manifestation attributable to AD neuropathology. More sensitive functional scales focusing on the functional domains sensitive to decline in preclinical AD are needed.

  8. The impact of IUGR on pancreatic islet development and β-cell function.

    PubMed

    Boehmer, Brit H; Limesand, Sean W; Rozance, Paul J

    2017-11-01

    Placental insufficiency is a primary cause of intrauterine growth restriction (IUGR). IUGR increases the risk of developing type 2 diabetes mellitus (T2DM) throughout life, which indicates that insults from placental insufficiency impair β-cell development during the perinatal period because β-cells have a central role in the regulation of glucose tolerance. The severely IUGR fetal pancreas is characterized by smaller islets, less β-cells, and lower insulin secretion. Because of the important associations among impaired islet growth, β-cell dysfunction, impaired fetal growth, and the propensity for T2DM, significant progress has been made in understanding the pathophysiology of IUGR and programing events in the fetal endocrine pancreas. Animal models of IUGR replicate many of the observations in severe cases of human IUGR and allow us to refine our understanding of the pathophysiology of developmental and functional defects in islet from IUGR fetuses. Almost all models demonstrate a phenotype of progressive loss of β-cell mass and impaired β-cell function. This review will first provide evidence of impaired human islet development and β-cell function associated with IUGR and the impact on glucose homeostasis including the development of glucose intolerance and diabetes in adulthood. We then discuss evidence for the mechanisms regulating β-cell mass and insulin secretion in the IUGR fetus, including the role of hypoxia, catecholamines, nutrients, growth factors, and pancreatic vascularity. We focus on recent evidence from experimental interventions in established models of IUGR to understand better the pathophysiological mechanisms linking placental insufficiency with impaired islet development and β-cell function. © 2017 Society for Endocrinology.

  9. Cognitive function affects trainability for physical performance in exercise intervention among older adults with mild cognitive impairment.

    PubMed

    Uemura, Kazuki; Shimada, Hiroyuki; Makizako, Hyuma; Doi, Takehiko; Yoshida, Daisuke; Tsutsumimoto, Kota; Anan, Yuya; Suzuki, Takao

    2013-01-01

    Although much evidence supports the hypothesis that cognitive function and physical function are interrelated, it is unclear whether cognitive decline with mild cognitive impairment influences trainability of physical performance in exercise intervention. The purpose of this study was to examine the association between cognitive function at baseline and change in physical performance after exercise intervention in older adults with mild cognitive impairment. Forty-four older adults diagnosed with mild cognitive impairment based on the Peterson criteria (mean age 74.8 years) consented to and completed a 6-month twice weekly exercise intervention. The Timed Up and Go (TUG) test was used as a measure of physical performance. The Mini-Mental State Examination (MMSE), Trail Making Test Part B, Geriatric Depression Scale, baseline muscle strength of knee extension, and attendance rate of intervention, were measured as factors for predicting trainability. In the correlation analysis, the change in TUG showed modest correlations with attendance rate in the exercise program (r = -0.354, P = 0.027) and MMSE at baseline (r = -0.321, P = 0.034). A multiple regression analysis revealed that change in TUG was independently associated with attendance rate (β = -0.322, P = 0.026) and MMSE score (β = -0.295, P = 0.041), controlling for age and gender. General cognitive function was associated with improvements in physical performance after exercise intervention in subjects with mild cognitive impairment. Further research is needed to examine the effects of exercise programs designed to address cognitive obstacles in older adults with mild cognitive impairment.

  10. Factors associated with cognitive impairment in patients with Parkinson disease: an urban study.

    PubMed

    Rosdinom, R; Fazli, A; Ruzyanei, N J Nik; Azlin, B; Srijit, D

    2011-01-01

    Parkinson disease (PD) is the second most prevalent neurodegenerative disorder after Alzheimer disease. Besides motor presentations, cognitive impairment is among the other likely complications as the illness progresses. This study aimed to determine the prevalence of cognitive impairment in PD and the factors associated with the cognitive impairment. A cross-sectional, descriptive study was conducted on all PD patients at different stages of their illness, in two major tertiary hospitals in Malaysia with their caregivers, over a three month period in 2002. Patients' cognitive functions were tested using the Mini Mental State Examination (MMSE). Important sociodemographic data and relevant clinical information of the patients as well as caregivers' information on income, duration of care-giving, relationship with the patient, and other relevant variables were gathered. Patients' level of functioning was assessed using the Activities of Daily Living (ADL) index. Staging of illness was done based on the Hoehn and Yahr Scale. Out of 115 eligible patients, 35% were in the 60-69 age group with 57% in stage 2 of illness, A total of 29% of patients experienced various degrees of cognitive impairment , with almost half (47%) in the stage 3 and 4 exhibiting MMSE scores <24. Factors which were significantly associated with impaired cognitions were race, educational level and stage of illness. Cognitive impairment was fairly common in PD and the severity of impairment in cognition and physical functioning increased with the advancement of the illness.

  11. The effects of aging on insight into illness in schizophrenia: a review†

    PubMed Central

    Gerretsen, Philip; Plitman, Eric; Rajji, Tarek K.; Graff-Guerrero, Ariel

    2015-01-01

    Objectives Impaired insight into illness is a prevalent feature of schizophrenia, which negatively influences treatment adherence and clinical outcomes. Little is known about the effects of aging on insight impairment. We aimed to review the available research literature on the effects of aging on insight into illness in schizophrenia, in relation to positive, negative, and cognitive symptoms. Ultimately, we propose a trajectory of insight in schizophrenia across the lifespan. Method A systematic Medline® literature search was conducted, searching for English language studies describing the relationship of insight into illness in schizophrenia with aging. Results We identified 62 studies. Insight impairment is associated with illness severity, premorbid intellectual function (i.e. IQ), executive function, and memory. Insight impairment improves modestly during midlife, worsening again in late life. It tends to fluctuate with each episode of psychosis, likely in relation to worsening positive symptoms that improve with antipsychotic treatment. The relationship between insight impairment and cognitive dysfunction appears to attenuate with age, while the relationship with lower premorbid intellectual function is preserved. The association between impaired insight and negative symptoms is unclear. Conclusions The available literature suggests that the course of insight impairment follows a U-shaped curve, where insight impairment is severe during the first episode of psychosis, modestly improves over midlife, and declines again in late life. Future studies are required to investigate the trajectory of insight into illness and its core domains across the lifespan from prodromal phase to late life. PMID:25055980

  12. Depression and pain impair daily functioning and quality of life in patients with major depressive disorder.

    PubMed

    Lin, Ching-Hua; Yen, Yung-Chieh; Chen, Ming-Chao; Chen, Cheng-Chung

    2014-09-01

    Depression and pain frequently occur together. The objective of this study was to investigate the effects of depression and pain on the impairment of daily functioning and quality of life (QOL) of depressed patients. We enrolled 131 acutely ill inpatients with major depressive disorder. Depression, pain, and daily functioning were assessed using the 17-item Hamilton Depression Rating Scale, the Short-Form 36 (SF-36) Body Pain Index, and the Work and Social Adjustment Scale. Health-related QOL was assessed using three primary domains of the SF-36: social functioning, vitality, and general health perceptions. Pearson׳s correlation and structural equation modeling were used to examine relationships among the study variables. Five models were proposed. In all, 129 patients completed all the measures. Model 5, both depression and pain impaired daily functioning and QOL, was the most fitted structural equation model (χ(2)=9.2, df=8, p=0.33, GFI=0.98, AGFI=0.94, TLI=0.99, CFI=0.99, RMSEA=0.03). The correlation between pain and depression was weak (r=-0.27, z=-2.95, p=0.003). This was a cross-sectional study with a small sample size. Depression and pain exert a direct influence on the impairment of daily functioning and QOL of depressed patients; this impairment could be expected regardless of increased pain, depression, or both pain and depression. Pain had a somewhat separate entity from depression. Copyright © 2014. Published by Elsevier B.V.

  13. Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis.

    PubMed

    Liu, Luyan; Okada, Satoshi; Kong, Xiao-Fei; Kreins, Alexandra Y; Cypowyj, Sophie; Abhyankar, Avinash; Toubiana, Julie; Itan, Yuval; Audry, Magali; Nitschke, Patrick; Masson, Cécile; Toth, Beata; Flatot, Jérome; Migaud, Mélanie; Chrabieh, Maya; Kochetkov, Tatiana; Bolze, Alexandre; Borghesi, Alessandro; Toulon, Antoine; Hiller, Julia; Eyerich, Stefanie; Eyerich, Kilian; Gulácsy, Vera; Chernyshova, Ludmyla; Chernyshov, Viktor; Bondarenko, Anastasia; Grimaldo, Rosa María Cortés; Blancas-Galicia, Lizbeth; Beas, Ileana Maria Madrigal; Roesler, Joachim; Magdorf, Klaus; Engelhard, Dan; Thumerelle, Caroline; Burgel, Pierre-Régis; Hoernes, Miriam; Drexel, Barbara; Seger, Reinhard; Kusuma, Theresia; Jansson, Annette F; Sawalle-Belohradsky, Julie; Belohradsky, Bernd; Jouanguy, Emmanuelle; Bustamante, Jacinta; Bué, Mélanie; Karin, Nathan; Wildbaum, Gizi; Bodemer, Christine; Lortholary, Olivier; Fischer, Alain; Blanche, Stéphane; Al-Muhsen, Saleh; Reichenbach, Janine; Kobayashi, Masao; Rosales, Francisco Espinosa; Lozano, Carlos Torres; Kilic, Sara Sebnem; Oleastro, Matias; Etzioni, Amos; Traidl-Hoffmann, Claudia; Renner, Ellen D; Abel, Laurent; Picard, Capucine; Maródi, László; Boisson-Dupuis, Stéphanie; Puel, Anne; Casanova, Jean-Laurent

    2011-08-01

    Chronic mucocutaneous candidiasis disease (CMCD) may be caused by autosomal dominant (AD) IL-17F deficiency or autosomal recessive (AR) IL-17RA deficiency. Here, using whole-exome sequencing, we identified heterozygous germline mutations in STAT1 in 47 patients from 20 kindreds with AD CMCD. Previously described heterozygous STAT1 mutant alleles are loss-of-function and cause AD predisposition to mycobacterial disease caused by impaired STAT1-dependent cellular responses to IFN-γ. Other loss-of-function STAT1 alleles cause AR predisposition to intracellular bacterial and viral diseases, caused by impaired STAT1-dependent responses to IFN-α/β, IFN-γ, IFN-λ, and IL-27. In contrast, the 12 AD CMCD-inducing STAT1 mutant alleles described here are gain-of-function and increase STAT1-dependent cellular responses to these cytokines, and to cytokines that predominantly activate STAT3, such as IL-6 and IL-21. All of these mutations affect the coiled-coil domain and impair the nuclear dephosphorylation of activated STAT1, accounting for their gain-of-function and dominance. Stronger cellular responses to the STAT1-dependent IL-17 inhibitors IFN-α/β, IFN-γ, and IL-27, and stronger STAT1 activation in response to the STAT3-dependent IL-17 inducers IL-6 and IL-21, hinder the development of T cells producing IL-17A, IL-17F, and IL-22. Gain-of-function STAT1 alleles therefore cause AD CMCD by impairing IL-17 immunity.

  14. Apathy, but not depression, is associated with executive dysfunction in cerebral small vessel disease

    PubMed Central

    Hollocks, Matthew J.; Morris, Robin G.; Markus, Hugh S.

    2017-01-01

    Objective To determine the prevalence of apathy and depression in cerebral small vessel disease (SVD), and the relationships between both apathy and depression with cognition. To examine whether apathy is specifically related to impairment in executive functioning and processing speed. Methods 196 patients with a clinical lacunar stroke and an anatomically corresponding lacunar infarct on MRI were compared to 300 stroke-free controls. Apathy and depression were measured using the Geriatric Depression Scale, and cognitive functioning was assessed using an SVD cognitive screening tool, the Brief Memory and Executive Test, which measures executive functioning/processing speed and memory/orientation. Path analysis and binary logistic regression were used to assess the relation between apathy, depression and cognitive impairment. Results 31 participants with SVD (15.8%) met criteria for apathy only, 23 (11.8%) for both apathy and depression, and 2 (1.0%) for depression only. In the SVD group the presence of apathy was related to global cognition, and specifically to impaired executive functioning/processing speed, but not memory/orientation. The presence of depression was not related to global cognition, impaired executive functioning/processing speed or memory/orientation. Conclusions Apathy is a common feature of SVD and is associated with impaired executive functioning/processing speed suggesting the two may share biological mechanisms. Screening for apathy should be considered in SVD, and further work is required to develop and evaluate effective apathy treatment or management in SVD. PMID:28493898

  15. Robotic Characterization of Ipsilesional Motor Function in Subacute Stroke.

    PubMed

    Semrau, Jennifer A; Herter, Troy M; Kenzie, Jeffrey M; Findlater, Sonja E; Scott, Stephen H; Dukelow, Sean P

    2017-06-01

    Poststroke impairments of the ipsilesional arm are often discussed, but rarely receive focused rehabilitation. Ipsilesional deficits may affect daily function and although many studies have investigated them in chronic stroke, few characterizations have been made in the subacute phase. Furthermore, most studies have quantified ipsilesional deficits using clinical measures that can fail to detect subtle, but important deficits in motor function. We aimed to quantify reaching deficits of the contra- and ipsilesional limbs in the subacute phase poststroke. A total of 227 subjects with first-time, unilateral stroke completed a unilateral assessment of motor function (visually guided reaching) using a KINARM robot. Subjects completed the task with both the ipsi- and contralesional arms. Subjects were assessed on a variety of traditional clinical measures (Functional Independence Measure, Chedoke-McMaster Stroke Assessment, Purdue Pegboard, Behavioral Inattention Test) to compare with robotic measures of motor function. Ipsilesional deficits were common and occurred in 37% (n = 84) of subjects. Impairments of the ipsilesional and contralesional arm were weakly to moderately correlated on robotic measures. Magnitude of impairment of the contralesional arm was similar for subjects with and without ipsilesional deficits. Furthermore, we found that a higher percentage of subjects with right-hemisphere stroke had ipsilesional deficits and more subjects with left-hemisphere subcortical strokes did not have ipsilesional deficits. Magnitude of contralesional impairment and lesion location may be poor predictors of individuals with ipsilesional impairments after stroke. Careful characterization of ipsilesional deficits could identify individuals who may benefit from rehabilitation of the less affected arm.

  16. Cognitive functioning in the first-episode of major depressive disorder: A systematic review and meta-analysis.

    PubMed

    Ahern, Elayne; Semkovska, Maria

    2017-01-01

    Cognitive deficits are frequently observed in major depression. Yet, when these deficits emerge and how they relate to the depressed state is unclear. The aim of this 2-part systematic review and meta-analysis is to determine the pattern and extent of cognitive deficits during a first-episode of depression (FED) and their persistence following FED remission. Published, peer-reviewed articles on cognitive function in FED patients through October 2015 were searched. Meta-analyses with random-effects modeling were conducted. Part 1 assessed weighted, mean effect sizes of cognitive function in FED patients relative to healthy controls. Moderator analyses of clinical and demographical variables effects were conducted. Part 2 assessed weighted, mean effect sizes of change in cognitive function at remission compared with acute FED performance in longitudinal studies. Thirty-one studies including 994 FED patients were retained in Part 1. Relative to healthy controls, small to large impairments were observed across most cognitive domains. Remission was associated with a normalization of function in processing speed, learning and memory, autobiographical memory, shifting, and IQ. Lower FED age was associated with higher IQ, but more impairment in word-list delayed memory. Four studies including 92 FED patients were retained in Part 2. Following remission, FED patients showed small improvements in processing speed and shifting but persistent impairment in inhibition and verbal fluency. Significant cognitive deficits are already identifiable during a FED, with some functions showing persistent impairment upon remission. Clinicians must consider cognitive impairment alongside mood symptoms to ensure functional recovery from the FED. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  17. Central Processing Energetic Factors Mediate Impaired Motor Control in ADHD Combined Subtype but Not in ADHD Inattentive Subtype

    ERIC Educational Resources Information Center

    Egeland, Jens; Ueland, Torill; Johansen, Susanne

    2012-01-01

    Participants with attention-deficit/hyperactivity disorder (ADHD) are often impaired in visuomotor tasks. However, little is known about the contribution of modal impairment in motor function relative to central processing deficits or whether different processes underlie the impairment in ADHD combined (ADHD-C) versus ADHD inattentive (ADHD-I)…

  18. Assessing Psychosocial Impairment in Children and Adolescents: A Review of the Barkley Functional Impairment Scale (BFIS)

    ERIC Educational Resources Information Center

    McGill, Ryan J.

    2014-01-01

    Appraising psychosocial impairment is an essential enterprise of diagnostic decision-making in the field of school psychology. Despite its importance, few practitioners utilize systematic procedures when engaging in this process, despite the fact that a number of impairment measures and scales have been developed specifically for this purpose. The…

  19. Residual symptoms and specific functional impairments in euthymic patients with bipolar disorder.

    PubMed

    Samalin, Ludovic; de Chazeron, Ingrid; Vieta, Eduard; Bellivier, Frank; Llorca, Pierre-Michel

    2016-03-01

    The aims of the present study were to confirm the impact of residual symptoms on overall functioning in a large sample of euthymic patients with bipolar disorder in real-life conditions and to explore the relationship between residual symptoms and specific areas of functional impairment. This was a multicenter, cross-sectional, non-interventional study of euthymic outpatients with bipolar disorder. The Functioning Assessment Short Test was used to assess overall and specific domains of functioning (autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time). Various residual symptoms were assessed (residual mood symptoms, emotional dysregulation, sleep and sexual disorders, stigma, and perceived cognitive impairment). Logistic regression was used to determine the best model of association between functional domains and residual symptoms. Almost half of the 468 patients included (42%) had poor overall functioning. Residual depressive symptoms appeared to have an impact on overall functioning and in nearly all areas of functioning. In addition, specific residual symptoms had significantly more negative effects on some domains of functioning in euthymic patients with bipolar disorder (residual manic symptoms and occupational stigma on autonomy, emotional inhibition on occupational functioning, residual manic symptoms on financial issues, family stigma on interpersonal relationships, and sexual function and occupational stigma on leisure time). Our findings highlight the importance of evaluating overall functioning in clinical practice as well as functional domains. They also indicate that some residuals symptoms in patients with bipolar disorder should be targeted in personalized treatment plans, in order to improve functioning in the domains in which the patient is most impaired. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Key neurological impairments influence function-related group outcomes after stroke.

    PubMed

    Han, Lu; Law-Gibson, Diane; Reding, Michael

    2002-07-01

    The function-related group (FRG) classification is based on functional assessment and has been assumed to encompass the effects of different patterns and severity of neurological impairments. This assumption may not be correct. It has been proposed as a means of comparing rehabilitation outcome across institutions. If neurological impairments significantly affect FRG outcome, then higher FRG outcome scores may reflect selection bias favoring patients with fewer neurological impairments rather than better quality of rehabilitation care. The goal of this study was to assess the influence of motor, somatosensory, and hemianopic visual impairments on FRG outcomes after stroke. All 288 consecutive stroke patients discharged in 1999 from an acute rehabilitation hospital were assigned to 1 of 5 FRGs on the basis of their Functional Independence Measure (FIM) mobility subscore and age. Each FRG was also stratified into 1 of 4 cohorts on the basis of the presence or absence of key neurological impairments: motor impairment only (M), motor plus either somatosensory or hemianopic visual impairment (MS/MV), motor plus somatosensory plus hemianopic visual impairment (MSV), and other combinations of impairments. FIM scores were available every 10 days for all patients from admission to discharge. The effect of impairment group on outcome was assessed within each FRG category through repeated-measures analysis of variance to assess differences in serial FIM scores across the 4 impairment groups. The distribution of each of the 4 impairment groups across the 5 FRGs was assessed with chi2 analysis. The numbers of patients in each of the 5 FRGs from the lowest level, FRG-11, to the highest, FRG-15, were as follows: 78 (27%), 47 (16%), 75 (26%), 55 (19%), and 33 (11%). Different neurological impairments were associated with significantly different mean+/-SD discharge FIM scores as follows: for FRG-11, MSV=63+/-16, MS/MV=68+/-19, and M=81+/-13 (P=0.04); for FRG-12, MSV=47+/-14, MS/MV=61+/-12, and M=75+/-11 (P=0.01); and for FRG-13, MSV=79+/-20, MS/MV=85+/-19, and M=96+/-10 (P<0.02). For FRG-14 and FRG-15, those with M impairments had the highest and those with MSV impairments had the lowest discharge FIM scores, but the differences did not reach statistical significance. The chi2 analysis showed a highly significant difference in representation of MSV impairments across FRG-11 through FRG-15 as follows: 35 of 78 (45%), 20 of 47 (43%), 11 of 74 (15%), 4 of 55 (7%), and 2 of 33 (6%). For patients classified as having an M deficit only or other impairment, the results were as follows: 19 of 78 (24%), 15 of 47 (32%), 41 of 75 (55%), 41 of 55 (75%), and 27 of 33 (82%) (chi(2) analysis=78.7, P<0.0001). The presence of motor, somatosensory, and hemianopic visual impairment significantly affects FRG outcome and should be included in future outcome assessment tools. Comparisons of FIM change and efficiency scores across institutions are potentially biased by referral and selection criteria favoring equally dysfunctional but less neurologically impaired individuals.

  1. Functional Impairment and Painful Physical Symptoms in Patients with Major Depressive Disorder Treated with Antidepressants: Real-World Evidence from the Middle East.

    PubMed

    Hong, Jihyung; Novick, Diego; Moneta, Maria Victoria; El-Shafei, Ahmed; Dueñas, Héctor; Haro, Josep Maria

    2017-01-01

    The Global Burden of Disease 2010 study reported the relative size of major depressive disorder (MDD) burden to be greater in the Middle East and North Africa than anywhere else. However, little research has been carried out to examine the comparative effectiveness of antidepressants in this region. To assess and compare functioning levels in Middle Eastern patients with MDD treated with either duloxetine or a selective serotonin reuptake inhibitor (SSRI), and to examine the impacts of depression-related pain on functioning by the type of treatment. This post-hoc analysis, which focused on Middle Eastern patients, used data from a 6-month prospective observational study that included 1,549 MDD patients without sexual dysfunction. Levels of functional impairment and depression-related pain were assessed using the Sheehan Disability Scale (SDS) and the modified Somatic Symptom Inventory, respectively. A mixed model with repeated measures (MMRM) was employed. The mean age of the patients was 37.3 (SD=8.4) years, and 34.6% were female. Patient functioning was, on average, moderately impaired at baseline, but improved substantially during follow-up in both the duloxetine (n=152) and the SSRI (n=123) cohorts. The MMRM results showed a lower level of functional impairment at 24 weeks in the duloxetine cohort than in the SSRI cohort (p<0.001). Pain severity at baseline was positively associated with functional impairment during follow-up only in the SSRI cohort (p=0.003). Duloxetine-treated MDD patients achieved better functioning than SSRI-treated patients. This treatment difference was partly driven by depression-related pain.

  2. Is Early-onset in Major Depression a Predictor of Specific Clinical Features with More Impaired Social Function?

    PubMed Central

    Liu, Yan-Hong; Chen, Lin; Su, Yun-Ai; Fang, Yi-Ru; Srisurapanont, Manit; Hong, Jin Pyo; Hatim, Ahmad; Chua, Hong Choon; Bautista, Dianne; Si, Tian-Mei

    2015-01-01

    Background: Early-onset major depressive disorder (MDD) (EOD) is often particularly malignant due to its special clinical features, accompanying impaired social function, protracted recovery time, and frequent recurrence. This study aimed to observe the effects of age onset on clinical characteristics and social function in MDD patients in Asia. Methods: In total, 547 out-patients aged 18–65 years who were from 13 study sites in five Asian countries were included. These patients had MDD diagnose according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria. Clinical features and social function were assessed using Symptom Checklist-90-revised (SCL-90-R) and Sheehan Disability Scale (SDS). Quality of life was assessed by a 36-item Short-form Health Survey (SF-36). Analyses were performed using a continuous or dichotomous (cut-off: 30 years) age-of-onset indicator. Results: Early-onset MDD (EOD, <30 years) was associated with longer illness (P = 0.003), unmarried status (P < 0.001), higher neuroticism (P ≤ 0.002) based on the SCL-90-R, and more limited social function and mental health (P = 0.006, P = 0.007) based on the SF-36 and SDS. The impairment of social function and clinical severity were more prominent at in-patients with younger onset ages. Special clinical features and more impaired social function and quality of life were associated with EOD, as in western studies. Conclusions: EOD often follows higher levels of neuroticism. Age of onset of MDD may be a predictor of clinical features and impaired social function, allowing earlier diagnosis and treatment. PMID:25758278

  3. Illness Denial in Schizophrenia Spectrum Disorders: A Function of Left Hemisphere Dominance

    PubMed Central

    Gerretsen, Philip; Menon, Mahesh; Chakravarty, M. Mallar; Lerch, Jason P; Mamo, David C.; Remington, Gary; Pollock, Bruce G; Graff-Guerrero, Ariel

    2014-01-01

    Impaired illness awareness or anosognosia is a common, but poorly understood feature of schizophrenia that contributes to medication nonadherence and poor treatment outcomes. Here we present a functional imaging study to measure brain activity at the moment of illness denial. To accomplish this, participants with schizophrenia (n = 18) with varying degrees of illness awareness were confronted with their illness beliefs while undergoing functional MRI. To link structure with function, we explored the relationships among impaired illness awareness and brain activity during the illness denial task with cortical thickness (CT). Impaired illness awareness was associated with increased brain activity in the left temporoparietooccipital junction (TPO) and left medial prefrontal cortex (mPFC) at the moment of illness denial. Brain activity in the left mPFC appeared to be a function of participants’ degree of self-reflectiveness, while the activity in the left TPO was associated with cortical thinning in this region and more specific to illness denial. Participants with impaired illness awareness had slower response times to illness related stimuli than those with good illness awareness. Increased left hemisphere brain activity in association with illness denial is consistent with the literature in other neuropsychiatric conditions attributing anosognosia or impaired illness awareness to left hemisphere dominance. The TPO and mPFC may represent putative targets for non-invasive treatment interventions, such as transcranial magnetic or direct current stimulation. PMID:25209949

  4. More than Memory Impairment in Voltage-Gated Potassium Channel Complex Encephalopathy

    PubMed Central

    Bettcher, Brianne M.; Gelfand, Jeffrey M.; Irani, Sarosh R.; Neuhaus, John; Forner, Sven; Hess, Christopher P.; Geschwind, Michael D.

    2014-01-01

    Objective Autoimmune encephalopathies (AE) are a heterogeneous group of neurological disorders that affect cognition. Although memory difficulties are commonly endorsed, few reports of AE inclusively assess all cognitive domains in detail. Our aim was to perform an unbiased cognitive evaluation of AE patients with voltage-gated potassium channel complex antibodies (VGKCC-Abs) in order to delineate cognitive strengths and weaknesses. Methods We assessed serial VGKCC-Abs AE subjects (n=12) with a comprehensive evaluation of memory, executive functions, visuospatial skills, and language. Clinical MRI (n=10/12) was evaluated. Five subjects had serial cognitive testing available, permitting descriptive analysis of change. Results Subjects demonstrated mild to moderate impairment in memory (mean Z=−1.9) and executive functions (mean Z=−1.5), with variable impairments in language and sparing of visuospatial skills. MRI findings showed T2 hyperintensities in medial temporal lobe (10/10) and basal ganglia (2/10). Serial cognitive examination revealed heterogeneity in cognitive function; whereas most patients improved in one or more domains, residual impairments were observed in some patients. Conclusions This study augments prior neuropsychological analyses in VGKCC-Ab AE by identifying not only memory and executive function deficits, but also language impairments, with preservation of visuospatial functioning. This study further highlights the importance of domain-specific testing to parse out the complex cognitive phenotypes of VGKCC-Ab AE. PMID:24981998

  5. Maintaining routine despite ongoing exposure to terrorism: a healthy strategy for adolescents?

    PubMed

    Pat-Horenczyk, Ruth; Schiff, Miriam; Doppelt, Osnat

    2006-08-01

    To examine the association between ongoing terrorism and Israeli adolescents' routine activities. A total of 1336 junior high and high school students from Jerusalem (46.9% boys and 53.1% girls) self-reported on measures of maintaining or reducing their level of routine activities, perceived parental monitoring, posttraumatic symptoms (PTS) and functional impairment. We used linear regressions to explore possible associations between decreasing (or maintaining) level of routine activities, parental monitoring, and PTS and functional impairment. A majority of the adolescents reported that under the recurrent threat of terrorism they maintained their routine (i.e., 65.8% continued using public transportation). Similarly, more than half the students perceived their parents as encouraging them to maintain their routine activities. Furthermore, greater exposure to terrorism was associated with more PTS symptoms and functional impairment. Nonetheless, a reduced level of routine activities was a significant predictor for higher PTS and functional impairment, even after controlling for level of exposure to terrorism, gender and age. Similarly, perceived parental limiting of routine activities was a significant predictor for higher PTS and functional impairment, even after controlling for gender, age and the level of exposure to terrorism. Our results support practitioners' recommendations to encourage continuity in daily routine. Disruption of routine activities may result in the development of avoidance reactions that can lead to posttraumatic stress disorder.

  6. Getting the Words Out: Case Studies in Facilitated Communication Training.

    ERIC Educational Resources Information Center

    Crossley, Rosemary

    1992-01-01

    Case studies are presented of three individuals with severe communication impairments who had been judged to be intellectually impaired but revealed unexpected achievements after training in nonspeech communication. The communication training used facilitation to circumvent hand function impairments. (JDD)

  7. Relations of Metabolically Healthy and Unhealthy Obesity to Digital Vascular Function in Three Community-Based Cohorts: A Meta-Analysis.

    PubMed

    Brant, Luisa C C; Wang, Na; Ojeda, Francisco M; LaValley, Michael; Barreto, Sandhi M; Benjamin, Emelia J; Mitchell, Gary F; Vasan, Ramachandran S; Palmisano, Joseph N; Münzel, Thomas; Blankenberg, Stefan; Wild, Philipp S; Zeller, Tanja; Ribeiro, Antonio L P; Schnabel, Renate B; Hamburg, Naomi M

    2017-03-08

    Microvascular dysfunction is a marker of early vascular disease that predicts cardiovascular events. Whether metabolically healthy obese individuals have impaired microvascular function remains unclear. The aim of this study was to evaluate the relation of obesity phenotypes stratified by metabolic status to microvascular function. We meta-analyzed aggregate data from 3 large cohorts (Brazilian Longitudinal Study of Adult Health, the Framingham Heart Study, and the Gutenberg Heart Study; n=16 830 participants, age range 19-90, 51.3% men). Regression slopes between cardiovascular risk factors and microvascular function, measured by peripheral arterial tonometry (PAT), were calculated. Individuals were classified as normal-weight, overweight, or obese by body mass index (BMI) and stratified by healthy or unhealthy metabolic status based on metabolic syndrome using the ATP-III criteria. Male sex, BMI, and metabolic risk factors were associated with higher baseline pulse amplitude and lower PAT ratio. There was stepwise impairment of vascular measures from normal weight to obesity in both metabolic status strata. Metabolically healthy obese individuals had more impaired vascular function than metabolically healthy normal-weight individuals (baseline pulse amplitude 6.12±0.02 versus 5.61±0.01; PAT ratio 0.58±0.01 versus 0.76±0.01, all P <0.0001). Metabolically unhealthy obese individuals had more impaired vascular function than metabolically healthy obese individuals (baseline pulse amplitude 6.28±0.01 versus 6.12±0.02; PAT ratio 0.49±0.01 versus 0.58±0.01, all P <0.0001). Metabolically healthy obese individuals have impaired microvascular function, though the degree of impairment is less marked than in metabolically unhealthy obese individuals. Our findings suggest that obesity is detrimental to vascular health irrespective of metabolic status. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  8. Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury

    PubMed Central

    De Simoni, Sara; Jenkins, Peter O; Bourke, Niall J; Fleminger, Jessica J; Jolly, Amy E; Patel, Maneesh C; Leech, Robert; Sharp, David J

    2018-01-01

    Abstract Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with measures of executive dysfunction. We show for the first time that altered subcortical connectivity is associated with large-scale network disruption in traumatic brain injury and that this disruption is related to the cognitive impairments seen in these patients. PMID:29186356

  9. Symptoms of Problematic Cellular Phone Use, Functional Impairment and Its Association with Depression among Adolescents in Southern Taiwan

    ERIC Educational Resources Information Center

    Yen, Cheng-Fang; Tang, Tze-Chun; Yen, Ju-Yu; Lin, Huang-Chi; Huang, Chi-Fen; Liu, Shu-Chun; Ko, Chih-Hung

    2009-01-01

    The aims of this study were: (1) to examine the prevalence of symptoms of problematic cellular phone use (CPU); (2) to examine the associations between the symptoms of problematic CPU, functional impairment caused by CPU and the characteristics of CPU; (3) to establish the optimal cut-off point of the number of symptoms for functional impairment…

  10. Executive Function Variation in Children with Conduct Problems: Influences of Coexisting Reading Difficulties

    ERIC Educational Resources Information Center

    Kallitsoglou, Angeliki

    2018-01-01

    It is unknown whether children with conduct problems (CP) and poor reading (PR) skills exhibit more profound executive function impairments than children with CP only and whether such impairments are explained by coexisting PR. Executive functions were compared in four groups of 7- to 8-year-old children: 26 CP only, 35 PR only, 27 CP-PR, and 31…

  11. Effect of sensory and motor connectivity on hand function in pediatric hemiplegia.

    PubMed

    Gupta, Disha; Barachant, Alexandre; Gordon, Andrew M; Ferre, Claudio; Kuo, Hsing-Ching; Carmel, Jason B; Friel, Kathleen M

    2017-11-01

    We tested the hypothesis that somatosensory system injury would more strongly affect movement than motor system injury in children with unilateral cerebral palsy (USCP). This hypothesis was based on how somatosensory and corticospinal circuits adapt to injury during development; whereas the motor system can maintain connections to the impaired hand from the uninjured hemisphere, this does not occur in the somatosensory system. As a corollary, cortical injury strongly impairs sensory function, so we hypothesized that cortical lesions would impair hand function more than subcortical lesions. Twenty-four children with unilateral cerebral palsy had physiological and anatomical measures of the motor and somatosensory systems and lesion classification. Motor physiology was performed with transcranial magnetic stimulation and somatosensory physiology with vibration-evoked electroencephalographic potentials. Tractography of the corticospinal tract and the medial lemniscus was performed with diffusion tensor imaging, and lesions were classified by magnetic resonance imaging. Anatomical and physiological results were correlated with measures of hand function using 2 independent statistical methods. Children with disruptions in the somatosensory connectivity and cortical lesions had the most severe upper extremity impairments, particularly somatosensory function. Motor system connectivity was significantly correlated with bimanual function, but not unimanual function or somatosensory function. Both sensory and motor connectivity impact hand function in children with USCP. Somatosensory connectivity could be an important target for recovery of hand function in children with USCP. Ann Neurol 2017;82:766-780. © 2017 American Neurological Association.

  12. Visual function of children with visual and other disabilities in Oman: A case series.

    PubMed

    Gogri, Urmi; Khandekar, Rajiv; Al Harby, Salah

    2016-12-01

    We assessed the visual functioning of the children with special needs in Oman between 2009 and 2012. We present the methods of assessing different visual functions, outcomes, and interventions carried out to improve their functioning. Optometrists assessed visual functions of children of "Day care centres" in Oman. Experts further assessed them and provided low vision care. Ocular movements, refractive corrections, near, distance, contrast color, motion, field of vision, and cognitive visual function test results were noted. Feedback to caregivers was given to improve visual functioning of these children. We grouped 321 participants, (196 [61.1%] boys, age range of 3-18 years) into 61; Down syndrome (DS), 72 with intellectual disabilities (IDs), 67; hearing impaired and 121 with other conditions. Refractive error and lag of accommodation were 26 (42.6%) and 14 (22.6%) among children with DS. Contrast sensitivity was impaired in 8 (12.7%) among hearing impaired children. Defective distant and near vision was in 162 (70%) and 104 (42%) of our cohort. Children with ID were most difficult to assess. Children in a group of other disabilities had a higher proportion of impaired visual functioning. They were given low vision aids (telescopes [22], filters [7], and magnifiers [3]) in large numbers compared to those in other groups. Visual functioning of children with other disabilities show great variation and difficult to group. The care, therefore, should be at individual level. All visual functions cannot be assessed at one time.

  13. Pharmacokinetics of the Novel Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone (BAY 94-8862) in Individuals With Renal Impairment.

    PubMed

    Heinig, Roland; Kimmeskamp-Kirschbaum, Nina; Halabi, Atef; Lentini, Silvia

    2016-11-01

    Finerenone (BAY 94-8862) is a nonsteroidal mineralocorticoid receptor antagonist in development for the treatment of diabetic kidney disease. This observational trial compared the pharmacokinetics of a single oral dose of finerenone 10 mg (immediate-release tablet) in adults with mild (creatinine clearance [CL CR ] 50-80 mL/min; n = 8), moderate (CL CR 30 to < 50 mL/min; n = 8), or severe (CL CR < 30 mL/min; n  =  9) renal impairment with those in adults with normal renal function (CL CR > 80 mL/min; n  = 8) over 96 hours postdose. Exposure to finerenone was not affected by mild renal impairment. In participants with moderate or severe renal impairment, exposure to finerenone was increased compared with those with normal renal function (increase in area under the curve for unbound finerenone, 57.1% [outlier excluded] and 46.5%, respectively), with moderate to high interindividual variability. Renal impairment had no consistent effect on the maximum plasma concentration, C max (differences in C max for unbound finerenone of +12% and -7% with moderate [outlier excluded] and severe impairment vs normal renal function, respectively). Renal elimination of finerenone is minimal. However, changes in exposure may occur because of the effects of renal impairment on nonrenal routes of elimination. © 2016, The American College of Clinical Pharmacology.

  14. A continuum of executive function deficits in early subcortical vascular cognitive impairment: A systematic review and meta-analysis

    PubMed Central

    Sudo, Felipe Kenji; Amado, Patricia; Alves, Gilberto Sousa; Laks, Jerson; Engelhardt, Eliasz

    2017-01-01

    ABSTRACT. Background. Subcortical Vascular Cognitive Impairment (SVCI) is a clinical continuum of vascular-related cognitive impairment, including Vascular Mild Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive Function (EF) are hallmarks of the disorder, but the best methods to assess this function have yet to be determined. The insidious and almost predictable course of SVCI and the multidimensional concept of EF suggest that a temporal dissociation of impairments in EF domains exists early in the disorder. Objective: This study aims to review and analyze data from the literature about performance of VaMCI patients on the most used EF tests through a meta-analytic approach. Methods: Medline, Web of Knowledge and PsycINFO were searched, using the terms: “vascular mild cognitive impairment” OR “vascular cognitive impairment no dementia” OR “vascular mild neurocognitive disorder” AND “dysexecutive” OR “executive function”. Meta-analyses were conducted for each of the selected tests, using random-effect models. Results: Systematic review showed major discrepancies among the results of the studies included. Meta-analyses evidenced poorer performance on the Trail-Making Test part B and the Stroop color test by VaMCI patients compared to controls. Conclusion: A continuum of EF impairments has been proposed in SVCI. Early deficits appear to occur in cognitive flexibility and inhibitory control. PMID:29354217

  15. Proverb comprehension impairments in schizophrenia are related to executive dysfunction.

    PubMed

    Thoma, Patrizia; Hennecke, Marie; Mandok, Tobias; Wähner, Alfred; Brüne, Martin; Juckel, Georg; Daum, Irene

    2009-12-30

    The study aimed to investigate the pattern of proverb comprehension impairment and its relationship to proverb familiarity and executive dysfunction in schizophrenia. To assess the specificity of the impairment pattern to schizophrenia, alcohol-dependent patients were included as a psychiatric comparison group, as deficits of executive function and theory of mind as well as dysfunction of the prefrontal cortex, which have been related to proverb comprehension difficulties, are common in both disorders. Twenty-four schizophrenia patients, 20 alcohol-dependent patients and 34 healthy controls were administered a multiple-choice proverb interpretation task incorporating ratings of subjective familiarity and measures of executive function. Schizophrenia patients chose the correct abstract and meaningful interpretations less frequently and instead chose the incorrect concrete (both meaningless and meaningful) proverb interpretations more often than alcohol-dependent patients and healthy controls. Relative to healthy controls, schizophrenia patients also chose more abstract-meaningless response alternatives and were impaired in all executive domains. Impaired divided attention was most consistently associated with proverb interpretation deficits in both patient groups. Taken together, schizophrenia patients showed a specific pattern of proverb comprehension impairments related to executive dysfunction and symptoms. The comparison with the alcohol-dependent subgroup suggests that a more comprehensive and severe impairment of complex higher-order cognitive functions including executive behavioural control and non-literal language comprehension might be associated with frontal dysfunction in schizophrenia as compared to alcohol use disorder.

  16. Impaired Calcium Entry into Cells Is Associated with Pathological Signs of Zinc Deficiency12

    PubMed Central

    O’Dell, Boyd L.; Browning, Jimmy D.

    2013-01-01

    Zinc is an essential trace element whose deficiency gives rise to specific pathological signs. These signs occur because an essential metabolic function is impaired as the result of failure to form or maintain a specific metal-ion protein complex. Although zinc is a component of many essential metalloenzymes and transcription factors, few of these have been identified with a specific sign of incipient zinc deficiency. Zinc also functions as a structural component of other essential proteins. Recent research with Swiss murine fibroblasts, 3T3 cells, has shown that zinc deficiency impairs calcium entry into cells, a process essential for many cell functions, including proliferation, maturation, contraction, and immunity. Impairment of calcium entry and the subsequent failure of cell proliferation could explain the growth failure associated with zinc deficiency. Defective calcium uptake is associated with impaired nerve transmission and pathology of the peripheral nervous system, as well as the failure of platelet aggregation and the bleeding tendency of zinc deficiency. There is a strong analogy between the pathology of genetic diseases that result in impaired calcium entry and other signs of zinc deficiency, such as decreased and cyclic food intake, taste abnormalities, abnormal water balance, skin lesions, impaired reproduction, depressed immunity, and teratogenesis. This analogy suggests that failure of calcium entry is involved in these signs of zinc deficiency as well. PMID:23674794

  17. The role of executive functions in social impairment in Autism Spectrum Disorder.

    PubMed

    Leung, Rachel C; Vogan, Vanessa M; Powell, Tamara L; Anagnostou, Evdokia; Taylor, Margot J

    2016-01-01

    Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by socio-communicative impairments. Executive dysfunction may explain some key characteristics of ASD, both social and nonsocial hallmarks. Limited research exists exploring the relations between executive function and social impairment in ASD and few studies have used a comparison control group. Thus, the objective of the present study was to investigate the relations between executive functioning using the Behavioral Rating Inventory of Executive Functioning (BRIEF), social impairment as measured by the Social Responsiveness Scale (SRS), and overall autistic symptomology as measured by the Autism Diagnostic Observation Schedule (ADOS) in children and adolescents with and without ASD. Seventy children and adolescents diagnosed with ASD and 71 typically developing controls were included in this study. Findings showed that behavioral regulation executive processes (i.e., inhibition, shifting, and emotional control) predicted social function in all children. However, metacognitive executive processes (i.e., initiation, working memory, planning, organization, and monitoring) predicted social function only in children with ASD and not in typically developing children. Our findings suggest a distinct metacognitive executive function-social symptom link in ASD that is not present in the typical population. Understanding components of executive functioning that contribute to the autistic symptomology, particularly in the socio-communicative domain, is crucial for developing effective interventions that target key executive processes as well as underlying behavioral symptoms.

  18. Specific Language Impairment in Language-Minority Children from Low-Income Families

    ERIC Educational Resources Information Center

    Engel de Abreu, Pascale M. J.; Cruz-Santos, Anabela; Puglisi, Marina L.

    2014-01-01

    Background: Recent evidence suggests that specific language impairment (SLI) might be secondary to general cognitive processing limitations in the domain of executive functioning. Previous research has focused almost exclusively on monolingual children with SLI and offers little evidence-based guidance on executive functioning in bilingual…

  19. Visuo-Spatial Processing and Executive Functions in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Marton, Klara

    2008-01-01

    Background: Individual differences in complex working memory tasks reflect simultaneous processing, executive functions, and attention control. Children with specific language impairment (SLI) show a deficit in verbal working memory tasks that involve simultaneous processing of information. Aims: The purpose of the study was to examine executive…

  20. Executive Function in Preschoolers with Primary Language Impairment

    ERIC Educational Resources Information Center

    Yang, Hui-Chun; Gray, Shelley

    2017-01-01

    Purpose: The purpose of this study was to evaluate whether preschoolers with primary language impairment (PLI) show deficits in executive function (EF) compared with their peers with typical development (TD) when inhibition, updating, and mental-set shifting are examined using both linguistically based and visually based tasks. Method: Twenty-two…

  1. RELATIONSHIP BETWEEN ETHINYLESTRADIOL-MEDIATED CHANGES IN ENDOCRINE FUNCTION AND REPRODUCTION IMPAIRMENT IN JAPANESE MEDAKA (ORYZIAS LATIPES)

    EPA Science Inventory

    Many biochemical endpoints currently are used to describe endocrine function in fish; however, the sensitivity of these parameters as biomarkers of impaired reproduction or sexual development is not well understood. In the present study, adult Japanese medaka (Oryzias latipes) we...

  2. Executive and Intellectual Functioning in School-Aged Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Kuusisto, Marika A.; Nieminen, Pirkko E.; Helminen, Mika T.; Kleemola, Leenamaija

    2017-01-01

    Background: Earlier research and clinical practice show that specific language impairment (SLI) is often associated with nonverbal cognitive deficits and weakened skills in executive functions (EFs). Executive deficits may have a remarkable influence on a child's everyday activities in the home and school environments. However, research…

  3. Impaired mechanical stability, migration and contractile capacity in vimentin-deficient fibroblasts

    NASA Technical Reports Server (NTRS)

    Eckes, B.; Dogic, D.; Colucci-Guyon, E.; Wang, N.; Maniotis, A.; Ingber, D.; Merckling, A.; Langa, F.; Aumailley, M.; Delouvee, A.; hide

    1998-01-01

    Loss of a vimentin network due to gene disruption created viable mice that did not differ overtly from wild-type littermates. Here, primary fibroblasts derived from vimentin-deficient (-/-) and wild-type (+/+) mouse embryos were cultured, and biological functions were studied in in vitro systems resembling stress situations. Stiffness of -/- fibroblasts was reduced by 40% in comparison to wild-type cells. Vimentin-deficient cells also displayed reduced mechanical stability, motility and directional migration towards different chemo-attractive stimuli. Reorganization of collagen fibrils and contraction of collagen lattices were severely impaired. The spatial organization of focal contact proteins, as well as actin microfilament organization was disturbed. Thus, absence of a vimentin filament network does not impair basic cellular functions needed for growth in culture, but cells are mechanically less stable, and we propose that therefore they are impaired in all functions depending upon mechanical stability.

  4. Quality of life in patients with visual impairment in Ibadan: a clinical study in primary care.

    PubMed

    Adigun, Kehinde; Oluleye, Tunji S; Ladipo, Modupe Ma; Olowookere, Samuel Anu

    2014-01-01

    Visual function is important for optimal orientation in functional and social life, and has an effect on physical and emotional well-being. Visual impairment, therefore, leads to restrictions in all aspects of daily living and is related to quality of life. The aim of this study was to provide information on the causes of visual impairment in patients presenting to their family physician, the spectrum of impairment, and its impact on quality of life for these patients. This descriptive cross-sectional study of 375 adult patients with ocular symptoms was performed in the general outpatient department of the University College Hospital, Ibadan, from July to September, 2009. After checking their presenting visual acuity, the patients were interviewed using the Vision-Related Quality of Life questionnaire to determine the impact of visual impairment on their quality of life. Ophthalmic examinations were performed to determine the causes of visual impairment. The results were analyzed using proportions and percentages. The main causes of visual impairment were cataracts (58.7%), refractive error (19.4%), and glaucoma (2.9%). Visual impairment was found to be associated with advancing age, low education, and unemployment (P<0.001). Most patients (85.1%) were found to have good quality of life overall. Quality of life was found to be poor in the domains of visual function (64.2%) and social interaction (50.9%). Quality of life was found to be related to the degree of visual impairment, ie, blind patients reported poor quality of life (41.4%) when compared with those having low vision (8.6%) or near normal vision (2.4%, P<0.001). This study identified poor quality of life in patients with a higher degree of visual impairment. Family physicians need to identify these visually impaired patients early and make timely referrals.

  5. Preexisting cognitive impairment in intracerebral hemorrhage.

    PubMed

    Laible, M; Horstmann, S; Möhlenbruch, M; Schueler, S; Rizos, T; Veltkamp, R

    2017-06-01

    Preexisting cognitive impairment is a predictor of cognitive decline after ischemic stroke, but evidence in intracerebral hemorrhage (ICH) is limited. We aimed to determine the prevalence of premorbid cognitive impairment in patients with ICH. We included patients with acute ICH. Pre-ICH cognitive impairment was determined based on the results of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) that uses information from close relatives. Patients were assessed as having been cognitively impaired with an IQCODE score of ≥3.44; an IQCODE ≥4.00 indicated pre-ICH dementia. CT and MRI images were reviewed to determine the extent of white matter lesions and to measure the radial width of the temporal horn as marker of brain atrophy. We investigated differences of cardiovascular risk factors and imaging data between patients with and without pre-ICH cognitive impairment using correlation analyses, uni- and multivariable regression models. Functional neurological state was assessed using the modified Rankin Scale (mRS). The mRS was dichotomized at the level of 3, and a premorbid mRS of 0-2 was considered as functional independency. Among the 89 participants, median age was 70 years (interquartile range 58-78) and 52 (58.4%) were male. IQCODE indicated pre-ICH cognitive impairment in 18.0% (16 of 89), and 83.1% were functionally independent before ICH. Cognitive impairment was associated with a premorbid mRS≥3 (chi squared test, P=0.009). In multivariable analysis, prior stroke/transient ischemic attack (OR 18.29, 95%-CI 1.945-172.033, P=.011) and hematoma volume (OR 0.90, 95%-CI 0.812-0.991, P=.033) were independently associated with pre-ICH cognitive impairment. In conclusion, cognitive impairment frequently precedes ICH. A higher frequency of cerebrovascular events suggests a role of vascular processes in the development of cognitive impairment before ICH. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Development of a virtual reality assessment of everyday living skills.

    PubMed

    Ruse, Stacy A; Davis, Vicki G; Atkins, Alexandra S; Krishnan, K Ranga R; Fox, Kolleen H; Harvey, Philip D; Keefe, Richard S E

    2014-04-23

    Cognitive impairments affect the majority of patients with schizophrenia and these impairments predict poor long term psychosocial outcomes.  Treatment studies aimed at cognitive impairment in patients with schizophrenia not only require demonstration of improvements on cognitive tests, but also evidence that any cognitive changes lead to clinically meaningful improvements.  Measures of "functional capacity" index the extent to which individuals have the potential to perform skills required for real world functioning.  Current data do not support the recommendation of any single instrument for measurement of functional capacity.  The Virtual Reality Functional Capacity Assessment Tool (VRFCAT) is a novel, interactive gaming based measure of functional capacity that uses a realistic simulated environment to recreate routine activities of daily living. Studies are currently underway to evaluate and establish the VRFCAT's sensitivity, reliability, validity, and practicality. This new measure of functional capacity is practical, relevant, easy to use, and has several features that improve validity and sensitivity of measurement of function in clinical trials of patients with CNS disorders.

  7. Long-term functional outcomes of patients with very mild stroke: does a NIHSS score of 0 mean no disability? An interim analysis of the KOSCO study.

    PubMed

    Chang, Won Hyuk; Sohn, Min Kyun; Lee, Jongmin; Kim, Deog Young; Lee, Sam-Gyu; Shin, Yong-Il; Oh, Gyung-Jae; Lee, Yang-Soo; Joo, Min Cheol; Han, Eun Young; Kim, Min Su; Jang, Shin Yi; Kim, Jeong Hyun; Kim, Yun-Hee

    2017-05-01

    To explore the long-term functional outcomes of stroke patients with very mild severity at 6 months after stroke. This study presents the interim results of the Korean Stroke Cohort for Functioning and Rehabilitation. On day 7, stroke evaluation was performed using the functional assessment battery including the National Institute of Health Stroke Scale (NIHSS). At 6 months after stroke, functional outcomes using the face-to-face functional assessment battery including Functional Independence Measure (FIM) were analyzed in the patients who had a score of 0 on the NIHSS at 7 days after stroke onset. In the very mild stroke group, 455 patients were followed up at 6 months. Out of these patients, 11.0% had impairments in cognitive function, 14.1% had motor impairment, and 2.1% had impairments in their mobility measured by the functional assessment battery. At 6 months after onset, 3.3% of stroke survivors without recurrence showed dependency according to the FIM. Many acute stroke patients with mild stroke severity as assessed by the NIHSS had impairments in various functional domains, and could have been easily overlooked for intensive rehabilitation therapy. Candidates for comprehensive rehabilitation therapy might be better identified by the functional assessment battery. Implications for rehabilitation Many acute stroke patients with mild stroke severity assessed by NIHSS could be easily overlooked for intensive rehabilitation therapy. Candidates for comprehensive rehabilitation therapy should be evaluated using a functional assessment battery rather than the NIHSS.

  8. Brief Exposure to Secondhand Smoke Reversibly Impairs Endothelial Vasodilatory Function

    PubMed Central

    2014-01-01

    Introduction: We sought to determine the effects of brief exposures to low concentrations of tobacco secondhand smoke (SHS) on arterial flow-mediated dilation (FMD, a nitric oxide-dependent measure of vascular endothelial function), in a controlled animal model never before exposed to smoke. In humans, SHS exposure for 30min impairs FMD. It is important to gain a better understanding of the acute effects of exposure to SHS at low concentrations and for brief periods of time. Methods: We measured changes in FMD in rats exposed to a range of real-world levels of SHS for durations of 30min, 10min, 1min, and 4 breaths (roughly 15 s). Results: We observed a dose-response relationship between SHS particle concentration over 30min and post-exposure impairment of FMD, which was linear through the range typically encountered in smoky restaurants and then saturated at higher concentrations. One min of exposure to SHS at moderate concentrations was sufficient to impair FMD. Conclusions: Brief SHS exposure at real-world levels reversibly impairs FMD. Even 1min of SHS exposure can cause reduction of endothelial function. PMID:24302638

  9. Does Emotion Dysregulation Mediate the Association Between Sluggish Cognitive Tempo and College Students' Social Impairment?

    PubMed

    Flannery, Andrew J; Becker, Stephen P; Luebbe, Aaron M

    2016-09-01

    Studies demonstrate an association between sluggish cognitive tempo (SCT) and social impairment, although no studies have tested possible mechanisms of this association. This study aimed to (a) examine SCT in relation to college students' social functioning; (b) test if SCT is significantly associated with emotion dysregulation beyond depressive, anxious, and ADHD symptoms; and (c) test if emotion dysregulation mediates the association between SCT symptoms and social impairment. College students (N = 158) completed measures of psychopathology symptoms, emotion dysregulation, and social functioning. Participants with elevated SCT (12%) had higher ADHD, depressive, and anxious symptoms in addition to poorer emotion regulation and social adjustment than participants without elevated SCT. Above and beyond other psychopathologies, SCT was significantly associated with social impairment but not general interpersonal functioning. SCT was also associated with emotion dysregulation, even after accounting for the expectedly strong association between depression and emotion dysregulation. Further analyses supported emotion dysregulation as a mediator of the association between SCT and social impairment. These findings are important for theoretical models of SCT and underscore the need for additional, longitudinal research. © The Author(s) 2014.

  10. An Examination of Brain Abnormalities and Mobility in Individuals with Mild Cognitive Impairment and Alzheimer's Disease

    PubMed Central

    Fischer, Barbara L.; Bacher, Rhonda; Bendlin, Barbara B.; Birdsill, Alex C.; Ly, Martina; Hoscheidt, Siobhan M.; Chappell, Richard J.; Mahoney, Jane E.; Gleason, Carey E.

    2017-01-01

    Background: Mobility changes are concerning for elderly patients with cognitive decline. Given frail older individuals' vulnerability to injury, it is critical to identify contributors to limited mobility. Objective: To examine whether structural brain abnormalities, including reduced gray matter volume and white matter hyperintensities, would be associated with limited mobility among individuals with cognitive impairment, and to determine whether cognitive impairment would mediate this relationship. Methods: Thirty-four elderly individuals with mild cognitive impairment (MCI) and Alzheimer's disease underwent neuropsychological evaluation, mobility assessment, and structural brain neuroimaging. Linear regression was conducted with predictors including gray matter volume in six regions of interest (ROI) and white matter hyperintensity (WMH) burden, with mobility measures as outcomes. Results: Lower gray matter volume in caudate nucleus was associated with slower speed on a functional mobility task. Higher cerebellar volume was also associated with slower functional mobility. White matter hyperintensity burden was not significantly associated with mobility. Conclusion: Our findings provide evidence for associations between subcortical gray matter volume and speed on a functional mobility task among cognitively impaired individuals. PMID:28424612

  11. Ameliorative effect of Noni fruit extract on streptozotocin-induced memory impairment in mice.

    PubMed

    Pachauri, Shakti D; Verma, Priya Ranjan P; Dwivedi, Anil K; Tota, Santoshkumar; Khandelwal, Kiran; Saxena, Jitendra K; Nath, Chandishwar

    2013-08-01

    This study evaluated the effects of a standardized ethyl acetate extract of Morinda citrifolia L. (Noni) fruit on impairment of memory, brain energy metabolism, and cholinergic function in intracerebral streptozotocin (STZ)-treated mice. STZ (0.5 mg/kg) was administered twice at an interval of 48 h. Noni (50 and 100 mg/kg, postoperatively) was administered for 21 days following STZ administration. Memory function was evaluated using Morris Water Maze and passive avoidance tests, and brain levels of cholinergic function, oxidative stress, energy metabolism, and brain-derived neurotrophic factor (BDNF) were estimated. STZ caused memory impairment in Morris Water Maze and passive avoidance tests along with reduced brain levels of ATP, BDNF, and acetylcholine and increased acetylcholinesterase activity and oxidative stress. Treatment with Noni extract (100 mg/kg) prevented the STZ-induced memory impairment in both behavioral tests along with reduced oxidative stress and acetylcholinesterase activity, and increased brain levels of BDNF, acetylcholine, and ATP level. The study shows the beneficial effects of Noni fruit against STZ-induced memory impairment, which may be attributed to improved brain energy metabolism, cholinergic neurotransmission, BDNF, and antioxidative action.

  12. Muscle mitochondrial metabolism and calcium signaling impairment in patients treated with statins

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sirvent, P., E-mail: pascal.sirvent@univ-bpclermont.fr; CHRU Montpellier, 34295 Montpellier; Clermont Université, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en conditions Physiologiques et Pathologiques

    2012-03-01

    The most common and problematic side effect of statins is myopathy. To date, the patho-physiological mechanisms of statin myotoxicity are still not clearly understood. In previous studies, we showed that acute application in vitro of simvastatin caused impairment of mitochondrial function and dysfunction of calcium homeostasis in human and rat healthy muscle samples. We thus evaluated in the present study, mitochondrial function and calcium signaling in muscles of patients treated with statins, who present or not muscle symptoms, by oxygraphy and recording of calcium sparks, respectively. Patients treated with statins showed impairment of mitochondrial respiration that involved mainly the complexmore » I of the respiratory chain and altered frequency and amplitude of calcium sparks. The muscle problems observed in statin-treated patients appear thus to be related to impairment of mitochondrial function and muscle calcium homeostasis, confirming the results we previously reported in vitro. -- Highlights: ► The most common and problematic side effect of statins is myopathy. ► Patients treated with statins showed impairment of mitochondrial respiration. ► Statins-treated patients showed altered frequency and amplitude of calcium sparks.« less

  13. Life satisfaction two-years after stroke onset: the effects of gender, sex occupational status, memory function and quality of life among stroke patients (Newsqol) and their family caregivers (Whoqol-bref) in Luxembourg

    PubMed Central

    2012-01-01

    Background Life satisfaction (LS) of cerebrovascular disease survivors and their family caregivers may relate to socioeconomic factors, impaired functions, health-related quality of life (QoL), but their respective influences remain unclear. This study assessed, two years post-stroke onset, the effects of these factors on patients’ LS and family caregivers’ LS in Luxembourg. Methods All stroke patients admitted to all hospitals in Luxembourg were identified by the ‘Inspection Général de la Sécurité Sociale’ using the only national system database for care expenditure reimbursement. Their diagnosis was confirmed by medical investigator. The sample included ninety four patients living at home having given consent (mean age 65.5 years) and sixty two main caregivers (mean age 59.3 years). Questionnaires were completed during face-to-face interviews. LS was assessed via European single question (range 1–10), survivors’ QoL via Newsqol (11 dimensions), and caregivers’ QoL via Whoqol-bref (4 domains) (range 0–100). Data were analysed using multiple regression models. Results Two years after stroke onset, 44.7% of patients suffered from impaired sensory function, 35.1% from impaired motor function, and 31.9% from impaired memory function. Mean patient’ LS was 7.1/10 (SD 1.9). It was higher in women (+12.4) and lower among unemployed socioeconomically active patients (−13.1, vs. retired people). Adjusted for sex, occupation, impaired motor and memory functions, LS positively correlated with scores of Newsqol feelings, sleep, emotion, cognition and pain dimensions (slopes 0.20 to 0.31), but did not correlate with those of caregivers’ Whoqol-bref domains. Family caregiver’ LS was 7.2 (SD 1.7). It was lower in those with patients suffering from impaired memory function (−12.8) as well as from feelings and emotion issues (slopes 0.22). It was associated with all caregivers’ Whoqol-bref domains (physical health, psychological health, environment, and social relationships) (slopes 0.53 to 0.68). Conclusions Two-year post-cerebrovascular disease patient’ LS was associated with gender, occupation, and impaired memory function. It correlated with feelings, sleep, emotion, cognition, and pain issues. Family caregivers of patients with impaired memory function had lower LS. Family caregiver’ LS correlated with dimensions of patients’ feelings (less independent, yourself, life changed, depressed, useless, less control because of stroke) and emotion (get more emotional, fear of another stroke or to become dependent on others), and with their own QoL. LS, Newsqol, and Whoqol appeared to be appropriate tools. Our findings may be useful for policy makers in relation to family and medical-social issues of stroke home-based rehabilitation. PMID:23009364

  14. Life satisfaction two-years after stroke onset: the effects of gender, sex occupational status, memory function and quality of life among stroke patients (Newsqol) and their family caregivers (Whoqol-bref) in Luxembourg.

    PubMed

    Baumann, Michèle; Couffignal, Sophie; Le Bihan, Etienne; Chau, Nearkasen

    2012-09-25

    Life satisfaction (LS) of cerebrovascular disease survivors and their family caregivers may relate to socioeconomic factors, impaired functions, health-related quality of life (QoL), but their respective influences remain unclear. This study assessed, two years post-stroke onset, the effects of these factors on patients' LS and family caregivers' LS in Luxembourg. All stroke patients admitted to all hospitals in Luxembourg were identified by the 'Inspection Général de la Sécurité Sociale' using the only national system database for care expenditure reimbursement. Their diagnosis was confirmed by medical investigator. The sample included ninety four patients living at home having given consent (mean age 65.5 years) and sixty two main caregivers (mean age 59.3 years). Questionnaires were completed during face-to-face interviews. LS was assessed via European single question (range 1-10), survivors' QoL via Newsqol (11 dimensions), and caregivers' QoL via Whoqol-bref (4 domains) (range 0-100). Data were analysed using multiple regression models. Two years after stroke onset, 44.7% of patients suffered from impaired sensory function, 35.1% from impaired motor function, and 31.9% from impaired memory function. Mean patient' LS was 7.1/10 (SD 1.9). It was higher in women (+12.4) and lower among unemployed socioeconomically active patients (-13.1, vs. retired people). Adjusted for sex, occupation, impaired motor and memory functions, LS positively correlated with scores of Newsqol feelings, sleep, emotion, cognition and pain dimensions (slopes 0.20 to 0.31), but did not correlate with those of caregivers' Whoqol-bref domains. Family caregiver' LS was 7.2 (SD 1.7). It was lower in those with patients suffering from impaired memory function (-12.8) as well as from feelings and emotion issues (slopes 0.22). It was associated with all caregivers' Whoqol-bref domains (physical health, psychological health, environment, and social relationships) (slopes 0.53 to 0.68). Two-year post-cerebrovascular disease patient' LS was associated with gender, occupation, and impaired memory function. It correlated with feelings, sleep, emotion, cognition, and pain issues. Family caregivers of patients with impaired memory function had lower LS. Family caregiver' LS correlated with dimensions of patients' feelings (less independent, yourself, life changed, depressed, useless, less control because of stroke) and emotion (get more emotional, fear of another stroke or to become dependent on others), and with their own QoL. LS, Newsqol, and Whoqol appeared to be appropriate tools. Our findings may be useful for policy makers in relation to family and medical-social issues of stroke home-based rehabilitation.

  15. [Cognitive impairments accompanying the burnout syndrome - a review].

    PubMed

    Riedrich, Karin; Weiss, Elisabeth M; Dalkner, Nina; Reininghaus, Eva; Papousek, Ilona; Schwerdtfeger, Andreas; Lackner, Helmut K; Reininghaus, Bernd

    2017-03-01

    The rising prevalence of the burnout syndrome has increasingly moved it into the focus of scientific interest. In addition to emotional exhaustion and depersonalization, particularly reduced personal accomplishment has strong societal and economic effects. In recent years reduced personal accomplishment has increasingly been linked to cognitive impairment. However, up to now only a few studies have objectively assessed cognitive deficits in burnout patients. This article gives an overview of 16 studies which examined cognitive abilities in burnout patients. The findings are partly contradictory, probably due to methodical differences. Consensus has emerged concerning impairments of executive functions, i.a. vigilance, and memory updating and monitoring. Multifactorial causation may underlie the cognitive impairments. Targeted longitudinal studies are necessary in order to identify the affected cognitive functions and be able to make causal inferences on links between the burnout syndrome and specific cognitive impairments.

  16. Intact imitation of emotional facial actions in autism spectrum conditions.

    PubMed

    Press, Clare; Richardson, Daniel; Bird, Geoffrey

    2010-09-01

    It has been proposed that there is a core impairment in autism spectrum conditions (ASC) to the mirror neuron system (MNS): If observed actions cannot be mapped onto the motor commands required for performance, higher order sociocognitive functions that involve understanding another person's perspective, such as theory of mind, may be impaired. However, evidence of MNS impairment in ASC is mixed. The present study used an 'automatic imitation' paradigm to assess MNS functioning in adults with ASC and matched controls, when observing emotional facial actions. Participants performed a pre-specified angry or surprised facial action in response to observed angry or surprised facial actions, and the speed of their action was measured with motion tracking equipment. Both the ASC and control groups demonstrated automatic imitation of the facial actions, such that responding was faster when they acted with the same emotional expression that they had observed. There was no difference between the two groups in the magnitude of the effect. These findings suggest that previous apparent demonstrations of impairments to the MNS in ASC may be driven by a lack of visual attention to the stimuli or motor sequencing impairments, and therefore that there is, in fact, no MNS impairment in ASC. We discuss these findings with reference to the literature on MNS functioning and imitation in ASC, as well as theories of the role of the MNS in sociocognitive functioning in typical development. Copyright 2010 Elsevier Ltd. All rights reserved.

  17. Influence of childhood scleroderma on physical function and quality of life.

    PubMed

    Baildam, Eileen M; Ennis, Holly; Foster, Helen E; Shaw, Lindsay; Chieng, Alice S E; Kelly, Jane; Herrick, Ariane L; Richards, Helen L

    2011-01-01

    there have been few studies of quality of life in childhood scleroderma and these focused predominantly on self-perception and the influence of skin lesions. Our cross-sectional study aimed to describe the influence of childhood scleroderma on physical function and quality of life in relation to clinical and demographic measures. children with either localized scleroderma or systemic sclerosis (SSc) attending pediatric rheumatology clinics, together with their parents or guardians, were asked to complete a set of 4 validated measures. Clinical and demographic data were provided by consultant pediatric rheumatologists. in total, 28 children and their parents/guardians participated in the study (68% female, median age 13 yrs; 86% localized scleroderma, 14% SSc). The median Child Health Assessment Questionnaire (CHAQ) score was 0.1 (range 0-3, 0 indicating no impairment), the median Child Dermatology Life Quality Index (CDLQI) score was 5 (range 0-30, 0 indicating no impairment), and the median Child Quality of Life Questionnaire (CQOL) function score was 26 (range 0-105, 0 indicating no impairment). Family activity, measured by the Child Health Questionnaire (CHQ-PF50), was also moderately impaired by scleroderma, with a median score of 83 (0-100, 100 indicating no impairment). scleroderma had only a moderate effect on quality of life and physical function as measured by the 4 validated instruments. Although a small number of children reported greater impairment, this is an encouraging finding, given its potential disfiguring and debilitating effects.

  18. Patterns of prefrontal dysfunction in alcoholics with and without Korsakoff’s syndrome, patients with Parkinson’s disease, and patients with rupture and repair of the anterior communicating artery

    PubMed Central

    Dirksen, Courtney L; Howard, Julie A; Cronin-Golomb, Alice; Oscar-Berman, Marlene

    2006-01-01

    This study compared patterns of frontal-lobe dysfunction in alcoholics with Korsakoff’s syndrome (KS: n = 9), non-Korsakoff alcoholics (AL: n = 28), patients with Parkinson’s disease (PD: n = 18), and patients with rupture and repair of the anterior communicating artery (ACoA: n = 4) relative to healthy non-neurological control (NC) participants (n = 70). The tests administered were sensitive to functions of dorsolateral prefrontal and orbito-frontal subsystems. Measures included perseverative errors on the Wisconsin Card Sorting Test (WCST-pe), errors on object alternation (OA), errors on Trails B, number of words generated on the Controlled Oral Word Association Test (COWAT), and number of categories completed on the WCST (WCST-cc). KS patients were as impaired as AL participants on orbitofrontal measures and, on dorsolateral prefrontal measures, were impaired relative to AL participants, whose performance did not differ from controls. Patients with PD also were impaired on tests of orbitofrontal and dorsolateral prefrontal functioning but to a lesser extent than the KS patients. Moreover, most of the PD deficits were driven by the impaired performance of patients whose initial symptoms were on the right side of the body. The ACoA patients were significantly impaired on tests of orbitofrontal but not dorsolateral prefrontal functioning relative to the control group. Together, the results confirm different patterns of frontal-system impairments in patient groups having compromised frontal lobe functioning consequent to varying etiologies. PMID:19412479

  19. Cerebral microbleeds, cognitive impairment, and MRI in patients with diabetes mellitus.

    PubMed

    Zhou, Hong; Yang, Juan; Xie, Peihan; Dong, Yulan; You, Yong; Liu, Jincai

    2017-07-01

    Cerebral microbleeds (CMBs), a typical imaging manifestation marker of sporadic cerebral small vessel disease, play a critical role in vascular cognitive impairment, which is often accompanied by diabetes mellitus (DM). Hence, CMBs may, in part, be responsible for the occurrence and development of cognitive impairment in patients with diabetes. Novel magnetic resonance imaging (MRI) sequences, such as susceptibility-weighted imaging and T2*-weighted gradient-echo, have the capability of noninvasively revealing CMBs in the brain. Moreover, a correlation between CMBs and cognitive impairment in patients with diabetes has been suggested in applications of functional MRI (fMRI). Since pathological changes in the brain occur prior to observable decline in cognitive function, neuroimaging may help predict the progression of cognitive impairment in diabetic patients. In this article, we review the detection of CMBs using MRI in diabetic patients exhibiting cognitive impairment. Future studies should emphasize the development and establishment of a novel MRI protocol, including fMRI, for diabetic patients with cognitive impairment to detect CMBs. A reliable MRI protocol would also be helpful in understanding the pathological mechanisms of cognitive impairment in this important patient population. Copyright © 2017. Published by Elsevier B.V.

  20. Acute lesions that impair affective empathy

    PubMed Central

    Oishi, Kenichi; Hsu, John; Lindquist, Martin; Gottesman, Rebecca F.; Jarso, Samson; Crainiceanu, Ciprian; Mori, Susumu

    2013-01-01

    Functional imaging studies of healthy participants and previous lesion studies have provided evidence that empathy involves dissociable cognitive functions that rely on at least partially distinct neural networks that can be individually impaired by brain damage. These studies converge in support of the proposal that affective empathy—making inferences about how another person feels—engages at least the following areas: prefrontal cortex, orbitofrontal gyrus, anterior insula, anterior cingulate cortex, temporal pole, amygdala and temporoparietal junction. We hypothesized that right-sided lesions to any one of these structures, except temporoparietal junction, would cause impaired affective empathy (whereas bilateral damage to temporoparietal junction would be required to disrupt empathy). We studied 27 patients with acute right hemisphere ischaemic stroke and 24 neurologically intact inpatients on a test of affective empathy. Acute impairment of affective empathy was associated with infarcts in the hypothesized network, particularly temporal pole and anterior insula. All patients with impaired affective empathy were also impaired in comprehension of affective prosody, but many patients with impairments in prosodic comprehension had spared affective empathy. Patients with impaired affective empathy were older, but showed no difference in performance on tests of hemispatial neglect, volume of infarct or sex distribution compared with patients with intact affective empathy. PMID:23824490

  1. Renal impairment in stroke patients: A comparison between the haemorrhagic and ischemic variants.

    PubMed

    Shrestha, Pratyush; Thapa, Shalima; Shrestha, Shikher; Lohani, Subash; Bk, Suresh; MacCormac, Oscar; Thapa, Lekhjung; Devkota, Upendra Prasad

    2017-01-01

    Background: Renal impairment is regularly seen in hospitalized stroke patients, affecting the outcome of patients, as well as causing difficulties in their management. A prospective cohort study was conducted to assess the trend of renal function in hospitalized ischemic and haemorrhagic stroke patients. The incidence of renal impairment in these subgroups, the contributing factors and the need for renal replacement in renal impaired patients was evaluated. Methods: Alternate day renal function testing was performed in hospitalized stroke patients. Estimated glomerular filtration rate (e-GFR) was calculated and the trend of renal function in the two stroke subgroups (haemorrhagic and ischemic) was assessed, with renal impairment defined as e-GFR < 60mL/ minute per 1.73m 2 . Results: Among 52 patients, 25 had haemorrhagic stroke (mean age 59.81 ± 14.67) and 27 had ischemic stroke (mean age 56.12 ± 13.08). The mean e-GFR (mL/minute per 1.732m 2 ) at admission in the haemorrhagic stroke subgroup was 64.79 ± 25.85 compared to 86.04 ± 26.09 in the ischemic stroke subgroup (p=0.005). Sixteen out of 25 (64%) patients in the haemorrhagic stroke subgroup and 9 out of 27 (33.3%) patients in the ischemic subgroup developed renal impairment (p=0.027). The location of the bleed (p=0.8), volume of hematoma (p=0.966) and surgical intervention (p=0.4) did not predispose the patients to renal impairment. One out of 16 patients with haemorrhagic stroke (who eventually died), and 2 out of 9 patients with ischemic stroke required renal replacement. Conclusion : Renal impairment is commonly seen in stroke patients, more so in patients who suffered haemorrhagic strokes.  The impairment, however, is transient and rarely requires renal replacement therapy.

  2. Delayed recovery of cognitive function following hypoglycemia in adults with type 1 diabetes: effect of impaired awareness of hypoglycemia.

    PubMed

    Zammitt, Nicola N; Warren, Roderick E; Deary, Ian J; Frier, Brian M

    2008-03-01

    Recovery times of cognitive functions were examined after exposure to hypoglycemia in people with diabetes with and without impaired hypoglycemia awareness. A total of 36 subjects with type 1 diabetes were studied (20 with normal hypoglycemia awareness [NHA] and 16 with impaired hypoglycemia awareness [IHA]). A hyperinsulinemic glucose clamp was used to lower blood glucose to 2.5 mmol/l (45 mg/dl) (hypoglycemia) for 1 h or to maintain blood glucose at 4.5 mmol/l (81 mg/dl) (euglycemia) on separate occasions. Cognitive tests were applied during each experimental condition and were repeated at 10- to 15-min intervals for 90 min after euglycemia had been restored. In the NHA group, performance was impaired on all cognitive tasks during hypoglycemia and remained impaired for up to 75 min on the choice reaction time (CRT) task (P = 0.03, eta(2) = 0.237). In the IHA group, performance did not deteriorate significantly during hypoglycemia. When all subjects were analyzed within the same general linear model, performance was impaired during hypoglycemia on all tasks. Significant impairment during recovery persisted for up to 40 min on the CRT task (P = 0.04, eta(2) = 0.125) with a significant glycemia-awareness interaction for CRT after one hour of hypoglycemia (P = 0.045, eta(2) = 0.124). Performance on the trail-making B task was impaired for up to 10 min after euglycemia was restored (P = 0.024, eta(2) = 0.158). Following hypoglycemia, the recovery time for different cognitive tasks varied considerably. In the IHA group, performance was not significantly impaired during hypoglycemia. The state of awareness of hypoglycemia may influence cognitive function during and after hypoglycemia.

  3. Peak oxygen uptake and left ventricular ejection fraction, but not depressive symptoms, are associated with cognitive impairment in patients with chronic heart failure

    PubMed Central

    Steinberg, Gerrit; Lossnitzer, Nicole; Schellberg, Dieter; Mueller-Tasch, Thomas; Krueger, Carsten; Haass, Markus; Ladwig, Karl Heinz; Herzog, Wolfgang; Juenger, Jana

    2011-01-01

    Background The aim of the present study was to assess cognitive impairment in patients with chronic heart failure (CHF) and its associations with depressive symptoms and somatic indicators of illness severity, which is a matter of controversy. Methods and results Fifty-five patients with CHF (mean age 55.3 ± 7.8 years; 80% male; New York Heart Association functional class I–III) underwent assessment with an expanded neuropsychological test battery (eg, memory, complex attention, mental flexibility, psychomotor speed) to evaluate objective and subjective cognitive impairment. Depressive symptoms were assessed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID) and a self-report inventory (Hospital Anxiety and Depression Scale [HADS]). A comprehensive clinical dataset, including left ventricular ejection fraction, peak oxygen uptake, and a 6-minute walk test, was obtained for all patients. Neuropsychological functioning revealed impairment in 56% of patients in at least one measure of our neuropsychological test battery. However, the Mini Mental State Examination (MMSE) could only detect cognitive impairment in 1.8% of all patients, 24% had HADS scores indicating depressive symptoms, and 11.1% met SCID criteria for a depressive disorder. No significant association was found between depressive symptoms and cognitive impairment. Left ventricular ejection fraction was related to subjective cognitive impairment, and peak oxygen uptake was related to objective cognitive impairment. Conclusion Cognitive functioning was substantially reduced in patients with CHF and should therefore be diagnosed and treated in routine clinical practice. Caution is advised when the MMSE is used to identify cognitive impairment in patients with CHF. PMID:22267941

  4. Influence of hepatic impairment on the pharmacokinetics of the dopamine agonist rotigotine.

    PubMed

    Cawello, Willi; Fichtner, Andreas; Boekens, Hilmar; Braun, Marina

    2014-09-01

    The transdermally applied dopamine receptor agonist rotigotine is extensively metabolized in the liver. An open-label, parallel-group study was conducted to evaluate the effects of moderate hepatic impairment on the pharmacokinetics, safety and tolerability of rotigotine. Eight subjects with normal hepatic function and nine with moderate hepatic impairment (Child-Pugh class B) received one rotigotine transdermal patch (providing a dose of 2 mg/24 h) daily for 3 days with a 24-h patch-on period. Blood and urine samples were collected to evaluate pharmacokinetic parameters characterizing drug bioavailability and elimination. Primary variables included plasma and urine concentrations of unconjugated rotigotine (active parent compound) and total rotigotine (unconjugated rotigotine plus sulfate and glucuronide conjugates) under steady-state (SS) conditions. For unconjugated rotigotine, point estimates for the ratios of AUC(0-24)SS and C max,SS between the two groups (normal vs. impaired hepatic function) were near 1: AUC(0-24)SS, 0.90 (90 % CI 0.59, 1.38) and C max,SS, 0.94 (90 % CI 0.66, 1.35); t max,SS and t 1/2 were lower in subjects with hepatic impairment, while renal clearance was unaffected and overall clearance was higher. For total rotigotine, C max,SS was higher in subjects with hepatic impairment compared with those with normal hepatic function (P = 0.0239, ANOVA). A tendency to reduced non-renal clearance was observed in subjects with hepatic impairment, consistent with their higher plasma concentrations of total rotigotine. Thus, moderate hepatic impairment did not influence the pharmacokinetics of unconjugated rotigotine under steady-state conditions suggesting that dose adjustment will not be required for patients with mild or moderate hepatic insufficiency. In addition, the rotigotine patch was well tolerated in subjects with moderate hepatic impairment.

  5. Impairment and quality of life in individuals with generalized anxiety disorder.

    PubMed

    Henning, Eric R; Turk, Cynthia L; Mennin, Douglas S; Fresco, David M; Heimberg, Richard G

    2007-01-01

    Once considered to be a disorder associated with minimal impairment, the link between generalized anxiety disorder (GAD) and impairment across a broad constellation of domains is now well established. However, less is known about how comorbidity affects these relationships or how GAD impacts one's perceived life satisfaction or quality of life. To investigate these questions, data from 52 treatment-seeking individuals with GAD (33 with comorbid Axis I diagnoses) were compared to data from 55 nonanxious controls. Individuals with GAD reported more impairment at work and in their social functioning than they did with home and family responsibilities. They also reported lower quality of life than nonanxious controls, particularly in regard to self-esteem, goals and values, money, work, play, learning, creativity, friends, and relatives. Trait worry was positively correlated with impairment and inversely related to life satisfaction within the clinical sample. Individuals with GAD, with and without comorbid Axis I diagnoses, showed few differences on measures of impairment (differing only on impairment in social functioning). However, individuals with GAD and comorbid disorders perceived their lives as less satisfying than did individuals with GAD without comorbid diagnoses.

  6. Haptic wearables as sensory replacement, sensory augmentation and trainer - a review.

    PubMed

    Shull, Peter B; Damian, Dana D

    2015-07-20

    Sensory impairments decrease quality of life and can slow or hinder rehabilitation. Small, computationally powerful electronics have enabled the recent development of wearable systems aimed to improve function for individuals with sensory impairments. The purpose of this review is to synthesize current haptic wearable research for clinical applications involving sensory impairments. We define haptic wearables as untethered, ungrounded body worn devices that interact with skin directly or through clothing and can be used in natural environments outside a laboratory. Results of this review are categorized by degree of sensory impairment. Total impairment, such as in an amputee, blind, or deaf individual, involves haptics acting as sensory replacement; partial impairment, as is common in rehabilitation, involves haptics as sensory augmentation; and no impairment involves haptics as trainer. This review found that wearable haptic devices improved function for a variety of clinical applications including: rehabilitation, prosthetics, vestibular loss, osteoarthritis, vision loss and hearing loss. Future haptic wearables development should focus on clinical needs, intuitive and multimodal haptic displays, low energy demands, and biomechanical compliance for long-term usage.

  7. Cognitive impairment as measured by the THINC-integrated tool (THINC-it): Association with psychosocial function in major depressive disorder.

    PubMed

    Cha, Danielle S; Carmona, Nicole E; Subramaniapillai, Mehala; Mansur, Rodrigo B; Lee, Yena; Hon Lee, Jae; Lee, JungGoo; Rosenblat, Joshua D; Shekotikhina, Margarita; Park, Caroline; Rong, Carola; Greer, Tracy L; Lam, Raymond; Baune, Bernhard T; Harrison, John; McIntyre, Roger S

    2017-11-01

    Psychosocial impairment represents an important treatment target in major depressive disorder (MDD). The majority of patients with MDD do not regain premorbid levels of psychosocial functioning despite the resolution of core depressive symptoms. This study aimed to investigate the respective effects of cognitive function and depression severity on impaired psychosocial function in MDD. Adults aged 18-65 with moderate-to-severe MDD (n = 100) and age-, sex-, and education-matched healthy controls participated in a cross-sectional study validating the THINC-integrated tool (THINC-it), a cognitive screening tool comprised of objective and subjective measures of cognitive function. Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale and psychosocial function was assessed using the Sheehan Disability Scale (SDS). Subjects with MDD reported greater impairment in psychosocial function than healthy controls, with significant differences in SDS total and domain scores (ps < .01) after controlling for age, sex, and education. Generalized linear models indicated that subjective cognitive function was most strongly associated with SDS total score (RR = .14, p = .01) and SDS domains of work/school (RR = .15, p = .03), family and home responsibilities (RR = .15, p = .02), and economic days lost (RR = .18, p =.03). Depression severity was most strongly associated with SDS social life (RR = .08, p < .01) and economic days underproductive (RR = .07, p < .01). Objective cognitive function was not significantly associated with any SDS outcomes. The cross-sectional, observational study design limits temporal inferences. The self-report nature of measures included may have influenced associations observed. Potential medication effects are not noted. Cognitive deficits, as measured by the THINC-it, are associated with significant psychosocial impairment in MDD. These results provide empirical support for the assessment of both subjective and objective measures of cognition, as they are not associated with each other and have differential effects on functional trajectory. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Altered fronto-striatal functions in the Gdi1-null mouse model of X-linked Intellectual Disability.

    PubMed

    Morè, Lorenzo; Künnecke, Basil; Yekhlef, Latefa; Bruns, Andreas; Marte, Antonella; Fedele, Ernesto; Bianchi, Veronica; Taverna, Stefano; Gatti, Silvia; D'Adamo, Patrizia

    2017-03-06

    RAB-GDP dissociation inhibitor 1 (GDI1) loss-of-function mutations are responsible for a form of non-specific X-linked Intellectual Disability (XLID) where the only clinical feature is cognitive impairment. GDI1 patients are impaired in specific aspects of executive functions and conditioned response, which are controlled by fronto-striatal circuitries. Previous molecular and behavioral characterization of the Gdi1-null mouse revealed alterations in the total number/distribution of hippocampal and cortical synaptic vesicles as well as hippocampal short-term synaptic plasticity, and memory deficits. In this study, we employed cognitive protocols with high translational validity to human condition that target the functionality of cortico-striatal circuitry such as attention and stimulus selection ability with progressive degree of complexity. We previously showed that Gdi1-null mice are impaired in some hippocampus-dependent forms of associative learning assessed by aversive procedures. Here, using appetitive-conditioning procedures we further investigated associative learning deficits sustained by the fronto-striatal system. We report that Gdi1-null mice are impaired in attention and associative learning processes, which are a key part of the cognitive impairment observed in XLID patients. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Electrohypersensitivity: a functional impairment due to an inaccessible environment.

    PubMed

    Johansson, Olle

    2015-01-01

    In Sweden, electrohypersensitivity is recognized as a functional impairment which implies only the environment as the culprit. The Swedish view provides persons with this impairment a maximal legal protection, it gives them the right to get accessibility measures for free, as well as governmental subsidies and municipality economic support, and to provide them with special Ombudsmen (at the municipality, the EU, and the UN level, respectively), the right and economic means to form disability organizations and allow these to be part of national and international counterparts, all with the simple and single aim to allow persons with the functional impairment electrohypersensitivity to live an equal life in a society based on equality. They are not seen as patients, the do not have an overriding medical diagnosis, but the 'patient' is only the inferior and potentially toxic environment. This does not mean that a subjective symptom of a functionally impaired can not be treated by a physician, as well as get sick-leave from their workplace as well as economic compensation, and already in the year 2000 such symptoms were identified in the Internal Code of Diagnoses, version 10 (ICD-10; R68.8/now W90), and have been since. But the underlying cause still remains only the environment.

  10. Acute neuropsychological effects of MDMA and ethanol (co-)administration in healthy volunteers.

    PubMed

    Dumont, G J H; Wezenberg, E; Valkenberg, M M G J; de Jong, C A J; Buitelaar, J K; van Gerven, J M A; Verkes, R J

    2008-04-01

    In Western societies, a considerable percentage of young people expose themselves to 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"). Commonly, ecstasy is used in combination with other substances, in particular alcohol (ethanol). MDMA induces both arousing as well as hallucinogenic effects, whereas ethanol is a general central nervous system depressant. The aim of the present study is to assess the acute effects of single and co-administration of MDMA and ethanol on executive, memory, psychomotor, visuomotor, visuospatial and attention function, as well as on subjective experience. We performed a four-way, double-blind, randomised, crossover, placebo-controlled study in 16 healthy volunteers (nine male, seven female) between the ages of 18-29. MDMA was given orally (100 mg) and blood alcohol concentration was maintained at 0.6 per thousand by an ethanol infusion regime. Co-administration of MDMA and ethanol was well tolerated and did not show greater impairment of performance compared to the single-drug conditions. Impaired memory function was consistently observed after all drug conditions, whereas impairment of psychomotor function and attention was less consistent across drug conditions. Co-administration of MDMA and ethanol did not exacerbate the effects of either drug alone. Although the impairment of performance by all drug conditions was relatively moderate, all induced significant impairment of cognitive function.

  11. Narcissistic Personality Disorder: Relations with distress and functional impairment

    PubMed Central

    Miller, Joshua D.; Campbell, W. Keith; Pilkonis, Paul A.

    2007-01-01

    This study examined the construct validity of Narcissistic Personality Disorder (NPD) by examining the relations between NPD and measures of psychological distress and functional impairment both concurrently and prospectively across two samples. In particular, the goal was to address whether NPD typically “meets” Criterion C of the DSM-IV definition of Personality Disorder, which requires that the symptoms lead to clinically significant distress or impairment in functioning. Sample 1 (N =152) was composed of individuals receiving psychiatric treatment, while Sample 2 (N=151) was composed of both psychiatric patients (46%) and individuals from the community. NPD was linked to ratings of depression, anxiety, and several measures of impairment both concurrently and at 6-month follow-up. However, the relations between NPD and psychological distress were (a) small, especially in concurrent measurements, and (b) largely mediated by impaired functioning. NPD was most strongly related to causing pain and suffering to others, and this relationship was significant even when other Cluster B personality disorders were controlled. These findings suggest that NPD is a maladaptive personality style which primarily causes dysfunction and distress in interpersonal domains. The behavior of narcissistic individuals ultimately leads to problems and distress for the narcissistic individuals and for those with whom they interact. PMID:17292708

  12. Paradoxical effect of mitochondrial respiratory chain impairment on insulin signaling and glucose transport in adipose cells.

    PubMed

    Shi, Xiarong; Burkart, Alison; Nicoloro, Sarah M; Czech, Michael P; Straubhaar, Juerg; Corvera, Silvia

    2008-11-07

    Adipocyte function is crucial for the control of whole body energy homeostasis. Pathway analysis of differentiating 3T3-L1 adipocytes reveals that major metabolic pathways induced during differentiation involve mitochondrial function. However, it is not clear why differentiated white adipocytes require enhanced respiratory chain activity relative to pre-adipocytes. To address this question, we used small interference RNA to interfere with the induction of the transcription factor Tfam, which is highly induced between days 2 and 4 of differentiation and is crucial for replication of mitochondrial DNA. Interference with Tfam resulted in cells with decreased respiratory chain capacity, reflected by decreased basal oxygen consumption, and decreased mitochondrial ATP synthesis, but no difference in many other adipocyte functions or expression levels of adipose-specific genes. However, insulin-stimulated GLUT4 translocation to the cell surface and subsequent glucose transport are impaired in Tfam knockdown cells. Paradoxically, insulin-stimulated Akt phosphorylation is significantly enhanced in these cells. These studies reveal independent links between mitochondrial function, insulin signaling, and glucose transport, in which impaired respiratory chain activity enhances insulin signaling to Akt phosphorylation, but impairs GLUT4 translocation. These results indicate that mitochondrial respiratory chain dysfunction in adipocytes can cause impaired insulin responsiveness of GLUT4 translocation by a mechanism downstream of the Akt protein kinase.

  13. Rehabilitation in practice: management of lower motor neuron weakness.

    PubMed

    Ramdharry, Gita M

    2010-05-01

    This series of articles for rehabilitation in practice aims to cover a knowledge element of the rehabilitation medicine curriculum. Nevertheless they are intended to be of interest to a multidisciplinary audience. The competency addressed in this article is 'The trainee consistently demonstrates a knowledge of the pathophysiology of various specific impairments including lower motor neuron weakness' and 'management approaches for specific impairments including lower motor neuron weakness'.This article explores weakness as a lower motor symptom. Weakness as a primary impairment of neuromuscular diseases is addressed, with recognition of the phenomenon of disuse atrophy, and how weakness impacts on the functional abilities of people with myopathy and neuropathy. Interventions to reduce weakness or address the functional consequences of weakness are evaluated with consideration of safety and clinical application. This paper will allow readers to: (1) appraise the contribution of research in rehabilitation of lower motor neuron weakness to clinical decision making and (2) engage with the issues that arise when researching rehabilitation interventions for lower motor neuron weakness. Impairments associated with neuromuscular conditions can lead to significant functional difficulties that can impact on a person's daily participation. This article focuses on the primary impairment of weakness and explores the research evidence for rehabilitation interventions that directly influence weakness or address the impact of weakness on function.

  14. Socio-demographic characteristics, lifestyle factors and burden of morbidity associated with self-reported hearing and vision impairments in older British community-dwelling men: a cross-sectional study.

    PubMed

    Liljas, A E M; Wannamethee, S G; Whincup, P H; Papacosta, O; Walters, K; Iliffe, S; Lennon, L T; Carvalho, L A; Ramsay, S E

    2016-06-01

    Hearing and vision problems are common in older adults. We investigated the association of self-reported sensory impairment with lifestyle factors, chronic conditions, physical functioning, quality of life and social interaction. A population-based cross-sectional study of participants of the British Regional Heart Study aged 63-85 years. A total of 3981 men (82% response rate) provided data. Twenty-seven per cent (n = 1074) reported hearing impairment including being able to hear with aid (n = 482), being unable to hear (no aid) (n = 424) and being unable to hear despite aid (n = 168). Three per cent (n = 124) reported vision impairment. Not being able to hear, irrespective of use of hearing aid, was associated with poor quality of life, poor social interaction and poor physical functioning. Men who could not hear despite hearing aid were more likely to report coronary heart disease (CHD) [age-adjusted odds ratios (ORs) 1.89 (95% confidence interval 1.36-2.63)]. Vision impairment was associated with symptoms of CHD including breathlessness [OR 2.06 (1.38-3.06)] and chest pain [OR 1.58 (1.07-2.35)]. Vision impairment was also associated with poor quality of life, poor social interaction and poor physical functioning. Sensory impairment is associated with poor physical functioning, poor health and poor social interaction in older men. Further research is warranted on pathways underlying these associations. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Insight Into Illness and Cognition in Schizophrenia in Earlier and Later Life.

    PubMed

    Gerretsen, Philip; Voineskos, Aristotle N; Graff-Guerrero, Ariel; Menon, Mahesh; Pollock, Bruce G; Mamo, David C; Mulsant, Benoit H; Rajji, Tarek K

    2017-04-01

    Impaired insight into illness in schizophrenia is associated with illness severity and deficits in premorbid intellectual function, executive function, and memory. A previous study of patients aged 60 years and older found that illness severity and premorbid intellectual function accounted for variance in insight impairment. As such, we aimed to test whether similar relationships would be observed in earlier life. A retrospective analysis was performed on 1 large sample of participants (n = 171) with a DSM-IV-TR diagnosis of schizophrenia aged 19 to 79 years acquired from 2 studies: (1) a psychosocial intervention trial for older persons with schizophrenia (June 2008 to May 2014) and (2) a diffusion tensor imaging and genetics study of psychosis across the life span (February 2007 to December 2013). We assessed insight into illness using the Positive and Negative Syndrome Scale (PANSS) item G12 and explored its relationship to illness severity (PANSS total modified), premorbid intellectual function (Wechsler Test of Adult Reading [WTAR]), and cognition. Insight impairment was more severe in later life (≥ 60 years) than in earlier years (t = -3.75, P < .001). Across the whole sample, the variance of impaired insight was explained by PANSS total modified (Exp[B] = 1.070, P < .001) and WTAR scores (Exp[B] = 0.970, P = .028). Although age and cognition were correlated with impaired insight, they did not independently contribute to its variance. However, the relationships between impaired insight and illness severity and between impaired insight and cognition, particularly working memory, were stronger in later life than in earlier life. These results suggest an opportunity for intervention may exist with cognitive-enhancing neurostimulation or medications to improve insight into illness in schizophrenia across the life span. Original study registered on ClinicalTrials.gov (identifier: NCT00832845). © Copyright 2017 Physicians Postgraduate Press, Inc.

  16. Changes in hippocampal synaptic functions and protein expression in monosodium glutamate-treated obese mice during development of glucose intolerance.

    PubMed

    Sasaki-Hamada, Sachie; Hojo, Yuki; Koyama, Hajime; Otsuka, Hayuma; Oka, Jun-Ichiro

    2015-05-01

    Glucose is the sole neural fuel for the brain and is essential for cognitive function. Abnormalities in glucose tolerance may be associated with impairments in cognitive function. Experimental obese model mice can be generated by an intraperitoneal injection of monosodium glutamate (MSG; 2 mg/g) once a day for 5 days from 1 day after birth. MSG-treated mice have been shown to develop glucose intolerance and exhibit chronic neuroendocrine dysfunction associated with marked cognitive malfunctions at 28-29  weeks old. Although hippocampal synaptic plasticity is impaired in MSG-treated mice, changes in synaptic transmission remain unknown. Here, we investigated whether glucose intolerance influenced cognitive function, synaptic properties and protein expression in the hippocampus. We demonstrated that MSG-treated mice developed glucose intolerance due to an impairment in the effectiveness of insulin actions, and showed cognitive impairments in the Y-maze test. Moreover, long-term potentiation (LTP) at Schaffer collateral-CA1 pyramidal synapses in hippocampal slices was impaired, and the relationship between the slope of extracellular field excitatory postsynaptic potential and stimulus intensity of synaptic transmission was weaker in MSG-treated mice. The protein levels of vesicular glutamate transporter 1 and GluA1 glutamate receptor subunits decreased in the CA1 region of MSG-treated mice. These results suggest that deficits in glutamatergic presynapses as well as postsynapses lead to impaired synaptic plasticity in MSG-treated mice during the development of glucose intolerance, though it remains unknown whether impaired LTP is due to altered inhibitory transmission. It may be important to examine changes in glucose tolerance in order to prevent cognitive malfunctions associated with diabetes. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  17. Acute stress symptoms in children: results from an international data archive.

    PubMed

    Kassam-Adams, Nancy; Palmieri, Patrick A; Rork, Kristine; Delahanty, Douglas L; Kenardy, Justin; Kohser, Kristen L; Landolt, Markus A; Le Brocque, Robyne; Marsac, Meghan L; Meiser-Stedman, Richard; Nixon, Reginald D V; Bui, Eric; McGrath, Caitlin

    2012-08-01

    To describe the prevalence of acute stress disorder (ASD) symptoms and to examine proposed DSM-5 symptom criteria in relation to concurrent functional impairment in children and adolescents. From an international archive, datasets were identified that included assessment of acute traumatic stress reactions and concurrent impairment in children and adolescents 5 to 17 years of age. Data came from 15 studies conducted in the United States, United Kingdom, Australia, and Switzerland and included 1,645 children and adolescents. Dichotomized items were created to indicate the presence or absence of each of the 14 proposed ASD symptoms and functional impairment. The performance of a proposed diagnostic criterion (number of ASD symptoms required) was examined as a predictor of concurrent impairment. Each ASD symptom was endorsed by 14% to 51% of children and adolescents; 41% reported clinically relevant impairment. Children and adolescents reported from 0 to 13 symptoms (mean = 3.6). Individual ASD symptoms were associated with greater likelihood of functional impairment. The DSM-5 proposed eight-symptom requirement was met by 202 individuals (12.3%) and had low sensitivity (0.25) in predicting concurrent clinically relevant impairment. Requiring fewer symptoms (three to four) greatly improved sensitivity while maintaining moderate specificity. This group of symptoms appears to capture aspects of traumatic stress reactions that can create distress and interfere with children's and adolescents' ability to function in the acute post-trauma phase. Results provide a benchmark for comparison with adult samples; a smaller proportion of children and adolescents met the eight-symptom criterion than reported for adults. Symptom requirements for the ASD diagnosis may need to be lowered to optimally identify children and adolescents whose acute distress warrants clinical attention. Copyright © 2012 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  18. Cognitive impairment associated with locomotive syndrome in community-dwelling elderly women in Japan.

    PubMed

    Nakamura, Misa; Tazaki, Fumie; Nomura, Kazuki; Takano, Taeko; Hashimoto, Masashi; Hashizume, Hiroshi; Kamei, Ichiro

    2017-01-01

    In our worldwide aging society, elderly people should maintain cognitive and physical function to help avoid health problems. Dementia is a major brain disease among elderly people, and is caused by cognitive impairment. The locomotive syndrome (LS) refers to a condition in which people require healthcare services because of problems associated with locomotion. The purpose of this study was to determine the association between cognitive impairment and LS. Study participants were 142 healthy elderly female volunteers living in a rural area in Japan. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). A score of ≤26 points on the MMSE was used to indicate categorically defined poor cognitive performance (cognitive impairment). The LS was defined by a score ≥16 points, and non-LS as <16 points, on the 25-question Geriatric Locomotive Function Scale (GLFS-25). Twenty-one participants (14.8%) had an MMSE score ≤26, and 19.0% were found to have LS. Compared with the MMSE >26 group, the ≤26 group was significantly older, had a higher percentage of body fat, and a higher GLFS-25 score. Those with LS were significantly older, had a higher body mass index, a higher percentage of body fat, and a lower MMSE score. Participants in the LS group had higher odds of cognitive impairment than those without LS [odds ratio (OR) =3.08] by logistic regression analysis adjusted for age. Furthermore, participants with GLFS-25 scores ≥6 had higher odds of cognitive impairment than those with a GLFS-25 score <6 by logistic regression analysis adjusted for both age (OR =4.44), and age and percent body fat (OR =4.12). These findings suggest that a strong relationship exists between the early stage of decreased motor function and cognitive impairment.

  19. Effects of functional remediation on neurocognitively impaired bipolar patients: enhancement of verbal memory.

    PubMed

    Bonnin, C M; Reinares, M; Martínez-Arán, A; Balanzá-Martínez, V; Sole, B; Torrent, C; Tabarés-Seisdedos, R; García-Portilla, M P; Ibáñez, A; Amann, B L; Arango, C; Ayuso-Mateos, J L; Crespo, J M; González-Pinto, A; Colom, F; Vieta, E

    2016-01-01

    Functional remediation is a novel intervention with demonstrated efficacy at improving functional outcome in euthymic bipolar patients. However, in a previous trial no significant changes in neurocognitive measures were detected. The objective of the present analysis was to test the efficacy of this therapy in the enhancement of neuropsychological functions in a subgroup of neurocognitively impaired bipolar patients. A total of 188 out of 239 DSM-IV euthymic bipolar patients performing below two standard deviations from the mean of normative data in any neurocognitive test were included in this subanalysis. Repeated-measures analyses of variance were conducted to assess the impact of the treatment arms [functional remediation, psychoeducation, or treatment as usual (TAU)] on participants' neurocognitive and functional outcomes in the subgroup of neurocognitively impaired patients. Patients receiving functional remediation (n = 56) showed an improvement on delayed free recall when compared with the TAU (n = 63) and psychoeducation (n = 69) groups as shown by the group × time interaction at 6-month follow-up [F 2,158 = 3.37, degrees of freedom (df) = 2, p = 0.037]. However, Tukey post-hoc analyses revealed that functional remediation was only superior when compared with TAU (p = 0.04), but not with psychoeducation (p = 0.10). Finally, the patients in the functional remediation group also benefited from the treatment in terms of functional outcome (F 2,158 = 4.26, df = 2, p = 0.016). Functional remediation is effective at improving verbal memory and psychosocial functioning in a sample of neurocognitively impaired bipolar patients at 6-month follow-up. Neurocognitive enhancement may be one of the active ingredients of this novel intervention, and, specifically, verbal memory appears to be the most sensitive function that improves with functional remediation.

  20. Episodic memory and executive functioning in currently depressed patients compared to healthy controls.

    PubMed

    Pauls, Franz; Petermann, Franz; Lepach, Anja Christina

    2015-01-01

    At present, little is still known about the link between depression, memory and executive functioning. This study examined whether there are memory-related impairments in depressed patients and whether the size of such deficits depends on the age group and on specific types of cognitive measures. Memory performances of 215 clinically depressed patients were compared to the data of a matched control sample. Regression analyses were performed to determine the extent to which executive dysfunctions contributed to episodic memory impairments. When compared with healthy controls, significantly lower episodic memory and executive functioning performances were found for depressed patients of all age groups. Effect sizes appeared to vary across different memory and executive functioning measures. The extent to which executive dysfunctions could explain episodic memory impairments varied depending on the type of measure examined. These findings emphasise the need to consider memory-related functioning of depressed patients in the context of therapeutic treatments.

  1. The Role of Eye Movement Driven Attention in Functional Strabismic Amblyopia

    PubMed Central

    2015-01-01

    Strabismic amblyopia “blunt vision” is a developmental anomaly that affects binocular vision and results in lowered visual acuity. Strabismus is a term for a misalignment of the visual axes and is usually characterized by impaired ability of the strabismic eye to take up fixation. Such impaired fixation is usually a function of the temporally and spatially impaired binocular eye movements that normally underlie binocular shifts in visual attention. In this review, we discuss how abnormal eye movement function in children with misaligned eyes influences the development of normal binocular visual attention and results in deficits in visual function such as depth perception. We also discuss how eye movement function deficits in adult amblyopia patients can also lead to other abnormalities in visual perception. Finally, we examine how the nonamblyopic eye of an amblyope is also affected in strabismic amblyopia. PMID:25838941

  2. Imbalance between GABAergic and Glutamatergic Transmission Impairs Adult Neurogenesis in an Animal Model of Alzheimer’s Disease

    PubMed Central

    Sun, Binggui; Halabisky, Brian; Zhou, Yungui; Palop, Jorge J.; Yu, Guiqiu; Mucke, Lennart; Gan, Li

    2009-01-01

    SUMMARY Adult neurogenesis regulates plasticity and function in the hippocampus, which is critical for memory and vulnerable to Alzheimer’s disease (AD). Promoting neurogenesis may improve hippocampal function in AD brains. However, how amyloid β (Aβ), the key AD pathogen, affects the development and function of adult-born neurons remains unknown. Adult-born granule cells (GCs) in human amyloid precursor protein (hAPP) transgenic mice, an AD model, showed greater dendritic length, spine density, and functional responses than controls early in development, but were impaired morphologically and functionally during later maturation. Early inhibition of GABAA receptors to suppress GABAergic signaling or late inhibition of calcineurin to enhance glutamatergic signaling normalized the development of adult-born GCs in hAPP mice with high Aβ levels. Aβ-induced increases in GABAergic neurotransmission or an imbalance between GABAergic and glutamatergic neurotransmission may contribute to impaired neurogenesis in AD. PMID:19951690

  3. The neuropsychology of prefrontal function in antisocial personality disordered offenders with varying degrees of psychopathy.

    PubMed

    Dolan, M

    2012-08-01

    Despite methodological differences between studies, it has been suggested that psychopathy may be associated with a ventromedial prefrontal cortex (VMPFC) deficit and antisocial personality disorder (ASPD), as classified in the DSM-IV, with a broader range of deficits in dorsolateral prefrontal cortex (DLPFC) and VMPFC function. Ninety-six male offenders with ASPD who were assessed using the psychopathy checklist: screening version (PCL:SV) and 49 male right-handed healthy controls (HCs), matched for age and IQ, completed a neuropsychological test battery. Offenders with ASPD displayed subtle impairments on executive function tasks of planning ability and set shifting and behavioural inhibition compared to HCs. However, among the offenders with ASPD there was no significant association between executive function impairment and scores on the measure of psychopathy. Psychopathic traits in offenders with ASPD are not associated with greater executive function impairment.

  4. Attention Contributes to Arithmetic Deficits in New-Onset Childhood Absence Epilepsy.

    PubMed

    Cheng, Dazhi; Yan, Xiuxian; Gao, Zhijie; Xu, Keming; Chen, Qian

    2017-01-01

    Neuropsychological studies indicate that new-onset childhood absence epilepsy (CAE) is associated with deficits in attention and executive functioning. However, the contribution of these deficits to impaired academic performance remains unclear. We aimed to examine whether attention and executive functioning deficits account for the academic difficulties prevalent in patients with new-onset CAE. We analyzed cognitive performance in several domains, including language, mathematics, psychomotor speed, spatial ability, memory, general intelligence, attention, and executive functioning, in 35 children with new-onset CAE and 33 control participants. Patients with new-onset CAE exhibited deficits in mathematics, general intelligence, attention, and executive functioning. Furthermore, attention deficits, as measured by a visual tracing task, accounted for impaired arithmetic performance in the new-onset CAE group. Therefore, attention deficits, rather than impaired general intelligence or executive functioning, may be responsible for arithmetic performance deficits in patients with new-onset CAE.

  5. On-road assessment of fitness-to-drive in persons with MS with cognitive impairment: A prospective study.

    PubMed

    Morrow, Sarah A; Classen, Sherrilene; Monahan, Miriam; Danter, Tim; Taylor, Robert; Krasniuk, Sarah; Rosehart, Heather; He, Wenqing

    2017-08-01

    Cognitive impairment is common in multiple sclerosis (MS). In other populations, cognitive impairment is known to affect fitness-to-drive. Few studies have focused on fitness-to-drive in MS and no studies have solely focused on the influence of cognitive impairment. To assess fitness-to-drive in persons with MS with cognitive impairment and low physical disability. Persons with MS, aged 18-59 years with EDSS ⩽ 4.0, impaired processing speed, and impairment on at least one measure of memory or executive function, were recruited. Cognition was assessed using the Minimal Assessment of Cognitive Function battery. A formal on-road driving assessment was conducted. Chi-square analysis examined the association between the fitness-to-drive (pass/fail) and the neuropsychological test results (normal/impaired). Bayesian statistics predicting failure of the on-road assessment were calculated. Of 36 subjects, eight (22.2%) were unfit to drive. Only the BVMTR-IR, measuring visual-spatial memory, predicted on-road driving assessment failure ( X 2 ( df = 1, N = 36) = 3.956; p = 0.047) with a sensitivity of 100%, but low specificity (35.7%) due to false positives (18/25). In persons with MS and impaired processing speed, impairment on the BVMTR-IR should lead clinicians to address fitness-to-drive.

  6. Cannabis Use Frequency and Use-Related Impairment among African American and White Users: The Impact of Cannabis Use Motives

    PubMed Central

    Shah, Sonia M.; Dean, Kimberlye E.; Zvolensky, Michael J.

    2015-01-01

    Objectives Cannabis use motives are differentially related to cannabis-related impairment and coping motives appear to have the strongest relation to use-related impairment. However, it is currently unknown whether African American individuals differ from White persons in reasons for using cannabis. It is also unknown whether motives’ relations to cannabis use and related impairment vary as a function of race. The present study examined the role of race on cannabis use motives and tested whether motives’ relations with cannabis use and related impairment differed by race. Design The sample consisted of 111 (67.6% non-Hispanic White, 32.4% African American) current cannabis-using adults. Results African American participants did not significantly differ from White participants on cannabis use frequency or use-related impairment. African American participants endorsed more social motives than White participants. Race interacted with social, coping, and conformity motives to predict cannabis-related impairment such that these motives were positively related to cannabis impairment among African American, but not White, participants. Conclusion Although African American and White participants do not differ in their cannabis use frequency or cannabis-related impairment, they appear to use cannabis for different reasons. Further, conformity, coping, and social motives were differentially associated with cannabis-related impairment as a function of race. Findings suggest motives for cannabis use should be contexualized in the context of race. PMID:26264291

  7. Cannabis use frequency and use-related impairment among African-American and White users: the impact of cannabis use motives.

    PubMed

    Buckner, Julia D; Shah, Sonia M; Dean, Kimberlye E; Zvolensky, Michael J

    2016-01-01

    Cannabis use motives are differentially related to cannabis-related impairment and coping motives appear to have the strongest relation to use-related impairment. However, it is currently unknown whether African-American individuals differ from White persons in reasons for using cannabis. It is also unknown whether motives' relations to cannabis use and related impairment vary as a function of race. The present study examined the role of race on cannabis use motives and tested whether motives' relations with cannabis use and related impairment differed by race. The sample consisted of 111 (67.6% non-Hispanic White, 32.4% African-American) current cannabis-using adults. African-American participants did not significantly differ from White participants on cannabis use frequency or use-related impairment. African-American participants endorsed more social motives than White participants. Race interacted with social, coping, and conformity motives to predict cannabis-related impairment such that these motives were positively related to cannabis impairment among African-American, but not White, participants. Although African-American and White participants do not differ in their cannabis use frequency or cannabis-related impairment, they appear to use cannabis for different reasons. Further, conformity, coping, and social motives were differentially associated with cannabis-related impairment as a function of race. Findings suggest motives for cannabis use should be contexualised in the context of race.

  8. Self-Reported Decline in Everyday Function, Cognitive Symptoms, and Cognitive Function in People With HIV.

    PubMed

    Laverick, Rosanna; Haddow, Lewis; Daskalopoulou, Marina; Lampe, Fiona; Gilson, Richard; Speakman, Andrew; Antinori, Andrea; Bruun, Tina; Vassilenko, Anna; Collins, Simon; Rodger, Alison

    2017-11-01

    We determined factors associated with self-reported decline in activities of daily living (ADLs) and symptoms of cognitive impairment in HIV positive adults in 5 European clinics. HIV+ adults underwent computerized and pen-and-paper neuropsychological tests and questionnaires of cognitive symptoms and ADLs. We considered cognitive function in 5 domains, psychosocial factors, and clinical parameters as potentially associated with symptoms. Separate regression analyses were used to determine factors associated with a decline in ADL (defined as self-reported decline affecting ≥2 ADLs and attributed to cognitive difficulties) and self-reported frequency of symptoms of cognitive impairment. We also estimated the diagnostic accuracy of both questionnaires as tests for cognitive impairment. Four hundred forty-eight patients completed the assessments [mean age 45.8 years, 84% male, 87% white, median CD4 count 550 cells/mm, median time since HIV diagnosis 9.9 years, 81% virologically suppressed (HIV-1 plasma RNA <50 copies/mL)]. Ninety-six (21.4%) reported decline in ADLs and attributed this to cognitive difficulties. Self-reported decline in ADLs and increased symptoms of cognitive impairment were both associated with worse performance on some cognitive tests. There were also strong associations with financial difficulties, depressive and anxiety symptoms, unemployment, and longer time since HIV diagnosis. Both questionnaires performed poorly as diagnostic tests for cognitive impairment. Patients' own assessments of everyday function and symptoms were associated with objectively measured cognitive function. However, there were strong associations with other psychosocial issues including mood and anxiety disorders and socioeconomic hardship. This should be considered when assessing HIV-associated cognitive impairment in clinical care or research studies.

  9. Incorporating Geriatric Assessment into a Nephrology Clinic: Preliminary Data from Two Models of Care.

    PubMed

    Hall, Rasheeda K; Haines, Carol; Gorbatkin, Steven M; Schlanger, Lynn; Shaban, Hesham; Schell, Jane O; Gurley, Susan B; Colón-Emeric, Cathleen S; Bowling, C Barrett

    2016-10-01

    Older adults with advanced chronic kidney disease (CKD) experience functional impairment that can complicate CKD management. Failure to recognize functional impairment may put these individuals at risk of further functional decline, nursing home placement, and missed opportunities for timely goals-of-care conversations. Routine geriatric assessment could be a useful tool for identifying older adults with CKD who are at risk of functional decline and provide contextual information to guide clinical decision-making. Two innovative programs were implemented in the Veterans Health Administration that incorporate geriatric assessment into a nephrology visit. In one program, a geriatrician embedded in a nephrology clinic used standardized geriatric assessment tools with individuals with CKD aged 70 and older (Comprehensive Geriatric Assessment for CKD) (CGA-4-CKD). In the second program, a nephrology clinic used comprehensive appointments for individuals aged 75 and older to conduct geriatric assessments and CKD care (Renal Silver). Data on 68 veterans who had geriatric assessments through these programs between November 2013 and May 2015 are reported. In CGA-4-CKD, difficulty with one or more activities of daily living (ADLs), history of falls, and cognitive impairment were each found in 27.3% of participants. ADL difficulty was found in 65.7%, falls in 28.6%, and cognitive impairment in 51.6% of participants in Renal Silver. Geriatric assessment guided care processes in 45.4% (n = 15) of veterans in the CGA-4-CKD program and 37.1% (n = 13) of those in Renal Silver. Findings suggest there is a significant burden of functional impairment in older adults with CKD. Knowledge of this impairment is applicable to CKD management. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  10. Mild cognitive impairment is associated with poor physical function but not bone structure or density in late adulthood: findings from the Hertfordshire cohort study.

    PubMed

    Patel, A; Jameson, K A; Edwards, M H; Ward, K; Gale, C R; Cooper, C; Dennison, Elaine M

    2018-04-24

    This study investigated the association between mild cognitive impairment (MCI) and physical function and bone health in older adults. MCI was associated with poor physical performance but not bone mineral density or bone microarchitecture. Cross-sectional study to investigate the association between mild cognitive impairment (MCI) and physical performance, and bone health, in a community-dwelling cohort of older adults. Cognitive function of 222 men and 221 women (mean age 75.5 and 75.8 years in men and women, respectively) was assessed by the Strawbridge questionnaire and Mini Mental State Exam (MMSE). Participants underwent dual-energy X-ray absorptiometry (DXA), peripheral-quantitative computed tomography (pQCT) and high-resolution peripheral-quantitative computed tomography (HR-pQCT) scans to assess their bone density, strength and microarchitecture. Their physical function was assessed and a physical performance (PP) score was recorded. In the study, 11.8% of women and 8.1% of men were cognitively impaired on the MMSE (score < 24). On the Strawbridge questionnaire, 24% of women were deemed cognitively impaired compared to 22.3% of men. Cognitive impairment on the Strawbridge questionnaire was associated with poorer physical performance score in men but not in women in the unadjusted analysis. MMSE < 24 was strongly associated with the risk of low physical performance in men (OR 12.9, 95% CI 1.67, 99.8, p = 0.01). Higher MMSE score was associated with better physical performance in both sexes. Poorer cognitive function, whether assessed by the Strawbridge questionnaire, or by MMSE score, was not associated with bone density, shape or microarchitecture, in either sex. MCI in older adults was associated with poor physical performance, but not bone density, shape or microarchitecture.

  11. Low intrinsic exercise capacity in rats predisposes to age-dependent cardiac remodeling independent of macrovascular function

    PubMed Central

    Ritchie, Rebecca H.; Leo, Chen Huei; Qin, Chengxue; Stephenson, Erin J.; Bowden, Marissa A.; Buxton, Keith D.; Lessard, Sarah J.; Rivas, Donato A.; Koch, Lauren G.; Britton, Steven L.; Woodman, Owen L.

    2013-01-01

    Rats selectively bred for low (LCR) or high (HCR) intrinsic running capacity simultaneously present with contrasting risk factors for cardiovascular and metabolic disease. However, the impact of these phenotypes on left ventricular (LV) morphology and microvascular function, and their progression with aging, remains unresolved. We tested the hypothesis that the LCR phenotype induces progressive age-dependent LV remodeling and impairments in microvascular function, glucose utilization, and β-adrenergic responsiveness, compared with HCR. Hearts and vessels isolated from female LCR (n = 22) or HCR (n = 26) were studied at 12 and 35 wk. Nonselected N:NIH founder rats (11 wk) were also investigated (n = 12). LCR had impaired glucose tolerance and elevated plasma insulin (but not glucose) and body-mass at 12 wk compared with HCR, with early LV remodeling. By 35 wk, LV prohypertrophic and glucose transporter GLUT4 gene expression were up- and downregulated, respectively. No differences in LV β-adrenoceptor expression or cAMP content between phenotypes were observed. Macrovascular endothelial function was predominantly nitric oxide (NO)-mediated in both phenotypes and remained intact in LCR for both age-groups. In contrast, mesenteric arteries microvascular endothelial function, which was impaired in LCR rats regardless of age. At 35 wk, endothelial-derived hyperpolarizing factor-mediated relaxation was impaired whereas the NO contribution to relaxation is intact. Furthermore, there was reduced β2-adrenoceptor responsiveness in both aorta and mesenteric LCR arteries. In conclusion, diminished intrinsic exercise capacity impairs systemic glucose tolerance and is accompanied by progressive development of LV remodeling. Impaired microvascular perfusion is a likely contributing factor to the cardiac phenotype. PMID:23262135

  12. Trends in Visual Health Inequalities in Childhood Through Associations of Visual Function With Sex and Social Position Across 3 UK Birth Cohorts.

    PubMed

    Bountziouka, Vasiliki; Cumberland, Phillippa M; Rahi, Jugnoo S

    2017-09-01

    Despite the existing country-specific strategies tackling social inequalities in visual health in adults, little is known about trends in visual function in childhood and its association with social position. To investigate the distribution of childhood visual function in the United Kingdom and associations with early-life social position between 1961 and 1986, a period of significant social change. Longitudinal cohort study using harmonized data sets from the British 1946, 1958, and 1970 national birth cohorts. In total, 14 283 cohort members with complete data on visual acuity at age 15 or 16 years, measured in 1961, 1974, and 1986, respectively, for each cohort, and social position were assessed. Using habitual distance visual acuity (with correction if prescribed), participants were assigned to a visual function category ranging from bilateral normal to visual impairment/severe visual impairment/blindness (International Statistical Classification of Diseases, Tenth Revision, Clinical Modification). Distribution of visual function over time and associations with social position (risk ratios [RRs] and 95% confidence intervals) were analyzed. Complete data were available for 3152 participants (aged 15 years; 53% boys [n = 1660]) in the 1946 Medical Research Council National Survey of Health and Development, 6683 participants (aged 16 years; 51% boys [n = 3420]) in the 1958 National Child Development Study, and 4448 participants (aged 16 years; 48% boys [n = 2156]) in the 1970 British Birth Cohort Study. The proportion of children with bilateral normal vision decreased by 1.3% (95% CI, -5.1% to 2.7%) in 1974 and 1.7% (95% CI, -5.9% to 2.7%) in 1986. The risk of overall impaired vision increased by 1.20 times (95% CI, 1.01-1.43) and the risk of visual impairment/severe visual impairment/blindness by 1.75 times (95% CI, 1.03-2.98) during this period. Girls were consistently at increased risk of all vision impairment categories. Higher social position at birth and in childhood was associated with reduced risk of visual impairment/severe visual impairment/blindness (RR, 0.58; 95% CI, 0.20-1.68) and unilateral impairment (RR, 0.89; 95% CI, 0.72-1.11), respectively. Our study provides evidence of temporal decline in childhood visual function between 1961 and 1986. Despite the limited power of the analysis owing to the small sample size of those with impaired vision, we found an emergence of a contribution of sociodemographic status to the cohort effect that may be the antecedent of the current picture of childhood blindness. Equally, early-life social position may also have contributed to the current social patterning in visual function in older adults in the United Kingdom. These findings highlight the potential value of targeting children in national ophthalmic public policies tackling inequalities.

  13. The impact of cognitive impairment, neurological soft signs and subdepressive symptoms on functional outcome in bipolar disorder.

    PubMed

    Baş, Tuba Öcek; Poyraz, Cana Aksoy; Baş, Alper; Poyraz, Burç Çağrı; Tosun, Musa

    2015-03-15

    Cognitive impairments and subsyndromal depressive symptoms are present during euthymic periods of bipolar disorder (BD). Most studies have determined that cognitive impairments and residual depressive symptoms have major impacts on psychosocial functioning. The aim of the present study was to identify the major factor responsible for low psychosocial functioning in a subgroup of patients with BD despite clinical recovery. Sixty patients with bipolar I disorder and 41 healthy subjects were enrolled in this study. Cognitive performance, neurological soft signs (NSSs), psychosocial functioning, residual mood symptoms and illness characteristics were assessed. Using the median value of the Functioning Assessment Short Test (FAST) as the cut-off point, the patients were divided into two groups, high- (n=29) or low-functioning (n=31), and they were compared based on total NSS, residual depressive symptoms, cognitive performance and clinical variables. Performances on the verbal memory tests and social functioning were significantly worse in the euthymic patients with BD. Increased rates of NSS were identified in the patients compared with the normal controls. The low-functioning patients performed significantly worse on verbal memory, and their NSS and residual depressive symptoms were significantly higher compared to high-functioning patients. In the regression analysis, subsyndromal depressive symptoms and verbal learning measures were identified as the best predictors of psychosocial functioning. The patients were artificially separated into two groups based on a FAST score cut-off. In this study, residual depressive symptoms and verbal memory impairments were the most prominent factors associated with the level of functioning. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Sexual Dysfunctions in Men and Women with Inflammatory Bowel Disease: The Influence of IBD-Related Clinical Factors and Depression on Sexual Function.

    PubMed

    Bel, Linda G J; Vollebregt, Anna M; Van der Meulen-de Jong, Andrea E; Fidder, Herma H; Ten Hove, Willem R; Vliet-Vlieland, Cornelia W; Ter Kuile, Moniek M; de Groot, Helena E; Both, Stephanie

    2015-07-01

    Inflammatory bowel disease (IBD) is likely to have an impact on sexual function because of its symptoms, like diarrhea, fatigue, and abdominal pain. Depression is commonly reported in IBD and is also related to impaired sexual function. This study aimed to evaluate sexual function and its association with depression among patients with IBD compared with controls. IBD patients registered at two hospitals participated. The control group consisted of a general practitioner practice population. The web-based questionnaire included the Female Sexual Function Index (FSFI) for women and the International Index of Erectile Function (IIEF) for men. Other variables evaluated were depression, disease activity, IBD-related quality of life, body image, and fatigue. In total, 168 female and 119 male patients were available for analysis (response rate 24%). Overall, patients with IBD did not significantly differ in prevalence of sexual dysfunctions from controls: female patients 52%, female controls 44%, male patients and male controls both 25%. However, men and women with an active disease scored significantly lower than patients in remission and controls, indicating impaired sexual functioning during disease activity. Significant associations were found between active disease, fatigue, depressive mood, quality of life, and sexual function for both male and female patients. The association between disease activity and sexual function was totally mediated by depression. Male and female IBD patients with an active disease show impaired sexual function relative to patients in remission and controls. Depression is the most important determinant for impaired sexual function in IBD. © 2015 International Society for Sexual Medicine.

  15. Regulation of brain insulin signaling: A new function for tau

    PubMed Central

    Gratuze, Maud; Planel, Emmanuel

    2017-01-01

    In this issue of JEM, Marciniak et al. (https://doi.org/10.1084/jem.20161731) identify a putative novel function of tau protein as a regulator of insulin signaling in the brain. They find that tau deletion impairs hippocampal response to insulin through IRS-1 and PTEN dysregulation and suggest that, in Alzheimer’s disease, impairment of brain insulin signaling might occur via tau loss of function. PMID:28652305

  16. Social Resources That Preserve Functional Independence After Memory Loss

    DTIC Science & Technology

    2015-05-01

    20, 471 (May, 2005). 3. A. M. Jette, Toward a common language for function, disability, and health. Physical therapy 86, 726 (May, 2006). 4. R. D...impairment. We found strong associations between decreased cognitive functioning and incident ADL and IADL limitations. Physical activity may help to...ADL limitations among those with cognitive impairments. We also found that physical activity is associated with lower risk of future nursing home

  17. The influence of unilateral saccular impairment on functional balance performance and self-report dizziness.

    PubMed

    McCaslin, Devin L; Jacobson, Gary P; Grantham, Sarah L; Piker, Erin G; Verghese, Susha

    2011-09-01

    Postural stability in humans is largely maintained by vestibular, visual, and somatosensory inputs to the central nervous system. Recent clinical advances in the assessment of otolith function (e.g., cervical and ocular vestibular evoked myogenic potentials [cVEMPs and oVEMPs], subjective visual vertical [SVV] during eccentric rotation) have enabled investigators to identify patients with unilateral otolith impairments. This research has suggested that patients with unilateral otolith impairments perform worse than normal healthy controls on measures of postural stability. It is not yet known if patients with unilateral impairments of the saccule and/or inferior vestibular nerve (i.e., unilaterally abnormal cVEMP) perform differently on measures of postural stability than patients with unilateral impairments of the horizontal SCC (semicircular canal) and/or superior vestibular nerve (i.e., unilateral caloric weakness). Further, it is not known what relationship exists, if any, between otolith system impairment and self-report dizziness handicap. The purpose of this investigation was to determine the extent to which saccular impairments (defined by a unilaterally absent cVEMP) and impairments of the horizontal semicircular canal (as measured by the results of caloric testing) affect vestibulospinal function as measured through the Sensory Organization Test (SOT) of the computerized dynamic posturography (CDP). A secondary objective of this investigation was to measure the effects, if any, that saccular impairment has on a modality-specific measure of health-related quality of life. A retrospective cohort study. Subjects were assigned to one of four groups based on results from balance function testing: Group 1 (abnormal cVEMP response only), Group 2 (abnormal caloric response only), Group 3 (abnormal cVEMP and abnormal caloric response), and Group 4 (normal control group). Subjects were 92 adult patients: 62 were seen for balance function testing due to complaints of dizziness, vertigo, or unsteadiness, and 30 served as controls. All subjects underwent videonystagmography or electronystagmography (VNG/ENG), vestibular evoked myogenic potentials (VEMPs), self-report measures of self-perceived dizziness disability/handicap (Dizziness Handicap Inventory), and tests of postural control (Neurocom Equitest). Subjects were categorized into one of four groups based on balance function test results. All variables were subjected to a multifactor analysis of variance (ANOVA). The Dizziness Handicap Inventory (DHI) total scores and equilibrium scores served as the dependent variables. Results showed that patients with abnormal unilateral saccular or inferior vestibular nerve function (i.e., abnormal cVEMP) demonstrated significantly impaired postural control when compared to normal participants. However, this group demonstrated significantly better postural stability when compared to the group with abnormal caloric responses alone and the group with abnormal caloric responses and abnormal cVEMP results. Patients with an abnormal cVEMP did not differ significantly on the DHI compared to the other two impaired groups. We interpret these findings as evidence that a significantly asymmetrical cVEMP in isolation negatively impacts performance on measures of postural control compared to normal subjects but not compared to patients with significant caloric weaknesses. However, patients with a unilaterally abnormal cVEMP do not differ from patients with significant caloric weaknesses in regard to self-perceived dizziness handicap. American Academy of Audiology.

  18. Resting-State Functional Connectivity Predicts Cognitive Impairment Related to Alzheimer's Disease.

    PubMed

    Lin, Qi; Rosenberg, Monica D; Yoo, Kwangsun; Hsu, Tiffany W; O'Connell, Thomas P; Chun, Marvin M

    2018-01-01

    Resting-state functional connectivity (rs-FC) is a promising neuromarker for cognitive decline in aging population, based on its ability to reveal functional differences associated with cognitive impairment across individuals, and because rs-fMRI may be less taxing for participants than task-based fMRI or neuropsychological tests. Here, we employ an approach that uses rs-FC to predict the Alzheimer's Disease Assessment Scale (11 items; ADAS11) scores, which measure overall cognitive functioning, in novel individuals. We applied this technique, connectome-based predictive modeling, to a heterogeneous sample of 59 subjects from the Alzheimer's Disease Neuroimaging Initiative, including normal aging, mild cognitive impairment, and AD subjects. First, we built linear regression models to predict ADAS11 scores from rs-FC measured with Pearson's r correlation. The positive network model tested with leave-one-out cross validation (LOOCV) significantly predicted individual differences in cognitive function from rs-FC. In a second analysis, we considered other functional connectivity features, accordance and discordance, which disentangle the correlation and anticorrelation components of activity timecourses between brain areas. Using partial least square regression and LOOCV, we again built models to successfully predict ADAS11 scores in novel individuals. Our study provides promising evidence that rs-FC can reveal cognitive impairment in an aging population, although more development is needed for clinical application.

  19. Association between cognitive impairment and eating habits in elderly Chinese subjects over 90 years of age.

    PubMed

    Gao, Lingyun; Dong, Birong; Hao, Qiu Kui; Ding, Xiang

    2013-08-01

    Eating habits may have a key influence on cognitive function, however, the relationship between dietary intake and cognitive impairment in the elderly Chinese population has not been explored. The present study investigated the association between cognitive impairment and eating habits in elderly Chinese subjects >90 years of age. This study comprised data from subjects included in the 2005 Project of Longevity and Ageing in Dujiangyan, China. Subjects were divided into two groups: cognitive impairment group and normal group. Sociodemographic and dietary habit data were collected and cognitive function was assessed in all subjects using the Mini-Mental State Examination. Data from 763 subjects (249 men, 514 women) were included. There was no statistically significant difference in eating habits between the two groups. Education level in the cognitive impairment group was significantly lower than in the normal group. Significant between-group differences were detected in factors relating to subjects' professions. Eating habits were not related to cognitive impairment in elderly Chinese people >90 years of age.

  20. Are empathic abilities impaired in posttraumatic stress disorder?

    PubMed

    Nietlisbach, Gabriela; Maercker, Andreas; Rössler, Wulf; Haker, Helene

    2010-06-01

    Trauma survivors with PTSD show social interaction and relationship impairments. It is hypothesized that traumatic experiences lead to known PTSD symptoms, empathic ability impairment, and difficulties in sharing affective, emotional, or cognitive states. A PTSD group (N=16) and a nontraumatized Control group (N=16) were compared on empathic abilities, namely the Empathic Resonance Test, Reading the Mind in the Eyes Test, and Faux Pas Test. The Interpersonal Reactivity Index as a self-report measure of empathy and measures of non-social cognitive functions, namely the Verbal Fluency Test, the Five-Point Test, and the Stroop Test, were also administered. The PTSD group showed lower empathic resonance. No clear indications of other impairments in social cognitive functions were found. The PTSD group had significantly higher personal distress. Empathic resonance impairments did not correlate with subjective severity of PTSD symptomatology. This article discusses whether impaired empathic resonance in PTSD trauma survivors is a consequence of trauma itself or a protective coping strategy.

  1. Sleep deprivation during a specific 3-hour time window post-training impairs hippocampal synaptic plasticity and memory

    PubMed Central

    Prince, Toni-Moi; Wimmer, Mathieu; Choi, Jennifer; Havekes, Robbert; Aton, Sara; Abel, Ted

    2014-01-01

    Sleep deprivation disrupts hippocampal function and plasticity. In particular, long-term memory consolidation is impaired by sleep deprivation, suggesting that a specific critical period exists following learning during which sleep is necessary. To elucidate the impact of sleep deprivation on long-term memory consolidation and synaptic plasticity, long-term memory was assessed when mice were sleep deprived following training in the hippocampus-dependent object place recognition task. We found that 3 hours of sleep deprivation significantly impaired memory when deprivation began 1 hour after training. In contrast, 3 hours of deprivation beginning immediately post-training did not impair spatial memory. Furthermore, a 3-hour sleep deprivation beginning 1 hour after training impaired hippocampal long-term potentiation (LTP), whereas sleep deprivation immediately after training did not affect LTP. Together, our findings define a specific 3-hour critical period, extending from 1 to 4 hours after training, during which sleep deprivation impairs hippocampal function. PMID:24380868

  2. [Poststroke cognitive, emotional impairment and sleep quality: efficience of treatment with melaxen].

    PubMed

    Kulesh, A A; Shestakov, V V

    2014-01-01

    To study melatonin secretion and its correlations with poststroke cognitive, emotional impairment and sleep quality in the acute period of stroke and to assess treatment efficacy of melaxen. We studied 96 patients with acute stroke. A battery of tests and scales for assessment of neurological deficit, neuropsychological status and emotional impairment was used. The night urinary level of 6-sulfatoxymelatonin was assessed. The relationship between 6-sulfatoxymelatonin and cognitive, emotional status and sleep parameters was analyzed. The level of 6-sulfatoxymelatonin was decreased in the night urine. Patients with dysexecutive poststroke cognitive impairment had higher level of 6-sulfatoxymelatonin and patients with dysmnestic and mixed cognitive impairment had lower level of 6-sulfatoxymelatonin in comparison with patients with normal cognitive functions. Melaxen improved cognitive function and sleep parameters, reduced the level of anxiety in the early recovery period of stroke. A role of chronobiological processes in the development of clinical signs of stroke in the aspect of cognitive impairment is discussed.

  3. The effect of flexible body armour on pulmonary function.

    PubMed

    Armstrong, Nicola C; Gay, Louise A

    2016-05-01

    The additional mass and fit of current military in-service body armour (ISBA) can reduce pulmonary function in a way that is characteristic of a restrictive respiratory impairment. This could ultimately impair exercise capacity and military performance. This study compared pulmonary function (forced vital capacity [FVC] and forced expiratory volume in 1 s [FEV1]) in UK ISBA (15.3 kg) and three flexible body armours (BAs) (FA1: 10 kg; FA2: 7.8 kg; FA3: 10 kg) in eight male soldiers. The design of the ballistic plates differed between the BAs to improve the flexibility. FVC and FEV1 were reduced by 4-6%, without reduction in FEV1/FVC for ISBA, FA2 and FA3, when compared to NoBA (p < 0.05). No difference was observed between FA1 and NoBA. As expected, wearing BA caused a mild restrictive ventilatory impairment; however, modifications to BA design can reduce the degree of this impairment. Practitioner Summary: This study showed that wearing body armour caused a mild restrictive ventilatory impairment. However, the design of the armour can be modified to reduce the degree of this impairment. This may lead to improvements in soldier performance during tasks that require body armour.

  4. Invariance of ADHD Symptoms Across Sex and Age: a Latent Analysis of ADHD and Impairment Ratings from Early Childhood into Adolescence.

    PubMed

    Leopold, Daniel R; Christopher, Micaela E; Olson, Richard K; Petrill, Stephen A; Willcutt, Erik G

    2018-04-25

    A population-based longitudinal sample of 489 twin pairs was assessed at six time points over ten years to examine the measurement invariance and stability of attention-deficit/hyperactivity disorder (ADHD) symptoms, as well as the developmental relations between inattention (IN), hyperactivity-impulsivity (HI), and multiple aspects of functional impairment. Parent ratings of ADHD symptoms and functional impairment were obtained in preschool and after the completion of kindergarten, first, second, fourth, and ninth grades. Results of the temporal and sex invariance models indicated that parent ratings of the 18 ADHD symptoms function in the same manner for females and males from early childhood into adolescence. In addition to establishing this prerequisite condition for the interpretation of longitudinal and between-sex differences in the IN and HI symptom dimensions, cross-lagged models indicated that both IN and HI were associated with increased risk for both concurrent and future overall, social, and recreational impairment, whereas only IN was uniquely associated with later academic impairment. Taken together, the current results demonstrate that IN and HI are highly stable from preschool through ninth grade, invariant between females and males, and indicative of risk for impairment in multiple areas, thereby providing strong support for the validity of the symptom dimensions among both sexes.

  5. A medical record review for functional somatic symptoms in children.

    PubMed

    Rask, Charlotte Ulrikka; Borg, Carsten; Søndergaard, Charlotte; Schulz-Pedersen, Søren; Thomsen, Per Hove; Fink, Per

    2010-04-01

    The objectives of this study were to develop and test a systematic medical record review for functional somatic symptoms (FSSs) in paediatric patients and to estimate the inter-rater reliability of paediatricians' recognition of FSSs and their associated impairments while using this method. We developed the Medical Record Review for Functional Somatic Symptoms in Children (MRFC) for retrospective medical record review. Described symptoms were categorised as probably, definitely, or not FSSs. FSS-associated impairment was also determined. Three paediatricians performed the MRFC on the medical records of 54 children with a diagnosed, well-defined physical disease and 59 with 'symptom' diagnoses. The inter-rater reliabilities of the recognition and associated impairment of FSSs were tested on 20 of these records. The MRFC allowed identification of subgroups of children with multisymptomatic FSSs, long-term FSSs, and/or impairing FSSs. The FSS inter-rater reliability was good (combined kappa=0.69) but only fair as far as associated impairment was concerned (combined kappa=0.29). In the hands of skilled paediatricians, the MRFC is a reliable method for identifying paediatric patients with diverse types of FSSs for clinical research. However, additional information is needed for reliable judgement of impairment. The method may also prove useful in clinical practice. Copyright 2010 Elsevier Inc. All rights reserved.

  6. Sensory impairments of the lower limb after stroke: a pooled analysis of individual patient data.

    PubMed

    Tyson, Sarah F; Crow, J Lesley; Connell, Louise; Winward, Charlotte; Hillier, Susan

    2013-01-01

    To obtain more generalizable information on the frequency and factors influencing sensory impairment after stroke and their relationship to mobility and function. A pooled analysis of individual data of stroke survivors (N = 459); mean (SD) age = 67.2 (14.8) years, 54% male, mean (SD) time since stroke = 22.33 (63.1) days, 50% left-sided weakness. Where different measurement tools were used, data were recorded. Descriptive statistics described frequency of sensory impairments, kappa coefficients investigated relationships between sensory modalities, binary logistic regression explored the factors influencing sensory impairments, and linear regression assessed the impact of sensory impairments on activity limitations. Most patients' sensation was intact (55%), and individual sensory modalities were highly associated (κ = 0.60, P < .001). Weakness and neglect influenced sensory impairment (P < .001), but demographics, stroke pathology, and spasticity did not. Sensation influenced independence in activities of daily living, mobility, and balance but less strongly than weakness. Pooled individual data analysis showed sensation of the lower limb is grossly preserved in most stroke survivors but, when present, it affects function. Sensory modalities are highly interrelated; interventions that treat the motor system during functional tasks may be as effective at treating the sensory system as sensory retraining alone.

  7. The combined effect of visual impairment and cognitive impairment on disability in older people.

    PubMed

    Whitson, Heather E; Cousins, Scott W; Burchett, Bruce M; Hybels, Celia F; Pieper, Carl F; Cohen, Harvey J

    2007-06-01

    To determine the risk of disability in individuals with coexisting visual and cognitive impairment and to compare the magnitude of risk associated with visual impairment, cognitive impairment, or the multimorbidity. Prospective cohort. North Carolina. Three thousand eight hundred seventy-eight participants in the North Carolina Established Populations for the Epidemiologic Studies of the Elderly with nonmissing visual status, cognitive status, and disability status data at baseline Short Portable Mental Status Questionnaire (cognitive impairment defined as > or =4 errors), self reported visual acuity (visual impairment defined as inability to see well enough to recognize a friend across the street or to read newspaper print), demographic and health-related variables, disability status (activities of daily living (ADLs), instrumental activities of daily living (IADLs), mobility), death, and time to nursing home placement. Participants with coexisting visual and cognitive impairment were at greater risk of IADL disability (odds ratio (OR)=6.50, 95% confidence interval (CI)=4.34-9.75), mobility disability (OR=4.04, 95% CI=2.49-6.54), ADL disability (OR=2.84, 95% CI=1.87-4.32), and incident ADL disability (OR=3.66, 95%, CI=2.36-5.65). In each case, the estimated OR associated with the multimorbidity was greater than the estimated OR associated with visual or cognitive impairment alone, a pattern that was not observed for other adverse outcomes assessed. No significant interactions were observed between cognitive impairment and visual impairment as predictors of disability status. Individuals with coexisting visual impairment and cognitive impairment are at high risk of disability, with each condition contributing additively to disability risk. Further study is needed to improve functional trajectories in patients with this prevalent multimorbidity. When visual or cognitive impairment is present, efforts to maximize the other function may be beneficial.

  8. Multimodal investigation of triple network connectivity in patients with 22q11DS and association with executive functions.

    PubMed

    Padula, Maria C; Schaer, Marie; Scariati, Elisa; Maeder, Johanna; Schneider, Maude; Eliez, Stephan

    2017-04-01

    Large-scale brain networks play a prominent role in cognitive abilities and their activity is impaired in psychiatric disorders, such as schizophrenia. Patients with 22q11.2 deletion syndrome (22q11DS) are at high risk of developing schizophrenia and present similar cognitive impairments, including executive functions deficits. Thus, 22q11DS represents a model for the study of neural biomarkers associated with schizophrenia. In this study, we investigated structural and functional connectivity within and between the Default Mode (DMN), the Central Executive (CEN), and the Saliency network (SN) in 22q11DS using resting-state fMRI and DTI. Furthermore, we investigated if triple network impairments were related to executive dysfunctions or the presence of psychotic symptoms. Sixty-three patients with 22q11DS and sixty-eighty controls (age 6-33 years) were included in the study. Structural connectivity between main nodes of DMN, CEN, and SN was computed using probabilistic tractography. Functional connectivity was computed as the partial correlation between the time courses extracted from each node. Structural and functional connectivity measures were then correlated to executive functions and psychotic symptom scores. Our results showed mainly reduced structural connectivity within the CEN, DMN, and SN, in patients with 22q11DS compared with controls as well as reduced between-network connectivity. Functional connectivity appeared to be more preserved, with impairments being evident only within the DMN. Structural connectivity impairments were also related to executive dysfunctions. These findings show an association between triple network structural alterations and executive deficits in patients with the microdeletion, suggesting that 22q11DS and schizophrenia share common psychopathological mechanisms. Hum Brain Mapp 38:2177-2189, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. The natural history of children with joint hypermobility syndrome and Ehlers-Danlos hypermobility type: a longitudinal cohort study.

    PubMed

    Scheper, Mark C; Nicholson, Lesley L; Adams, Roger D; Tofts, Louise; Pacey, Verity

    2017-12-01

    The objective of the manuscript was to describe the natural history of complaints and disability in children diagnosed with joint hypermobility syndrome (JHS)/Ehlers-Danlos-hypermobility type (EDS-HT) and to identify the constructs that underlie functional decline. One hundred and one JHS/EDS-HT children were observed over 3 years and assessed at three time points on the following: functional impairments, quality of life, connective tissue laxity, muscle function, postural control and musculoskeletal and multi-systemic complaints. Cluster analysis was performed to identify subgroups in severity. Clinical profiles were determined for these subgroups, and differences were assessed by multivariate analysis of covariance. Mixed linear regression models were used to determine the subsequent trajectories. Finally, an exploratory factor analysis was used to uncover the underlying constructs of functional impairment. Three clusters of children were identified in terms of functional impairment: mild, moderately and severely affected. Functional impairment at baseline was predictive of worsening trajectories in terms of reduced walking distance and decreased quality of life (P ⩽ 0.05) over 3 years. Multiple interactions between the secondary outcomes were observed, with four underlying constructs identified. All four constructs (multi-systemic effects, pain, fatigue and loss of postural control) contributed significantly to disability (P ⩽ 0.046). Children diagnosed with JHS/EDS-HT who have a high incidence of multi-systemic complaints (particularly, orthostatic intolerance, urinary incontinence and diarrhoea) and poor postural control in addition to high levels of pain and fatigue at baseline are most likely to have a deteriorating trajectory of functional impairment and, accordingly, warrant clinical prioritization. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  10. Impact of low vision rehabilitation on functional vision performance of children with visual impairment.

    PubMed

    Ganesh, Suma; Sethi, Sumita; Srivastav, Sonia; Chaudhary, Amrita; Arora, Priyanka

    2013-09-01

    To evaluate the impact of low vision rehabilitation on functional vision of children with visual impairment. The LV Prasad-Functional Vision Questionnaire, designed specifically to measure functional performance of visually impaired children of developing countries, was used to assess the level of difficulty in performing various tasks pre and post visual rehabilitation in children with documented visual impairment. Chi-square test was used to assess the impact of rehabilitation intervention on functional vision performance; a P < 0.05 was considered significant. LogMAR visual acuity prior to the introduction of low vision devices (LVDs) was 0.90 ± 0.05 for distance and for near it was 0.61 ± 0.05. After the intervention, the acuities improved significantly for distance (0.2 ± 0.27; P < 0.0001) and near (0.42 ± 0.17; P = 0.001). The most common reported difficulties were related to their academic activities like copying from the blackboard (80%), reading textbook at arm's length (77.2%), and writing along a straight line (77.2%). Absolute raw score of disability pre-LVD was 15.05 which improved to 7.58 post-LVD. An improvement in functional vision post visual rehabilitation was especially found in those activities related to their studying lifestyle like copying from the blackboard (P < 0.0001), reading textbook at arm's length (P < 0.0001), and writing along a straight line (P = 0.003). In our study group, there was a significant improvement in functional vision post visual rehabilitation, especially with those activities which are related to their academic output. It is important for these children to have an early visual rehabilitation to decrease the impairment associated with these decreased visual output and to enhance their learning abilities.

  11. Combination of exercise training and diet restriction normalizes limited exercise capacity and impaired skeletal muscle function in diet-induced diabetic mice.

    PubMed

    Suga, Tadashi; Kinugawa, Shintaro; Takada, Shingo; Kadoguchi, Tomoyasu; Fukushima, Arata; Homma, Tsuneaki; Masaki, Yoshihiro; Furihata, Takaaki; Takahashi, Masashige; Sobirin, Mochamad A; Ono, Taisuke; Hirabayashi, Kagami; Yokota, Takashi; Tanaka, Shinya; Okita, Koichi; Tsutsui, Hiroyuki

    2014-01-01

    Exercise training (EX) and diet restriction (DR) are essential for effective management of obesity and insulin resistance in diabetes mellitus. However, whether these interventions ameliorate the limited exercise capacity and impaired skeletal muscle function in diabetes patients remains unexplored. Therefore, we investigated the effects of EX and/or DR on exercise capacity and skeletal muscle function in diet-induced diabetic mice. Male C57BL/6J mice that were fed a high-fat diet (HFD) for 8 weeks were randomly assigned for an additional 4 weeks to 4 groups: control, EX, DR, and EX+DR. A lean group fed with a normal diet was also studied. Obesity and insulin resistance induced by a HFD were significantly but partially improved by EX or DR and completely reversed by EX+DR. Although exercise capacity decreased significantly with HFD compared with normal diet, it partially improved with EX and DR and completely reversed with EX+DR. In parallel, the impaired mitochondrial function and enhanced oxidative stress in the skeletal muscle caused by the HFD were normalized only by EX+DR. Although obesity and insulin resistance were completely reversed by DR with an insulin-sensitizing drug or a long-term intervention, the exercise capacity and skeletal muscle function could not be normalized. Therefore, improvement in impaired skeletal muscle function, rather than obesity and insulin resistance, may be an important therapeutic target for normalization of the limited exercise capacity in diabetes. In conclusion, a comprehensive lifestyle therapy of exercise and diet normalizes the limited exercise capacity and impaired muscle function in diabetes mellitus.

  12. Impairment in emotion perception from body movements in individuals with bipolar I and bipolar II disorder is associated with functional capacity.

    PubMed

    Vaskinn, Anja; Lagerberg, Trine Vik; Bjella, Thomas D; Simonsen, Carmen; Andreassen, Ole A; Ueland, Torill; Sundet, Kjetil

    2017-12-01

    Individuals with bipolar disorder present with moderate impairments in social cognition during the euthymic state. The impairment extends to theory of mind and to the perception of emotion in faces and voices, but it is unclear if emotion perception from body movements is affected. The main aim of this study was to examine if participants with bipolar disorder perform worse than healthy control participants on a task using point-light displays of human full figures moving in a manner indicative of a basic emotion (angry, happy, sad, fearful, neutral/no emotion). A secondary research question was whether diagnostic subtypes (bipolar I, bipolar II) and history of psychosis impacted on this type of emotion perception. Finally, symptomatic, neurocognitive, and functional correlates of emotion perception from body movements were investigated. Fifty-three individuals with bipolar I (n = 29) or bipolar II (n = 24) disorder, and 84 healthy control participants were assessed for emotion perception from body movements. The bipolar group also underwent clinical, cognitive, and functional assessment. Research questions were analyzed using analyses of variance and bivariate correlations. The bipolar disorder group differed significantly from healthy control participants for emotion perception from body movements (Cohen's d = 0.40). Analyses of variance yielded no effects of sex, diagnostic subtype (bipolar I, bipolar II), or history of psychosis. There was an effect of emotion, indicating that some emotions are easier to recognize. The lack of a significant group × emotion interaction effect points, however, to this being so regardless of the presence of bipolar disorder. Performance was unrelated to manic and depressive symptom load but showed significant associations with neurocognition and functional capacity. Individuals with bipolar disorder had a small but significant impairment in the ability to perceive emotions from body movement. The impairment was global, i.e., affecting all emotions and equally present for males and females. The impairment was associated with neurocognition and functional capacity, but not symptom load. Our findings identify pathopsychological factors underlying the functional impairment in bipolar disorder and suggest the consideration of social cognition training as part of the treatment for bipolar disorder.

  13. Importance of functional and metabolic impairments in the characterization of the C-26 murine model of cancer cachexia

    PubMed Central

    Murphy, Kate T.; Chee, Annabel; Trieu, Jennifer; Naim, Timur; Lynch, Gordon S.

    2012-01-01

    SUMMARY Cancer cachexia describes the progressive skeletal muscle wasting and weakness that is associated with many cancers. It impairs quality of life and accounts for >20% of all cancer-related deaths. The main outcome that affects quality of life and mortality is loss of skeletal muscle function and so preclinical models should exhibit similar functional impairments in order to maximize translational outcomes. Mice bearing colon-26 (C-26) tumors are commonly used in cancer cachexia studies but few studies have provided comprehensive assessments of physiological and metabolic impairment, especially those factors that impact quality of life. Our aim was to characterize functional impairments in mildly and severely affected cachectic mice, and determine the suitability of these mice as a preclinical model. Metabolic abnormalities are also evident in cachectic patients and we investigated whether C-26-tumor-bearing mice had similar metabolic aberrations. Twelve-week-old CD2F1 mice received a subcutaneous injection of PBS (control) or C-26 tumor cells. After 18–20 days, assessments were made of grip strength, rotarod performance, locomotor activity, whole body metabolism, and contractile properties of tibialis anterior (TA) muscles (in situ) and diaphragm muscle strips (in vitro). Injection of C-26 cells reduced body and muscle mass, and epididymal fat mass. C-26-tumor-bearing mice exhibited lower grip strength and rotarod performance. Locomotor activity was impaired following C-26 injection, with reductions in movement distance, duration and speed compared with controls. TA muscles from C-26-tumor-bearing mice had lower maximum force (−27%) and were more susceptible to fatigue. Maximum specific (normalized) force of diaphragm muscle strips was reduced (−10%) with C-26 injection, and force during fatiguing stimulation was also lower. C-26-tumor-bearing mice had reduced carbohydrate oxidation and increased fat oxidation compared with controls. The range and consistency of functional and metabolic impairments in C-26-tumor-bearing mice confirm their suitability as a preclinical model for cancer cachexia. We recommend the use of these comprehensive functional assessments to maximize the translation of findings to more accurately identify effective treatments for cancer cachexia. PMID:22563056

  14. Theory of mind and neurocognition in early psychosis: a quasi-experimental study.

    PubMed

    Langdon, Robyn; Connors, Michael H; Still, Megan; Ward, Philip B; Catts, Stanley

    2014-12-04

    People with chronic psychosis often display theory of mind impairments that are not fully accounted for by other, more general neurocognitive deficits. In these patients, both theory of mind and neurocognitive deficits contribute to poor functioning, independently of psychotic symptoms. In young people with recent-onset psychosis, however, it is unclear the extent to which theory of mind impairment is independent of neurocognitive deficits. The primary aim of this study was to examine the evidence for specific theory of mind impairments in early psychosis. A secondary aim was to explore the relations between theory of mind, neurocognition, symptom severity, and functional outcomes. Twenty-three patients who were within two years of their first psychotic episode and 19 healthy controls completed theory of mind and neurocognitive batteries. Social functioning, quality of life, and symptom severity were also assessed in patients. Patients demonstrated deficits in tasks assessing theory of mind and neurocognition relative to controls. Patients' deficits in theory of mind were evident even after adjusting for their deficits in neurocognition. Neither theory of mind nor neurocognition predicted social functioning or quality of life in this early psychosis sample. Severity of negative symptoms, however, was a significant predictor of both outcomes. While a specific theory of mind impairment was evident in this early psychosis sample, severity of negative symptoms emerged as the best predictor of poor functional outcome. Further early psychosis research is needed to examine the longitudinal progression of theory of mind impairments - independent of neurocognitive deficits - and their impact on psychosocial function.

  15. Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis

    PubMed Central

    Liu, Luyan; Okada, Satoshi; Kong, Xiao-Fei; Kreins, Alexandra Y.; Cypowyj, Sophie; Abhyankar, Avinash; Toubiana, Julie; Itan, Yuval; Audry, Magali; Nitschke, Patrick; Masson, Cécile; Toth, Beata; Flatot, Jérome; Migaud, Mélanie; Chrabieh, Maya; Kochetkov, Tatiana; Bolze, Alexandre; Borghesi, Alessandro; Toulon, Antoine; Hiller, Julia; Eyerich, Stefanie; Eyerich, Kilian; Gulácsy, Vera; Chernyshova, Ludmyla; Chernyshov, Viktor; Bondarenko, Anastasia; María Cortés Grimaldo, Rosa; Blancas-Galicia, Lizbeth; Madrigal Beas, Ileana Maria; Roesler, Joachim; Magdorf, Klaus; Engelhard, Dan; Thumerelle, Caroline; Burgel, Pierre-Régis; Hoernes, Miriam; Drexel, Barbara; Seger, Reinhard; Kusuma, Theresia; Jansson, Annette F.; Sawalle-Belohradsky, Julie; Belohradsky, Bernd; Jouanguy, Emmanuelle; Bustamante, Jacinta; Bué, Mélanie; Karin, Nathan; Wildbaum, Gizi; Bodemer, Christine; Lortholary, Olivier; Fischer, Alain; Blanche, Stéphane; Al-Muhsen, Saleh; Reichenbach, Janine; Kobayashi, Masao; Rosales, Francisco Espinosa; Lozano, Carlos Torres; Kilic, Sara Sebnem; Oleastro, Matias; Etzioni, Amos; Traidl-Hoffmann, Claudia; Renner, Ellen D.; Abel, Laurent; Picard, Capucine; Maródi, László; Boisson-Dupuis, Stéphanie

    2011-01-01

    Chronic mucocutaneous candidiasis disease (CMCD) may be caused by autosomal dominant (AD) IL-17F deficiency or autosomal recessive (AR) IL-17RA deficiency. Here, using whole-exome sequencing, we identified heterozygous germline mutations in STAT1 in 47 patients from 20 kindreds with AD CMCD. Previously described heterozygous STAT1 mutant alleles are loss-of-function and cause AD predisposition to mycobacterial disease caused by impaired STAT1-dependent cellular responses to IFN-γ. Other loss-of-function STAT1 alleles cause AR predisposition to intracellular bacterial and viral diseases, caused by impaired STAT1-dependent responses to IFN-α/β, IFN-γ, IFN-λ, and IL-27. In contrast, the 12 AD CMCD-inducing STAT1 mutant alleles described here are gain-of-function and increase STAT1-dependent cellular responses to these cytokines, and to cytokines that predominantly activate STAT3, such as IL-6 and IL-21. All of these mutations affect the coiled-coil domain and impair the nuclear dephosphorylation of activated STAT1, accounting for their gain-of-function and dominance. Stronger cellular responses to the STAT1-dependent IL-17 inhibitors IFN-α/β, IFN-γ, and IL-27, and stronger STAT1 activation in response to the STAT3-dependent IL-17 inducers IL-6 and IL-21, hinder the development of T cells producing IL-17A, IL-17F, and IL-22. Gain-of-function STAT1 alleles therefore cause AD CMCD by impairing IL-17 immunity. PMID:21727188

  16. Predictors of Adolescent Outcomes among 4–6 Year Old Children with Attention-Deficit/Hyperactivity Disorder

    PubMed Central

    Lahey, Benjamin B.; Lee, Steve S.; Sibley, Margaret H.; Applegate, Brooks; Molina, Brooke S. G.; Pelham, William E.

    2015-01-01

    Children who met DSM-IV criteria for attention-deficit/hyperactivity disorder (ADHD) with functional impairment in at least one setting at 4–6 years of age were followed prospectively through age 18 years. On average, the 125 children (107 boys) with ADHD at baseline improved over time, but still continued to exhibit more symptoms, functional impairment, and risky behavior through adolescence than demographically matched healthy comparison children. These findings support the predictive validity of the diagnosis of ADHD at younger ages by demonstrating that the symptoms and impairment are enduring. Nonetheless, there were marked variations in developmental outcomes. Among children with ADHD, higher numbers of inattention and hyperactivity-impulsivity symptoms and higher number of concurrent symptoms (oppositional, conduct disorder, anxiety, and depression) measured at baseline each predicted higher future levels of the same dimension of symptoms. In addition, higher baseline levels of inattention, oppositional, conduct disorder, and anxiety symptoms predicted greater future functional impairment. Among children with ADHD, girls and children from families with lower family incomes had relatively poorer outcomes. Although outcomes varied along a continuum, approximately 10% of the children with ADHD at 4–6 years could be classified as functioning in the normative range on multiple measures during 15–18 years. Although this finding awaits replication, lower levels of hyperactivity-impulsivity symptoms at 4–6 years predicted more normative functioning during adolescence. These findings suggest that ADHD identified in early childhood predicts an increased likelihood of functional impairment through adolescence for most, but not all, children. PMID:26854503

  17. Cholinergic depletion in nucleus accumbens impairs mesocortical dopamine activation and cognitive function in rats.

    PubMed

    Laplante, François; Zhang, Zi-Wei; Huppé-Gourgues, Frédéric; Dufresne, Marc M; Vaucher, Elvire; Sullivan, Ron M

    2012-11-01

    In rats, selective depletion of the cholinergic interneurons in the ventral striatum (nucleus accumbens or N.Acc.) results in heightened behavioural sensitivity to amphetamine and impaired sensorimotor gating processes, suggesting a hyper-responsiveness to dopamine (DA) activity in the N.Acc. We hypothesized that local cholinergic depletion may also trigger distal functional alterations, particularly in prefrontal cortex (PFC). Adult male Sprague-Dawley rats were injected bilaterally in the N.Acc. with an immunotoxin targeting choline acetyltransferase. Two weeks later, cognitive function was assessed using the delayed alternation paradigm in the T-maze. The rats were then implanted with voltammetric recording electrodes in the ventromedial PFC to measure in vivo extracellular DA release in response to mild tail pinch stress. The PFC was also examined for density of tyrosine hydroxylase (TH)-labelled varicosities. In another cohort of control and lesioned rats, we measured post mortem tissue content of DA. Depletion of cholinergic neurons (restricted to N.Acc.) significantly impaired delayed alternation performance across delay intervals. While (basal) post mortem indices of PFC DA function were unaffected by N.Acc. lesions, in vivo mesocortical DA activation was markedly reduced; this deficit correlated significantly with cognitive impairments. TH-labelled varicosities however, were unaffected in cortical layer V relative to controls. These data suggest that selective depletion of cholinergic interneurons in N.Acc. triggers widespread functional impairments in mesocorticolimbic DA function and cognition. The possible relevance of these findings is also discussed in relation to schizophrenia, where reduced density of cholinergic neurons in ventral striatum has been reported. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Substantiated Reports of Child Maltreatment From the Canadian Incidence Study of Reported Child Abuse and Neglect 2008: Examining Child and Household Characteristics and Child Functional Impairment.

    PubMed

    Afifi, Tracie O; Taillieu, Tamara; Cheung, Kristene; Katz, Laurence Y; Tonmyr, Lil; Sareen, Jitender

    2015-07-01

    Identifying child and household characteristics that are associated with specific child maltreatment types and child functional impairment are important for informing prevention and intervention efforts. Our objectives were to examine the distribution of several child and household characteristics among substantiated child maltreatment types in Canada; to determine if a specific child maltreatment type relative to all other types was associated with increased odds of child functional impairment; and to determine which child and household characteristics were associated with child functional impairment. Data were from the Canadian Incidence Study of Reported Child Abuse and Neglect (collection 2008) from 112 child welfare sites across Canada (n = 6163 children). Physical abuse, sexual abuse, and emotional maltreatment were highly prevalent among children aged 10 to 15 years. For single types of child maltreatment, the highest prevalence of single-parent homes (50.6%), social assistance (43.0%), running out of money regularly (30.7%), and unsafe housing (30.9%) were reported for substantiated cases of neglect. Being male, older age, living in a single-parent home, household running out of money, moving 2 or more times in the past year, and household overcrowding were associated with increased odds of child functional impairment. More work is warranted to determine if providing particular resources for single-parent families, financial counselling, and facilitating adequate and stable housing for families with child maltreatment histories or at risk for child maltreatment could be effective for improving child functional outcomes.

  19. Nutritional status and nutritional risk in patients with neuroendocrine tumors.

    PubMed

    Borre, Mette; Dam, Gitte Aarøe; Knudsen, Anne Wilkens; Grønbaek, Henning

    2018-03-01

    Malnutrition is frequent among patients with malignancies and associated with impaired function, reduced quality of life and increased mortality. Few data are available in patients with neuroendocrine tumors (NET) on nutritional status, nutritional risk, and nutrition impact symptoms (NIS). We aimed to assess nutritional status (NS) and risk, level of function and associations with NIS in NET patients. In a cross-sectional study of NET patients, we measured body mass index (BMI) and handgrip strength (HGS) as markers of NS and muscle function assessed by HGS. The nutritional risk score (NRS) was determined by NRS-2002. NIS was assessed by the eating symptoms questionnaire (ESQ), and disease-related appetite questionnaire (DRAQ). We included 186 patients (51% women), median age 66 years. We observed low BMI (<20.5 kg/m 2 ) in 12%, low HGS in 25%, and impaired level of function in 43% of the patients. About 38% were at nutritional risk, more frequent in patients with residual disease (45% versus 29%, p < .05). Both low HGS, impaired level of function and being at nutritional risk were associated with the NIS: Nausea, vomiting, stomach ache and dry mouth (p < .05) whereas poor appetite and early satiety were only associated with being at nutritional risk and having impaired level of function (p < .05, all). Almost 40% of NET patients were at nutritional risk; and 25% had impaired HGS associated with specific NIS that preclude food intake. We recommend that NET outpatients are screened with NRS-2002 and that HGS and NIS are determined if NET patients need nutritional therapy.

  20. The Study of Cognitive Function and Related Factors in Patients With Heart Failure

    PubMed Central

    Ghanbari, Atefeh; Moaddab, Fatemeh; Salari, Arsalan; Kazemnezhad Leyli, Ehsan; Sedghi Sabet, Mitra; Paryad, Ezzat

    2013-01-01

    Background: Cognitive impairment is increasingly recognized as a common adverse consequence of heart failure. Both Heart failure and cognitive impairment are associated with frequent hospitalization and increased mortality, particularly when they occur simultaneously. Objectives: To determine cognitive function and related factors in patients with heart failure. Materials and Methods: In this descriptive cross-sectional study, we assessed 239 patients with heart failure. Data were collected by Mini Mental status Examination, Charlson comorbidity index and NYHA classification system. Data were analyzed using descriptive statistics, Kolmogorov-Smirnov test, chi-square test, t-test and logistic regression analysis. Results: The mean score of cognitive function was 21.68 ± 4.51. In total, 155 patients (64.9%) had cognitive impairment. Significant associations were found between the status of cognitive impairment and gender (P < 0.002), education level (P < 0.000), living location (P < 0.000), marital status (P < 0.03), living arrangement (P < 0.001 ), employment status (P < 0.000), income (P < 0.02), being the head of family (P < 0.03), the family size (P < 0.02), having a supplemental insurance (P < 0.003) and the patient’s comorbidities (P < 0.02). However, in logistic regression analysis, only education and supplementary insurance could predict cognitive status which indicates that patients with supplementary insurance and higher education levels were more likely to maintain optimal cognitive function. Conclusions: More than a half of the subjects had cognitive impairment. As the level of patients cognitive functioning affects their behaviors and daily living activities, it is recommended that patients with heart failure should be assessed for their cognitive functioning. PMID:25414874

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