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4. Impact of clinical symptoms and diagnosis: the electronic Person-Specific Outcome Measure (ePSOM) development programme.

Author

Saunders, S., Sheehan, S., Muniz-Terrera, G., Luz, S., and Ritchie, C. W.

Subjects
ALZHEIMER'S disease diagnosis, ALZHEIMER'S disease, SAMPLE size (Statistics), NATURAL language processing, MILD cognitive impairment, HEALTH outcome assessment, HUMAN services programs, SURVEYS, INTER-observer reliability, T-test (Statistics), CHI-squared test, POPULATION-based case control, LATENT semantic analysis, DESCRIPTIVE statistics, RESEARCH funding, THEMATIC analysis, CLUSTER analysis (Statistics), SYMPTOMS
Abstract

Introduction: Regulatory bodies recommend that outcome measures used in Alzheimer's disease (AD) clinical trials capture clinically meaningful changes for the trial participant. However, commonly used outcome measures do not reflect the individual's views on what matters to them individually. The aim of the electronic Person-Specific Outcome Measure (ePSOM) programme is to better understand what outcomes matter to patients in early Alzheimer's disease. Methods: As part of the ePSOM programme, we designed and ran an online study to understand what matters to individuals when developing new treatments for AD. The ePSOM survey ran Aug 2019–Dec 2019 (UK) and collected primarily free text responses which were analysed using Natural Language Processing (NLP) techniques. In this paper, we focus our analyses on individuals who reported having a neurodegenerative disease diagnosis (primarily Mild Cognitive Impairment (MCI) or AD), reporting the most frequent and most important brain health priorities for this group. Due to a small sample size, the Diagnosis group was analysed as a whole. Finally, we compared the Diagnosis group to an age and gender matched control group using chi-squared tests to look for any differences between the Diagnosis and control groups' priorities. Results: The survey was completed by 5808 respondents, of whom 167 (2.9%) (women n = 91, men n = 69, other n = 7) had received one of our pre-defined neurodegenerative disease diagnosis: most commonly MCI n = 52, 1.1% (mean age 69.42, SD = 10.8); or Alzheimer's disease n = 48, 1.0% (mean age 71.24, SD = 9.79). Several thematic clusters were significantly more important for the target diagnostic group, e.g.: Expressing opinions; and less important, e.g., Cognitive Games. Conclusion: We conclude there are a range of outcomes which individuals consider important and what potential new treatments should help maintain or improve, suggesting that outcomes that matter shift along the preclinical, prodromal and overt dementia continuum. This has important implications for the development of outcome measures in long term prevention studies that last several years where participants may pass through different stages of disease. In the final stage of our project, we will design an electronic outcomes app which will employ the methodology tested in the large-scale survey to capture what matters to individuals about their brain health at an individual level. [ABSTRACT FROM AUTHOR]

Published
2022
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5. LifeTime and improving European healthcare through cell-based interceptive medicine

Author

Rajewsky, N., Almouzni, G., Gorski, S. A., Aerts, S., Amit, I., Bertero, M. G., Bock, C., Bredenoord, A. L., Cavalli, G., Chiocca, S., Clevers, H., De Strooper, B., Eggert, A., Ellenberg, J., Fernández, X. M., Figlerowicz, M., Gasser, S. M., Hubner, N., Kjems, J., Knoblich, J. A., Krabbe, G., Lichter, P., Linnarsson, S., Marine, J. -C, Marioni, J., Marti-Renom, M. A., Netea, M. G., Nickel, D., Nollmann, M., Novak, H. R., Parkinson, H., Piccolo, S., Pinheiro, I., Pombo, A., Popp, C., Reik, W., Roman-Roman, S., Rosenstiel, P., Schultze, J. L., Stegle, O., Tanay, A., Testa, G., Thanos, D., Theis, F. J., Torres-Padilla, M. -E, Valencia, A., Vallot, C., van Oudenaarden, A., Vidal, M., Voet, T., Alberi, L., Alexander, S., Alexandrov, T., Arenas, E., Bagni, C., Balderas, R., Bandelli, A., Becher, B., Becker, M., Beerenwinkel, N., Benkirame, M., Beyer, M., Bickmore, W., Biessen, E. E. A. L., Blomberg, N., Blumcke, I., Bodenmiller, B., Borroni, B., Boumpas, D. T., Bourgeron, T., Bowers, S., Braeken, D., Brooksbank, C., Brose, N., Bruining, H., Bury, J., Caporale, N., Cattoretti, G., Chabane, N., Chneiweiss, H., Cook, S. A., Curatolo, P., de Jonge, M. I., Deplancke, B., de Witte, P., Dimmeler, S., Draganski, B., Drews, A. -D, Dumbrava, C., Engelhardt, S., Gasser, T., Giamarellos-Bourboulis, E. J., Graff, C., Grün, D., Gut, I., Hansson, O., Henshall, D. C., Herland, Anna, Heutink, P., Heymans, S. R. B., Heyn, H., Huch, M., Huitinga, I., Jackowiak, P., Jongsma, K. R., Journot, L., Junker, J. P., Katz, S., Kehren, J., Kempa, S., Kirchhof, P., Klein, C., Koralewska, N., Korbel, J. O., Kühnemund, M., Lamond, A. I., Lauwers, E., Le Ber, I., Leinonen, V., Tobon, A. L., Lundberg, E., Lunkes, A., Maatz, H., Mann, M., Marelli, L., Matser, V., Matthews, P. M., Mechta-Grigoriou, F., Menon, R., Nielsen, A. F., Pagani, M., Pasterkamp, R. J., Pitkanen, A., Popescu, V., Pottier, C., Puisieux, A., Rademakers, R., Reiling, D., Reiner, O., Remondini, D., Ritchie, C., Rohrer, J. D., Saliba, A. -E, Sanchez-Valle, R., Santosuosso, A., Sauter, A., Scheltema, R. A., Scheltens, P., Schiller, H. B., Schneider, A., Seibler, P., Sheehan-Rooney, K., Shields, D., Sleegers, K., Smit, G., Smith, K. G. C., Smolders, I., Synofzik, M., Tam, W. L., Teichmann, S., Thom, M., Turco, M. Y., van Beusekom, H. M. M., Vandenberghe, R., den Hoecke, S. V., Van de Poel, I., der Ven, A., van der Zee, J., van Lunzen, J., van Minnebruggen, G., Van Paesschen, W., van Swieten, J., van Vught, R., Verhage, M., Verstreken, P., Villa, C. E., Vogel, J., von Kalle, C., Walter, J., Weckhuysen, S., Weichert, W., Wood, L., Ziegler, A. -G, Zipp, F., Community, LifeTime, Rajewsky, N., Almouzni, G., Gorski, S. A., Aerts, S., Amit, I., Bertero, M. G., Bock, C., Bredenoord, A. L., Cavalli, G., Chiocca, S., Clevers, H., De Strooper, B., Eggert, A., Ellenberg, J., Fernández, X. M., Figlerowicz, M., Gasser, S. M., Hubner, N., Kjems, J., Knoblich, J. A., Krabbe, G., Lichter, P., Linnarsson, S., Marine, J. -C, Marioni, J., Marti-Renom, M. A., Netea, M. G., Nickel, D., Nollmann, M., Novak, H. R., Parkinson, H., Piccolo, S., Pinheiro, I., Pombo, A., Popp, C., Reik, W., Roman-Roman, S., Rosenstiel, P., Schultze, J. L., Stegle, O., Tanay, A., Testa, G., Thanos, D., Theis, F. J., Torres-Padilla, M. -E, Valencia, A., Vallot, C., van Oudenaarden, A., Vidal, M., Voet, T., Alberi, L., Alexander, S., Alexandrov, T., Arenas, E., Bagni, C., Balderas, R., Bandelli, A., Becher, B., Becker, M., Beerenwinkel, N., Benkirame, M., Beyer, M., Bickmore, W., Biessen, E. E. A. L., Blomberg, N., Blumcke, I., Bodenmiller, B., Borroni, B., Boumpas, D. T., Bourgeron, T., Bowers, S., Braeken, D., Brooksbank, C., Brose, N., Bruining, H., Bury, J., Caporale, N., Cattoretti, G., Chabane, N., Chneiweiss, H., Cook, S. A., Curatolo, P., de Jonge, M. I., Deplancke, B., de Witte, P., Dimmeler, S., Draganski, B., Drews, A. -D, Dumbrava, C., Engelhardt, S., Gasser, T., Giamarellos-Bourboulis, E. J., Graff, C., Grün, D., Gut, I., Hansson, O., Henshall, D. C., Herland, Anna, Heutink, P., Heymans, S. R. B., Heyn, H., Huch, M., Huitinga, I., Jackowiak, P., Jongsma, K. R., Journot, L., Junker, J. P., Katz, S., Kehren, J., Kempa, S., Kirchhof, P., Klein, C., Koralewska, N., Korbel, J. O., Kühnemund, M., Lamond, A. I., Lauwers, E., Le Ber, I., Leinonen, V., Tobon, A. L., Lundberg, E., Lunkes, A., Maatz, H., Mann, M., Marelli, L., Matser, V., Matthews, P. M., Mechta-Grigoriou, F., Menon, R., Nielsen, A. F., Pagani, M., Pasterkamp, R. J., Pitkanen, A., Popescu, V., Pottier, C., Puisieux, A., Rademakers, R., Reiling, D., Reiner, O., Remondini, D., Ritchie, C., Rohrer, J. D., Saliba, A. -E, Sanchez-Valle, R., Santosuosso, A., Sauter, A., Scheltema, R. A., Scheltens, P., Schiller, H. B., Schneider, A., Seibler, P., Sheehan-Rooney, K., Shields, D., Sleegers, K., Smit, G., Smith, K. G. C., Smolders, I., Synofzik, M., Tam, W. L., Teichmann, S., Thom, M., Turco, M. Y., van Beusekom, H. M. M., Vandenberghe, R., den Hoecke, S. V., Van de Poel, I., der Ven, A., van der Zee, J., van Lunzen, J., van Minnebruggen, G., Van Paesschen, W., van Swieten, J., van Vught, R., Verhage, M., Verstreken, P., Villa, C. E., Vogel, J., von Kalle, C., Walter, J., Weckhuysen, S., Weichert, W., Wood, L., Ziegler, A. -G, Zipp, F., and Community, LifeTime

Abstract

LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade., QC 20201117Correction in: Nature, Volume 587, Issue 7834, Pages 377 - 386, 19 November 2020. DOI: 10.1038/s41586-021-03287-8, Scopus ID: 2-s2.0-85102698588

Published
2020
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7. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function (Nature Communications, (2018), 9, 1, (2098), 10.1038/s41467-018-04362-x)

Author

Davies, G, Lam, M, Harris, SE, Trampush, JW, Luciano, M, Hill, WD, Hagenaars, SP, Ritchie, SJ, Marioni, RE, Fawns-Ritchie, C, Liewald, DCM, Okely, JA, Ahola-Olli, AV, Barnes, CLK, Bertram, L, Bis, JC, Burdick, KE, Christoforou, A, DeRosse, P, Djurovic, S, Espeseth, T, Giakoumaki, S, Giddaluru, S, Gustavson, DE, Hayward, C, Hofer, E, Ikram, MA, Karlsson, R, Knowles, E, Lahti, J, Leber, M, Li, S, Mather, KA ; https://orcid.org/0000-0003-4143-8941, Melle, I, Morris, D, Oldmeadow, C, Palviainen, T, Payton, A, Pazoki, R, Petrovic, K, Reynolds, CA, Sargurupremraj, M, Scholz, M, Smith, JA, Smith, AV, Terzikhan, N, Thalamuthu, A ; https://orcid.org/0000-0002-7114-1260, Trompet, S, van der Lee, SJ, Ware, EB, Windham, BG, Wright, MJ, Yang, J, Yu, J, Ames, D, Amin, N, Amouyel, P, Andreassen, OA, Armstrong, NJ, Assareh, AA, Attia, JR, Attix, D, Avramopoulos, D, Bennett, DA, Böhmer, AC, Boyle, PA, Brodaty, H ; https://orcid.org/0000-0001-9487-6617, Campbell, H, Cannon, TD, Cirulli, ET, Congdon, E, Conley, ED, Corley, J, Cox, SR, Dale, AM, Dehghan, A, Dick, D, Dickinson, D, Eriksson, JG, Evangelou, E, Faul, JD, Ford, I, Freimer, NA, Gao, H, Giegling, I, Gillespie, NA, Gordon, SD, Gottesman, RF, Griswold, ME, Gudnason, V, Harris, TB, Hartmann, AM, Hatzimanolis, A, Heiss, G, Holliday, EG, Joshi, PK, Kähönen, M, Kardia, SLR, Karlsson, I, Kleineidam, L, Sachdev, Perminder ; https://orcid.org/0000-0002-9595-3220, Schofield, Peter ; https://orcid.org/0000-0003-2967-9662, Kwok, John ; https://orcid.org/0000-0001-9574-6195, Kochan, Nicole ; https://orcid.org/0000-0002-8630-6398, Lee, Teresa ; https://orcid.org/0000-0002-9734-6467, Reppermund, Simone ; https://orcid.org/0000-0003-4785-0224, Trollor, Julian ; https://orcid.org/0000-0002-7685-2977, Davies, G, Lam, M, Harris, SE, Trampush, JW, Luciano, M, Hill, WD, Hagenaars, SP, Ritchie, SJ, Marioni, RE, Fawns-Ritchie, C, Liewald, DCM, Okely, JA, Ahola-Olli, AV, Barnes, CLK, Bertram, L, Bis, JC, Burdick, KE, Christoforou, A, DeRosse, P, Djurovic, S, Espeseth, T, Giakoumaki, S, Giddaluru, S, Gustavson, DE, Hayward, C, Hofer, E, Ikram, MA, Karlsson, R, Knowles, E, Lahti, J, Leber, M, Li, S, Mather, KA ; https://orcid.org/0000-0003-4143-8941, Melle, I, Morris, D, Oldmeadow, C, Palviainen, T, Payton, A, Pazoki, R, Petrovic, K, Reynolds, CA, Sargurupremraj, M, Scholz, M, Smith, JA, Smith, AV, Terzikhan, N, Thalamuthu, A ; https://orcid.org/0000-0002-7114-1260, Trompet, S, van der Lee, SJ, Ware, EB, Windham, BG, Wright, MJ, Yang, J, Yu, J, Ames, D, Amin, N, Amouyel, P, Andreassen, OA, Armstrong, NJ, Assareh, AA, Attia, JR, Attix, D, Avramopoulos, D, Bennett, DA, Böhmer, AC, Boyle, PA, Brodaty, H ; https://orcid.org/0000-0001-9487-6617, Campbell, H, Cannon, TD, Cirulli, ET, Congdon, E, Conley, ED, Corley, J, Cox, SR, Dale, AM, Dehghan, A, Dick, D, Dickinson, D, Eriksson, JG, Evangelou, E, Faul, JD, Ford, I, Freimer, NA, Gao, H, Giegling, I, Gillespie, NA, Gordon, SD, Gottesman, RF, Griswold, ME, Gudnason, V, Harris, TB, Hartmann, AM, Hatzimanolis, A, Heiss, G, Holliday, EG, Joshi, PK, Kähönen, M, Kardia, SLR, Karlsson, I, Kleineidam, L, Sachdev, Perminder ; https://orcid.org/0000-0002-9595-3220, Schofield, Peter ; https://orcid.org/0000-0003-2967-9662, Kwok, John ; https://orcid.org/0000-0001-9574-6195, Kochan, Nicole ; https://orcid.org/0000-0002-8630-6398, Lee, Teresa ; https://orcid.org/0000-0002-9734-6467, Reppermund, Simone ; https://orcid.org/0000-0003-4785-0224, and Trollor, Julian ; https://orcid.org/0000-0002-7685-2977

Abstract

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.

Published
2019

8. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, G., Lam, M., Harris, S.E., Trampush, J.W., Luciano, M., Hill, W.D., Hagenaars, S.P., Ritchie, S.J., Marioni, R.E., Fawns-Ritchie, C., Liewald, D.C.M., Okely, J.A., Ahola-Olli, A.V., Barnes, C.L.K., Bertram, L., Bis, J.C., Burdick, K.E., Christoforou, A., DeRosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D.E., Hayward, C., Hofer, E., Ikram, M.A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K.A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C.A., Sargurupremraj, M., Scholz, M., Smith, J.A., Smith, A.V., Terzikhan, N., Thalamuthu, A., Trompet, S., van der Lee, S.J., Ware, E.B., Windham, B.G., Wright, M.J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O.A., Armstrong, N.J., Assareh, A.A., Attia, J.R., Attix, D., Avramopoulos, D., Bennett, D.A., Böhmer, A.C., Boyle, P.A., Brodaty, H., Campbell, H., Cannon, T.D., Cirulli, E.T., Congdon, E., Conley, E.D., Corley, J., Cox, S.R., Dale, A.M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J.G., Evangelou, E., Faul, J.D., Ford, I., Freimer, N.A., Gao, H., Giegling, I., Gillespie, N.A., Gordon, S.D., Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Hartmann, A.M., Hatzimanolis, A., Heiss, G., Holliday, E.G., Joshi, P.K., Kähönen, M., Kardia, S.L.R., Karlsson, I., Kleineidam, L., Knopman, D.S., Kochan, N.A., Konte, B., Kwok, J.B., Le Hellard, S., Lee, T., Lehtimäki, T., Li, S-C., Lill, C.M., Liu, T., Koini, M., London, E., Longstreth, W.T., Lopez, O.L., Loukola, A., Luck, T., Lundervold, A.J., Lundquist, A., Lyytikäinen, L-P, Martin, N.G., Montgomery, G.W., Murray, A.D., Need, A.C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R.A., Psaty, B.M., Reppermund, S., Riedel-Heller, S.G., Rose, R.J., Rotter, J.I., Roussos, P., Rovio, S.P., Saba, Y., Sabb, F.W., Sachdev, P.S., Satizabal, C.L., Schmid, M., Scott, R.J., Scult, M.A., Simino, J., Slagboom, P.E., Smyrnis, N., Soumaré, A., Stefanis, N.C., Stott, D.J., Straub, R.E., Sundet, K., Taylor, A.M., Taylor, K.D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A.N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K.H., Widen, E., Yang, Q., Zhao, W., Adams, H.H.H., Arking, D.E., Bilder, R.M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., De Jager, P.L., Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A.L., Gill, M., Glahn, D.C., Hägg, S., Hansell, N.K., Hariri, A.R., Ikram, M.K., Jukema, J.W., Vuoksimaa, E., Keller, M.C., Kremen, W.S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N.L., Pendleton, N., Porteous, D.J., Räikkönen, K., Raitakari, O.T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P.W., Schofield, P.R., Starr, J.M., Steen, V.M., Trollor, J.N., Turner, S.T., van Duijn, C.M., Villringer, A., Weinberger, D.R., Weir, D.R., Wilson, J.F., Malhotra, A., McIntosh, A.M., Gale, C.R., Seshadri, S., Mosley, T.H., Bressler, J., Lencz, T., Deary, I.J., Davies, G., Lam, M., Harris, S.E., Trampush, J.W., Luciano, M., Hill, W.D., Hagenaars, S.P., Ritchie, S.J., Marioni, R.E., Fawns-Ritchie, C., Liewald, D.C.M., Okely, J.A., Ahola-Olli, A.V., Barnes, C.L.K., Bertram, L., Bis, J.C., Burdick, K.E., Christoforou, A., DeRosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D.E., Hayward, C., Hofer, E., Ikram, M.A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K.A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C.A., Sargurupremraj, M., Scholz, M., Smith, J.A., Smith, A.V., Terzikhan, N., Thalamuthu, A., Trompet, S., van der Lee, S.J., Ware, E.B., Windham, B.G., Wright, M.J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O.A., Armstrong, N.J., Assareh, A.A., Attia, J.R., Attix, D., Avramopoulos, D., Bennett, D.A., Böhmer, A.C., Boyle, P.A., Brodaty, H., Campbell, H., Cannon, T.D., Cirulli, E.T., Congdon, E., Conley, E.D., Corley, J., Cox, S.R., Dale, A.M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J.G., Evangelou, E., Faul, J.D., Ford, I., Freimer, N.A., Gao, H., Giegling, I., Gillespie, N.A., Gordon, S.D., Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Hartmann, A.M., Hatzimanolis, A., Heiss, G., Holliday, E.G., Joshi, P.K., Kähönen, M., Kardia, S.L.R., Karlsson, I., Kleineidam, L., Knopman, D.S., Kochan, N.A., Konte, B., Kwok, J.B., Le Hellard, S., Lee, T., Lehtimäki, T., Li, S-C., Lill, C.M., Liu, T., Koini, M., London, E., Longstreth, W.T., Lopez, O.L., Loukola, A., Luck, T., Lundervold, A.J., Lundquist, A., Lyytikäinen, L-P, Martin, N.G., Montgomery, G.W., Murray, A.D., Need, A.C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R.A., Psaty, B.M., Reppermund, S., Riedel-Heller, S.G., Rose, R.J., Rotter, J.I., Roussos, P., Rovio, S.P., Saba, Y., Sabb, F.W., Sachdev, P.S., Satizabal, C.L., Schmid, M., Scott, R.J., Scult, M.A., Simino, J., Slagboom, P.E., Smyrnis, N., Soumaré, A., Stefanis, N.C., Stott, D.J., Straub, R.E., Sundet, K., Taylor, A.M., Taylor, K.D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A.N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K.H., Widen, E., Yang, Q., Zhao, W., Adams, H.H.H., Arking, D.E., Bilder, R.M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., De Jager, P.L., Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A.L., Gill, M., Glahn, D.C., Hägg, S., Hansell, N.K., Hariri, A.R., Ikram, M.K., Jukema, J.W., Vuoksimaa, E., Keller, M.C., Kremen, W.S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N.L., Pendleton, N., Porteous, D.J., Räikkönen, K., Raitakari, O.T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P.W., Schofield, P.R., Starr, J.M., Steen, V.M., Trollor, J.N., Turner, S.T., van Duijn, C.M., Villringer, A., Weinberger, D.R., Weir, D.R., Wilson, J.F., Malhotra, A., McIntosh, A.M., Gale, C.R., Seshadri, S., Mosley, T.H., Bressler, J., Lencz, T., and Deary, I.J.

Abstract

These authors contributed equally: Gail Davies, Max Lam. These authors jointly supervised this work: Todd Lencz, Ian J. Deary.

Published
2019

10. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, G, Lam, M, Harris, SE, Trampush, JW, Luciano, M, Hill, WD, Hagenaars, SP, Ritchie, SJ, Marioni, RE, Fawns-Ritchie, C, Liewald, DCM, Okely, JA, Ahola-Olli, AV, Barnes, CLK, Bertram, L, Bis, JC, Burdick, KE, Christoforou, A, Derosse, P, Djurovic, S, Espeseth, T, Giakoumaki, S, Giddaluru, S, Gustavson, DE, Hayward, C, Hofer, E, Ikram, MA, Karlsson, R, Knowles, E, Lahti, J, Leber, M, Li, S, Mather, KA ; https://orcid.org/0000-0003-4143-8941, Melle, I, Morris, D, Oldmeadow, C, Palviainen, T, Payton, A, Pazoki, R, Petrovic, K, Reynolds, CA, Sargurupremraj, M, Scholz, M, Smith, JA, Smith, AV, Terzikhan, N, Thalamuthu, A ; https://orcid.org/0000-0002-7114-1260, Trompet, S, Van Der Lee, SJ, Ware, EB, Windham, BG, Wright, MJ, Yang, J, Yu, J, Ames, D, Amin, N, Amouyel, P, Andreassen, OA, Armstrong, NJ, Assareh, AA, Attia, JR, Attix, D, Avramopoulos, D, Bennett, DA, Böhmer, AC, Boyle, PA, Brodaty, H ; https://orcid.org/0000-0001-9487-6617, Campbell, H, Cannon, TD, Cirulli, ET, Congdon, E, Conley, ED, Corley, J, Cox, SR, Dale, AM, Dehghan, A, Dick, D, Dickinson, D, Eriksson, JG, Evangelou, E, Faul, JD, Ford, I, Freimer, NA, Gao, H, Giegling, I, Gillespie, NA, Gordon, SD, Gottesman, RF, Griswold, ME, Gudnason, V, Harris, TB, Hartmann, AM, Hatzimanolis, A, Heiss, G, Holliday, EG, Joshi, PK, Kähönen, M, Kardia, SLR, Karlsson, I, Kleineidam, L, Sachdev, Perminder ; https://orcid.org/0000-0002-9595-3220, Schofield, Peter ; https://orcid.org/0000-0003-2967-9662, Reppermund, Simone ; https://orcid.org/0000-0003-4785-0224, Kochan, Nicole ; https://orcid.org/0000-0002-8630-6398, Lee, Teresa ; https://orcid.org/0000-0002-9734-6467, Kwok, John ; https://orcid.org/0000-0001-9574-6195, Trollor, Julian ; https://orcid.org/0000-0002-7685-2977, Davies, G, Lam, M, Harris, SE, Trampush, JW, Luciano, M, Hill, WD, Hagenaars, SP, Ritchie, SJ, Marioni, RE, Fawns-Ritchie, C, Liewald, DCM, Okely, JA, Ahola-Olli, AV, Barnes, CLK, Bertram, L, Bis, JC, Burdick, KE, Christoforou, A, Derosse, P, Djurovic, S, Espeseth, T, Giakoumaki, S, Giddaluru, S, Gustavson, DE, Hayward, C, Hofer, E, Ikram, MA, Karlsson, R, Knowles, E, Lahti, J, Leber, M, Li, S, Mather, KA ; https://orcid.org/0000-0003-4143-8941, Melle, I, Morris, D, Oldmeadow, C, Palviainen, T, Payton, A, Pazoki, R, Petrovic, K, Reynolds, CA, Sargurupremraj, M, Scholz, M, Smith, JA, Smith, AV, Terzikhan, N, Thalamuthu, A ; https://orcid.org/0000-0002-7114-1260, Trompet, S, Van Der Lee, SJ, Ware, EB, Windham, BG, Wright, MJ, Yang, J, Yu, J, Ames, D, Amin, N, Amouyel, P, Andreassen, OA, Armstrong, NJ, Assareh, AA, Attia, JR, Attix, D, Avramopoulos, D, Bennett, DA, Böhmer, AC, Boyle, PA, Brodaty, H ; https://orcid.org/0000-0001-9487-6617, Campbell, H, Cannon, TD, Cirulli, ET, Congdon, E, Conley, ED, Corley, J, Cox, SR, Dale, AM, Dehghan, A, Dick, D, Dickinson, D, Eriksson, JG, Evangelou, E, Faul, JD, Ford, I, Freimer, NA, Gao, H, Giegling, I, Gillespie, NA, Gordon, SD, Gottesman, RF, Griswold, ME, Gudnason, V, Harris, TB, Hartmann, AM, Hatzimanolis, A, Heiss, G, Holliday, EG, Joshi, PK, Kähönen, M, Kardia, SLR, Karlsson, I, Kleineidam, L, Sachdev, Perminder ; https://orcid.org/0000-0002-9595-3220, Schofield, Peter ; https://orcid.org/0000-0003-2967-9662, Reppermund, Simone ; https://orcid.org/0000-0003-4785-0224, Kochan, Nicole ; https://orcid.org/0000-0002-8630-6398, Lee, Teresa ; https://orcid.org/0000-0002-9734-6467, Kwok, John ; https://orcid.org/0000-0001-9574-6195, and Trollor, Julian ; https://orcid.org/0000-0002-7685-2977

Abstract

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

Published
2018

11. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, G., Lam, M., Harris, S.E., Trampush, J.W., Luciano, M., Hill, W.D., Hagenaars, S.P., Ritchie, S.J., Marioni, R.E., Fawns-Ritchie, C., Liewald, D.C.M., Okely, J.A., Ahola-Olli, A.V., Barnes, C.L.K., Bertram, L., Bis, J.C., Burdick, K.E., Christoforou, A., DeRosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D.E., Hayward, C., Hofer, E., Ikram, M.A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K.A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C.A., Sargurupremraj, M., Scholz, M., Smith, J.A., Smith, A.V., Terzikhan, N., Thalamuthu, A., Trompet, S., van der Lee, S.J., Ware, E.B., Windham, B.G., Wright, M.J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O.A., Armstrong, N.J., Assareh, A.A., Attia, J.R., Attix, D., Avramopoulos, D., Bennett, D.A., Böhmer, A.C., Boyle, P.A., Brodaty, H., Campbell, H., Cannon, T.D., Cirulli, E.T., Congdon, E., Conley, E.D., Corley, J., Cox, S.R., Dale, A.M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J.G., Evangelou, E., Faul, J.D., Ford, I., Freimer, N.A., Gao, H., Giegling, I., Gillespie, N.A., Gordon, S.D., Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Hartmann, A.M., Hatzimanolis, A., Heiss, G., Holliday, E.G., Joshi, P.K., Kähönen, M., Kardia, S.L.R., Karlsson, I., Kleineidam, L., Knopman, D.S., Kochan, N.A., Konte, B., Kwok, J.B., Le Hellard, S., Lee, T., Lehtimäki, T., Li, S-C, Liu, T., Koini, M., London, E., Longstreth, W.T., Lopez, O.L., Loukola, A., Luck, T., Lundervold, A.J., Lundquist, A., Lyytikäinen, L-P, Martin, N.G., Montgomery, G.W., Murray, A.D., Need, A.C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R.A., Psaty, B.M., Reppermund, S., Riedel-Heller, S.G., Rose, R.J., Rotter, J.I., Roussos, P., Rovio, S.P., Saba, Y., Sabb, F.W., Sachdev, P.S., Satizabal, C.L., Schmid, M., Scott, R.J., Scult, M.A., Simino, J., Slagboom, P.E., Smyrnis, N., Soumaré, A., Stefanis, N.C., Stott, D.J., Straub, R.E., Sundet, K., Taylor, A.M., Taylor, K.D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A.N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K.H., Widen, E., Yang, Q., Zhao, W., Adams, H.H.H., Arking, D.E., Bilder, R.M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., De Jager, P.L., Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A.L., Gill, M., Glahn, D.C., Hägg, S., Hansell, N.K., Hariri, A.R., Ikram, M.K., Jukema, J.W., Vuoksimaa, E., Keller, M.C., Kremen, W.S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N.L., Pendleton, N., Porteous, D.J., Räikkönen, K., Raitakari, O.T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P.W., Schofield, P.R., Starr, J.M., Steen, V.M., Trollor, J.N., Turner, S.T., van Duijn, C.M., Villringer, Arno, Weinberger, D.R., Weir, D.R., Wilson, J.F., Malhotra, A., McIntosh, A.M., Gale, C.R., Seshadri, S., Mosley, T.H., Bressler, J., Lencz, T., Deary, I.J., Davies, G., Lam, M., Harris, S.E., Trampush, J.W., Luciano, M., Hill, W.D., Hagenaars, S.P., Ritchie, S.J., Marioni, R.E., Fawns-Ritchie, C., Liewald, D.C.M., Okely, J.A., Ahola-Olli, A.V., Barnes, C.L.K., Bertram, L., Bis, J.C., Burdick, K.E., Christoforou, A., DeRosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D.E., Hayward, C., Hofer, E., Ikram, M.A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K.A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C.A., Sargurupremraj, M., Scholz, M., Smith, J.A., Smith, A.V., Terzikhan, N., Thalamuthu, A., Trompet, S., van der Lee, S.J., Ware, E.B., Windham, B.G., Wright, M.J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O.A., Armstrong, N.J., Assareh, A.A., Attia, J.R., Attix, D., Avramopoulos, D., Bennett, D.A., Böhmer, A.C., Boyle, P.A., Brodaty, H., Campbell, H., Cannon, T.D., Cirulli, E.T., Congdon, E., Conley, E.D., Corley, J., Cox, S.R., Dale, A.M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J.G., Evangelou, E., Faul, J.D., Ford, I., Freimer, N.A., Gao, H., Giegling, I., Gillespie, N.A., Gordon, S.D., Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Hartmann, A.M., Hatzimanolis, A., Heiss, G., Holliday, E.G., Joshi, P.K., Kähönen, M., Kardia, S.L.R., Karlsson, I., Kleineidam, L., Knopman, D.S., Kochan, N.A., Konte, B., Kwok, J.B., Le Hellard, S., Lee, T., Lehtimäki, T., Li, S-C, Liu, T., Koini, M., London, E., Longstreth, W.T., Lopez, O.L., Loukola, A., Luck, T., Lundervold, A.J., Lundquist, A., Lyytikäinen, L-P, Martin, N.G., Montgomery, G.W., Murray, A.D., Need, A.C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R.A., Psaty, B.M., Reppermund, S., Riedel-Heller, S.G., Rose, R.J., Rotter, J.I., Roussos, P., Rovio, S.P., Saba, Y., Sabb, F.W., Sachdev, P.S., Satizabal, C.L., Schmid, M., Scott, R.J., Scult, M.A., Simino, J., Slagboom, P.E., Smyrnis, N., Soumaré, A., Stefanis, N.C., Stott, D.J., Straub, R.E., Sundet, K., Taylor, A.M., Taylor, K.D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A.N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K.H., Widen, E., Yang, Q., Zhao, W., Adams, H.H.H., Arking, D.E., Bilder, R.M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., De Jager, P.L., Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A.L., Gill, M., Glahn, D.C., Hägg, S., Hansell, N.K., Hariri, A.R., Ikram, M.K., Jukema, J.W., Vuoksimaa, E., Keller, M.C., Kremen, W.S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N.L., Pendleton, N., Porteous, D.J., Räikkönen, K., Raitakari, O.T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P.W., Schofield, P.R., Starr, J.M., Steen, V.M., Trollor, J.N., Turner, S.T., van Duijn, C.M., Villringer, Arno, Weinberger, D.R., Weir, D.R., Wilson, J.F., Malhotra, A., McIntosh, A.M., Gale, C.R., Seshadri, S., Mosley, T.H., Bressler, J., Lencz, T., and Deary, I.J.

Abstract

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16–102) and find 148 genome-wide significant independent loci (P < 5 × 10−8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

Published
2018

12. GWAS for executive function and processing speed suggests involvement of the CADM2 gene

Author

Ibrahim-Verbaas, CA, Bressler, J, Debette, S, Schuur, M, Smith, AV, Bis, JC, Davies, G, Trompet, S, Smith, JA, Wolf, C, Chibnik, LB, Liu, Y, Vitart, V, Kirin, M, Petrovic, K, Polasek, O, Zgaga, L, Fawns-Ritchie, C, Hoffmann, P, Karjalainen, J, Lahti, J, Llewellyn, DJ, Schmidt, CO, Mather, KA ; https://orcid.org/0000-0003-4143-8941, Chouraki, V, Sun, Q, Resnick, SM, Rose, LM, Oldmeadow, C, Stewart, M, Smith, BH, Gudnason, V, Yang, Q, Mirza, SS, Jukema, JW, DeJager, PL, Harris, TB, Liewald, DC, Amin, N, Coker, LH, Stegle, O, Lopez, OL, Schmidt, R, Teumer, A, Ford, I, Karbalai, N, Becker, JT, Jonsdottir, MK, Au, R, Fehrmann, RSN, Herms, S, Nalls, M, Zhao, W, Turner, ST, Yaffe, K, Lohman, K, Van Swieten, JC, Kardia, SLR, Knopman, DS, Meeks, WM, Heiss, G, Holliday, EG, Schofield, PW, Tanaka, T, Stott, DJ, Wang, J, Ridker, P, Gow, AJ, Pattie, A, Starr, JM, Hocking, LJ, Armstrong, NJ, McLachlan, S, Shulman, JM, Pilling, LC, Eiriksdottir, G, Scott, RJ, Kochan, NA ; https://orcid.org/0000-0002-8630-6398, Palotie, A, Hsieh, YC, Eriksson, JG, Penman, A, Gottesman, RF, Oostra, BA, Yu, L, DeStefano, AL, Beiser, A, Garcia, M, Rotter, JI, Nöthen, MM, Hofman, A, Slagboom, PE, Westendorp, RGJ, Buckley, BM, Wolf, PA, Uitterlinden, AG, Psaty, BM, Grabe, HJ, Bandinelli, S, Chasman, DI, Sachdev, Perminder ; https://orcid.org/0000-0002-9595-3220, Ibrahim-Verbaas, CA, Bressler, J, Debette, S, Schuur, M, Smith, AV, Bis, JC, Davies, G, Trompet, S, Smith, JA, Wolf, C, Chibnik, LB, Liu, Y, Vitart, V, Kirin, M, Petrovic, K, Polasek, O, Zgaga, L, Fawns-Ritchie, C, Hoffmann, P, Karjalainen, J, Lahti, J, Llewellyn, DJ, Schmidt, CO, Mather, KA ; https://orcid.org/0000-0003-4143-8941, Chouraki, V, Sun, Q, Resnick, SM, Rose, LM, Oldmeadow, C, Stewart, M, Smith, BH, Gudnason, V, Yang, Q, Mirza, SS, Jukema, JW, DeJager, PL, Harris, TB, Liewald, DC, Amin, N, Coker, LH, Stegle, O, Lopez, OL, Schmidt, R, Teumer, A, Ford, I, Karbalai, N, Becker, JT, Jonsdottir, MK, Au, R, Fehrmann, RSN, Herms, S, Nalls, M, Zhao, W, Turner, ST, Yaffe, K, Lohman, K, Van Swieten, JC, Kardia, SLR, Knopman, DS, Meeks, WM, Heiss, G, Holliday, EG, Schofield, PW, Tanaka, T, Stott, DJ, Wang, J, Ridker, P, Gow, AJ, Pattie, A, Starr, JM, Hocking, LJ, Armstrong, NJ, McLachlan, S, Shulman, JM, Pilling, LC, Eiriksdottir, G, Scott, RJ, Kochan, NA ; https://orcid.org/0000-0002-8630-6398, Palotie, A, Hsieh, YC, Eriksson, JG, Penman, A, Gottesman, RF, Oostra, BA, Yu, L, DeStefano, AL, Beiser, A, Garcia, M, Rotter, JI, Nöthen, MM, Hofman, A, Slagboom, PE, Westendorp, RGJ, Buckley, BM, Wolf, PA, Uitterlinden, AG, Psaty, BM, Grabe, HJ, Bandinelli, S, Chasman, DI, and Sachdev, Perminder ; https://orcid.org/0000-0002-9595-3220

Abstract

To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32 070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10 -8) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10 -9 after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10 -4). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10 -15), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10 -11) and neuron cell-cell adhesion (P-value=1.48 × 10 -13). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.

Published
2016

13. Physical, Psychological, Social, and Existential Symptoms in Older Homeless-Experienced Adults: An Observational Study of the Hope Home Cohort.

Author

Patanwala, M., Tieu, L., Ponath, C., Guzman, D., Ritchie, C. S., and Kushel, Margot

Subjects
HOMELESS persons, AGE factors in disease, SOCIODEMOGRAPHIC factors, CHRONIC diseases, HEALTH of older people
Abstract

Background: The homeless population in the United States is aging. Aging-associated comorbidities are associated with increased symptoms.Objective: To describe the prevalence of symptoms among older homeless-experienced adults, analyze factors associated with moderate-high physical symptom burden, and identify symptom clusters.Design: Cross-sectional analysis within longitudinal cohort study.Participants: Using population-based sampling from shelters, meal programs, encampments, and a recycling center in Oakland, CA, we recruited homeless adults aged ≥ 50 for a longitudinal cohort. This study includes participants who participated in the 18-month follow-up visit.Main Measures: We assessed physical symptoms using the Patient Health Questionnaire-15 (PHQ-15); psychological symptoms using the Center for Epidemiologic Studies Depression Scale (CES-D), Primary Care PTSD Screen (PC-PTSD), and psychiatric section of the Addiction Severity Index (ASI); loneliness using the Three-Item Loneliness Scale; and regret using a six-item regret scale.Key Results: Two hundred eighty-three participants (75.6% men and 82.3% African-Americans) completed symptoms interviews. Over a third (34.0%) had moderate-high physical symptom burden. The most prevalent physical symptoms were joint pain, fatigue, back pain, and sleep trouble. Over half (57.6%) had psychological symptoms; 39.6% exhibited loneliness and 26.5% had high regret. In a multivariate model, being a woman (AOR 2.54, 95% CI 1.28-5.03), childhood abuse (AOR 1.88, 95% CI 1.00-3.50), cannabis use (AOR 2.59, 95% CI 1.38-4.89), multimorbidity (AOR 2.50, 95% CI 1.36-4.58), anxiety (AOR 4.30, 95% CI 2.24-8.26), hallucinations (AOR 3.77, 95% CI 1.36-10.43), and loneliness (AOR 2.32, 95% CI 1.26-4.28) were associated with moderate-high physical symptom burden. We identified four symptom clusters: minimal overall (n = 129), moderate overall (n = 68), high physical and high psychological (n = 67), and high physical and low psychological (n = 17).Conclusions: Older homeless-experienced adults exhibit a high prevalence of symptoms across multiple dimensions. To reduce suffering, clinicians should recognize the interaction between symptoms and address multiple symptom dimensions. [ABSTRACT FROM AUTHOR]

Published
2018
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15. FOOD CHOICE AMONG HOMEBOUND OLDER ADULTS: MOTIVATIONS AND PERCEIVED BARRIERS.

Author

LOCHER, J. L., RITCHIE, C. S., ROTH, D. L., SEN, B., VICKERS, K. S., and VAILAS, L. I.

Subjects
MOTIVATION research, FOOD, OLDER people, DEMOGRAPHIC characteristics, DIET
Abstract

Objectives: The purpose of this paper is to identify: motivations and perceived barriers associated with food choices made by homebound older adults; whether motivations and perceived barriers vary according to social demographic characteristics; and whether motivations and perceived barriers are associated with dietary quality. Design: This was an observational study using standard interview methods where participants were administered a questionnaire and completed three 24-hour dietary recalls. Setting: Participants were interviewed in their homes. Participants: 185 homebound older adults were included. Measurement: Motivations were assessed using a modification of The Food Choice Questionnaire and perceived barriers were assessed using the Vailas Food Enjoyment Questionnaire. Participants answered questions regarding social demographic characteristics. Dietary quality measures of adequate intakes of calories, protein, vitamin D, and vitamin B12 were obtained from the three 24-hour dietary recalls. Results: Mean age was 78.9; 80% were female; and 36% were African American. Key motivations in food choice included sensory appeal, convenience, and price. Key barriers included health, being on a special diet, and being unable to shop. These varied little by social demographics, except for age. Dietary quality varied according to different motivations and barriers. Conclusion: Food choices are based upon a complex interaction between the social and environmental context, the individual, and the food. Efforts to change eating behaviors, especially community-based interventions involving self-management approaches, must carefully take into account individuals' self-perceived motivations and barriers to food selection. Incorporating foods that are tasty, easy to prepare, inexpensive, and that involve caregivers are critical for successful interventions. [ABSTRACT FROM AUTHOR]

Published
2009
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16. Atovaquone plus cholestyramine in patients coinfected with Babesia microti and Borrelia burgdorferi refractory to other treatment.

Author

Shoemaker RC, Hudnell HK, House DE, van Kempen A, Pakes GE, COL40155 Study Team, Shoemaker, Ritchie C, Hudnell, H Kenneth, House, Dennis E, Van Kempen, Amy, and Pakes, Gary E

Abstract

Ten percent of US patients with Lyme disease are coinfected with Babesia microti. A double-blind, placebo-controlled, crossover trial enrolled 25 patients with confirmed Borrelia burgdorferi/B microti coinfection, abnormal visual contrast sensitivity (VCS), and persistent symptoms despite prior treatment with atovaquone and azithromycin. Patients were randomly assigned to atovaquone suspension or placebo plus cholestyramine for 3 weeks, were crossed over for 3 weeks, and then received open-label atovaquone and cholestyramine for 6 weeks. Symptoms and VCS scores were recorded at baseline and after weeks 3, 6, 9, and 12. Improvements in symptoms and VCS deficits were observed only after at least 9 weeks of treatment. At week 12, 5 patients were asymptomatic, and 16 had a notable reduction in the number of symptoms. The entire cohort demonstrated significant increases in VCS scores. Adverse effects were rare. Patients coinfected with B burgdorferi and B microti derive measurable clinical benefit from prolonged treatment with atovaquone and cholestyramine. Longer-term combination therapy may be indicated. [ABSTRACT FROM AUTHOR]

Published
2006
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17. Application of red cell distribution width to screening for coeliac disease in insulin-dependent diabetes mellitus.

Author

Johnston, S., Ritchie, C., and Robinson, J.

Abstract

Coeliac disease has been reported to occur in 2–5 per cent of insulin-dependent diabetic patients (IDDM). Suitable non-invasive screening tests would allow identification of these patients. The aim of this study was to determine the value of the red cell distribution width (RDW) in detecting unrecognised coeliac disease in insulin-dependent diabetic patients (IDDM). All patients (n=208) attending the Diabetic out-patient clinics at 2 adjacent centres who had a full blood picture and RDW carried out in the past 18 months were included. IDDM patients with an elevated RDW were identified and their charts were reviewed to determine if they had symptoms or laboratory abnormalities compatible with coeliac disease. They were invited to attend for serological screening. Ninety-five of 208 patients had an elevated RDW of whom 66 had non-insulin dependent diabetes mellitus and 29 had IDDM. Two of the 29 IDDM patients had died in the interim period. Six of the remaining 27 IDDM patients had previously been tested for serological markers associated with coeliac disease, of whom 1 had a positive antigliadin antibody titre (IgA-AGA 199 EU) and normal duodenal biopsy. Eighteen of the remaining 21 patients with IDDM consented to serological testing of whom only 1 had a positive titre of antiendomysial antibody (IgA-EMA) and villous atrophy. Although the RDW is known from previous studies to be a sensitive predictor for coeliac disease, this study has demonstrated its poor specificity in predicting IDDM patients who may have coeliac disease. The RDW is not recommended as a screening test for coeliac disease in patients with IDDM. [ABSTRACT FROM AUTHOR]

Published
1999
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18. Is a random urinary albumin concentration a useful screening test in insulin-treated diabetic patients?

Author

Beatty, O., Ritchie, C., Hadden, D., Kennedy, L., Bell, P., and Atkinson, A.

Abstract

The debate continues on how to screen for microalbuminuria in clinical practice in patients with insulin-dependent diabetes mellitus. Our study assesses the value of a spot morning urine specimen obtained at a clinic visit. In 1984, as part of a randomised survey of our diabetes clinic, 43 of 249 patients with insulin treated diabetes mellitus, were found to have microalbuminuria (urinary albumin concentration 35-300 ug ml) on a spot morning urine sample. These subjects were compared with an age-matched control group from the 1984 cohort who did not have microalbuminuria. Eight years later, in the group with microalbuminuria, 10 had died compared to six in the control group (p=0.17) with 62.5% of all deaths being from cardiovascular disease. In the group with microalbuminuria, 10 of 27 still had incipient nephropathy while five had progressed to nephropathy. In the group without microalbuminuria only three of 33 patients had progressed to microalbuminuria while none had progressed to nephropathy. In conclusion a spot morning urine sample is a useful screening test to identify patients at risk of progression to nephropathy. [ABSTRACT FROM AUTHOR]

Published
1994
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21. Effects of the nicotinic antagonist mecamylamine on inspection time.

Author

Thompson, J. C., Stough, C., Ames, D., Ritchie, C., and Nathan, P. J.

Subjects
NICOTINE, HUMAN information processing, MECAMYLAMINE, CHOLINESTERASE inhibitors, PLACEBOS
Abstract

Abstract Rationale: Several lines of evidence suggest that nicotinic acetylcholine receptors (nAchRs) are involved in speed of information processing, and inspection time appears to be particularly sensitive to nicotinic manipulation. Objective: The present study sought to examine the effects of the nAchR antagonist mecamylamine on inspection time. Furthermore, the extent to which the anticholinesterase donepezil would reverse the effects of mecamylamine on inspection time was also examined. Methods: A double-blind, repeated measures design was employed. Subjects (n=6) received placebo, mecamylamine (20 mg PO) or mecamylamine (20 mg PO) and donepezil (5 mg PO). Inspection time and physiological measures were then assessed. Results: The mecamylamine condition and the mecamylamine and donepezil condition were associated with an increase in heart rate, when compared to the placebo condition. There was a significant slowing of inspection time in the mecamylamine condition, compared to placebo, which was partly reversed by donepezil. Conclusions: The slowing of inspection time following mecamylamine is consistent with the role of nAchRs in speed of information processing, and add to the evidence that IT may in part index nAchR system integrity. [ABSTRACT FROM AUTHOR]

Published
2000
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22. Transcriptomic signatures in whole blood of patients who acquire a chronic inflammatory response syndrome (CIRS) following an exposure to the marine toxin ciguatoxin

Author

James C. Ryan, Ritchie C. Shoemaker, and Qingzhong Wu

Subjects
Adult, Male, Proteomics, Ciguatoxin, Light, Microarray, Chronic illness, Biology, Bioinformatics, Polymerase Chain Reaction, Mice, Genetics, Animals, Humans, Genetics(clinical), Transcriptomics, Genetics (clinical), Oligonucleotide Array Sequence Analysis, Inflammation, Principal Component Analysis, Microarray analysis techniques, Gene Expression Profiling, Ciguatera Poisoning, Computational Biology, Ciguatera, Chronic inflammation, Middle Aged, Acquired immune system, Immunity, Innate, Fold change, HLA, Immune, Gene Expression Regulation, Immunoglobulin G, Immunology, Chronic inflammatory response, Female, RNA, Long Noncoding, Gene expression, DNA microarray, Transcriptome, Marine toxin, Research Article
Abstract

Background Ciguatoxins (CTXs) are polyether marine neurotoxins found in multiple reef-fish species and are potent activators of voltage-gated sodium channels. It is estimated that up to 500,000 people annually experience acute ciguatera poisoning from consuming toxic fish and a small percentage of these victims will develop a chronic, multisymptom, multisystem illness, which can last years, termed a Chronic Inflammatory Response Syndrome (CIRS). Symptoms of ciguatera CIRS include fatigue, cognitive deficits, neurologic deficits, pain and sensitivity to light. There are few treatment options for ciguatera CIRS since little is known about its pathophysiology. Methods This study characterizes the transcriptional profile in whole blood of 11 patients with ciguatera-induced CIRS and 11 normal controls run in duplicate using Agilent one color whole genome microarrays. Differential expression was determined by using a combination of moderated t-test p-value and fold change (FC). Significant genes were subjected to gene ontology, principal component analysis and SVM classification. Seven significant genes found by microarray were validated by PCR. Results Using a low stringency (p 1.4) and a high stringency (p 1.5) filter, the resulting gene sets of 185 and 55, respectively, showed clear separation of cases and controls by PCA as well as 100% classification accuracy by SVM, indicating that the gene profiles can separate patients from controls. PCR results of 7 genes showed a 95% correlation to microarray data. Several genes identified by microarray are important in wound healing (CD9, CD36, vWF and Factor XIII), adaptive immunity (HLA-DQB1, DQB2, IL18R1 and IL5RA) and innate immunity (GZMK, TOLLIP, SIGIRR and VIPR2), overlapping several areas shown to be disrupted in a mouse model of acute exposure to ciguatoxin. Another area of interest was differential expression of long, non-coding sequences, or lncRNA. Conclusions Disruptions of innate and adaptive immune mechanisms were recorded at both the genomic and proteomic level. A disruption in the HLA-T cell receptor axis could indicate HLA haplotype sensitivity for this chronic syndrome, as noted in many autoimmune conditions. Taken together, these indicators of illness provide additional insights into pathophysiology and potential therapies. Electronic supplementary material The online version of this article (doi:10.1186/s12920-015-0089-x) contains supplementary material, which is available to authorized users.

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23. Response.

Author

Ritchie C, Baker P, Buchanan I, and Magee P

Published
2007

24. Hypercalcaemia due to thynotoxicosis.

Author

Hayes, J. and Ritchie, C.

Abstract

Thyrotoxicosis presenting with hypercalcaemia of unusual severity is reported in a 51 year old man. Responses of hypercalcaemia to treatment with beta-blockers and anti-thyroid drugs, the mechanism of hypercalcaemia in thyrotoxicosis, and the modification of the symptoms of thyrotoxicosis by hypercalcaemia are discussed. [ABSTRACT FROM AUTHOR]

Published
1983
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