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Risk of dementia in elderly patients with the use of proton pump inhibitors

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European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

Drugs that modify the risk of dementia in the elderly are of potential interest for dementia prevention. Proton pump inhibitors (PPIs) are widely used to reduce gastric acid production, but information on the risk of dementia is lacking. We assessed association between the use of PPIs and the risk of dementia in elderly people. Data were derived from a longitudinal, multicenter cohort study in elderly primary care patients, the German Study on Aging, Cognition and Dementia in Primary Care Patients (AgeCoDe), including 3,327 community-dwelling persons aged ≥75 years. From follow-up 1 to follow-up 4 (follow-up interval 18 months), we identified a total of 431 patients with incident any dementia, including 260 patients with Alzheimer’s disease. We used time-dependent Cox regression to estimate hazard ratios of incident any dementia and Alzheimer’s disease. Potential confounders included in the analysis comprised age, sex, education, the Apolipoprotein E4 (ApoE4) allele status, polypharmacy, and the comorbidities depression, diabetes, ischemic heart disease, and stroke. Patients receiving PPI medication had a significantly increased risk of any dementia [Hazard ratio (HR) 1.38, 95 % confidence interval (CI) 1.04–1.83] and Alzheimer’s disease (HR 1.44, 95 % CI 1.01–2.06) compared with nonusers. Due to the major burden of dementia on public health and the lack of curative medication, this finding is of high interest to research on dementia and provides indication for dementia prevention.

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Acknowledgments

This study is part of the German Research Network on Dementia (KND) and the German Research Network on Degenerative Dementia (KNDD) and was funded by the German Federal Ministry of Education and Research (Grants KND: 01GI0102, 01GI0420, 01GI0422, 01GI0423, 01GI0429, 01GI0431, 01GI0433, 01GI0434; Grants KNDD: 01GI0710, 01GI0711, 01GI0712, 01GI0713, 01GI0714, 01GI0715, 01GI0716).

Conflict of interest

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. German Center for Neurodegenerative Diseases (DZNE), c/o Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany

    Britta Haenisch, Klaus von Holt, Frank Jessen & Wolfgang Maier

  2. Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany

    Britta Haenisch & Karl Broich

  3. Department of Psychiatry, University of Bonn, Bonn, Germany

    Britta Haenisch, Frank Jessen & Wolfgang Maier

  4. Institute for General Practice, Hannover Medical School, Hannover, Germany

    Birgitt Wiese & Jana Prokein

  5. Department of Primary Medical Care, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Carolin Lange, Annette Ernst & Martin Scherer

  6. Department of Health Economics and Health Services Research, Hamburg Center for Health Economics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Christian Brettschneider & Hans-Helmut König

  7. Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany

    Jochen Werle & Siegfried Weyerer

  8. Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Leipzig, Germany

    Melanie Luppa & Steffi G. Riedel-Heller

  9. Institute of General Practice (IFAM), Medical Faculty of the Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

    Angela Fuchs & Michael Pentzek

  10. Department of Psychiatry, Technical University of Munich, Munich, Germany

    Dagmar Weeg & Horst Bickel

Authors
  1. Britta Haenisch
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  2. Klaus von Holt
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  3. Birgitt Wiese
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  4. Jana Prokein
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  5. Carolin Lange
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  6. Annette Ernst
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  7. Christian Brettschneider
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  8. Hans-Helmut König
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  9. Jochen Werle
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  10. Siegfried Weyerer
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  11. Melanie Luppa
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  12. Steffi G. Riedel-Heller
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  13. Angela Fuchs
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  14. Michael Pentzek
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  15. Dagmar Weeg
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  16. Horst Bickel
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  17. Karl Broich
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  18. Frank Jessen
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  19. Wolfgang Maier
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  20. Martin Scherer
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Corresponding author

Correspondence to Britta Haenisch.

Additional information

For the AgeCoDe study group.

Appendices

Appendix: Members of the AgeCoDe Study Group

Principal Investigators*: Wolfgang Maier and Martin Scherer

Heinz-Harald Abholz, Christian Brettschneider, Cadja Bachmann, Horst Bickel, Wolfgang Blank, Hendrik van den Bussche, Sandra Eifflaender-Gorfer, Marion Eisele, Annette Ernst, Angela Fuchs, Kathrin Heser, Frank Jessen, Hanna Kaduszkiewicz, Teresa Kaufeler, Mirjam Köhler, Hans-Helmut König, Alexander Koppara, Carolin Lange, Tobias Luck, Melanie Luppa, Manfred Mayer, Edelgard Mösch, Julia Olbrich, Michael Pentzek, Jana Prokein, Anna Schumacher, Steffi Riedel-Heller, Janine Stein, Susanne Steinmann, Franziska Tebarth, Michael Wagner, Klaus Weckbecker, Dagmar Weeg, Jochen Werle, Siegfried Weyerer, Birgitt Wiese, Steffen Wolfsgruber, Thomas Zimmermann.

*Hendrik van den Bussche (2002–2011)

We want to thank both all participating patients and their general practitioners for their good collaboration.

GPs participating at the time of Follow-up V

Bonn

Claudia Adrian, Hanna Liese, Inge Bürfent, Johann von Aswege, Wolf-Dietrich Honig, Peter Gülle, Heribert Schützendorf, Elisabeth Benz, Annemarie Straimer, Arndt Uhlenbrock, Klaus-Michael Werner, Maria Göbel-Schlatholt, Hans-Jürgen Kaschell, Klaus Weckbecker, Theodor Alfen, Markus Stahlschmidt, Klaus Fischer, Wolf-Rüdiger Weisbach, Martin Tschoke, Jürgen Dorn, Helmut Menke, Erik Sievert, Ulrich Kröckert, Gabriele Salingré, Christian Mörchen, Peter Raab, Angela Baszenski, Clärli Loth, Christian Knaak, Peter Hötte, Jörg Pieper, Dirk Wassermann, Hans Josef Leyendecker, Gerhard Gohde, Barbara Simons, Achim Brünger, Uwe Petersen, Heike Wahl, Rainer Tewes, Doris Junghans-Kullmann, Angela Grimm-Kraft, Harald Bohnau, Ursula Pinsdorf, Thomas Busch, Gisela Keller, Susanne Fuchs-Römer, Wolfgang Beisel.

Düsseldorf

Birgitt Richter-Polynice, Florinela Cupsa, Roland Matthias Unkelbach, Gerhard Schiller, Barbara Damanakis, Michael Frenkel, Klaus-Wolfgang Ebeling, Pauline Berger, Kurt Gillhausen, Uwe Hellmessen, Helga Hümmerich, Hans-Christian Heede, Boguslaw- Marian Kormann, Wolfgang Josef Peters, Ulrich Schott, Dirk Matzies, Andre Schumacher, Tim Oliver Flettner, Winfried Thraen, Harald Siegmund, Claus Levacher, Tim Blankenstein, Eliane Lamborelle, Ralf Hollstein, Edna Hoffmann, Ingeborg Ghane, Regine Claß, Stefan-Wolfgang Meier, Leo W. Moers, Udo Wundram, Klaus Schmitt, Rastin Missghian, Karin Spallek, Christiane Schlösser.

Hamburg

Kathrin Groß, Winfried Bouché, Ursula Linn, Gundula Bormann, Gerhard Schulze, Klaus Stelter, Heike Gatermann, Doris Fischer-Radizi, Otto-Peter Witt, Stefanie Kavka, Günther Klötzl, Karl-Christian Münter, Michael Baumhöfener, Maren Oberländer, Cornelia Schiewe, Jörg Hufnagel, Anne-Marei Kressel, Michael Kebschull, Christine Wagner, Fridolin Burkhardt, Martina Hase, Matthias Büttner, Karl-Heinz Houcken, Christiane Zebidi, Johann Bröhan, Christiane Russ, Frank Bethge, Gisela Rughase-Block, Margret Lorenzen, Arne Elsen, Lerke Stiller, Angelika Giovanopoulos, Daniela Korte, Ursula Jedicke, Rosemarie Müller-Mette, Andrea Richter, Sanna Rauhala-Parrey, Constantin Zoras, Gabriele Pfeil-Woltmann, Annett Knöppel-Frenz, Martin Kaiser, Johannes Bruns, Joachim Homann, Georg Gorgon, Niklas Middendorf, Kay Menschke, Hans Heiner Stöver, Hans H. Bayer, Rüdiger Quandt, Gisela Rughase-Block, Hans-Michael Köllner, Enno Strohbehn, ThomasHaller, Nadine Jesse, Martin Domsch, Marcus Dahlke.

Leipzig

Thomas Lipp, Ina Lipp, Martina Amm, Horst Bauer, Gabriele Rauchmaul, Hans Jochen Ebert, Angelika Gabriel-Müller, Hans-Christian Taut, Hella Voß, Ute Mühlmann, Holger Schmidt, Gabi Müller, Eva Hager, Bettina Tunze, Barbara Bräutigam, Thomas Paschke, Heinz-Michael Assmann, Ina Schmalbruch, Gunter Kässner, Iris Pförtzsch, Brigitte Ernst-Brennecke, Uwe Rahnefeld, Petra Striegler, Marga Gierth, Anselm Krügel, Margret Boehm, Dagmar Harnisch, Simone Kornisch-Koch, Birgit Höne, Lutz Schönherr, Frank Hambsch, Katrin Meitsch, Britta Krägelin-Nobahar, Cornelia Herzig, Astrid Georgi, Erhard Schwarzmann, Gerd Schinagl, Ulrike Pehnke, Mohammed Dayab, Sabine Müller, Jörg-Friedrich Onnasch, Michael Brosig, Dorothea Frydetzki, Uwe Abschke, Volkmar Sperling, Ulrich Gläser, Frank Lebuser, Detlef Hagert.

Mannheim

Gerhard Arnold, Viet-Harold Bauer, Hartwig Becker, Hermine Becker, Werner Besier, Hanna Böttcher-Schmidt, Susanne Füllgraf-Horst, Enikö Göry, Hartmut Grella, Hans Heinrich Grimm, Petra Heck, Werner Hemler, Eric Henn, Violetta Löb, Grid Maaßen-Kalweit, Manfred Mayer, Hubertus Mühlig, Arndt Müller, Gerhard Orlovius, Helmut Perleberg, Brigitte Radon, Helmut Renz, Carsten Rieder, Michael Rosen, Georg Scheer, Michael Schilp, Angela Schmid, Matthias Schneider, Christian Schneider, Rüdiger Stahl, Christian Uhle, Jürgen Wachter, Necla Weihs, Brigitte Weingärtner, Monika Werner, Hans- Georg Willhauck, Eberhard Wochele, Bernhard Wolfram.

Munich

Andreas Hofmann, Eugen Allwein, Helmut Ruile, Andreas Koeppel, Peter Dick, Karl-Friedrich Holtz, Gabriel Schmidt, Lutz-Ingo Fischer, Johann Thaller, Guntram Bloß, Franz Kreuzer, Günther Holthausen, Karl Ludwig Maier, Walter Krebs, Christoph Mohr, Heinz Koschine, Richard Ellersdorfer, Michael Speth, Maria Kleinhans, Panagiota Koutsouva-Sack, Gabriele Staudinger, Johann Eiber, Stephan Thiel, Cornelia Gold, Andrea Nalbach, Kai Reichert, Markus Rückgauer, Martin Neef, Viktor Fleischmann, Natalija Mayer, Andreas Spiegl, Fritz Renner, Eva Weishappel-Ketisch, Thomas Kochems, Hartmut Hunger, Marianne Hofbeck, Alfred Neumeier, Elfriede Goldhofer, Thomas Bommer, Reinhold Vollmuth, Klaus Lanzinger, Simone Bustami-Löber, Ramona Pauli, Jutta Lindner, Gerlinde Brandt, Otto Hohentanner, Rosita Urban-Hüttner, Peter Porz, Bernd Zimmerhackl, Barbara Naumann, Margarete Vach, Alexander Hallwachs, Claudia Haseke, Andreas Ploch, Paula Bürkle-Grasse, Monika Swobodnik, Corina Tröger, Detlev Jost, Roman Steinhuber, Renate Narr, Gabriele Nehmann-Hörwick, Christiane Eder, Helmut Pillin, Frank Loth, Beate Rücker, Nicola Fritz, Michael Rafferzeder, Dietmar Zirpel.

GPs who participated at baseline

Bonn

Heinz-Peter Romberg, Hanna Liese, Inge Bürfent, Johann von Aswege, Wolf-Dietrich Honig, Peter Gülle, Heribert Schützendorf, Manfred Marx, Annemarie Straimer, Arndt Uhlenbrock, Klaus-Michael Werner, Maria Göbel-Schlatholt, Eberhard Prechtel, Hans-Jürgen Kaschell, Klaus Weckbecker, Theodor Alfen, Jörg Eimers-Kleene, Klaus Fischer, Wolf- Rüdiger Weisbach, Martin Tschoke.

Düsseldorf

Birgitt Richter-Polynice, Michael Fliedner, Binjamin Hodgson, Florinela Cupsa, Werner Hamkens, Roland Matthias Unkelbach, Gerhard Schiller, Barbara Damanakis, Angela Ackermann, Michael Frenkel, Klaus-Wolfgang Ebeling, Bernhard Hoff, Michael Kirsch, Vladimir Miasnikov, Pauline Berger, Kurt Gillhausen, Uwe Hellmessen, Helga Hümmerich, Hans-Christian Heede, Boguslaw-Marian Kormann, Dieter Lüttringhaus, Wolfgang Josef Peters, Ulrich Schott, Dirk Matzies, Andre Schumacher, Tim Oliver Flettner, Winfried Thraen, Clemens Wirtz, Harald Siegmund.

Hamburg

Kathrin Groß, Bernd-Uwe Krug, Petra Hütter, Dietrich Lau, Gundula Bormann, Ursula Schröder-Höch, Wolfgang Herzog, Klaus Weidner, Doris Fischer-Radizi, Otto-Peter Witt, Stefanie Kavka, Günther Klötzl, Ljudmila Titova, Andrea Moritz.

Leipzig

Thomas Lipp, Ina Lipp, Martina Amm, Horst Bauer, Gabriele Rauchmaul, Hans Jochen Ebert, Angelika Gabriel-Müller, Hans-Christian Taut, Hella Voß, Ute Mühlmann, Holger Schmidt, Gabi Müller, Eva Hager, Bettina Tunze, Barbara Bräutigam, Sabine Ziehbold, Thomas Paschke, Heinz-Michael Assmann, Ina Schmalbruch, Gunter Kässner.

Mannheim

Gerhard Arnold, Viet-Harold Bauer, Werner Besier, Hanna Böttcher-Schmidt, Hartmut Grella, Ingrid Ludwig, Manfred Mayer, Arndt Müller, Adolf Noky, Gerhard Orlovius, Helmut Perleberg, Carsten Rieder, Michael Rosen, Georg Scheer, Michael Schilp, Gerhard Kunzendorf, Matthias Schneider, Jürgen Wachter, Brigitte Weingärtner, Hans- Georg Willhauck.

Munich

Helga Herbst, Andreas Hofmann, Eugen Allwein, Helmut Ruile, Andreas Koeppel, Peter Friedrich, Hans-Georg Kirchner, Elke Kirchner, Luitpold Knauer, Peter Dick, Karl- Friedrich Holtz, Elmar Schmid, Gabriel Schmidt, Lutz-Ingo Fischer, Johann Thaller, Guntram Bloß, Franz Kreuzer, Ulf Kahmann, Günther Holthausen, Karl Ludwig Maier, Walter Krebs, Christoph Mohr, Heinz Koschine, Richard Ellersdorfer, Michael Speth.

GPs who used to participate in the study

Bonn

Heinz-Peter Romberg, Eberhard Prechtel, Manfred Marx, Jörg Eimers-Kleene, Paul Reich, Eberhard Stahl, Reinhold Lunow, Klaus Undritz, Bernd Voss, Achim Spreer, Oliver Brenig, Bernhard G. Müller, Ralf Eich, Angelika Vossel, Dieter Leggewie, Angelika Schmidt, Nahid Aghdai-Heuser, Lutz Witten, Michael Igel.

Düsseldorf

Michael Fliedner, Benjamin Hodgson, Werner Hamkens, Angela Ackermann, Bernhard Hoff, Michael Kirsch, Vladimir Miasnikov, Dieter Lüttringhaus, Clemens Wirtz, Rolf Opitz, Jürgen Bausch, Dirk Mecking, Friederike Ganßauge, Elmar Peters, Alfons Wester.

Hamburg

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Haenisch, B., von Holt, K., Wiese, B. et al. Risk of dementia in elderly patients with the use of proton pump inhibitors. Eur Arch Psychiatry Clin Neurosci 265, 419–428 (2015). https://doi.org/10.1007/s00406-014-0554-0

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