Steffen Wolfsgruber1, Frank Jessen2, Alexander Koppara2, Luca Kleineidam2, Klaus Schmidtke2, Lutz Frölich2, Alexander Kurz2, Stefanie Schulz2, Harald Hampel2, Isabella Heuser2, Oliver Peters2, Friedel M Reischies2, Holger Jahn2, Christian Luckhaus2, Michael Hüll2, Hermann-Josef Gertz2, Johannes Schröder2, Johannes Pantel2, Otto Rienhoff2, Eckart Rüther2, Fritz Henn2, Jens Wiltfang2, Wolfgang Maier2, Johannes Kornhuber2, Michael Wagner2. 1. From the Department of Psychiatry (S.W., F.J., A. Koppara, L.K., W.M., M.W.), University of Bonn; German Center for Neurodegenerative Diseases (S.W., F.J. A. Koppara, L.K., W.M., M.W.), Bonn; Center for Geriatric Medicine (K.S.), Ortenau Klinikum, Offenburg-Gengenbach; Department of Gerontopsychiatry (L.F.), Central Institute of Mental Health, Mannheim; Department of Psychiatry (A. Kurz), Technical University of Munich; Department of Neurology (S.S.), University of Aachen; Department of Psychiatry and Psychotherapy (S.S., E.R., J.W.), University of Göttingen, Germany; AXA Research Fund & UPMC Chair Sorbonne Universités (H.H.), Université Pierre et Marie Curie, Paris; Institut de la Mémoire et de la Maladie d'Alzheimer (H.H.), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris; INSERM U1127 (H.H.), Institut du Cerveau et de la Moelle épinière, Paris, France; Department of Psychiatry (I.H., O.P., F.M.R.), Charité Berlin, Campus Benjamin Franklin, Berlin; Department of Psychiatry (H.J.), University of Hamburg; Department of Psychiatry (C.L.), University of Düsseldorf; Center for Geriatric Medicine and Gerontology (M.H.), University of Freiburg; Department of Psychiatry (H.-J.G.), University of Leipzig; Department of Psychiatry (J.S.), University of Heidelberg; Department of General Medicine (J.P.), University of Frankfurt, Frankfurt am Main; Department of Medical Informatics (O.R.), University of Göttingen, Germany; Brookhaven National Laboratory (F.H.), Upton, New York; and Department of Psychiatry (J.K.), Friedrich-Alexander University Erlangen, Germany. F.J. is currently with the Department of Psychiatry, University of Cologne. steffen.wolfsgruber@ukb.uni-bonn.de. 2. From the Department of Psychiatry (S.W., F.J., A. Koppara, L.K., W.M., M.W.), University of Bonn; German Center for Neurodegenerative Diseases (S.W., F.J. A. Koppara, L.K., W.M., M.W.), Bonn; Center for Geriatric Medicine (K.S.), Ortenau Klinikum, Offenburg-Gengenbach; Department of Gerontopsychiatry (L.F.), Central Institute of Mental Health, Mannheim; Department of Psychiatry (A. Kurz), Technical University of Munich; Department of Neurology (S.S.), University of Aachen; Department of Psychiatry and Psychotherapy (S.S., E.R., J.W.), University of Göttingen, Germany; AXA Research Fund & UPMC Chair Sorbonne Universités (H.H.), Université Pierre et Marie Curie, Paris; Institut de la Mémoire et de la Maladie d'Alzheimer (H.H.), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris; INSERM U1127 (H.H.), Institut du Cerveau et de la Moelle épinière, Paris, France; Department of Psychiatry (I.H., O.P., F.M.R.), Charité Berlin, Campus Benjamin Franklin, Berlin; Department of Psychiatry (H.J.), University of Hamburg; Department of Psychiatry (C.L.), University of Düsseldorf; Center for Geriatric Medicine and Gerontology (M.H.), University of Freiburg; Department of Psychiatry (H.-J.G.), University of Leipzig; Department of Psychiatry (J.S.), University of Heidelberg; Department of General Medicine (J.P.), University of Frankfurt, Frankfurt am Main; Department of Medical Informatics (O.R.), University of Göttingen, Germany; Brookhaven National Laboratory (F.H.), Upton, New York; and Department of Psychiatry (J.K.), Friedrich-Alexander University Erlangen, Germany. F.J. is currently with the Department of Psychiatry, University of Cologne.
Abstract
OBJECTIVE: To test whether, in individuals with mild cognitive impairment (MCI), different measures of subjective cognitive decline (SCD) in the memory domain predict abnormal CSF biomarkers of Alzheimer disease (AD). METHODS: We analyzed the multicenter baseline (cross-sectional) data of 245 patients with MCI. SCD was measured quantitatively with the Subjective Memory Decline Scale (SMDS) and qualitatively by assessing particular concerns associated with self-experienced worsening of memory. Logistic regression models were used to examine associations between SCD and abnormal CSF biomarkers, taking into account objective memory impairment, depressive symptoms, and education as covariates. RESULTS: Abnormal CSF β-amyloid 1-42 (Aβ42) and more depressive symptoms were associated with higher SMDS scores and with the report of memory concerns. Risk of abnormal CSF Aβ42 increased by an estimated 57% for a 1-SD increase in SMDS scores and was doubled in patients who had SMDS scores >4 or who reported memory concerns, respectively. In addition, both SCD measures predicted risk of having a biomarker signature indicative of prodromal AD defined as presence of low CSF Aβ42 together with either high CSF tau or CSF phosphorylated tau 181 levels. CONCLUSIONS: In MCI, specific aspects of SCD severity and quality are related to CSF biomarkers indicative of AD. This extends findings in pre-MCI samples and calls for an improved operational assessment of SCD in MCI. This might be useful for sample enrichment strategies for increased likelihood of AD pathology.
OBJECTIVE: To test whether, in individuals with mild cognitive impairment (MCI), different measures of subjective cognitive decline (SCD) in the memory domain predict abnormal CSF biomarkers of Alzheimer disease (AD). METHODS: We analyzed the multicenter baseline (cross-sectional) data of 245 patients with MCI. SCD was measured quantitatively with the Subjective Memory Decline Scale (SMDS) and qualitatively by assessing particular concerns associated with self-experienced worsening of memory. Logistic regression models were used to examine associations between SCD and abnormal CSF biomarkers, taking into account objective memory impairment, depressive symptoms, and education as covariates. RESULTS: Abnormal CSF β-amyloid 1-42 (Aβ42) and more depressive symptoms were associated with higher SMDS scores and with the report of memory concerns. Risk of abnormal CSF Aβ42 increased by an estimated 57% for a 1-SD increase in SMDS scores and was doubled in patients who had SMDS scores >4 or who reported memory concerns, respectively. In addition, both SCD measures predicted risk of having a biomarker signature indicative of prodromal AD defined as presence of low CSF Aβ42 together with either high CSFtau or CSF phosphorylated tau 181 levels. CONCLUSIONS: In MCI, specific aspects of SCD severity and quality are related to CSF biomarkers indicative of AD. This extends findings in pre-MCI samples and calls for an improved operational assessment of SCD in MCI. This might be useful for sample enrichment strategies for increased likelihood of AD pathology.
Authors: José L Molinuevo; Laura A Rabin; Rebecca Amariglio; Rachel Buckley; Bruno Dubois; Kathryn A Ellis; Michael Ewers; Harald Hampel; Stefan Klöppel; Lorena Rami; Barry Reisberg; Andrew J Saykin; Sietske Sikkes; Colette M Smart; Beth E Snitz; Reisa Sperling; Wiesje M van der Flier; Michael Wagner; Frank Jessen Journal: Alzheimers Dement Date: 2016-11-05 Impact factor: 21.566
Authors: Piotr Lewczuk; Peter Riederer; Sid E O'Bryant; Marcel M Verbeek; Bruno Dubois; Pieter Jelle Visser; Kurt A Jellinger; Sebastiaan Engelborghs; Alfredo Ramirez; Lucilla Parnetti; Clifford R Jack; Charlotte E Teunissen; Harald Hampel; Alberto Lleó; Frank Jessen; Lidia Glodzik; Mony J de Leon; Anne M Fagan; José Luis Molinuevo; Willemijn J Jansen; Bengt Winblad; Leslie M Shaw; Ulf Andreasson; Markus Otto; Brit Mollenhauer; Jens Wiltfang; Martin R Turner; Inga Zerr; Ron Handels; Alexander G Thompson; Gunilla Johansson; Natalia Ermann; John Q Trojanowski; Ilker Karaca; Holger Wagner; Patrick Oeckl; Linda van Waalwijk van Doorn; Maria Bjerke; Dimitrios Kapogiannis; H Bea Kuiperij; Lucia Farotti; Yi Li; Brian A Gordon; Stéphane Epelbaum; Stephanie J B Vos; Catharina J M Klijn; William E Van Nostrand; Carolina Minguillon; Matthias Schmitz; Carla Gallo; Andrea Lopez Mato; Florence Thibaut; Simone Lista; Daniel Alcolea; Henrik Zetterberg; Kaj Blennow; Johannes Kornhuber Journal: World J Biol Psychiatry Date: 2017-10-27 Impact factor: 4.132
Authors: Rachel F Buckley; Bernard Hanseeuw; Aaron P Schultz; Patrizia Vannini; Sarah L Aghjayan; Michael J Properzi; Jonathan D Jackson; Elizabeth C Mormino; Dorene M Rentz; Reisa A Sperling; Keith A Johnson; Rebecca E Amariglio Journal: JAMA Neurol Date: 2017-12-01 Impact factor: 18.302
Authors: Rachel F Buckley; Victor L Villemagne; Colin L Masters; Kathryn A Ellis; Christopher C Rowe; Keith Johnson; Reisa Sperling; Rebecca Amariglio Journal: J Mol Neurosci Date: 2016-08-11 Impact factor: 3.444