TY - JOUR
T1 - Memory concerns, memory performance and risk of dementia in patients with mild cognitive impairment
AU - Wolfsgruber, Steffen
AU - Wagner, Michael
AU - Schmidtke, Klaus
AU - Frölich, Lutz
AU - Kurz, Alexander
AU - Schulz, Stefanie
AU - Hampel, Harald
AU - Heuser, Isabella
AU - Peters, Oliver
AU - Reischies, Friedel M.
AU - Jahn, Holger
AU - Luckhaus, Christian
AU - Hüll, Michael
AU - Gertz, Hermann Josef
AU - Schröder, Johannes
AU - Pantel, Johannes
AU - Rienhoff, Otto
AU - Rüther, Eckart
AU - Henn, Fritz
AU - Wiltfang, Jens
AU - Maier, Wolfgang
AU - Kornhuber, Johannes
AU - Jessen, Frank
N1 - Funding Information:
Klaus Schmidtke has obtained honoraria from Nutricia and Merz for participation in advisory board meetings, and from Merz for lectures and for the preparation of manuscripts. Lutz Frölich holds/has held a board membership in Eisai, Elan/Weyth, Eli Lilly, GE Health Care, Janssen-Cilag, Lundbeck, Merz Pharma, Novartis, Pfizer, Schering-Plough. He has received payment for consultancy, expert testimony, honorarium or travelling support from AstraZeneca, Merz Pharma, Myriad, Neurochem, Novartis, Pfizer, Schering-Plough, Apotex Inc. and has received a research grant from Novartis, Pfizer paid to his institution. Harald Hampel has received lecture honoraria and/or research grants and/or travel funding and/or participated in scientific advisory boards for several pharmaceutical companies including Boehringer-Ingelheim, BMS, Elan, Wyeth, Novartis, Eisai, Pfizer, Schwabe, Sanofi-Aventis, Roche Pharmaceuticals and Diagnostics, GE Healthcare, Astra-Zeneca, Avid, Eli Lilly and Company, Janssen-Cilag, Merz Pharmaceuticals, GSK-Bio, Jung-Diagnostics, Thermo Fisher Scientific Clinical Diagnostics B•R•A•H•M•S GmbH. He is co-inventor in the following pending patent submissions (“Method for predicting whether subjects with mild cognitive impairment (MCI) will develop Alzheimer's disease”, PCT/US03/35516; “3-Hydroxykynurenin im Serum als diagnostischer Marker für die Demenz vom Alzheimer-Typ”, PCT/EP2006/002907; “Neurodegenerative markers for psychiatric conditions”, EP2006002907; “Ratio Aβ42/40 im Plasma in der Früh- und Differentialdiagnose der Alzheimer Krankheit”, IIIB8/823/06; “Liquordiagnostisches in vitro Verfahren zur Diagnose von Demenz-Erkrankungen und neuroinflammatorischen Erkrankungen”, PCT/EP2006007141; “In vitro Verfahren zur Diagnose von neurodegenerativen Erkrankungen”, PCT/EP2006007272; “In vitro Verfahren zur Diagnose und Frühdiagnose von neurodegenerativen Erkrankungen”, PCT/EP2007010331) and has received no royalties. Michael Hüll is PI in clinical studies from Pfizer Inc, Noscira Inc and Abbvie, has received a research grant from Schwabe GmbH, has received speakers honoraria from Pfizer Inc, Merz Pharmaceuticals, Glaxo Smith Kline and served on an advisory board for Hoffman La Roche. Johannes Pantel has received lecture honoraria from Merz, Janssen-Cilag, Novartis. Eckart Rüther is a Merz GmbH-collaborator, is on the speakers' bureau of/has received a travel grant from BMS, Lundbeck, Servier and Otsouka and has received a research grant from Lilly, BMS, Astra-Zeneca and Lundbeck. Fritz Henn has been a consultant to Astra-Zeneca in the area of depression between June 2011 and November 2012. Jens Wiltfang is on the Advisory Board for Eli Lilly and has received consulting fee or honorarium and support for travelling to Board meetings. He received payment for lectures from Novartis and has received research grants from the EU and the German Federal Ministry of Education and Research paid to his institution for various research projects in some of which he served as coordinator. Wolfgang Maier has received a research grant from the German Federal Ministry of Education and Research paid to his institution and is on the speakers' bureau/has received payment for educational lectures from Merz. Johannes Kornhuber has received grants from the BMBF (Bundesministerium für Bildung und Forschung) and the German Research Foundation (DFG). Furthermore, he has received financial support for conducting clinical trials from various pharmaceutical companiesmanufacturing anti-dementia drugs. He is mentioned as coinventor on the following patents: Substituted piperidines or pyrrolidine compounds for treating sigma-receptor modulated disorders (WO001996031208A3); Method of differentially diagnosing dementias (WO002008058764A1); Soluble amyloid precursor proteins in cerebrospinal fluid as biomarkers of Alzheimer's disease (EP000002068151A1); Immunglobulin-bound Aβ and immunglobulins-binding Aβ peptides in diagnosis and therapy of Alzheimer's disease (WO002007082750A1); Method of diagnosing acute cerebral ischemia (WO002008058764A1). Frank Jessen has received consultation board honoraria and speaker's fees from AC Immune, Lilly, GE Healthcare, Janssen, USB, Schwabe, Esai, Pfizer, Novartis, Roche. He has received a research grant paid to his institution from Schwabe. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
PY - 2014/7/14
Y1 - 2014/7/14
N2 - Background: Concerns about worsening memory ("memory concerns"; MC) and impairment in memory performance are both predictors of Alzheimer's dementia (AD). The relationship of both in dementia prediction at the pre-dementia disease stage, however, is not well explored. Refined understanding of the contribution of both MC and memory performance in dementia prediction is crucial for defining at-risk populations. We examined the risk of incident AD by MC and memory performance in patients with mild cognitive impairment (MCI). Methods: We analyzed data of 417 MCI patients from a longitudinal multicenter observational study. Patients were classified based on presence (n = 305) vs. absence (n = 112) of MC. Risk of incident AD was estimated with Cox Proportional-Hazards regression models. Results: Risk of incident AD was increased by MC (HR = 2.55, 95%CI: 1.33-4.89), lower memory performance (HR = 0.63, 95%CI: 0.56-0.71) and ApoE4-genotype (HR = 1.89, 95%CI: 1.18-3.02). An interaction effect between MC and memory performance was observed. The predictive power of MC was greatest for patients with very mild memory impairment and decreased with increasing memory impairment. Conclusions: Our data suggest that the power of MC as a predictor of future dementia at the MCI stage varies with the patients' level of cognitive impairment. While MC are predictive at early stage MCI, their predictive value at more advanced stages of MCI is reduced. This suggests that loss of insight related to AD may occur at the late stage of MCI.
AB - Background: Concerns about worsening memory ("memory concerns"; MC) and impairment in memory performance are both predictors of Alzheimer's dementia (AD). The relationship of both in dementia prediction at the pre-dementia disease stage, however, is not well explored. Refined understanding of the contribution of both MC and memory performance in dementia prediction is crucial for defining at-risk populations. We examined the risk of incident AD by MC and memory performance in patients with mild cognitive impairment (MCI). Methods: We analyzed data of 417 MCI patients from a longitudinal multicenter observational study. Patients were classified based on presence (n = 305) vs. absence (n = 112) of MC. Risk of incident AD was estimated with Cox Proportional-Hazards regression models. Results: Risk of incident AD was increased by MC (HR = 2.55, 95%CI: 1.33-4.89), lower memory performance (HR = 0.63, 95%CI: 0.56-0.71) and ApoE4-genotype (HR = 1.89, 95%CI: 1.18-3.02). An interaction effect between MC and memory performance was observed. The predictive power of MC was greatest for patients with very mild memory impairment and decreased with increasing memory impairment. Conclusions: Our data suggest that the power of MC as a predictor of future dementia at the MCI stage varies with the patients' level of cognitive impairment. While MC are predictive at early stage MCI, their predictive value at more advanced stages of MCI is reduced. This suggests that loss of insight related to AD may occur at the late stage of MCI.
UR - https://www.scopus.com/pages/publications/84904209187
U2 - 10.1371/journal.pone.0100812
DO - 10.1371/journal.pone.0100812
M3 - Article
C2 - 25019225
AN - SCOPUS:84904209187
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 7
M1 - e100812
ER -