Rüther, Eckart

[["dc.bibliographiccitation.firstpage","872"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Alzheimer's & Dementia"],["dc.bibliographiccitation.lastpage","881"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Louwersheimer, Eva"],["dc.contributor.author","Wolfsgruber, Steffen"],["dc.contributor.author","Espinosa, Ana"],["dc.contributor.author","Lacour, André"],["dc.contributor.author","Heilmann-Heimbach, Stefanie"],["dc.contributor.author","Alegret, Montserrat"],["dc.contributor.author","Hernández, Isabel"],["dc.contributor.author","Rosende-Roca, Maitée"],["dc.contributor.author","Tárraga, Lluís"],["dc.contributor.author","Boada, Mercè"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Peters, Oliver"],["dc.contributor.author","Frölich, Lutz"],["dc.contributor.author","Hüll, Michael"],["dc.contributor.author","Rüther, Eckart"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Scherer, Martin"],["dc.contributor.author","Riedel-Heller, Steffi"],["dc.contributor.author","Jessen, Frank"],["dc.contributor.author","Nöthen, Markus M."],["dc.contributor.author","Maier, Wolfgang"],["dc.contributor.author","Koene, Ted"],["dc.contributor.author","Scheltens, Philip"],["dc.contributor.author","Holstege, Henne"],["dc.contributor.author","Wagner, Michael"],["dc.contributor.author","Ruiz, Agustín"],["dc.contributor.author","van der Flier, Wiesje M."],["dc.contributor.author","Becker, Tim"],["dc.contributor.author","Ramirez, Alfredo"],["dc.date.accessioned","2017-09-07T11:44:36Z"],["dc.date.available","2017-09-07T11:44:36Z"],["dc.date.issued","2016"],["dc.description.abstract","IntroductionWe evaluated the effect of Alzheimer's disease (AD) susceptibility loci on endophenotypes closely related with AD pathology in patients with mild cognitive impairment (MCI).MethodsWe selected 1730 MCI patients from four independent data sets. Weighted polygenic risk scores (PGS) were constructed of 18 non-apolipoprotein E (APOE) AD risk variants. In addition, we determined APOE genotype. AD endophenotypes were cognitive decline over time and cerebrospinal fluid (CSF) biomarkers (aβ, tau, ptau).ResultsPGS was modestly associated with cognitive decline over time, as measured by mini-mental state examination (MMSE) (β ± SE:−0.24 ± 0.10; P = .012), and with CSF levels of tau and ptau (tau: 1.38 ± 0.36, P = 1.21 × 10−4; ptau: 1.40 ± 0.36, P = 1.02 × 10−4).DiscussionIn MCI, we observed a joint effect of AD susceptibility loci on nonamyloid endophenotypes, suggesting a link of these genetic loci with neuronal degeneration in general rather than with Alzheimer-related amyloid deposition."],["dc.identifier.doi","10.1016/j.jalz.2016.01.006"],["dc.identifier.gro","3151698"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8517"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","chake"],["dc.relation.issn","1552-5260"],["dc.title","Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","6644"],["dc.bibliographiccitation.issue","24"],["dc.bibliographiccitation.journal","Human Molecular Genetics"],["dc.bibliographiccitation.lastpage","6658"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Ramirez, Alfredo"],["dc.contributor.author","van der Flier, Wiesje M."],["dc.contributor.author","Herold, Christine"],["dc.contributor.author","Ramonet, David"],["dc.contributor.author","Heilmann, Stefanie"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Popp, Julius"],["dc.contributor.author","Lacour, André"],["dc.contributor.author","Drichel, Dmitriy"],["dc.contributor.author","Louwersheimer, Eva"],["dc.contributor.author","Kummer, Markus P."],["dc.contributor.author","Cruchaga, Carlos"],["dc.contributor.author","Hoffmann, Per"],["dc.contributor.author","Teunissen, Charlotte E."],["dc.contributor.author","Holstege, Henne"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Peters, Oliver"],["dc.contributor.author","Naj, Adam C."],["dc.contributor.author","Chouraki, Vincent"],["dc.contributor.author","Bellenguez, Céline"],["dc.contributor.author","Gerrish, Amy"],["dc.contributor.author","Heun, Reiner"],["dc.contributor.author","Frölich, Lutz"],["dc.contributor.author","Hüll, Michael"],["dc.contributor.author","Buscemi, Lara"],["dc.contributor.author","Herms, Stefan"],["dc.contributor.author","Kölsch, Heike"],["dc.contributor.author","Scheltens, Philip"],["dc.contributor.author","Breteler, Monique M."],["dc.contributor.author","Rüther, Eckart"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Goate, Alison"],["dc.contributor.author","Jessen, Frank"],["dc.contributor.author","Maier, Wolfgang"],["dc.contributor.author","Heneka, Michael T."],["dc.contributor.author","Becker, Tim"],["dc.contributor.author","Nöthen, Markus M."],["dc.date.accessioned","2017-09-07T11:44:26Z"],["dc.date.available","2017-09-07T11:44:26Z"],["dc.date.issued","2014"],["dc.description.abstract","Alzheimer’s disease (AD) is a complex disorder in which severalpathways contribute to pathology and clinical phenotype. Delineationof each pathological pathway and identification of thefactors which modulate them are crucial for the developmentof effective treatment. Information on individual pathologicalpathways is provided by biomarkers. In AD, cerebrospinalfluid (CSF) levels of Ab1–42 and phosphorylated Tau (pTau)reflect cerebral amyloid deposition and tau-related neurodegeneration,respectively. However, many of the biological factorsthat influence these core AD pathways remain elusive.Research has shown that AD risk genes contribute to CSFmarker variance (1–4). However, genes may also exist thataffect CSF markers without conferring disease susceptibility.These genes may be promising candidates for modulation ofthe disease process.The aim of the present study was to identify genetic factorsrelated to heterogeneity in pathological pathways involved inamyloid deposition and tau-related neurodegeneration—asmanifested through CSF Ab1–42 and pTau levels—and whichmight influence the clinical course of AD. To achieve this, weperformed a four-step investigation involving analysis andmeta-analysis of data from genome-wide association studies(GWASs) of these two CSF biomarkers; replication of our topfindings in an independent sample; and specific analyses andfunctional experiments to follow-up promising findings. In contrastto previous GWAS of CSF biomarkers (1,4,5), the presentGWAS was restricted to patients with dementia secondary toAD only in order to enrich for genetic effects occurring afterdisease onset."],["dc.identifier.doi","10.1093/hmg/ddu372"],["dc.identifier.gro","3151650"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8467"],["dc.language.iso","en"],["dc.notes.status","public"],["dc.notes.submitter","chake"],["dc.relation.issn","1460-2083"],["dc.title","SUCLG2 identified as both a determinator of CSF Aβ1–42 levels and an attenuator of cognitive decline in Alzheimer's disease"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","593"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Epigenomics"],["dc.bibliographiccitation.lastpage","598"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Bey, Katharina"],["dc.contributor.author","Wolfsgruber, Steffen"],["dc.contributor.author","Karaca, Ilker"],["dc.contributor.author","Wagner, Holger"],["dc.contributor.author","Lardenoije, Roy"],["dc.contributor.author","Becker, Julian"],["dc.contributor.author","Milz, Esther"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Peters, Oliver"],["dc.contributor.author","Frölich, Lutz"],["dc.contributor.author","Hüll, Michael"],["dc.contributor.author","Rüther, Eckart"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Riedel-Heller, Steffi"],["dc.contributor.author","Scherer, Martin"],["dc.contributor.author","Jessen, Frank"],["dc.contributor.author","Maier, Wolfgang"],["dc.contributor.author","van den Hove, Daniel L."],["dc.contributor.author","Rutten, Bart P. F."],["dc.contributor.author","Wagner, Michael"],["dc.contributor.author","Ramirez, Alfredo"],["dc.date.accessioned","2017-09-07T11:44:25Z"],["dc.date.available","2017-09-07T11:44:25Z"],["dc.date.issued","2016"],["dc.description.abstract","Alterations in DNA methylation have been associated with cognitive decline and Alzheimer's disease. A recent study of mild cognitive impairment (MCI) reported a significant association between annual decline in cognitive function and the rs11887120 SNP located in DNMT3A, a gene implicated in DNA methylation. Here, we aimed to replicate this finding in two independent MCI cohorts (n = 1024); however, no significant association was observed in either cohort or the pooled dataset. In stratified analyses for conversion to Alzheimer's disease status, no association between rs11887120 and cognitive decline was observed in either converters or nonconverters. In conclusion, our analyses provide no support for the hypothesis that genetic variants in DNMT3A are implicated in cognitive performance decline in individuals with MCI."],["dc.identifier.doi","10.2217/epi-2015-0014"],["dc.identifier.gro","3151644"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8460"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","chake"],["dc.relation.issn","1750-1911"],["dc.title","No association of the variant rs11887120 in DNMT3A with cognitive decline in individuals with mild cognitive impairment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","E3"],["dc.bibliographiccitation.issue","7545"],["dc.bibliographiccitation.journal","Nature"],["dc.bibliographiccitation.lastpage","E5"],["dc.bibliographiccitation.volume","520"],["dc.contributor.author","Heilmann, Stefanie"],["dc.contributor.author","Drichel, Dmitriy"],["dc.contributor.author","Clarimon, Jordi"],["dc.contributor.author","Fernández, Victoria"],["dc.contributor.author","Lacour, André"],["dc.contributor.author","Wagner, Holger"],["dc.contributor.author","Thelen, Mathias"],["dc.contributor.author","Hernández, Isabel"],["dc.contributor.author","Fortea, Juan"],["dc.contributor.author","Alegret, Montserrat"],["dc.contributor.author","Blesa, Rafael"],["dc.contributor.author","Mauleón, Ana"],["dc.contributor.author","Roca, Maitée Rosende"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Peters, Oliver"],["dc.contributor.author","Heun, Reinhard"],["dc.contributor.author","Frölich, Lutz"],["dc.contributor.author","Hüll, Michael"],["dc.contributor.author","Heneka, Michael T."],["dc.contributor.author","Rüther, Eckart"],["dc.contributor.author","Riedel-Heller, Steffi"],["dc.contributor.author","Scherer, Martin"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Jessen, Frank"],["dc.contributor.author","Becker, Tim"],["dc.contributor.author","Tárraga, Lluís"],["dc.contributor.author","Boada, Mercè"],["dc.contributor.author","Maier, Wolfgang"],["dc.contributor.author","Lleó, Alberto"],["dc.contributor.author","Ruiz, Agustin"],["dc.contributor.author","Nöthen, Markus M."],["dc.contributor.author","Ramirez, Alfredo"],["dc.date.accessioned","2017-09-07T11:44:27Z"],["dc.date.available","2017-09-07T11:44:27Z"],["dc.date.issued","2015"],["dc.description.abstract","Interest in the role of rare genetic variants in the aetiology of complex diseases such as Alzheimer's disease is increasing1,2. Recently, Cruchaga et al.3 provided evidence supporting the role of rare variants in the phospholipase D3 (PLD3) gene in both familial late-onset Alzheimer's disease (age at onset >65 years) and in non-familial Alzheimer's disease. In a follow-up study of 3,568 non-familial Alzheimer's disease cases and 3,867 controls of German or Spanish descent, we failed to replicate the latter finding. Our results therefore cast doubt on the aetiological relevance of rare coding PLD3 variants in non-familial Alzheimer's disease."],["dc.identifier.doi","10.1038/nature14039"],["dc.identifier.gro","3151672"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8490"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","chake"],["dc.relation.issn","0028-0836"],["dc.title","PLD3 in non-familial Alzheimer's disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1663"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Alzheimer's Disease"],["dc.bibliographiccitation.lastpage","1678"],["dc.bibliographiccitation.volume","88"],["dc.contributor.author","Polcher, Alexandra"],["dc.contributor.author","Wolfsgruber, Steffen"],["dc.contributor.author","Peters, Oliver"],["dc.contributor.author","Frölich, Lutz"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Hüll, Michael"],["dc.contributor.author","Rüther, Eckart"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Maier, Wolfgang"],["dc.contributor.author","Wagner, Michael"],["dc.date.accessioned","2022-09-01T09:51:05Z"],["dc.date.available","2022-09-01T09:51:05Z"],["dc.date.issued","2022"],["dc.description.abstract","Background: Consideration of many tests from different cognitive domains in defining mild cognitive impairment (MCI) is clinical routine, but guidelines for a neuropsychological operationalization of MCI are lacking. Objective: Among different operational MCI criteria, to identify those which are best in predicting either conversion to dementia, or a biomarker profile indicative for Alzheimer’s disease (AD). Methods: Memory clinic patients without dementia (N = 558; mean age = 66; up to 3 years of follow-up; n = 360 with baseline CSF biomarkers) were included in an observational study using most liberal criteria of cognitive impairment. Four operational definitions of MCI were retrospectively applied: 1) amnestic MCI (CERAD word list delayed recall), 2) CERAD total score, 3) comprehensive criteria and 4) base rate corrected CERAD. We compared their accuracy in predicting incident all-cause dementia or AD dementia within three years, or a concurrent CSF Aβ42/tau-ratio indicative of AD. Results: The four definitions overlapped considerably, classified 35–58% of the original sample as impaired and were associated with markedly increased PPVs regarding incident all-cause dementia (39–46% versus 26% of the original sample), AD dementia and AD biomarker positivity. The base rate corrected MCI definition had the highest prognostic accuracy. Conclusion: he operational criteria examined seem suitable to specify MCI in memory clinic settings, as they identify subjects at high risk of clinical progression. Depending on the neuropsychological battery in use, one or several of these criteria could help to calibrate the clinical judgment of test results, reduce false-positive decisions, and define risk-enriched groups for clinical trials."],["dc.identifier.doi","10.3233/JAD-215548"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113879"],["dc.notes.intern","DOI-Import GROB-597"],["dc.relation.eissn","1875-8908"],["dc.relation.issn","1387-2877"],["dc.title","A Comparison of Operational Definitions for Mild Cognitive Impairment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Alzheimer's Research & Therapy"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Morgen, Katrin"],["dc.contributor.author","Schneider, Michael"],["dc.contributor.author","Frölich, Lutz"],["dc.contributor.author","Tost, Heike"],["dc.contributor.author","Plichta, Michael M."],["dc.contributor.author","Kölsch, Heike"],["dc.contributor.author","Rakebrandt, Fabian"],["dc.contributor.author","Rienhoff, Otto"],["dc.contributor.author","Jessen, Frank"],["dc.contributor.author","Peters, Oliver"],["dc.contributor.author","Jahn, Holger"],["dc.contributor.author","Luckhaus, Christian"],["dc.contributor.author","Hüll, Michael"],["dc.contributor.author","Gertz, Hermann-Josef"],["dc.contributor.author","Schröder, Johannes"],["dc.contributor.author","Hampel, Harald"],["dc.contributor.author","Teipel, Stefan J."],["dc.contributor.author","Pantel, Johannes"],["dc.contributor.author","Heuser, Isabella"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Rüther, Eckart"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Maier, Wolfgang"],["dc.contributor.author","Meyer-Lindenberg, Andreas"],["dc.date.accessioned","2017-09-07T11:44:26Z"],["dc.date.available","2017-09-07T11:44:26Z"],["dc.date.issued","2015"],["dc.description.abstract","ntroductionWhite matter (WM) magnetic resonance imaging (MRI) hyperintensities are common in Alzheimer’s disease (AD), but their pathophysiological relevance and relationship to genetic factors are unclear. In the present study, we investigated potential apolipoprotein E (APOE)-dependent effects on the extent and cognitive impact of WM hyperintensities in patients with AD.MethodsWM hyperintensity volume on fluid-attenuated inversion recovery images of 201 patients with AD (128 carriers and 73 non-carriers of the APOE ε4 risk allele) was determined globally as well as regionally with voxel-based lesion mapping. Clinical, neuropsychological and MRI data were collected from prospective multicenter trials conducted by the German Dementia Competence Network.ResultsWM hyperintensity volume was significantly greater in non-carriers of the APOE ε4 allele. Lesion distribution was similar among ε4 carriers and non-carriers. Only ε4 non-carriers showed a correlation between lesion volume and cognitive performance.ConclusionThe current findings indicate an increased prevalence of WM hyperintensities in non-carriers compared with carriers of the APOE ε4 allele among patients with AD. This is consistent with a possibly more pronounced contribution of heterogeneous vascular risk factors to WM damage and cognitive impairment in patients with AD without APOE ε4-mediated risk."],["dc.identifier.doi","10.1186/s13195-015-0111-8"],["dc.identifier.gro","3151652"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8469"],["dc.language.iso","en"],["dc.notes.status","public"],["dc.notes.submitter","chake"],["dc.relation.issn","1758-9193"],["dc.title","Apolipoprotein E-dependent load of white matter hyperintensities in Alzheimer’s disease: a voxel-based lesion mapping study"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1025"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","1044"],["dc.bibliographiccitation.volume","139"],["dc.contributor.author","Kleineidam, Luca"],["dc.contributor.author","Chouraki, Vincent"],["dc.contributor.author","Próchnicki, Tomasz"],["dc.contributor.author","van der Lee, Sven J."],["dc.contributor.author","Madrid-Márquez, Laura"],["dc.contributor.author","Wagner-Thelen, Holger"],["dc.contributor.author","Karaca, Ilker"],["dc.contributor.author","Weinhold, Leonie"],["dc.contributor.author","Wolfsgruber, Steffen"],["dc.contributor.author","Boland, Anne"],["dc.contributor.author","Martino Adami, Pamela V."],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Popp, Julius"],["dc.contributor.author","Brosseron, Frederic"],["dc.contributor.author","Jansen, Iris E."],["dc.contributor.author","Hulsman, Marc"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Peters, Oliver"],["dc.contributor.author","Berr, Claudine"],["dc.contributor.author","Heun, Reinhard"],["dc.contributor.author","Frölich, Lutz"],["dc.contributor.author","Tzourio, Christophe"],["dc.contributor.author","Dartigues, Jean-François"],["dc.contributor.author","Hüll, Michael"],["dc.contributor.author","Espinosa, Ana"],["dc.contributor.author","Hernández, Isabel"],["dc.contributor.author","de Rojas, Itziar"],["dc.contributor.author","Orellana, Adelina"],["dc.contributor.author","Valero, Sergi"],["dc.contributor.author","Stringa, Najada"],["dc.contributor.author","van Schoor, Natasja M."],["dc.contributor.author","Huisman, Martijn"],["dc.contributor.author","Scheltens, Philip"],["dc.contributor.author","Rüther, Eckart"],["dc.contributor.author","Deleuze, Jean-Francois"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Tarraga, Lluis"],["dc.contributor.author","Schmid, Matthias"],["dc.contributor.author","Scherer, Martin"],["dc.contributor.author","Riedel-Heller, Steffi"],["dc.contributor.author","Heneka, Michael T."],["dc.contributor.author","Amouyel, Philippe"],["dc.contributor.author","Jessen, Frank"],["dc.contributor.author","Boada, Merce"],["dc.contributor.author","Maier, Wolfgang"],["dc.contributor.author","Schneider, Anja"],["dc.contributor.author","González-Pérez, Antonio"],["dc.contributor.author","van der Flier, Wiesje M."],["dc.contributor.author","Wagner, Michael"],["dc.contributor.author","Lambert, Jean-Charles"],["dc.contributor.author","Holstege, Henne"],["dc.contributor.author","Sáez, Mª Eugenia"],["dc.contributor.author","Latz, Eicke"],["dc.contributor.author","Ruiz, Agustin"],["dc.contributor.author","Ramirez, Alfredo"],["dc.date.accessioned","2020-12-10T14:10:28Z"],["dc.date.available","2020-12-10T14:10:28Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1007/s00401-020-02138-6"],["dc.identifier.eissn","1432-0533"],["dc.identifier.issn","0001-6322"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/70767"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","PLCG2 protective variant p.P522R modulates tau pathology and disease progression in patients with mild cognitive impairment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","939"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Alzheimer's Disease"],["dc.bibliographiccitation.lastpage","950"],["dc.bibliographiccitation.volume","58"],["dc.contributor.author","Wolfsgruber, Steffen"],["dc.contributor.author","Polcher, Alexandra"],["dc.contributor.author","Koppara, Alexander"],["dc.contributor.author","Kleineidam, Luca"],["dc.contributor.author","Frölich, Lutz"],["dc.contributor.author","Peters, Oliver"],["dc.contributor.author","Hüll, Michael"],["dc.contributor.author","Rüther, Eckart"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Maier, Wolfgang"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Jessen, Frank"],["dc.contributor.author","Wagner, Michael"],["dc.contributor.editor","Tales, Andrea"],["dc.date.accessioned","2020-12-10T18:44:10Z"],["dc.date.available","2020-12-10T18:44:10Z"],["dc.date.issued","2017"],["dc.description.abstract","Background: There is very limited data on the prevalence of abnormal cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and their predictive value for clinical progression in memory clinic patients with subjective cognitive decline (SCD). Objective: To assess the frequency of abnormal CSF biomarkers of AD and their predictive value for clinical progression in memory clinic patients with SCD in comparison to patients with mild cognitive impairment (MCI) from the same cohort. Methods: We analyzed prospective data from memory clinic patients of the German Competence Network Dementia cohort with a baseline diagnosis of SCD (n = 82) or MCI (n = 134), distinguished by actuarial neuropsychological MCI criteria (\" Jak-Bondi criteria\"). Risk of clinical progression during 3-year follow-up was evaluated with Cox-Proportional-Hazard models. Results: Prevalence of abnormal values in CSF markers of tau-mediated neurodegeneration (67.8% versus 46.3%) but not of amyloid deposition (40.3% versus 35.4%) was significantly higher in MCI compared to SCD. The rate of incident AD dementia (26.1% versus 12.2%) was also significantly higher in MCI. In SCD, additional 22% progressed to MCI during follow-up. Combined amyloid/tau abnormality was the strongest predictor of clinical progression in both groups. Conclusion: High prevalence of biomarker abnormality and clinical progression, together with the predictive value of CSF biomarkers, in memory clinic patients with SCD support the validity and usefulness of this condition as a \"pre-MCI\" at risk stage of AD."],["dc.identifier.doi","10.3233/JAD-161252"],["dc.identifier.eissn","1875-8908"],["dc.identifier.isi","000402995800029"],["dc.identifier.issn","1387-2877"],["dc.identifier.pmid","28527210"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78354"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Ios Press"],["dc.relation.issn","1875-8908"],["dc.relation.issn","1387-2877"],["dc.title","Cerebrospinal Fluid Biomarkers and Clinical Progression in Patients with Subjective Cognitive Decline and Mild Cognitive Impairment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","547"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Alzheimer's Disease"],["dc.bibliographiccitation.lastpage","560"],["dc.bibliographiccitation.volume","49"],["dc.contributor.author","Koppara, Alexander"],["dc.contributor.author","Wolfsgruber, Steffen"],["dc.contributor.author","Kleineidam, Luca"],["dc.contributor.author","Schmidtke, Klaus"],["dc.contributor.author","Frölich, Lutz"],["dc.contributor.author","Kurz, Alexander"],["dc.contributor.author","Schulz, Stefanie"],["dc.contributor.author","Hampel, Harald"],["dc.contributor.author","Heuser, Isabella"],["dc.contributor.author","Peters, Oliver"],["dc.contributor.author","Reischies, Friedel M."],["dc.contributor.author","Jahn, Holger"],["dc.contributor.author","Luckhaus, Christian"],["dc.contributor.author","Hüll, Michael"],["dc.contributor.author","Gertz, Hermann-Josef"],["dc.contributor.author","Schröder, Johannes"],["dc.contributor.author","Pantel, Johannes"],["dc.contributor.author","Rienhoff, Otto"],["dc.contributor.author","Rüther, Eckart"],["dc.contributor.author","Henn, Fritz"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Maier, Wolfgang"],["dc.contributor.author","Jessen, Frank"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Wagner, Michael"],["dc.date.accessioned","2017-09-07T11:44:26Z"],["dc.date.available","2017-09-07T11:44:26Z"],["dc.date.issued","2016"],["dc.description.abstract","Background:The recently proposed latent variable δ is a new tool for dementia case finding. It is built in a structural equation modeling framework of cognitive and functional data and constitutes a novel endophenotype for Alzheimer’s disease (AD) research and clinical trials. Objective:To investigate the association of δ with AD biomarkers and to compare the prediction of δ with established scales for conversion to dementia in patients with mild cognitive impairment (MCI). Methods:Using data from a multicenter memory clinic study, we examined the external associations of the latent variable δ and compared δ with well-established cognitive and functional scales and cognitive-functional composite scores. For that purpose, logistic regressions with cerebrospinal fluid (CSF) biomarkers and conversion to dementia as dependent variables were performed with the investigated scores. The models were tested for significant differences. Results:In patients with MCI, δ based on a broad range of cognitive scales (including the ADAS-cog, the MMSE, and the CERAD neuropsychological battery) predicted an abnormal CSF Aβ42/tau ratio indicative of AD (n = 340, AUC = 0.78, p <  0.001), and predicted incident dementia within 1–3 years of follow-up (n = 525, AUC = 0.84, p <  0.001). These associations were generally stronger than for any other scale or cognitive-functional composite examined. Homologs of δ based on reduced test batteries yielded somewhat lower effects. Conclusion:These findings support the interpretation of δ as a construct capturing the disease-related “essence” of cognitive and functional impairments in patients with MCI and dementia, and suggest that δ might become an analytical tool for dementia research."],["dc.identifier.doi","10.3233/jad-150257"],["dc.identifier.gro","3151655"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8471"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","chake"],["dc.relation.issn","1387-2877"],["dc.title","The Latent Dementia Phenotype δ is Associated with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease and Predicts Conversion to Dementia in Subjects with Mild Cognitive Impairment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","84"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Alzheimer's Research & Therapy"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Frölich, Lutz"],["dc.contributor.author","Peters, Oliver"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Gruber, Oliver"],["dc.contributor.author","Teipel, Stefan J."],["dc.contributor.author","Gertz, Hermann J."],["dc.contributor.author","Jahn, Holger"],["dc.contributor.author","Jessen, Frank"],["dc.contributor.author","Kurz, Alexander"],["dc.contributor.author","Luckhaus, Christian"],["dc.contributor.author","Hüll, Michael"],["dc.contributor.author","Pantel, Johannes"],["dc.contributor.author","Reischies, Friedel M."],["dc.contributor.author","Schröder, Johannes"],["dc.contributor.author","Wagner, Michael"],["dc.contributor.author","Rienhoff, Otto"],["dc.contributor.author","Wolf, Stefanie"],["dc.contributor.author","Bauer, Chris"],["dc.contributor.author","Schuchhardt, Johannes"],["dc.contributor.author","Heuser, Isabella"],["dc.contributor.author","Rüther, Eckart"],["dc.contributor.author","Henn, Fritz"],["dc.contributor.author","Maier, Wolfgang"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Kornhuber, Johannes"],["dc.date.accessioned","2020-12-10T18:39:07Z"],["dc.date.available","2020-12-10T18:39:07Z"],["dc.date.issued","2017"],["dc.description.abstract","Abstract Background The progression of mild cognitive impairment (MCI) to Alzheimer’s disease (AD) dementia can be predicted by cognitive, neuroimaging, and cerebrospinal fluid (CSF) markers. Since most biomarkers reveal complementary information, a combination of biomarkers may increase the predictive power. We investigated which combination of the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR)-sum-of-boxes, the word list delayed free recall from the Consortium to Establish a Registry of Dementia (CERAD) test battery, hippocampal volume (HCV), amyloid-beta1–42 (Aβ42), amyloid-beta1–40 (Aβ40) levels, the ratio of Aβ42/Aβ40, phosphorylated tau, and total tau (t-Tau) levels in the CSF best predicted a short-term conversion from MCI to AD dementia. Methods We used 115 complete datasets from MCI patients of the “Dementia Competence Network”, a German multicenter cohort study with annual follow-up up to 3 years. MCI was broadly defined to include amnestic and nonamnestic syndromes. Variables known to predict progression in MCI patients were selected a priori. Nine individual predictors were compared by receiver operating characteristic (ROC) curve analysis. ROC curves of the five best two-, three-, and four-parameter combinations were analyzed for significant superiority by a bootstrapping wrapper around a support vector machine with linear kernel. The incremental value of combinations was tested for statistical significance by comparing the specificities of the different classifiers at a given sensitivity of 85%. Results Out of 115 subjects, 28 (24.3%) with MCI progressed to AD dementia within a mean follow-up period of 25.5 months. At baseline, MCI-AD patients were no different from stable MCI in age and gender distribution, but had lower educational attainment. All single biomarkers were significantly different between the two groups at baseline. ROC curves of the individual predictors gave areas under the curve (AUC) between 0.66 and 0.77, and all single predictors were statistically superior to Aβ40. The AUC of the two-parameter combinations ranged from 0.77 to 0.81. The three-parameter combinations ranged from AUC 0.80–0.83, and the four-parameter combination from AUC 0.81–0.82. None of the predictor combinations was significantly superior to the two best single predictors (HCV and t-Tau). When maximizing the AUC differences by fixing sensitivity at 85%, the two- to four-parameter combinations were superior to HCV alone. Conclusion A combination of two biomarkers of neurodegeneration (e.g., HCV and t-Tau) is not superior over the single parameters in identifying patients with MCI who are most likely to progress to AD dementia, although there is a gradual increase in the statistical measures across increasing biomarker combinations. This may have implications for clinical diagnosis and for selecting subjects for participation in clinical trials."],["dc.identifier.doi","10.1186/s13195-017-0301-7"],["dc.identifier.eissn","1758-9193"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15155"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77546"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","In goescholar not merged with http://resolver.sub.uni-goettingen.de/purl?gs-1/16989 but duplicate"],["dc.publisher","BioMed Central"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)."],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Incremental value of biomarker combinations to predict progression of mild cognitive impairment to Alzheimer’s dementia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]