eprintid: 23593
rev_number: 12
eprint_status: archive
userid: 1589
dir: disk0/00/02/35/93
datestamp: 2017-10-23 07:49:42
lastmod: 2024-04-27 22:39:32
status_changed: 2017-10-23 07:49:42
type: article
metadata_visibility: show
creators_name: Frölich, Lutz
creators_name: Peters, Oliver
creators_name: Lewczuk, Piotr
creators_name: Gruber, Oliver
creators_name: Teipel, Stefan J.
creators_name: Gertz, Hermann J.
creators_name: Jahn, Holger
creators_name: Jessen, Frank
creators_name: Kurz, Alexander
creators_name: Luckhaus, Christian
creators_name: Hüll, Michael
creators_name: Pantel, Johannes
creators_name: Reischies, Friedel M.
creators_name: Schröder, Johannes
creators_name: Wagner, Michael
creators_name: Rienhoff, Otto
creators_name: Wolf, Stefanie
creators_name: Bauer, Chris
creators_name: Schuchhardt, Johannes
creators_name: Heuser, Isabella
creators_name: Rüther, Eckart
creators_name: Henn, Fritz
creators_name: Maier, Wolfgang
creators_name: Wiltfang, Jens
creators_name: Kornhuber, Johannes
title: Incremental value of biomarker combinations to predict progression of mild cognitive impairment to Alzheimer’s dementia
subjects: 610
divisions: 851200
divisions: 910600
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.
date: 2017
publisher: Biomed Central
id_scheme: DOI
ppn_swb: 1657068595
own_urn: urn:nbn:de:bsz:16-heidok-235936
language: eng
bibsort: FROLICHLUTINCREMENTA2017
full_text_status: public
publication: Alzheimer's Research & Therapy
volume: 9
number: 84
place_of_pub: London
pagerange: 1-15
issn: 1758-9193
citation:   Frölich, Lutz ; Peters, Oliver ; Lewczuk, Piotr ; Gruber, Oliver ; Teipel, Stefan J. ; Gertz, Hermann J. ; Jahn, Holger ; Jessen, Frank ; Kurz, Alexander ; Luckhaus, Christian ; Hüll, Michael ; Pantel, Johannes ; Reischies, Friedel M. ; Schröder, Johannes ; Wagner, Michael ; Rienhoff, Otto ; Wolf, Stefanie ; Bauer, Chris ; Schuchhardt, Johannes ; Heuser, Isabella ; Rüther, Eckart ; Henn, Fritz ; Maier, Wolfgang ; Wiltfang, Jens ; Kornhuber, Johannes  (2017) Incremental value of biomarker combinations to predict progression of mild cognitive impairment to Alzheimer’s dementia.  Alzheimer's Research & Therapy, 9 (84).  pp. 1-15.  ISSN 1758-9193     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/23593/1/13195_2017_Article_301.pdf