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Incremental value of biomarker combinations to predict progression of mild cognitive impairment to Alzheimer’s dementia

Overview of attention for article published in Alzheimer's Research & Therapy, October 2017
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4 tweeters

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51 Dimensions

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160 Mendeley
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Title
Incremental value of biomarker combinations to predict progression of mild cognitive impairment to Alzheimer’s dementia
Published in
Alzheimer's Research & Therapy, October 2017
DOI 10.1186/s13195-017-0301-7
Pubmed ID
Authors

Lutz Frölich, Oliver Peters, Piotr Lewczuk, Oliver Gruber, Stefan J. Teipel, Hermann J. Gertz, Holger Jahn, Frank Jessen, Alexander Kurz, Christian Luckhaus, Michael Hüll, Johannes Pantel, Friedel M. Reischies, Johannes Schröder, Michael Wagner, Otto Rienhoff, Stefanie Wolf, Chris Bauer, Johannes Schuchhardt, Isabella Heuser, Eckart Rüther, Fritz Henn, Wolfgang Maier, Jens Wiltfang, Johannes Kornhuber

Abstract

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. 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%. 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. 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.

Twitter Demographics

The data shown below were collected from the profiles of 4 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 160 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 160 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 29 18%
Researcher 26 16%
Student > Bachelor 19 12%
Student > Ph. D. Student 16 10%
Other 9 6%
Other 25 16%
Unknown 36 23%
Readers by discipline Count As %
Medicine and Dentistry 34 21%
Psychology 21 13%
Neuroscience 16 10%
Biochemistry, Genetics and Molecular Biology 6 4%
Agricultural and Biological Sciences 5 3%
Other 25 16%
Unknown 53 33%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 October 2017.
All research outputs
#14,083,124
of 23,005,189 outputs
Outputs from Alzheimer's Research & Therapy
#1,101
of 1,241 outputs
Outputs of similar age
#173,151
of 324,392 outputs
Outputs of similar age from Alzheimer's Research & Therapy
#13
of 21 outputs
Altmetric has tracked 23,005,189 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,241 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 26.0. This one is in the 11th percentile – i.e., 11% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 324,392 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 21 others from the same source and published within six weeks on either side of this one. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.