The EMIF-AD Multimodal Biomarker Discovery study: design, methods and cohort characteristics.

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State: Public
Version: Final published version
Serval ID
serval:BIB_9FCF3DBEDCFC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The EMIF-AD Multimodal Biomarker Discovery study: design, methods and cohort characteristics.
Journal
Alzheimer's research & therapy
Author(s)
Bos I., Vos S., Vandenberghe R., Scheltens P., Engelborghs S., Frisoni G., Molinuevo J.L., Wallin A., Lleó A., Popp J., Martinez-Lage P., Baird A., Dobson R., Legido-Quigley C., Sleegers K., Van Broeckhoven C., Bertram L., Ten Kate M., Barkhof F., Zetterberg H., Lovestone S., Streffer J., Visser P.J.
ISSN
1758-9193 (Electronic)
Publication state
Published
Issued date
06/07/2018
Peer-reviewed
Oui
Volume
10
Number
1
Pages
64
Language
english
Notes
Publication types: Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
There is an urgent need for novel, noninvasive biomarkers to diagnose Alzheimer's disease (AD) in the predementia stages and to predict the rate of decline. Therefore, we set up the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study. In this report we describe the design of the study, the methods used and the characteristics of the participants.
Participants were selected from existing prospective multicenter and single-center European studies. Inclusion criteria were having normal cognition (NC) or a diagnosis of mild cognitive impairment (MCI) or AD-type dementia at baseline, age above 50 years, known amyloid-beta (Aβ) status, availability of cognitive test results and at least two of the following materials: plasma, DNA, magnetic resonance imaging (MRI) or cerebrospinal fluid (CSF). Targeted and untargeted metabolomic and proteomic analyses were performed in plasma, and targeted and untargeted proteomics were performed in CSF. Genome-wide SNP genotyping, next-generation sequencing and methylation profiling were conducted in DNA. Visual rating and volumetric measures were assessed on MRI. Baseline characteristics were analyzed using ANOVA or chi-square, rate of decline analyzed by linear mixed modeling.
We included 1221 individuals (NC n = 492, MCI n = 527, AD-type dementia n = 202) with a mean age of 67.9 (SD 8.3) years. The percentage Aβ+ was 26% in the NC, 58% in the MCI, and 87% in the AD-type dementia groups. Plasma samples were available for 1189 (97%) subjects, DNA samples for 929 (76%) subjects, MRI scans for 862 (71%) subjects and CSF samples for 767 (63%) subjects. For 759 (62%) individuals, clinical follow-up data were available. In each diagnostic group, the APOE ε4 allele was more frequent amongst Aβ+ individuals (p < 0.001). Only in MCI was there a difference in baseline Mini Mental State Examination (MMSE) score between the A groups (p < 0.001). Aβ+ had a faster rate of decline on the MMSE during follow-up in the NC (p < 0.001) and MCI (p < 0.001) groups.
The characteristics of this large cohort of elderly subjects at various cognitive stages confirm the central roles of Aβ and APOE ε4 in AD pathogenesis. The results of the multimodal analyses will provide new insights into underlying mechanisms and facilitate the discovery of new diagnostic and prognostic AD biomarkers. All researchers can apply for access to the EMIF-AD MBD data by submitting a research proposal via the EMIF-AD Catalog.
Keywords
Aged, Aged, 80 and over, Alzheimer Disease/blood, Alzheimer Disease/diagnosis, Amyloid beta-Peptides/blood, Biomarkers/blood, Biomedical Research/methods, Chitinase-3-Like Protein 1/blood, Cognitive Dysfunction, Cohort Studies, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neurofilament Proteins/blood, Neurogranin/blood, Neuropsychological Tests, Psychiatric Status Rating Scales, Research Design, Alzheimer’s disease, Biomarkers, Cerebrospinal fluid, DNA, Genomics, Magnetic resonance imaging, Metabolomics, Multimodal, Plasma, Proteomics
Pubmed
Web of science
Open Access
Yes
Create date
10/07/2018 13:45
Last modification date
20/08/2019 15:06
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