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Blood-based multivariate methylation risk score for cognitive impairment and dementia

Abstract INTRODUCTION The established link between DNA methylation and pathophysiology of dementia, along with its potential role as a molecular mediator of lifestyle and environmental influences, positions blood-derived DNA methylation as a promising tool for early dementia risk detection. METHODS...

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Hauptverfasser: Koetsier, Jarno (VerfasserIn) , Cavill, Rachel (VerfasserIn) , Reijnders, Rick (VerfasserIn) , Harvey, Joshua (VerfasserIn) , Homann, Jan (VerfasserIn) , Kouhsar, Morteza (VerfasserIn) , Deckers, Kay (VerfasserIn) , Köhler, Sebastian (VerfasserIn) , Eijssen, Lars M. T. (VerfasserIn) , van den Hove, Daniel L. A. (VerfasserIn) , Demuth, Ilja (VerfasserIn) , Düzel, Sandra (VerfasserIn) , for, the Alzheimer's Disease Neuroimaging Initiative (VerfasserIn) , Smith, Rebecca G. (VerfasserIn) , Smith, Adam R. (VerfasserIn) , Burrage, Joe (VerfasserIn) , Walker, Emma M. (VerfasserIn) , Shireby, Gemma (VerfasserIn) , Hannon, Eilis (VerfasserIn) , Dempster, Emma (VerfasserIn) , Frayling, Tim (VerfasserIn) , Mill, Jonathan (VerfasserIn) , Dobricic, Valerija (VerfasserIn) , Johannsen, Peter (VerfasserIn) , Wittig, Michael (VerfasserIn) , Franke, Andre (VerfasserIn) , Vandenberghe, Rik (VerfasserIn) , Schaeverbeke, Jolien (VerfasserIn) , Freund-Levi, Yvonne (VerfasserIn) , Frölich, Lutz (VerfasserIn) , Scheltens, Philip (VerfasserIn) , Teunissen, Charlotte E. (VerfasserIn) , Frisoni, Giovanni (VerfasserIn) , Blin, Olivier (VerfasserIn) , Richardson, Jill C. (VerfasserIn) , Bordet, Régis (VerfasserIn) , Engelborghs, Sebastiaan (VerfasserIn) , de Roeck, Ellen (VerfasserIn) , Martinez-Lage, Pablo (VerfasserIn) , Tainta, Mikel (VerfasserIn) , Lleó, Alberto (VerfasserIn) , Sala, Isabel (VerfasserIn) , Popp, Julius (VerfasserIn) , Peyratout, Gwendoline (VerfasserIn) , Verhey, Frans (VerfasserIn) , Tsolaki, Magda (VerfasserIn) , Andreasson, Ulf (VerfasserIn) , Blennow, Kaj (VerfasserIn) , Zetterberg, Henrik (VerfasserIn) , Streffer, Johannes (VerfasserIn) , Vos, Stephanie J. B. (VerfasserIn) , Lovestone, Simon (VerfasserIn) , Visser, Pieter-Jelle (VerfasserIn) , Lill, Christina M. (VerfasserIn) , Bertram, Lars (VerfasserIn) , Lunnon, Katie (VerfasserIn) , Pishva, Ehsan (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: October 2024
In: Alzheimer's and dementia
Year: 2024, Jahrgang: 20, Heft: 10, Pages: 6682-6698
ISSN:1552-5279
DOI:10.1002/alz.14061
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/alz.14061
Verlag, kostenfrei, Volltext: http://alz.journals.onlinelibrary.wiley.com/doi/10.1002/alz.14061
Volltext
Verfasserangaben:Jarno Koetsier, Rachel Cavill, Rick Reijnders, Joshua Harvey, Jan Homann, Morteza Kouhsar, Kay Deckers, Sebastian Köhler, Lars M.T. Eijssen, Daniel L.A. van den Hove, Ilja Demuth, Sandra Düzel, for the Alzheimer's Disease Neuroimaging Initiative, Rebecca G. Smith, Adam R. Smith, Joe Burrage, Emma M. Walker, Gemma Shireby, Eilis Hannon, Emma Dempster, Tim Frayling, Jonathan Mill, Valerija Dobricic, Peter Johannsen, Michael Wittig, Andre Franke, Rik Vandenberghe, Jolien Schaeverbeke, Yvonne Freund-Levi, Lutz Frölich, Philip Scheltens, Charlotte E. Teunissen, Giovanni Frisoni, Olivier Blin, Jill C. Richardson, Régis Bordet, Sebastiaan Engelborghs, Ellen de Roeck, Pablo Martinez-Lage, Mikel Tainta, Alberto Lleó, Isabel Sala, Julius Popp, Gwendoline Peyratout, Frans Verhey, Magda Tsolaki, Ulf Andreasson, Kaj Blennow, Henrik Zetterberg, Johannes Streffer, Stephanie J.B. Vos, Simon Lovestone, Pieter-Jelle Visser, Christina M. Lill, Lars Bertram, Katie Lunnon, Ehsan Pishva

MARC

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245 1 0 |a Blood-based multivariate methylation risk score for cognitive impairment and dementia  |c Jarno Koetsier, Rachel Cavill, Rick Reijnders, Joshua Harvey, Jan Homann, Morteza Kouhsar, Kay Deckers, Sebastian Köhler, Lars M.T. Eijssen, Daniel L.A. van den Hove, Ilja Demuth, Sandra Düzel, for the Alzheimer's Disease Neuroimaging Initiative, Rebecca G. Smith, Adam R. Smith, Joe Burrage, Emma M. Walker, Gemma Shireby, Eilis Hannon, Emma Dempster, Tim Frayling, Jonathan Mill, Valerija Dobricic, Peter Johannsen, Michael Wittig, Andre Franke, Rik Vandenberghe, Jolien Schaeverbeke, Yvonne Freund-Levi, Lutz Frölich, Philip Scheltens, Charlotte E. Teunissen, Giovanni Frisoni, Olivier Blin, Jill C. Richardson, Régis Bordet, Sebastiaan Engelborghs, Ellen de Roeck, Pablo Martinez-Lage, Mikel Tainta, Alberto Lleó, Isabel Sala, Julius Popp, Gwendoline Peyratout, Frans Verhey, Magda Tsolaki, Ulf Andreasson, Kaj Blennow, Henrik Zetterberg, Johannes Streffer, Stephanie J.B. Vos, Simon Lovestone, Pieter-Jelle Visser, Christina M. Lill, Lars Bertram, Katie Lunnon, Ehsan Pishva 
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520 |a Abstract INTRODUCTION The established link between DNA methylation and pathophysiology of dementia, along with its potential role as a molecular mediator of lifestyle and environmental influences, positions blood-derived DNA methylation as a promising tool for early dementia risk detection. METHODS In conjunction with an extensive array of machine learning techniques, we employed whole blood genome-wide DNA methylation data as a surrogate for 14 modifiable and non-modifiable factors in the assessment of dementia risk in independent dementia cohorts. RESULTS We established a multivariate methylation risk score (MMRS) for identifying mild cognitive impairment cross-sectionally, independent of age and sex (P = 2.0 ? 10?3). This score significantly predicted the prospective development of cognitive impairments in independent studies of Alzheimer's disease (hazard ratio for Rey's Auditory Verbal Learning Test (RAVLT)-Learning = 2.47) and Parkinson's disease (hazard ratio for MCI/dementia = 2.59). DISCUSSION Our work shows the potential of employing blood-derived DNA methylation data in the assessment of dementia risk. Highlights We used whole blood DNA methylation as a surrogate for 14 dementia risk factors. Created a multivariate methylation risk score for predicting cognitive impairment. Emphasized the role of machine learning and omics data in predicting dementia. The score predicts cognitive impairment development at the population level. 
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650 4 |a Alzheimer's disease 
650 4 |a dementia 
650 4 |a DNA methylation 
650 4 |a epigenetics 
650 4 |a machine learning 
650 4 |a mild cognitive impairments 
650 4 |a Parkinson's disease 
650 4 |a risk prediction 
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