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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Lill, Lars Bertram, Katie Lunnon, Ehsan Pishva","doi":"10.1002/alz.14061","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> INTRODUCTION</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>We established a multivariate methylation risk score (MMRS) for identifying mild cognitive impairment cross-sectionally, independent of age and sex (<i>P</i> = 2.0 × 10<sup>−3</sup>). 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引用次数: 0
摘要
简介：DNA甲基化与痴呆症病理生理学之间已建立的联系，以及其作为生活方式和环境影响分子介质的潜在作用，使血液中的DNA甲基化成为早期痴呆症风险检测的一种有前途的工具：结合广泛的机器学习技术，我们采用全血全基因组 DNA 甲基化数据作为 14 个可调节和不可调节因素的替代物，评估独立痴呆队列中的痴呆风险：我们建立了一个多变量甲基化风险评分（MMRS），用于横断面识别轻度认知障碍，不受年龄和性别的影响（P = 2.0 × 10-3）。在对阿尔茨海默病（Rey听觉言语学习测试（RAVLT）-学习的危险比为2.47）和帕金森病（MCI/痴呆的危险比为2.59）的独立研究中，该评分可明显预测认知障碍的前瞻性发展：讨论：我们的研究表明，血液中的DNA甲基化数据具有评估痴呆症风险的潜力：我们使用全血 DNA 甲基化作为 14 种痴呆症风险因素的替代物。创建了预测认知障碍的多变量甲基化风险评分。强调了机器学习和 omics 数据在预测痴呆症中的作用。该评分可在人群水平上预测认知障碍的发展。
Blood-based multivariate methylation risk score for cognitive impairment and dementia
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.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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