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Blood-based multivariate methylation risk score for cognitive impairment and dementia Number of Authors: 562024 (English)In: Alzheimer's & Dementia: Journal of the Alzheimer's Association, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 20, no 10, p. 6682-6692Article in journal (Refereed) Published

Abstract [en]

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.

Place, publisher, year, edition, pages

John Wiley & Sons, 2024. Vol. 20, no 10, p. 6682-6692

Keywords [en]

Alzheimer's disease, DNA methylation, Parkinson's disease, aging, dementia, epigenetics, machine learning, mild cognitive impairments, risk prediction

National Category

Neurosciences

Identifiers

URN: urn:nbn:se:oru:diva-115682DOI: 10.1002/alz.14061ISI: 001300072400001PubMedID: 39193899Scopus ID: 2-s2.0-85202550809OAI: oai:DiVA.org:oru-115682DiVA, id: diva2:1893242

Funder

EU, FP7, Seventh Framework Programme, FP7/2007-2013EU, Horizon Europe, 101053962Stiftelsen Gamla TjänarinnorAlzheimerfonden, #AF-930351, #AF-939721, #AF-968270The Swedish Brain Foundation, #FO2022-0270, #FO2017-0243, #ALZ2022-0006Swedish Research Council, #2022-01018; #2019-02397; #2017-00915; #2022-00732

Note

Funding information: ZonMw Memorabel/Alzheimer Nederland, Grant/Award Number: 733050516; Innovative Medicines Initiative Joint Undertaking, Grant/Award Number: 115372; Euro-pean Union’s Seventh Framework Program, Grant/Award Number: FP7/2007-2013; National Institute for Health and Care Research; Biomedical research Centre; Heisenberg grant of theGerman Research Foundation, Grant/Award Number: LI 2654/4–1; EU Joint Programme – Neurodegenerative Disease Research 2021″, Grant/Award Numbers: JPND2021, EPIC4ND; CureAlzheimer’s Fund, Grant/Award Number: EPIC4AD; European Union’s Horizon Europe research and innovation programme, Grant/Award Number: 101053962; Swedish State Support for Clin-ical Research, Grant/Award Number: #ALFGBG-71320; Alzheimer Drug Discovery Foundation (ADDF), USA, Grant/Award Number: #201809-2016862; AD Strategic Fund and the Alzheimer’sAssociation, Grant/Award Numbers: #ADSF-21-831376-C, #ADSF-21-831381-C, #ADSF-21-831377-C; Bluefield Project; Olav Thon Foundation; Familjen Erling-Perssons Stiftelse; Stiftelsen förGamla Tjänarinnor; Marie Skłodowska-Curie, Grant/Award Number: 860197; European Union Joint Programme – Neurodegenerative Disease Research, Grant/Award Number: JPND2021-00694;National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre; UK Dementia Research Institute; Swedish Alzheimer Foundation, Grant/AwardNumbers: #AF-930351, #AF-939721, #AF-968270; Hjärnfonden, Sweden, Grant/Award Numbers: #FO2022-0270, #FO2017-0243, #ALZ2022-0006; ALF-agreement, Grant/Award Numbers:#ALFGBG-715986, #ALFGBG-965240; European Union Joint Program for Neurodegenerative Disorders, Grant/Award Number: JPND2019-466-236; Alzheimer’s Association 2021 Zenith Award,Grant/Award Numbers: ZEN-21-848495, SG-23-1038904 QC; Alzheimer’s Society UK, Grant/Award Number: AS-PG-14-038; Medical Research Council; National Institute of Aging (NIA); NationalInstitutes of Health (NIH), Grant/Award Number: R01AG067015; Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health, Grant/Award Number: U01 AG024904; DODADNI (Department of Defense award, Grant/Award Number: W81XWH-12-2-0012; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Swedish ResearchCouncil, Grant/Award Numbers: #2022-01018, #2019-02397, #2017-00915, #2022-00732

Available from: 2024-08-29 Created: 2024-08-29 Last updated: 2024-11-06Bibliographically approved

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Freund-Levi, Yvonne

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