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

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; 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; Alzheimer's Disease Neuroimaging Initiative

doi:10.1002/alz.14061

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

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, Rebecca G Smith, Adam R Smith, Joe Burrage, Emma M Walker, Gemma Shireby, Eilis Hannon, Emma Dempster, Tim FraylingJonathan 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, Alzheimer's Disease Neuroimaging Initiative

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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.

Originalsprog	Engelsk
Tidsskrift	Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN	1552-5260
DOI	https://doi.org/10.1002/alz.14061
Status	E-pub ahead of print - 28 aug. 2024

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10.1002/alz.14061

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Koetsier, J., Cavill, R., Reijnders, R., Harvey, J., Homann, J., Kouhsar, M., Deckers, K., Köhler, S., Eijssen, L. M. T., van den Hove, D. L. A., Demuth, I., Düzel, S., Smith, R. G., Smith, A. R., Burrage, J., Walker, E. M., Shireby, G., Hannon, E., Dempster, E., ... Alzheimer's Disease Neuroimaging Initiative (2024). Blood-based multivariate methylation risk score for cognitive impairment and dementia. Alzheimer's & dementia : the journal of the Alzheimer's Association. Advance online publication. https://doi.org/10.1002/alz.14061

Koetsier, J, Cavill, R, Reijnders, R, Harvey, J, Homann, J, Kouhsar, M, Deckers, K, Köhler, S, Eijssen, LMT, van den Hove, DLA, Demuth, I, Düzel, S, Smith, RG, Smith, AR, Burrage, J, Walker, EM, Shireby, G, Hannon, E, Dempster, E, Frayling, T, Mill, J, Dobricic, V, Johannsen, P, Wittig, M, Franke, A, Vandenberghe, R, Schaeverbeke, J, Freund-Levi, Y, Frölich, L, Scheltens, P, Teunissen, CE, Frisoni, G, Blin, O, Richardson, JC, Bordet, R, Engelborghs, S, de Roeck, E, Martinez-Lage, P, Tainta, M, Lleó, A, Sala, I, Popp, J, Peyratout, G, Verhey, F, Tsolaki, M, Andreasson, U, Blennow, K, Zetterberg, H, Streffer, J, Vos, SJB & Alzheimer's Disease Neuroimaging Initiative 2024, 'Blood-based multivariate methylation risk score for cognitive impairment and dementia', Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.14061

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title = "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: 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.",

author = "Jarno Koetsier and Rachel Cavill and Rick Reijnders and Joshua Harvey and Jan Homann and Morteza Kouhsar and Kay Deckers and Sebastian K{\"o}hler and Eijssen, {Lars M T} and {van den Hove}, {Daniel L A} and Ilja Demuth and Sandra D{\"u}zel and Smith, {Rebecca G} and Smith, {Adam R} and Joe Burrage and Walker, {Emma M} and Gemma Shireby and Eilis Hannon and Emma Dempster and Tim Frayling and Jonathan Mill and Valerija Dobricic and Peter Johannsen and Michael Wittig and Andre Franke and Rik Vandenberghe and Jolien Schaeverbeke and Yvonne Freund-Levi and Lutz Fr{\"o}lich and Philip Scheltens and Teunissen, {Charlotte E} and Giovanni Frisoni and Olivier Blin and Richardson, {Jill C} and R{\'e}gis Bordet and Sebastiaan Engelborghs and {de Roeck}, Ellen and Pablo Martinez-Lage and Mikel Tainta and Alberto Lle{\'o} and Isabel Sala and Julius Popp and Gwendoline Peyratout and Frans Verhey and Magda Tsolaki and Ulf Andreasson and Kaj Blennow and Henrik Zetterberg and Johannes Streffer and Vos, {Stephanie J B} and {Alzheimer{\textquoteright}s Disease Neuroimaging Initiative (ADNI)}",

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doi = "10.1002/alz.14061",

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journal = "Alzheimer's & dementia : the journal of the Alzheimer's Association",

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T1 - Blood-based multivariate methylation risk score for cognitive impairment and dementia

AU - Koetsier, Jarno

AU - Cavill, Rachel

AU - Reijnders, Rick

AU - Harvey, Joshua

AU - Homann, Jan

AU - Kouhsar, Morteza

AU - Deckers, Kay

AU - Köhler, Sebastian

AU - Eijssen, Lars M T

AU - van den Hove, Daniel L A

AU - Demuth, Ilja

AU - Düzel, Sandra

AU - Smith, Rebecca G

AU - Smith, Adam R

AU - Burrage, Joe

AU - Walker, Emma M

AU - Shireby, Gemma

AU - Hannon, Eilis

AU - Dempster, Emma

AU - Frayling, Tim

AU - Mill, Jonathan

AU - Dobricic, Valerija

AU - Johannsen, Peter

AU - Wittig, Michael

AU - Franke, Andre

AU - Vandenberghe, Rik

AU - Schaeverbeke, Jolien

AU - Freund-Levi, Yvonne

AU - Frölich, Lutz

AU - Scheltens, Philip

AU - Teunissen, Charlotte E

AU - Frisoni, Giovanni

AU - Blin, Olivier

AU - Richardson, Jill C

AU - Bordet, Régis

AU - Engelborghs, Sebastiaan

AU - de Roeck, Ellen

AU - Martinez-Lage, Pablo

AU - Tainta, Mikel

AU - Lleó, Alberto

AU - Sala, Isabel

AU - Popp, Julius

AU - Peyratout, Gwendoline

AU - Verhey, Frans

AU - Tsolaki, Magda

AU - Andreasson, Ulf

AU - Blennow, Kaj

AU - Zetterberg, Henrik

AU - Streffer, Johannes

AU - Vos, Stephanie J B

AU - Alzheimer’s Disease Neuroimaging Initiative (ADNI)

PY - 2024/8/28

Y1 - 2024/8/28

N2 - 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.

AB - 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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U2 - 10.1002/alz.14061

DO - 10.1002/alz.14061

M3 - Journal article

C2 - 39193899

SN - 1552-5260

JO - Alzheimer's & dementia : the journal of the Alzheimer's Association

JF - Alzheimer's & dementia : the journal of the Alzheimer's Association

ER -

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

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