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

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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. | Frayling, T. | Mill, J. | Dobricic, V. | Johannsen, P. | Wittig, M. | Franke, A. | Vandenberghe, R. | Schaeverbeke, J. | Freund-Levi, Y. | Frölich, L. | Scheltens, P. | Teunissen, C. E. | Frisoni, G. | Blin, O. | Richardson, J. C. | Bordet, Regis | 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, S. J. B. | Lovestone, S. | Visser, P. J. | Lill, C. M. | Bertram, L. | Lunnon, K. | Pishva, E.

Edité par CCSD ; Alzheimer's Association / Wiley -

International audience. INTRODUCTIONThe 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.METHODSIn 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.RESULTSWe 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).DISCUSSIONOur work shows the potential of employing blood-derived DNA methylation data in the assessment of dementia risk.

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