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

ABSTRACT INTRODUCTION Given the established association between DNA methylation and the pathophysiology of dementia and its plausible role as a molecular mediator of lifestyle and environment, blood-derived DNA methylation data could enable early detection of dementia risk. 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 two independent cohorts of Alzheimer’s disease (AD) and Parkinson’s disease (PD). RESULTS We established a multivariate methylation risk score (MMRS) to identify the status of mild cognitive impairment (MCI) cross-sectionally, independent of age and sex. We further demonstrated significant predictive capability of this score for the prospective onset of cognitive decline in AD and PD. DISCUSSION Our work shows the potential of employing blood-derived DNA methylation data in the assessment of dementia risk.