MethylCog predicts six-year cognitive ability beyond blood-based ADRD biomarkers
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INTRODUCTION
MethylCog is a 29-CpG blood DNA methylation (DNAm) proxy for general cognitive ability (g). Its incremental association with blood biomarkers of Alzheimer’s disease and related dementias (ADRD) and prospective cognitive ability remains unclear.
METHODS
In the held-out test set from the original MethylCog study, we tested whether MethylCog explained baseline g beyond four ADRD blood biomarkers, and whether it predicted six-year follow-up g beyond baseline g and biomarkers.
RESULTS
MethylCog showed a stronger age-adjusted association with baseline g than individual biomarkers (r=.368 vs absolute r=.083–.162). MethylCog added 10.0% variance beyond all four biomarkers cross-sectionally (p<.001) and predicted six-year follow-up g in the biomarker-adjusted model (β=.108, p=.002). No individual ADRD biomarker independently predicted follow-up g.
DISCUSSION
MethylCog may provide cognition-related DNAm information complementary to blood-based ADRD biomarkers.
