Development and validation of MethylCog, a blood DNA methylation proxy for cognition
Year: 2026
Type: article
Abstract: INTRODUCTION: Heterogeneity in cognitive ability increases with age and predicts mild cognitive impairment (MCI) and dementia, but scalable blood-based biomarkers are lacking. We developed and validated MethylCog, a parsimonious DNA methylation (DNAm) marker of general cognitive ability (g). METHODS: MethylCog was developed using elastic net regression on principal components analysis (PCA) -derived g in a population-based cohort (n = 2,069; training/test split) externally validated (n = 112). Criterion validity, MCI discrimination, and specificity relative to GrimAge and Alzheimer's disease (AD) biomarkers were assessed. RESULTS: = 0.13), explaining ∼11% of variance beyond age and sex. MethylCog improved MCI discrimination beyond demographics (ΔAUC = 0.03-0.07) and outperformed GrimAge but did not add value beyond cognitive screeners. Exploratory analyses showed no significant associations with AD plasma biomarkers or MRI measures. DISCUSSION: MethylCog provides initial evidence that parsimonious DNAm scores can index individual differences in cognitive ability, with potential utility where direct assessment is unavailable.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.71421
Institutions: University of Miami, University of Miami Health System
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,200
OpenAlex ID: W7159685351