Circulating microRNAs are related to cognitive domains in the general population

INTRODUCTION Circulating microRNAs have been suggested as candidates for detecting and preventing subclinical cognitive dysfunction. However, replication of previous findings and identification of novel microRNAs associated with cognitive domains, including their relation to brain structure and the pathways they regulate, are still lacking. METHODS We examined circulating microRNAs and microRNA co-expression clusters in relation to cognitive domains, structural MRI measures, and target gene expression in 2869 participants of a population-based cohort. RESULTS Five previously identified and 10 novel microRNAs were associated with cognitive domains. Importantly, seven of these microRNAs were also associated with cortical thickness and two with hippocampal volume. Functional genomics analysis showed that the identified microRNAs regulated genes in pathways like neurogenesis, axon guidance, and synapse assembly. DISCUSSION We identified microRNAs associated with cognitive domains, brain regions, and neuronal processes affected by aging and neurodegeneration, making them promising candidate blood-based biomarkers or therapeutic targets of subclinical cognitive dysfunction.