Circulating miR-323–3p as a novel potential plasma biomarker for multimorbidity burden and cognitive decline in middle-aged and older adults: Results from the national institute for longevity sciences–longitudinal study of aging in Japan

• Association of two circulating miRNAs with multimorbidity burden was studied • Circulating miR-323-3p is positively associated with age and number of comorbidities • Circulating miR-323-3p is negatively associated with cognition • In men, miR-323-3p is negatively correlated with WAIS-R-SF subtests Several circulating microRNAs (miRNAs) in the blood are indicators of chronic diseases, but their association with multimorbidity burden is unknown. The aim of this study was to assess the association of plasma levels of circulating miR-323-3p and miR-135-3p with age, cognitive performance, and number of comorbidities in middle-aged and older individuals. Data from 295 community dwellers (≥40 years) who participated in the second wave (2000‒2002) of the National Institute for Longevity Sciences-Longitudinal Study of Aging in Japan were analyzed. miRNAs were isolated from the plasma, and miR-323-3p and miR-135-3p levels were measured using quantitative reverse-transcription polymerase chain reaction and normalized, with miR-16 as an endogenous reference gene. Cognitive performance was assessed using the Information and Similarities subtests and the Digit Symbol Substitution Test of the Wechsler Adult Intelligence Scale-Revised Short Form (WAIS-R-SF). Correlation tests and multivariate general linear regression analyses were performed to examine the relationship among circulating miRNA levels, burden of multimorbidity, and cognitive performance. The mean age of the participants was 59.1 ± 10.3 years. Pearson's correlation analysis revealed that the miR-323-3p level positively correlated with age and number of comorbidities but negatively correlated with WAIS-R-SF subtest performance. In men, miR-323-3p level negatively correlated with the performance of all three WAIS-R-SF subtests. The general linear regression analysis showed that the miR-323-3p level increased in participants with four comorbidities compared with those with one comorbidity. Circulating miR-323-3p level is associated with the burden of multimorbidity and decreased cognitive performance in middle-aged and older adults.