Interactions between plasma miRNAs and cognitive performance in males

Cognitive decline brought on by aging is a precursor to dementias like Alzheimer’s and can have a significant impact on a person’s ability to carry out essential daily tasks.

Image Credit: ART-ur/

Image Credit: ART-ur/

There has not been much research on extracellular miRNAs in the initial phases of cognitive decline, despite growing interest in extracellular microRNAs’ (miRNAs’) potential roles in disorders of the central nervous system (CNS).

Scientists from Columbia University Mailman School of Public Health, University of California San Diego, VA, Nicole Comfort, Haotian Wu, Peter De Hoff, Aishwarya Vuppala, Pantel S. Vokonas, Avron Spiro, Marc Weisskopf, Brent A. Coull, Louise C. Laurent, Andrea A. Baccarelli, and Joel Schwartz conducted a new study.

The longitudinal Normative Aging Study (NAS) cohort was used by the Boston Healthcare System, Boston University School of Medicine, and Harvard TH Chan School of Public Health to examine relationships between plasma miRNAs and cognitive performance in cognitively normal males.

In a cohort of older men from Massachusetts, we investigated associations between plasma miRNAs and global cognition and rate of global cognitive decline measured by the MMSE,” the researchers say.

Information from up to 530 NAS participants, with a median age of 71.0 years, was included in this study. A total of 1,331 person-visits were made between 1996 and 2013. (equal to 2,471 years of follow up). The Mini-Mental State Examination was used to evaluate global cognitive function (MMSE).

Small RNA sequencing was used to profile the plasma miRNAs. Using linear regression (N = 457) and linear mixed models (N = 530), correspondingly, it was determined if the expression of 381 miRNAs was associated with current cognitive function and the rate at which cognitive function was changing.

Two plasma miRNA levels were connected to higher MMSE scores in adjusted models (p < 0.05). The pace of change in MMSE scores over time was correlated with the expression of 33 plasma miRNAs (p < 0.05).

Hippo signaling and extracellular matrix-receptor interactions were among the enriched KEGG pathways for miRNAs connected to concurrent MMSE and MMSE trajectory. MMSE trajectory-related miRNA gene targets were also linked to prion disorders and fatty acid production.

The researchers further commented, “Circulating miRNAs were associated with both cross-sectional cognitive function and rate of change in cognitive function among cognitively normal men. Further research is needed to elucidate the potential functions of these miRNAs in the CNS and investigate relationships with other neurological outcomes.”

Journal reference:

Comfort, N., et al. (2022) Extracellular microRNA and cognitive function in a prospective cohort of older men: The Veterans Affairs Normative Aging Study. Aging.


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