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Extracellular microRNA and cognitive function in a prospective cohort of older men: The Veterans Affairs Normative

Nicole Comfort1, Haotian Wu1, Peter De Hoff2

  • 1Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY 10032, USA.

Aging
|September 7, 2022
PubMed
Abstract

Insights

Plasma microRNAs (miRNAs) show links to cognitive function in aging men. These circulating miRNAs may predict changes in cognitive decline, offering insights into early dementia stages.

Area of Science:

  • Neuroscience
  • Genetics
  • Biochemistry

Background:

  • Aging-related cognitive decline is a precursor to Alzheimer's disease and dementia.
  • Extracellular microRNAs (miRNAs) are increasingly studied for their role in central nervous system (CNS) pathologies.
  • Research on extracellular miRNAs in early cognitive decline is limited.

Purpose of the Study:

  • To investigate the association between plasma miRNAs and cognitive function in cognitively normal older men.
  • To explore the relationship between plasma miRNA expression and the rate of cognitive change over time.

Main Methods:

  • Utilized data from the longitudinal Normative Aging Study (NAS) cohort.
  • Assessed global cognitive function using the Mini-Mental State Examination (MMSE).
  • Profiled plasma miRNAs via small RNA sequencing and analyzed associations using regression and mixed-effects models.

Main Results:

  • Two plasma miRNAs were linked to higher MMSE scores.
  • Thirty-three plasma miRNAs correlated with the rate of change in MMSE scores.
  • Enriched pathways included Hippo signaling and extracellular matrix-receptor interactions; gene targets were linked to prion diseases and fatty acid biosynthesis.

Conclusions:

  • Circulating miRNAs are associated with cognitive function and its rate of change in cognitively normal men.
  • Further research is warranted to understand the CNS functions of these miRNAs and their relation to neurological outcomes.
Keywords:
RNA-seqcognitive declinecognitive impairmentextracellular RNAmicroRNAplasma

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