Association Between Cerebral Microbleeds and Circulating Levels of Mid-Regional Pro-Adrenomedullin

J Alzheimers Dis. 2022;88(2):731-741. doi: 10.3233/JAD-220195.

Abstract

Background: Mid-regional pro-adrenomedullin (MR-proADM) is a novel biomarker for cognitive decline based on its association with cerebral small vessel disease (SVD). Cerebral microbleeds (MBs) are characteristic of SVD; however, a direct association between MR-proADM and MBs has not been explored.

Objective: We aimed to examine whether circulating levels of MR-proADM are associated with the identification of MBs by brain magnetic resonance imaging (MRI) and whether this association could be linked with cognitive impairment.

Methods: In total, 214 participants (mean age: 75.9 years) without history of cerebral infarction or dementia were prospectively enrolled. All participants underwent brain MRI, higher cognitive function testing, blood biochemistry evaluation, lifestyle examination, and blood MR-proADM measurement using a time-resolved amplified cryptate emission technology assay. For between-group comparisons, the participants were divided into two groups according to whether their levels of MR-proADM were normal (< 0.65 nmol/L) or high (≥0.65 nmol/L).

Results: The mean MR-proADM level was 0.515±0.127 nmol/L. There were significant between-group differences in age, hypertension, and HbA1c levels (p < 0.05). In the high MR-proADM group, the MR-proADM level was associated with the identification of MBs on brain MR images and indications of mild cognitive impairment (MCI). In participants with ≥3 MBs and MCI, high MR-proADM levels remained a risk factor after multivariate adjustment (OR: 2.94; p < 0.05).

Conclusion: High levels of MR-proADM may be a surrogate marker for the early detection of cognitive decline associated with the formation of cerebral MBs. This marker would be valuable during routine clinical examinations of geriatric patients.

Keywords: Adrenomedullin; biomarkers; cerebral small vessel diseases; cognitive dysfunction; magnetic resonance imaging; peptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenomedullin*
  • Aged
  • Biomarkers
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / diagnostic imaging
  • Humans
  • Prognosis
  • Protein Precursors*
  • Risk Factors

Substances

  • Biomarkers
  • Protein Precursors
  • Adrenomedullin