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Public Health.

Rongrong Yang1

  • 1Karolinska Institutet, Stockholm, Sweden, Sweden; Tianjin University of Traditional Chinese Medicine, Tianjin, Tianjin, China.

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Summary
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Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to accelerated brain aging. Low-grade inflammation may partially explain this connection, highlighting potential risks even in middle-aged adults.

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Area of Science:

  • Neuroscience
  • Hepatology
  • Gerontology

Background:

  • Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized for its systemic effects.
  • Previous research suggests a link between MASLD and cognitive decline, prompting further investigation into its impact on brain health.

Purpose of the Study:

  • To investigate the association between MASLD and brain aging.
  • To explore the potential mediating role of low-grade inflammation in the MASLD-brain aging relationship.

Main Methods:

  • Utilized UK Biobank data from 30,386 adults, analyzing brain MRI scans and calculating brain age gap (BAG) using machine learning.
  • Assessed low-grade inflammation via an inflammation score (INFLA) incorporating blood markers.
  • Employed linear regression and structural equation models to analyze associations.

Main Results:

  • 24.2% of participants had MASLD or related conditions.
  • MASLD and its subtypes, including MetALD, were significantly associated with a larger BAG, indicating accelerated brain aging.
  • The association persisted across different age groups, sexes, and APOE ɛ4 carrier statuses.
  • Inflammation score (INFLA) mediated 13.53% of the link between MASLD and accelerated brain aging.

Conclusions:

  • MASLD is associated with accelerated brain aging, affecting even middle-aged individuals and those without the APOE ɛ4 risk allele.
  • Low-grade systemic inflammation appears to be a significant factor partially mediating the relationship between MASLD and accelerated brain aging.