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Causal relationship between sarcopenia and cognitive performance: A bidirectional Mendelian randomization study.

Yanling Zhou1, Xiucheng Guo2, Sunjuan Dong1

  • 1School of Nursing, Anhui University of Chinese Medicine, Hefei, China.

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Summary
This summary is machine-generated.

This study used Mendelian randomization to investigate the causal link between sarcopenia (SA) and cognitive impairment. Findings suggest that muscle strength and walking pace causally influence cognitive function, highlighting the importance of muscle health for brain health in aging populations.

Keywords:
Mendelian randomizationcausal relationshipcognitive performancesarcopenia

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Area of Science:

  • Gerontology
  • Neuroscience
  • Genetics

Background:

  • Global population aging is increasing the prevalence of sarcopenia (SA) and cognitive impairment, posing significant public health challenges.
  • Observational studies suggest a link between SA and cognitive decline, but are limited by confounding factors and reverse causation.
  • Previous Mendelian randomization (MR) studies on this relationship have produced inconsistent results.

Purpose of the Study:

  • To clarify the causal relationship between sarcopenia-related traits and cognitive performance using a bidirectional MR design.
  • To investigate whether genetically predicted sarcopenia influences cognitive function, and vice versa.

Main Methods:

  • A bidirectional Mendelian randomization (MR) design was employed.
  • Genetic instrumental variables for SA traits (hand grip strength, lean mass, walking pace) were obtained from UK Biobank.
  • Cognitive performance data were sourced from large genome-wide association studies meta-analyses and independent cohorts.
  • Primary analysis used the inverse variance weighted (IVW) method, validated by MR Egger, weighted median, and weighted mode approaches.
  • Robustness was assessed using heterogeneity and pleiotropy tests (Cochran Q, MR Egger intercept) and sensitivity analyses (leave-one-out, Steiger directionality).

Main Results:

  • Genetically predicted higher hand grip strength, lean mass (arms, legs, whole body), and faster walking pace were significantly associated with improved cognitive performance (e.g., OR for whole body fat-free mass = 1.081, P < 0.001; OR for walking pace = 1.414, P < 0.001).
  • Reverse MR analysis showed no significant causal effect of cognitive performance on most SA traits, except for a potential link with walking pace.
  • Bidirectional MR results indicated a strong causal relationship between walking pace and cognitive performance.

Conclusions:

  • Sarcopenia-related traits, particularly muscle strength and walking pace, have a significant positive causal effect on cognitive performance.
  • Cognitive impairment may not be a direct cause of sarcopenia, but sarcopenia could be a risk factor for cognitive decline.
  • Maintaining muscle health in older adults is crucial for potentially slowing cognitive decline, and interventions targeting walking pace may benefit cognitive function.