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Serum Uric Acid and the Risk of Dementia: A Systematic Review and Meta-Analysis

  • Zhou, Zhike1
  • Zhong, Shanshan2
  • Liang, Yifan2
  • Zhang, Xiaoqian2
  • Zhang, Rongwei1
  • Kang, Kexin1
  • Qu, Huiling3
  • Xu, Ying4, 5
  • Zhao, Chuansheng2
  • Zhao, Mei6
  • 1 Department of Geriatrics, The First Affiliated Hospital, China Medical University, Shenyang , (China)
  • 2 Department of Neurology, The First Affiliated Hospital, China Medical University, Shenyang , (China)
  • 3 Department of Neurology, People's Hospital of Liaoning Province, Shenyang , (China)
  • 4 Computational Systems Biology Laboratory, Department of Biochemistry and Molecular Biology and Institute of Bioinformatics, The University of Georgia, Athens, GA , (United States)
  • 5 Cancer Systems Biology Center, The China–Japan Union Hospital, Jilin University, Changchun , (China)
  • 6 Department of Cardiology, The Shengjing Affiliated Hospital, China Medical University, Shenyang , (China)
Published Article
Frontiers in Aging Neuroscience
Frontiers Media SA
Publication Date
Feb 25, 2021
DOI: 10.3389/fnagi.2021.625690
PMCID: PMC7947796
PubMed Central


Background: This meta-analysis aimed to evaluate the relationship between serum uric acid (UA) and the risk of dementia and its subtypes. Methods: Embase, PubMed, and Web of Science were searched from inception to July 2020. Random-effect models were employed to analyze the standard mean difference (SMD) with the corresponding 95% confidence intervals (CI). Results: Twenty-three eligible studies involving 5,575 participants were identified. The overall results showed lower levels of UA in dementia relative to non-dementia controls [SMD = −0.32 (−0.64; −0.01) p = 0.04]. The subgroup analysis of the type of dementia demonstrated a significant association of UA with Alzheimer's disease (AD) [SMD = −0.58 (−1.02; −0.15) p = 0.009] and Parkinson's disease with dementia (PDD) [SMD = −0.33 (−0.52; −0.14) p = 0.001] but not with vascular dementia (VaD). The stratification analysis of the concentrations of UA revealed that the UA quartile 1–2 was negatively correlated with dementia and neurodegenerative subtypes ( p < 0.05), whereas a positive correlation of UA quartile 4 with dementia was noted ( p = 0.028). Additionally, the meta-regression analysis on confounders showed that not age, body mass index, diabetes mellitus, hypertension, or smoking but education ( p = 0.003) exerted an influence of the UA in the risk estimate of dementia. Conclusions: Low concentrations of UA (< 292 μmol/L or 4.91 mg/dL) is a potential risk factor for AD and PDD but not for VaD. The mechanism of different concentrations of the UA in dementia needs to be confirmed through further investigation.

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