ORIGINAL RESEARCH article
Front. Neurol.
Sec. Cognitive and Behavioral Neurology
This article is part of the Research TopicPsychiatric Comorbidities of Neurogenetic and Neurodegenerative DiseasesView all 5 articles
Correlation Study between serum uric acid level and cognitive impairment in middle-aged and elderly patients with hypertension: based on an explainable predictive model
Provisionally accepted
Jiarui Wang1,2
Hetong Liao3Ping Zheng4
Qin-Fen Chen3Dongxu Lu1Yihong Huang5Di Wu1Jiajia Hu1
Juan Du1
Zhang Xiaoyun1*- 1The Ninth Medical Center of Chinese PLA General Hospital, Beijing, China
- 2Tianjin Medical University General Hospital, Tianjin, China
- 3The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- 4Chinese PLA General Hospital, Beijing, China
- 5Beijing Water Conservancy Hospital, Beijing, China
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Background Patients with primary hypertension are always comorbid with hyperuricemia. Serum uric acid exhibits a dual role in cognitive function. Evidence regarding the relationship between uric acid(SUA) and cognitive dysfunction in specific hypertensive patients remains inconsistent. Objective To develop a predictive model to evaluate the association between serum uric acid level and mild cognitive impairment (MCI) in hypertensive populations. Methods: This cross-sectional study involved 420 middle-aged and elderly hypertensive patients. Cognitive function was evaluated using MMSE and MoCA. Univariate and multivariate logistic regression, restricted cubic splines (RCS), and SHAP analysis were employed. Results: In MCI group, diabetes prevalence, hyperuricemia prevalence, arteriosclerosis prevalence, education level, MMSE score, MoCA score, AD8 score and HbA1c were higher, while weight, BMI, SUA, TC, LDL, Alb, TT3, TSH, and FT3 were lower. After adjusting for confounding factors, it was found that the SUA level (OR = 0.754, 95%CI: 0.578 - 0.985, 0.038) could still be used as an independent protective factor for MCI. Subgroup analyses indicated effects varied significantly with diabetes history and regular exercise. Shap values showed that SUA is the fifth most related factor, with more significant ones including age, education level, albumin and thyroxin. A nonlinear association was found between SUA and MCI risk, with an inflection point at approximately 450 μmol/L. Conclusions: SUA has a certain correlation with MCI in the middle-aged and elderly hypertensive populations. Although SUA is considered as a neuroprotective agent, its neuroprotective function gradually diminishes and may even become detrimental when SUA higher than a threshold. These results suggest maintaining SUA within an optimal range may help mitigate MCI risk in hypertensive populations.
Keywords: Hypertension, Serum uric acid, cognitive impairment, Regression modeling, Explainability, Non-linear effects
Received: 18 Sep 2025; Accepted: 06 Nov 2025.
Copyright: © 2025 Wang, Liao, Zheng, Chen, Lu, Huang, Wu, Hu, Du and Xiaoyun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zhang Xiaoyun, 93434126@qq.com
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