ORIGINAL RESEARCH article
Front. Hum. Neurosci.
Sec. Brain Health and Clinical Neuroscience
This article is part of the Research TopicPrecision Medicine and Biomarkers in Common Brain DisordersView all 3 articles
U-Shaped Association of the Non-HDL/HDL Ratio With Cognitive Impairment Identified by Conventional Analyses and Machine Learning in Health Examination Participants in Liuyang
Provisionally accepted
- 1Central People's Hospital of Zhanjiang, Zhanjiang, China
- 2The Second Affiliated Hospital of Shantou University Medical College, Shantou, China
- 3Central Hospital of Guangdong Nongken, Zhanjiang, China
- 4Liuyang Jili Hospital, Changsha, China
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Background: The non–high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is associated with cardiovascular risk, but its relationship with cognitive impairment has not been well studied. Methods: In this cross-sectional study, 1103 adults (median age, 68 years; 54.7% women) from Liuyang were included. Cognitive function was assessed by Mini-Mental State Examination. Restricted cubic splines were used to evaluate associations of NHHR with cognitive impairment. Breakpoint regression identified inflection points. Discrimination was compared using area under the curve (AUC). Machine learning with Shapley additive explanation (SHAP) was applied to assess the relative importance of NHHR and to further explore its relationship with cognitive impairment. Results: Overall, 241 participants (21.9%) had cognitive impairment. NHHR demonstrated a significant U-shaped association with cognitive impairment (overall and nonlinearity P < 0.001). Breakpoint regression identified an inflection point at 2.772; NHHR ≥2.772 was associated with increased risk (odds ratio, 3.36; 95% CI, 2.23–5.05; P < 0.001). Compared with LDL, HDL, and non–HDL, NHHR had the greatest AUC for discriminating cognitive impairment. SHAP analysis confirmed the U-shaped relationship and identified NHHR as the most influential lipid-related predictor. Conclusion: In this cross-sectional analysis, NHHR was associated with cognitive impairment in a U-shaped pattern and demonstrated better discrimination than individual lipid measures. These findings suggest that NHHR may serve as an alternative lipid-related index in studies of cognitive health, although longitudinal studies are needed to clarify its predictive value.
Keywords: Chinese rural residents, Cognitive Function, Cross-sectional study, lipid management, machine learning
Received: 25 Dec 2025; Accepted: 26 Jan 2026.
Copyright: © 2026 Chen, Lin, Zhao, He and Zhu. 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: Tieshi Zhu
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