Work

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

Year: 2026

Type: article

Abstract: 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, 1,103 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 exPlanations (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.

Source: Frontiers in Human Neuroscience

DOI: 10.3389/fnhum.2026.1775215

Authors: Xiaoyi Chen, Runzhui Lin, Le Zhao, Yong He, Tieshi Zhu

Institutions: Guangdong Medical College, Shantou University, Second Affiliated Hospital of Shantou University Medical College, Linyi City Chinese Medicine Hospital

Language: English

Topic: Dementia and Cognitive Impairment Research

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801