# 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

## TL;DR

A U-shaped relationship between a cholesterol ratio and cognitive impairment was found in older adults, suggesting this ratio could be a useful indicator for cognitive health.

## Contribution

The study identifies a novel U-shaped association between NHHR and cognitive impairment using both conventional and machine learning methods.

## Key findings

- NHHR showed a U-shaped association with cognitive impairment (p < 0.001).
- NHHR ≥ 2.772 was linked to a 3.36-fold increased risk of cognitive impairment.
- NHHR outperformed LDL, HDL, and non-HDL in predicting cognitive impairment.

## Abstract

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.

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.

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.

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.