Association of remnant cholesterol with cognitive impairment: a cross-sectional study

TL;DR

Higher levels of remnant cholesterol are linked to a greater risk of cognitive impairment in older adults.

Contribution

This study identifies remnant cholesterol as a potential modifiable risk factor for cognitive impairment.

Findings

Each 1-mmol/L increase in remnant cholesterol was associated with a 3.47-fold higher risk of cognitive impairment.

The association between remnant cholesterol and cognitive impairment was consistent across subgroups.

Machine learning analysis ranked remnant cholesterol as a top variable in predicting cognitive impairment risk.

Abstract

Although dyslipidemia has been implicated in the development of cognitive impairment, the association between remnant cholesterol (RC) and cognitive outcomes remains incompletely understood.

We conducted a cross-sectional study using data from 1,136 participants at Liuyang Jili Hospital from 2022. RC was calculated as total cholesterol minus low-density and high-density lipoprotein cholesterol, and cognitive function was assessed using the Mini-Mental State Examination. Restricted cubic spline and multivariable logistic regression models were used to evaluate associations between RC and cognitive impairment, with subgroup, and sensitivity analyses. Machine learning models with SHapley additive explanation (SHAP) values were applied to assess variable importance.

Participants had a median age of 68 years, and 21.2% had cognitive impairment. Higher RC levels were associated with increased risk of cognitive impairment (per 1-mmol/L increase: adjusted odds ratio, 3.47; 95% CI, 2.34–5.25; P < 0.01), with no evidence of a non-linear relationship. The association remained consistent across subgroups. In machine learning analyses, RC ranked third in variable importance after waist circumference, and body mass index, and SHAP dependency plots demonstrated a monotonic positive relationship between RC and cognitive impairment risk.

Elevated RC levels are positively associated with an increased risk of cognitive impairment. These findings suggest that remnant cholesterol may be an important and modifiable risk factor for cognitive dysfunction, warranting confirmation in prospective longitudinal studies.

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