Dementia risk rises with elevated remnant cholesterol, South Korean study reveals

By Priyanjana Pramanik, MSc.Reviewed by Lily Ramsey, LLMJul 30 2024

In a recent study published in The Lancet Healthy Longevity, researchers investigated how remnant cholesterol (remnant-C) levels are associated with the risk of developing dementia using a large dataset from South Korea.

Their findings indicate that higher concentrations of remnant-C are associated with an increased risk of all-cause dementia, vascular dementia, and Alzheimer's disease, suggesting that managing and monitoring these levels could be important in reducing dementia risk.

Study: Association of remnant cholesterol with risk of dementia: a nationwide population-based cohort study in South Korea. Image Credit: NPW-STUDIO/Shutterstock.com

Background

As a population ages, preventing dementia becomes increasingly crucial, especially since many risk factors can be modified. As much as 40% of dementia cases have been linked to factors like diabetes, hypertension, obesity, and dyslipidemia.

Dyslipidemia refers to abnormal levels of lipids, such as cholesterol and triglycerides, in the blood. Triglycerides are fats found in the blood, and when elevated, they can increase health risks.

Lipoproteins are particles that transport cholesterol and triglycerides in the bloodstream. High levels of these fats and lipoproteins, particularly remnant-C, are associated with increased risks of vascular dementia and Alzheimer's disease.

About the study

Researchers aimed to explore how remnant-C levels are linked to the risk of developing dementia, using data from South Korea's National Health Insurance Service (NHIS) covering nearly the entire population.

Researchers focused on individuals aged 40 and above who, in 2009, had taken part in a national health examination.

The study excluded people aged less than 40, those with very high triglyceride levels, individuals with existing dementia diagnoses, and those with missing data.

The researchers collected detailed demographic and lifestyle information through standardized questionnaires and medical exams. They measured various health indicators, including lipid profiles, body mass index (BMI), and blood pressure.

The primary outcome was the development of dementia, tracked using medical records and prescription data for dementia-related medications.

The study analyzed the relationship between levels of remnant-C and the probability of developing Alzheimer’s disease, vascular disease, and all-cause dementia, adjusting for factors like age, sex, smoking, alcohol consumption, exercise, income, and pre-existing conditions.

Researchers used statistical methods, including Kaplan-Meier analysis, which allowed them to estimate a survival function from data over the lifetime. Cox proportional hazard models explore the relationship between a patient’s survival and one or more variables to assess risk differences across remnant-C quartiles.

Findings

The study analyzed data from 2,621,596 adults, roughly equal numbers of males and females, to investigate the relationship between remnant-C levels and dementia risk.

Participants were divided into four groups (quartiles) based on their remnant-C levels. Those in the highest quartile (quartile 4) were more likely to be male and have less favorable health profiles, including higher BMI, triglycerides, fasting glucose, blood pressure, and lower high-density lipoprotein (HDL) cholesterol. They also had higher rates of smoking, heavy drinking, and less regular exercise.

The median time for follow-ups was 10.3 years, by which time 5.6% of participants had all-cause dementia, with Alzheimer's disease affecting 4.5% and vascular dementia 0.6%. The risk of developing dementia increased with higher levels of remnant-C.

For people among the highest quartile, the probability of having all-cause dementia was 11% higher, Alzheimer's disease 11% higher, and vascular dementia 15% higher compared to the lowest quartile. The increased risk was higher in younger participants and those with diabetes, especially with longer diabetes duration.

The study suggests that higher levels of remnant-C are associated with higher dementia risk, particularly in certain demographic and health subgroups.

Conclusions

The study's findings suggest that high remnant-C levels are significantly associated with an increased risk of vascular dementia, Alzheimer’s disease, and all-cause dementia, independent of total cholesterol and lipid-lowering medication use.

The risk is notably higher for vascular dementia; it is also more pronounced in middle-aged individuals and those with diabetes, particularly with a longer duration of the disease.

These results highlight the importance of monitoring remnant-C levels as a potential marker for dementia risk, especially in high-risk groups.

Previous research has focused on traditional lipids like low-density lipoprotein (LDL) and HDL cholesterol. Still, being the first large population-based analysis, this study adds significant weight to the evidence suggesting remnant-C as a crucial factor in dementia risk.

The study's strengths include its large sample size and long follow-up period. However, limitations include potential confounding factors, lack of education level data, and the inability to adjust for the apolipoprotein E (APOE) genotype, a strong dementia risk factor.

Future research should explore the mechanisms linking remnant-C to dementia and consider genetic factors and long-term monitoring of remnant-C levels for early intervention strategies.