April 6, 2025, 9:36 am | Read time: 8 minutes

While LDL is considered the “bad” cholesterol because it can promote heart disease, HDL is generally referred to as the “good” cholesterol. However, it appears that both can play a negative role in brain health, depending on their levels. A recent analysis from Korea shows that people with particularly low LDL levels were less likely to develop dementia — even if they were taking cholesterol-lowering drugs. However, even high HDL levels do not appear to guarantee protection.

HDL versus LDL

When it comes to cholesterol levels, a distinction is made between the two lipoproteins, LDL (“low-density lipoprotein”) and HDL (“high-density lipoprotein”). The former is considered the “bad” cholesterol because it transports the fat-like natural substance cholesterol from the liver to various tissues. This can lead to fatty deposits in the blood vessels (and corresponding secondary diseases). In contrast, the “good” cholesterol, i.e., HDL, transports the same cholesterol back to the liver. This means that it can be excreted from the body via the bile.

However, cholesterol levels should not only be monitored with regard to heart health; they are also increasingly becoming the focus of research into dementia.

Link Between Cholesterol and Cognitive Health?

While the role of LDL cholesterol in cardiovascular disease is well established, its role in dementia is controversial. While previous observational studies and warnings from the US Food and Drug Administration (FDA) suggested a link between very low LDL levels and cognitive decline, current clinical ones paint the opposite picture.¹ This study sought to clarify this uncertainty through a comprehensive analysis. The researchers investigated whether low LDL levels are associated with a lower risk of dementia (of any cause) and Alzheimer’s disease-related dementia (ADRD). They also investigated whether statins modify this effect.

The study could help to define more precise LDL target values in dementia prevention, and it shows how closely blood lipid levels are linked to cognitive health.

Course of the Study

The study is a retrospective, comparative cohort that analyzed data from eleven university hospitals in South Korea. Patients aged 18 and over were examined. Exclusion criteria included existing dementia diagnoses or less than 180 days of observation before inclusion in the cohort.

The subjects were categorized based on the LDL cholesterol levels measured at the start of the study:

• Group 1: Less than 70 milligrams of LDL cholesterol per deciliter of blood (or less than 1.8 millimoles per liter)
• Group 2: Less than 55 milligrams of LDL cholesterol per deciliter of blood (or less than 1.4 millimoles per liter)
• Reference group: More than 130 milligrams of LDL cholesterol per deciliter of blood (or more than 3.4 millimoles per liter)

The study used 1:1 propensity score matching to compare subjects from group 1 with the reference group. This made 108,980 subjects per group statistically comparable in terms of age, gender, previous illnesses, medication, smoking, and alcohol consumption. Of primary interest was the occurrence of any dementia and ADRD in particular. As a secondary research objective, the scientists investigated LDL thresholds below 55 milligrams per deciliter (group 2) and the influence of statin use.

Low LDL Cholesterol Can Reduce Dementia Risk by 26 Percent

The analysis showed that people with LDL levels below 70 milligrams per deciliter had a 26 percent lower risk of developing dementia compared to the reference group (more than 130 milligrams per deciliter). The risk reduction for Alzheimer’s-associated dementia (ADRD) was as high as 28 percent. Subjects from group 2 who had even lower LDL levels (below 55 milligrams per deciliter) had an 18 percent lower risk. A “the less, the better” effect, therefore, does not apply here. This was also shown when the study authors looked at people with extremely low levels below 30 milligrams per deciliter; no additional advantage was seen here.

Taking statins also had an independent protective effect. In group 1, the risk of all forms of dementia was reduced by a further 13 percent in statin users and by 12 percent in ADRD users compared to non-users. Interestingly, this protective effect was no longer detectable when LDL levels were below 55 milligrams per deciliter (group 2). Overall, the data suggest a threshold effect, where levels below 70 milligrams per deciliter appear to be optimal, with no additional benefit from a further drop.

Significance and Classification of the Study

This study provides robust evidence that targeted management of LDL cholesterol could prevent not only heart attacks but also dementia — an important step for preventive medicine. Of particular relevance is the reference to the threshold level of below 70 milligrams per deciliter, which was associated with the greatest cognitive benefit, while extremely low levels appear to confer no further benefit. In practice, this could help to avoid unnecessarily aggressive therapies. In addition, the combination of low LDL levels and statin use appears to be particularly effective — possibly due to the additional protective effects of statins on blood vessels and inflammation in the brain.

In the future, doctors could use LDL target values not only for heart disease but also for dementia. In addition, for people with an increased risk of dementia, for example, due to a family history of the disease, this opens up a further preventative adjustment screw that they can pay attention to in everyday life.

The study is impressive due to its high number of test subjects, methodological accuracy, and standardized data analysis. Nevertheless, there are limitations: The LDL values were only recorded once, and individual influencing factors such as diet or exercise were not taken into account in some cases. It remains unclear why extremely low LDL levels in statin users did not bring any additional benefit. In addition, the retrospective design does not allow any causal statements to be made. Future long-term studies with repeated measurements are needed to better understand the correlations.

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High HDL Levels Can Also Apparently Increase the Risk of Dementia

HDL cholesterol is known as the “good” counterpart to LDL cholesterol. However, some researchers are now questioning this clean image. An American study came to the conclusion that, contrary to what has long been assumed, the presence of HDL does not mean a certain degree of protection against heart disease for every person. And the facade is also crumbling when it comes to dementia: an Australian study from 2023 provided evidence that “good” cholesterol may also be a risk factor for dementia.

What Was Investigated?

The authors of the study examined data from a long-term study by the American College of Cardiology — the “Aspirin in Reducing Events in the Elderly (ASPREE)” — for a possible link between HDL cholesterol (HDL-C) and dementia. The researchers had access to data from a total of 18,668 study participants.²

High HDL Levels Increased the Risk by 27 Percent

4.6 percent of the test subjects developed dementia over a period of 6.3 years. Indeed, the scientists found evidence in their analysis that there is a link between high HDL-C levels and dementia. The researchers came to the conclusion that study participants with a high HDL-C level (over 80 milligrams per deciliter) had a 27 percent higher risk of dementia. It is also interesting to note that age seems to play a certain role. This is because the risk of this neurological disease was higher in the older test subjects (75 years and older) than in those under 75. However, the younger participants also showed an increased risk of dementia with higher HDL cholesterol.

Experts Explain: Cholesterol Can Be This High

Most people know that high cholesterol levels are unhealthy. What is less clear to many is which levels are okay — and, accordingly, which are not. In an interview with FITBOOK, internist and nutritionist Matthias Riedl, among others, clarified this: “The value for total cholesterol should be below 200 mg/dL. LDL cholesterol should not exceed a value of 150 mg/dL.” He added: “However, if you are a smoker, have high blood pressure, or are overweight, a value of 100 mg/dL is better for you in order to reduce the cardiovascular risk.” With regard to HDL cholesterol, Prof. Johannes Wechsler, MD, President of the Association of German Nutritionists, recommends: “HDL should be above 45 mg/dL for women and above 40 mg/dL for men.”

Researchers Recommend That HDL Levels Should Also Be Taken into Account for Early Detection of Dementia

The researchers considered their study findings to be so significant that they advocate using HDL levels for the early detection or assessment of an increased risk of dementia. However, the study was also unable to demonstrate causality or explain why and how HDL cholesterol promotes dementia. However, one thing is clear: there are increasing signs that the division into “good” and “bad” cholesterol is too simplistic and does not correctly reflect the complex reality of processes in the body.