Maintaining low cholesterol may help decrease dementia risk

New research suggests that cholesterol could play a key role in dementia risk.

• Dementia affects millions of people worldwide, and numbers are increasing rapidly.
• One factor that may increase the risk of dementia is high levels of blood cholesterol.
• Now, a study has found that low levels of LDL-C, or ‘bad’ cholesterol, may reduce the risk of developing dementia.
• Statins, a cholesterol-lowering medication, could reduce the risk of dementia further in people with low LDL-C.

Cholesterol performs many essential functions within the body, including building cell membranes, producing steroid hormones and helping create bile in the liver.

However, too much cholesterol — particularly low-density lipoprotein cholesterol (LDL-C) — can lead to health problems, such as cardiovascular disease.

Cholesterol levels may also affect a person’s risk of developing dementia but study findings are inconsistent. Some studies suggest that higher levels have a protective effect; others maintain that dementia risk is not linked to high cholesterol.

Another study has found very little association between LDL-C and dementia risk.

A new study by South Korean researchers has found that people with low, but not extremely low, LDL-C levels have a reduced risk of developing dementia, and this decrease appears to be enhanced if they take cholesterol-lowering statins.

The study is published in the BMJ Journal of Neurology, Neurosurgery and Psychiatry.

Emer MacSweeney, MD, CEO and consultant neuroradiologist at Re:Cognition Health, who was not involved in this study, explained for Medical News Today that:

“The study reinforces the importance of lipid management in overall health, including cognitive function. It also highlights the complexity of LDL-C’s role in dementia, suggesting that optimal levels exist rather than a ‘lower is always better’ approach. While promising, these findings should be interpreted with caution due to the observational nature of the study. More high-quality [randomized control trials] are needed to confirm these associations and inform clinical guidelines.”

Low LDL-C linked to reduced dementia risk

The researchers analyzed outpatient data, collected between 1986 and 2020, from more than 12 million people at 11 medical centers in South Korea.

United States Government guidelines state that a healthy level of LDL-C is under 100 milligrams per deciliter (mg/dL).

After an initial analysis, the researchers divided their final sample into two groups: 108,980 people with LDL-C greater than 130 mg/dL, and 108,980 with LDL-C under 70 mg/dL. All were followed for 180 days after testing, for comparison.

They recorded two outcomes — a primary outcome of all-cause dementia, and a secondary outcome of Alzheimer’s disease.

The researchers replicated their analysis with a subset of patients who had been prescribed statins before inclusion in the study, dividing them into three groups by LDL-C levels: less than 55 mg/dL, less than 70 mg/dL, and greater than 130mg/dL.

People with LDL-C levels below 70 mg/dL had a 26% lower risk of all-cause dementia and a 28% lower risk of Alzheimer’s disease related dementia, than those with LDL-C levels greater than 130mg/dL.

At LDL-C levels below 70 mg/dL, the reduction in dementia risk diminished. People with LDL-C at 55 mg/dL had only 18% risk reduction, and below 30 mg/dL, there was no reduction in dementia risk at all.

MacSweeney told MNT: “This is an interesting observation indicating a potential threshold effect, where reducing LDL-C beyond a certain point does not further improve cognitive outcomes. It aligns with previous research indicating that while high LDL-C is harmful, excessively low levels may not offer additional protective effects.”

And David Gill, MD, a neurologist at the University of Rochester Medical Center, similarly not involved in the study, explained further that:

“High levels of LDL-C are associated with higher rates of vascular disease such as coronary artery disease in the heart and lowering those levels to a point is associated with reduced risk of vascular disease but there does not appear to be additional benefit once they fall below a certain level and extremely low levels may actually be harmful.”

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Statins may amplify benefits of low LDL-C

Statins are medications used to help lower blood cholesterol levels, to reduce the risk of heart attacks and strokes. This study suggests that they might also reduce the risk of dementia.

In people with LDL-C below 70 mg/dL, statins were associated with a further 13% reduction in dementia risk, and a further 12% lowering of Alzheimer’s risk, compared with nonusers. The researchers found that statins slightly decreased risk in those with higher LDL-C levels, but had no effect in those with LDL-C levels below 55 mg/dL.

However, Gill cautioned that, “s[i]nce this was an observational study, we cannot use the results to say that statins reduced the risk, just that a patient being on a statin medication may have been associated with an even lower risk of dementia.“

“This is an important distinction because there is limited evidence that statin use is associated with less risk of dementia despite many studies looking at this risk,” he noted. “This study is yet another study to add to this list of studies that suggest there may be an association between statin use and a lower risk of dementia.”

“In general, I recommend statin or other lipid lowering medications be used according to recommended guidelines for prevention and treatment of coronary artery disease, stroke and peripheral vascular disease and not merely for dementia prevention given the lack of well controlled research studies to guide their use, as it is possible that statin medications do not reduce the risk of dementia and have their own risks.”– David Gill, MD

Why might lower cholesterol and statins reduce dementia risk?

The authors of the study state that higher levels of LDL-C lead to inflammation, oxidative stress and an imbalance in brain cholesterol homeostasis, all of which are implicated in the development of dementia.

Conversely, low LDL-C reduces the risk of atherosclerosis and cerebrovascular disease, which known risk factors for dementia.

Statins enhance the function of endothelial cells that line blood vessels, reduce neuroinflammation and regulate the metabolism of beta-amyloidTrusted Source, which forms the plaques that are characteristic of Alzheimer’s disease.

“This suggests that statins may have neuroprotective effects beyond simply lowering LDL-C, possibly through an anti-inflammatory or vascular mechanism,“ MacSweeney explained further.

“However,” she cautioned, “the effect size was modest and more research is needed to confirm causation.”

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Keep LDL-C low to enhance health

Although this study cannot prove that lower LDL-C decreases dementia risk, it does help protect against cardiovascular disease, so people are advised to keep their LDL-C levels below 100 mg/dL.

MacSweeney advised:

“To maintain healthy LDL-C levels while optimising cognitive benefits, it is advised to follow a heart-healthy diet rich in fruits, vegetables, whole grains, and healthy fats (e.g., olive oil, nuts, fatty fish).”

She also advocated engaging in regular physical activity, avoiding smoking and limiting alcohol consumption. In addition, she recommended that people manage their weight and control conditions like hypertension and diabetes, and only “consider statin therapy if clinically indicated, under a doctor’s guidance.”

https://www.medicalnewstoday.com/articles/maintaining-low-cholesterol-may-help-decrease-dementia-risk