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Too much HDL-C or ‘good cholesterol’ may be linked to an increased risk of dementia. urbazon/Getty Images
  • A new study shows high levels of HDL-C (“good cholesterol”) may be associated with an elevated risk of dementia in older adults.
  • One possible explanation could be that HDL cholesterol behaves very differently in the brain compared to the rest of the body. HDL cholesterol can lead to stiffening of the blood vessels, and in the brain, this could increase the risk of stroke.
  • Researchers found that high levels of HDL-C connected to dementia risk were uncommon and not related to diet but more likely to indicate a metabolic disorder.

According to a new study, high levels of HDL-C, more commonly referred to as ‘good cholesterol’, are linked to an increased risk of dementia in older adults.

The study authors explained that very high levels of HDL-C associated with dementia risk in their research were uncommon and not connected to diet, but there was a greater chance it indicated a metabolic disorder.

Researchers examined 18,668 healthy older participants who were mostly over the age of 70. During an average 6.3 years of follow-up, participants with very high HDL-C (>80 mg/dL or >2.07 mmol/L) at the start of the study had a 27% higher risk of dementia compared to those with optimal HDL-C levels (for men: 40 to 60 mg/dL or 1.03–1.55 mmol/L; for women: 50 to 60 mg/dL or 1.55–2.07 mmol/L).

In addition, participants who were 75 years and older demonstrated a 42% increased risk in dementia compared to those with optimal levels of HDL cholesterol.

Results showed 2,709 participants had very high HDL-C at the start of the study, with 38 cases of dementia in those who were younger than 75 years with very high levels, and 101 in those 75 and older with very high levels.

The findings were published in The Lancet Regional Health – Western Pacific.

“The terms ‘good’ and ‘bad’ cholesterol, I think, oversimplify the differences between HDL and LDL cholesterol, respectively,” said Dr. Corey Bradley, cardiologist and assistant professor of medicine at Columbia University Vagelos College of Physicians and Surgeons. “But in essence, HDL cholesterol has been traditionally thought of as ‘good’ because it helps to transport cholesterol out of the bloodstream and bring it back to the liver.”

On the other hand, “LDL cholesterol is considered ‘bad’ because it can build up in the walls of the arteries and lead to plaque formation, known as atherosclerosis. What we are learning now is that there is a lot more nuance to HDL’s role in the body. As a result, I usually explain to patients that it is more ‘neutral’ than ‘good’,” Bradley told Medical News Today.

Dr. Dylan Wint, a neurologist at the Cleveland Clinic Lou Ruvo Center for Brain Health, explained that when it comes to understanding the difference between good and bad cholesterol, it’s not quite that simple, as with most things in physiology.

“Low-density lipoproteins (LDL and very LDL) are necessary to carry cholesterol from the liver, through the bloodstream, to other organs. LDL were dubbed ‘bad’ cholesterol because LDL is the main type of cholesterol found in the plaques that accumulate in the walls of arteries, predisposing toward obstructions, clots, and inflammation. High levels of LDL are associated with ischemic diseases such as stroke and coronary disease,” said Dr. Wint.

“High-density lipoproteins (HDL) tend to bring cholesterol from the arteries to the liver. So, they would reduce the likelihood of plaque formation and are therefore considered ‘good.’ Both of these cholesterols, in proper balance, are necessary for ideal physiologic function,” he added.

“So far, we have no evidence of a causal link between HDL-C and dementia; however, this is not the first study to suggest an association,” said Bradley. “I think there is still a lot that we do not fully understand about this association, but it is certainly leading us to ask better questions and more fully investigate this relationship.”

Some possible explanations relate to how HDL cholesterol behaves very differently in the brain compared to the rest of the body, Bradley noted. HDL cholesterol can lead to stiffening of the blood vessels, and in the brain, this could increase the risk of stroke.

It also can cause pro-inflammatory changes to the brain, which may be related to some forms of dementia. Further, as the researchers suggested, levels of HDL in the body do not always directly relate to the functionality of the particle.

It is possible that when HDL is in high levels, it does not behave in the same way that it does when in “normal” ranges, Bradley added.

“[A]bnormal levels of just about anything—even things that are considered ‘good’—tend to cause problems. Health is typically characterized by moderation, balance, and aligning the systems of the body and brain with the uses for which they were intended.”
— Dr. Dylan Wint

“HDL is a transporter whose ‘primary cargo’ (we think) is cholesterol. Cholesterol is an important component of brain structures, and a change in the frequency or intensity of HDL interactions could degrade normal processes. As HDL levels become extremely high, the structure of the HDLs themselves changes, which could affect the ‘cholesterol economy’ of the brain. Finally, this may not be related to cholesterol per se, but to something else the HDL molecule does/has (or does not do/have) to preserve brain health,” Dr. Wint explained to MNT.

The study authors noted that high levels of HDL-C associated with dementia risk were uncommon and not linked to diet but more likely to indicate a metabolic disorder.

“The researchers in this study reported an association with HDL and dementia risk for levels >80 mg/dl. This is above what we consider ‘normal’ HDL levels, but levels vary widely based on the patient. While lifestyle choices certainly affect HDL levels, the role of genetics is also very important,” said Bradley.

“There are different genetic mutations that can cause the higher HDL levels described in this study. While the study did adjust for common genetic mutations to try to control for this, there is so much still to learn about the role of genetics that we do not yet understand. These genetic variances may relate to both HDL levels and dementia risk, there is just a lot more to learn about these associations,” he continued.

The biggest limitation of this study is the demographics.

“This study included relatively healthy, white patients,” Bradley pointed out.

“It remains unclear how and if this data applies to a diverse population. It is hard to apply the results from this study to most patient populations in the United States. This study is certainly hypothesis-generating and should lead to asking more questions about this association, but it is too early to draw any generalizable conclusions,” he said.

Dr. Wint also noted several limitations:

  • “Only 9% of the participants overall were non-white. It’s become clear that risk factors for dementia differ among racial-ethnic groups.
  • The type of genome analysis could not identify whether there might be a single genetic factor that predisposes to both extremely high HDL and dementia.
  • [There were] no dementia biomarkers that could offer a better understanding of what’s going on — ‘Is this vascular dementia? Alzheimer disease? Some other proteinopathy?’— and better insight into what HDL’s role might be.”