Both high and low HDL cholesterol tied to slight increase in risk of dementia

Experts say it’s important to keep close watch on your cholesterol levels.

A new study of older adults found a link between extreme levels of “good” HDL cholesterol and a small increase in dementia risk later in life.

The research tracked more than 184,000 adults for 17 years and found both high and low HDL cholesterol was associated with greater odds of developing dementia compared to middle-range levels.

However, no clear associations emerged between “bad” LDL cholesterol and dementia except in statin users, suggesting complex relationships between cholesterol and cognitive decline.

New research, published today in the journal Neurology, reports that high levels as well as low levels of “good” HDL cholesterol were associated with a higher risk of developing dementia.

The study involved more than 184,000 participants with an average of 70 years who were followed for 17 years.

The researchers were seeking to understand the relationship between two types of cholesterol, HDL-C and LDL-C, and the likelihood of developing dementia in older age.

While there have been some studies on this topic, not many have considered the influence of statin medications or examined the possibility of more complex associations.

The researchers explored these connections using extensive data from both survey responses and electronic health records.

Tracking dementia

The study subjects were members of the Kaiser Permanente Northern California health plan who were 55 or older.

These members had taken a health survey between 2002 and 2007, did not have dementia before the survey, and had their cholesterol measured within two years after the survey.

The research team tracked these members until December 2020 to see if they developed dementia.

They used specific methods and models to understand the data, ensuring they considered various factors such as demographics and medications.

The researchers said the findings showed that both very low and very high levels of HDL-C were linked to a higher risk of developing dementia.

Relationship between HDL-C levels and dementia risk

The researchers reported that people with the highest HDL cholesterol levels had a 15% higher dementia risk compared to those with mid-range levels.

Those with the lowest HDL levels had a 7% higher dementia risk versus the mid-range group.

Researchers said these relationships held even after accounting for other factors such as alcohol use, hypertension, cardiovascular disease, and diabetes.

On the other hand, levels of “bad” LDL-C cholesterol didn’t show a clear link to dementia risk for everyone. However, for those who were using statins, a higher LDL-C level indicated a slightly higher dementia risk.

Age also seemed to play a role in the relationship between HDL-C and dementia risk but not with LDL-C.

While this large study shows associations, it cannot prove high or low HDL cholesterol levels directly cause dementia.

Erin Ferguson, MPH, a lead study author and a former Boston University SPH student currently affiliated with the University of California San Francisco, told Medical News Today that “we found a U-shaped relationship between HDL-C and dementia risk, such that people with either lower or higher HDL-C had a slightly elevated risk of dementia.”

“Overall, we found no association between LDL-C and dementia,” Ferguson added.

Clifford Segil, DO, a neurologist at Providence Saint John’s Health Center in Calilfornia who was not involved in this research, told Medical News Today that “studies looking into how to prevent dementia are appreciated as our treatments for dementia in 2023 continue to only provide modest clinical improvements.”

As a reminder, the three most common dementias are Alzheimer’s dementia, vascular or multi-infarct dementia, and Lewy-Body dementia or Parkinson’s dementia. Statin use, or medication used to lower cholesterol in our blood, has been proven to decrease a risk of second lifetime heart attack and stroke. Statin use needs to be studied specifically regarding decreasing the risk of multi-infarct of vascular dementia.

Dr. Clifford Segil

“This study looked at using cholesterol-lowering medications to decrease all dementia rather than statin use to decrease multi-infarct or vascular dementia,” Dr. Segil pointed out.

Further research needed to understand complex associations

Ferguson noted that “this work suggests that some lipoproteins (like HDL) may be modifiable risk factors of dementia, even in late life, but to take advantage of this we need to next evaluate whether these effects are causal and how to effectively modify HDL.”

While the magnitude of the association is fairly small, these results suggest that the relationship between HDL-C and dementia is complex. Our work supports a body of recent literature showing there are nonlinear relationships between HDL and other diseases (like cardiovascular disease and cancer) and mortality. The mechanisms for why these nonlinear relationships exist are still unknown.

Erin Ferguson, MPH

“Future studies will need to investigate causal relationships at play to confirm that there is clinical relevance,” Ferguson explained.

Segil agreed, saying, “more research should follow this study specifically looking at the role of using statins, or cholesterol-lowering medications, on the development of multi-infarct or vascular dementia.”

“Patients with memory loss often have MRI brain [findings consistent] with chronic ischemic changes and statins use may decrease these small silent strokes, but further research is needed to determine if this is the case,” she added.

Segil concluded by saying “elderly patients should not start taking statin medications to prevent dementia based on this study.”

Both high cholesterol and high blood pressure may put people at risk of developing Alzheimer’s disease.

Researchers from a European collaboration have found that people at a genetically increased risk for high-density lipoprotein (HDL) cholesterol and high systolic blood pressure are also at a higher risk of developing Alzheimer’s disease.

Scientists believe these findings may provide new drug targets and improve early dementia prevention.

High cholesterol levels and high blood pressure are both known modifiable risk factors for Alzheimer’s disease — a type of dementia that causes loss of memory and cognitive decline.

Now, researchers from the European Alzheimer’s & Dementia Biobank Mendelian Randomization (EADB-MR) Collaboration have also found that genetically determined increased high-density lipoprotein (HDL) cholesterol and high systolic blood pressure are associated with a higher risk of developing Alzheimer’s disease.

Scientists think these genetic links could be used to develop new drug targets and treatments to prevent dementia.

This study was recently published in the journal JAMA Network OpenTrusted Source.

 What is HDL cholesterol?

 Cholesterol is a fat naturally made inside the body mostly by the liver and intestines.

 It is essential for helping the body make vitamin D and certain hormonesTrusted Source, such as estrogen and testosterone. And it is also an important building block for cell walls and body tissues, and also helps make up digestive bile in the digestive tract.

Because cholesterol is not water soluble, it is carried through the bloodstream via lipoproteinsTrusted Source.

There are two main types of cholesterol:

low-density lipoproteinTrusted Source (LDL) cholesterol, known as “bad” cholesterol, is known to build up in a person’s arteries, putting them at risk for stroke or heart attack.

High-density lipoprotein (HDL) cholesterol, known as “good” cholesterol, helps eliminate LDL cholesterol buildup from the arteries.

Although HDL cholesterol is considered “good” cholesterol, too much in the body may be harmful.

Previous studies show high HDL cholesterol may contribute to inflammation in the body. And other research found high levels of HDL cholesterol can be harmfulTrusted Source to the heart and are associated with an increased risk of all-cause deathTrusted Source and cardiovascular death in men.

What is high systolic blood pressure?

A person’s blood pressure measures the force it takes for blood to move around their cardiovascular system.

When a doctor takes a person’s blood pressure reading, there are two numbers involved:

The top number, known as the systolic pressure, measures the pressure in the arteries when the heart is actively contracting.

The bottom number, called diastolic pressure, measures the pressure in the arteries when the heart relaxes between contractions.

Typical or healthy blood pressure is defined as a systolic pressure of less than 120 over a diastolic pressure of less than 80.

High blood pressure — also known as hypertension — occurs when the heart needs to exert an unnatural amount of force to pump blood throughout the body.

Sometimes it is only the systolic portion of a person’s blood pressure that goes too high, over 130. This could be caused by:

Searching for genetic associations

According to Dr. Ruth Frikke-Schmidt, a clinical professor in the Department of Clinical Medicine at the University of Copenhagen, chief physician in the Department of Clinical Biochemistry at Copenhagen University Hospital – Rigshospitalet, and corresponding author of this study, it is estimated that up to 40% of dementiaTrusted Source cases can be prevented or delayed by modifying 12 risk factors throughout the life course.

“The evidence behind several of these risk factors is, however, of questionable quality. To recommend the most efficient preventive strategy, we need to pinpoint those modifiable risk factors that directly (are) a cause of dementia,” she told Medical News Today.

“Here, genetic studies of large populations can help us because a genetically determined modifiable risk factor is created at conception, and thus is a very clean estimate of the direct impact of that risk factor on future development of dementia,” Dr. Frikke-Schmidt said.

Because the genetic risk factor is determined at conception, Dr. Frikke-Schmidt continued, it will not be influenced by other potentially influencing risk factors happening throughout the life course.

“Therefore, these genetic studies of large populations can inform us robustly of the direct causal value of a specific risk factor. When we have this piece of evidence, we can with more confidence recommend preventing these risk factors (from) occurring, or if they are already present, they should be treated as early as possible,” she explained.

Treating health conditions to prevent dementia

After reviewing this study, Dr. David Merrill, a geriatric psychiatrist and director of the Pacific Neuroscience Institute’s Pacific Brain Health Center in Santa Monica, California, told Medical News Today that these are interesting findings looking at genetically-determined risks for what are considered modifiable risk factors for Alzheimer’s.

“So if somebody’s genetically at risk for high cholesterol or genetically at risk for high blood pressure — meaning in all likelihood they might have that throughout life — then that can relate to a higher risk in a causal way for Alzheimer’s dementia down the line,” he said.

Dr. Merrill said this might allow researchers to develop drugs treating systemic lifelong health conditions like abnormal cholesterol levels or elevated blood pressure.

“And by treating systemic health conditions more thoroughly or more aggressively throughout life, you can prevent the development of dementia so you never end up needing a treatment for the pathology of Alzheimer’s disease because it doesn’t happen — that’s exciting,” he said.

“We definitely need more studies of the genetic associations predisposing people to modifiable risks and the subsequent outcomes in terms of dementia. In the field of dementia, we need more curiosity and more effort to optimize systemic body health, including cholesterol and blood pressure, to ultimately prevent neurologic conditions in late life like Alzheimer’s.”

https://www.medicalnewstoday.com/articles/both-high-and-low-hdl-cholesterol-tied-to-slight-increase-in-risk-of-dementia