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High blood pressure and high cholesterol may contribute to increased dementia risk. Design by MNT; Photography by Jasmin Merdan/Getty Images & TEK IMAGE/SCIENCE PHOTO LIBRARY/Getty Images
  • 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 Open.

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 hormones, 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 lipoproteins.

There are two main types of cholesterol:

  • low-density lipoprotein (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 harmful to the heart and are associated with an increased risk of all-cause death and cardiovascular death in men.

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:

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 dementia 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.

For this study, Dr. Frikke-Schmidt and her team conducted a genetic association study involving 39,000 people clinically diagnosed with Alzheimer’s disease and 401,000 control participants without the condition.

Upon analysis, researchers found those genetically at-risk for developing high HDL cholesterol concentrations had an increased chance of getting Alzheimer’s disease.

“Our findings that genetically determined high HDL cholesterol concentrations were associated with a high risk of Alzheimer’s disease are in accordance with local properties of the HDL particle in the brain,” Dr. Frikke-Schmidt detailed.

“High HDL cholesterol is associated with the presence of large buoyant HDL particles that may be dysfunctional in local cholesterol transport inside the brain and across the blood-brain barrier, and this may have implications for cholesterol supply to the brain cells and clearance of sticky waste products.”
— Dr. Ruth Frikke-Schmidt

“Because we now suggest that high HDL cholesterol mimics causal pathways in the brain, this will encourage us to scrutinize the HDL pathways in the brain and to apply a recently developed multi-pronged strategy called genomics-driven drug discovery. Hopefully, we will come up with potential new drug targets,” she added.

Additionally, scientists found those genetically at a higher risk for developing high systolic blood pressure also had an increased risk for developing Alzheimer’s disease.

“High systolic blood pressure is a well-known risk factor for bad brain health. The very important novel finding from our study is that we now show that high systolic blood pressure most likely is a direct cause of future development of Alzheimer’s disease. This emphasizes the need for improved focus on early prevention and treatment.”

— Dr. Ruth Frikke-Schmidt

“It is well known that overweight and obesity (are) one of the causes of increased blood pressure, underscoring that early prevention of lifestyle risk factors is pivotal for preventing dementia as well as cardiovascular disease and diabetes,” Dr. Frikke-Schmidt added.

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.”
— Dr. David Merrill