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Alzheimer’s: High Blood Pressure, Cholesterol, Genes May Increase Risk

Dec 05, 2023Dec 05, 2023

A genetic predisposition to having higher systolic blood pressure and HDL cholesterol is linked to an increased risk of Alzheimer's disease, a new study suggests.

The study does not show that these directly cause the disease, only that there is an association.

However, other research has found that high blood pressure is a common modifiable risk factor for Alzheimer's disease.

The results of the new study may provide insight into "new drug targeting and improved early dementia prevention" for Alzheimer's disease, the authors write May 17 in JAMA Network Open.

In the United States, an estimated 5.8 million older adults had Alzheimer's disease in 2020, with this set to triple by 2060, predicts the Centers for Disease Control and Prevention.

Scientists don't completely understand what causes the disease. It is likely due to a combination of age-related changes in the brain, as well as genetic, environmental, and lifestyle factors.

While certain medications may slow the progress of the disease, there is currently no cure.

Over the past few decades, scientists have been working to decipher the underlying mechanisms of the disease and determine how to prevent and treat it.

In the new study, scientists were trying to understand which modifiable risk factors might increase a person's risk of developing Alzheimer's disease.

They analyzed data from the European Alzheimer & Dementia Biobank, a collection of genetic information on people with and without the disease. Genetic factors are estimated to account for 60% to 80% of Alzheimer's disease risk.

The new study included over 39,000 people with clinically diagnosed Alzheimer's disease and over 401,000 people who did not have the disease.

Researchers found that people with certain genes linked to higher levels of high-density lipoprotein (HDL) cholesterol had a slightly higher chance of developing Alzheimer's disease.

They found a similar increased risk for people with genes linked to higher systolic blood pressure — the pressure when the heart beats.

The increase in the risk of Alzheimer's disease was about 10% for every standard deviation increase in HDL cholesterol. And for every 10 millimeters of mercury (mm Hg) increase in systolic blood pressure, Alzheimer's disease risk increased by 22%.

Dr. James E. Galvin, professor at the University of Miami and director of the Comprehensive Center for Brain Health at UHealth — University of Miami Health System, pointed out that the study focused on genetic predispositions for potential risk factors, rather than people being diagnosed with these conditions.

However, "the finding of novel genetic associations could lead to testing and validation of novel drug targets for treatment and/or prevention of Alzheimer's disease," said Galvin, who was not involved in the new study.

In contrast, genes linked to other potentially modifiable risk factors such as blood lipids, alcohol consumption, and diabetes did not increase the chance of developing Alzheimer's disease. Results for genes linked to smoking and BMI were not clear.

Galvin also said it was surprising that factors such as diabetes, smoking, and obesity — which "travel" with high blood pressure and high cholesterol — did not seem to increase the Alzheimer's disease risk.

Although the study included a large number of people, most were of European ancestry. So the results may not apply to people from other parts of the world, who may have different gene variants related to Alzheimer's disease risk.

Even though the study was not designed to determine why high blood pressure and high HDL cholesterol may be risk factors for Alzheimer's disease, the authors have a few ideas.

Other research has shown that high blood pressure in midlife and late life increases the chance of developing Alzheimer's disease.

In addition, high systolic blood pressure may cause blood vessels to function poorly, which can disrupt blood flow to the brain, the authors write.

This suggests that treating high blood pressure may lower a person's Alzheimer's disease risk. Some research supports this, although the authors of the new study say the effects in these studies only lasted during the clinical trials.

Galvin said it was a bit surprising that increases in HDL, rather than LDL or other lipid components, was associated with increased Alzheimer's risk.

"LDL [low-density lipoprotein] cholesterol and triglycerides are more commonly associated with poorer health outcomes," he said, "while HDL is often referred to as ‘good’ cholesterol."

HDL cholesterol absorbs cholesterol in the blood and carries it to the liver. Higher HDL cholesterol levels can lower the risk of heart disease and stroke.

Higher levels of HDL cholesterol may contribute to dementia by disrupting the balance between particles in the blood and the fluid surrounding the brain, the authors of the new study say.

This does not mean lowering HDL cholesterol levels will reduce the risk of dementia.

It could be that high levels of HDL cholesterol protect people from heart attack or stroke, which enables them to live longer. Older age is a factor in the development of Alzheimer's disease.

More research is needed to understand this particular connection.

Regardless of whether genetic associations were found, the modifiable risk factors tested in the new study all play a role in the development of Alzheimer's disease, said Galvin.

"In cases where genetic associations were not found, environmental and/or lifestyle associations may be more likely to increase risk," he said.

A 2020 report by the Lancet commission on dementia estimates that making changes to 12 modifiable risk factors could prevent or delay up to 40% of dementia.

The new study and other research support the concept that Alzheimer's disease is a complex, chronic condition, said Galvin, one that will require treatment with several kinds of therapy.

"This approach will include medications, psychotherapy, lifestyle modifications, healthful behavioral change, risk reduction where possible, and control or management of co-morbid conditions," he said.

This also opens up the possibility that people may be able to reduce their risk of dementia, although because many factors are involved, they may not eliminate it entirely.

"Individuals with greater investments in brain health — such as performing resilience activities and reducing vulnerabilities — could see a greater resistance to developing Alzheimer's disease later in life," said Galvin.

According to a new study, a combination of genetically higher blood pressure and cholesterol may increase a person's risk of developing Alzheimer's. Earlier studies have also shown a link between high blood pressure in middle age and a higher risk of Alzheimer's later in life. Experts also noted that the risks of Alzheimer's increased with higher levels of HDL versus LDL cholesterol — LDL cholesterol is most associated with cardiovascular disease. Genetics as well as modifiable risk factors, including lifestyle and environment, all contribute to a person's overall risk of developing memory issues as they age.