Genetic predisposition toward higher blood pressure, cholesterol may be linked to Alzheimer’s risk, study finds

By Jen Christensen, CNN

(CNN) — A genetic tendency toward certain forms of higher blood pressure and cholesterol is linked to a potential increased risk of Alzheimer’s disease, a new study finds.

The exact cause of Alzheimer’s is unclear, and although there are medications available to slow the progress of the disease, there is still no cure.

Scientists have been racing to understand Alzheimer’s better so that they can figure out ways to prevent or treat it.

The understanding can’t come soon enough. More than 6 million Americans have the condition now, but the Alzheimer’s Association predicts that number will more than double by 2050, costing the country $1 trillion. Women and people who are Black or Hispanic are disproportionately affected by the disease.

The researchers on this study, published Wednesday in the journal JAMA Network Open, were trying to understand modifiable risk factors that might keep someone from developing Alzheimer’s. They also hoped to help guide drug development.

They analyzed data from the European Alzheimer & Dementia Biobank, a collection of DNA records from people with and without Alzheimer’s in 11 countries in Europe. Genetic factors account for up to 70% of attributable risk in common forms of Alzheimer’s, the Biobank says.

The new study included 39,106 people with clinically diagnosed Alzheimer’s and 401,577 controls who did not have the disease.

When the researchers compared the genetics of each, they found that people who had certain genes that led to higher levels of a type of cholesterol called high-density lipoprotein, also known as HDL or “good” cholesterol, had a slightly higher chance of developing Alzheimer’s. They found a similar increased risk for people with the genes responsible for higher systolic blood pressure.

The increase in the Alzheimer’s risk 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, the risk of developing Alzheimer’s disease increases 1.22 times.

The study did not find any consistent evidence for genetic associations with other lipid traits, nor did it find evidence that BMI, alcohol consumption, smoking or diabetes increased the odds of developing Alzheimer’s.

Other studies looking only at lifestyle factors that involve obesity, alcohol, smoking and diabetes – not the genetic risk for those factors – have shown a connection between them and a higher risk of Alzheimer’s.

The researchers said it’s important to note that while this is a large study, it cannot be generalized to the rest of the world because most of the participants were of European descent, and others may have different genetic factors for Alzheimer’s. The study also does not show that genes predetermine people to Alzheimer’s. More research needs to be done, the scientists say.

Although the researchers cannot pinpoint why this association may be a risk, they have a few ideas.

For people with a genetic predisposition to higher HDL, it may be about balance. HDL is sometimes called “good” cholesterol because it helps the body get rid of “bad” cholesterol, LDL, which can clog the arteries and make it hard for blood and oxygen to get to the heart.

In heart health, higher HDL can help prevent a stroke or a heart attack. But in brain health, higher HDL may upset the balance of a particular kind of protein that scientists suspect plays a role in the development of dementia.

Other studies have shown that high blood pressure at midlife can be a risk factor for Alzheimer’s, although research is more limited on its effects in later life.

Dr. Sudha Seshadri, director of UT Health San Antonio’s Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, said people should keep in mind that this is just one study.

“Overall, I would say it does offer some support for the fact that a lower blood pressure may be good. And the fact that higher HDL, it’s raising some concern about dementia, but there are many explanations for this,” said Seshadri, who was not involved with this research.

She said it could be something as simple as higher HDL protecting people from a heart attack or stroke, helping them live longer, and age is a factor in dementia.

“It’s research that needs to be replicated and better understood. It’s certainly interesting. But it’s just one piece of information,” Seshadri said.

Studies like this are good building blocks to understand how the disease works, said Dr. Rebecca M. Edelmayer, senior director of scientific engagement for the Alzheimer’s Association.

It’s an exciting time in the field, she said, as researchers are understanding that cognitive decline or dementia is probably due to family history and genetics but also risk factors that can be modified like diet, heart health and exercise.

“As noted in the paper, we believe a large proportion of global dementia cases could potentially be prevented or delayed by targeting modifiable risk factors and also understanding how we sort of tease out what might be genetic and what might be related to modifiable risk,” said Edelmayer, who was not involved in the new research.

It would help if more people signed up for clinical trials so scientists can better understand the causes of Alzheimer’s.

Edelmayer believes that in the future, treatment for Alzheimer’s disease and potentially other dementias will require a combination approach to address modifiable risk factors as well as involving powerful treatments.

One powerful area to target is heart health.

“I would say current population-level evidence suggests that risk for cognitive decline and possibly dementia could be reduced, especially by focusing on cardiovascular risk factors,” Edelmayer said.

Eating a healthy diet, getting regular exercise, quitting smoking and managing heart health and diabetes all should help.

“It really is what’s good for your heart is going to be good for your brain,” she said.

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