How Managing Diet, Exercise, and Hearing Loss Can Lower Alzheimer’s Risk

Risk factors of Alzheimer’s disease

Age is the greatest known risk factor of Alzheimer’s disease. Most people with the disease are 65 years and older. The risk doubles every 5 years after that and increases to almost one-third after 85, according to the Alzheimer’s Association.

In addition to age, genetics is a powerful indicator of risk. Fillit breaks down genetics into two categories.

The first is familial Alzheimer’s, which involves having a mutation in a gene for the protein that’s found in the brains of people with Alzheimer’s disease.

“Particularly the beta-amyloid protein, and when you have the mutation in that gene it means that you’re going to get Alzheimer’s disease, and it means that anybody in your family who has the same gene is going to get it,” Fillit said.

People who have these genes start showing symptoms of Alzheimer’s in their 30s, 40s, or 50s.

“There are other genes that have been discovered more recently that seem to be associated with Alzheimer’s disease like TREM2, but mainly it is in these beta-amyloid genes,” Fillit said.

The second category is genetic risk factors. This means if you have a certain gene type, you have an increased risk for developing Alzheimer’s disease but aren’t guaranteed to develop the disease.

“The important one here is a molecule called apolipoprotein E (APOE), [which] carries cholesterol, and it helps to traffic cholesterol in the brain and body,” Fillit said.

Fillit explains there are three kinds of APOE in humans. APOE2 is a protective gene, and those who have it have about a 5 percent chance of developing Alzheimer’s. About 70 percent of people who have APOE3 have a baseline risk of Alzheimer’s disease, he says.

“You can get any gene. One from mom and one from dad, so you could be a 2-2 or 2-3, and if you get a 2-3 you are somewhat protected from Alzheimer’s disease, and if you’re a 2-2 you’re really protected against Alzheimer’s disease,” Fillit explained.

Those with APOE4 have an increased risk as well.

“APOE 3-4 have an increased risk of about five times the general population, and they represent about 15 percent of people, and those who are 4-4 have about 15 times the risk of Alzheimer’s. Those with APOE4-4 represent about 5 percent of the population, and they get the disease about 10 years earlier than the average person, so maybe at 65 rather than 75,” Fillit said.

While the increases associated with APOE are known, he adds that with all genetic risks it’s hard to figure out exactly what the genes are doing to cause or contribute to Alzheimer’s disease.

Additional factors for Alzheimer’s disease include:

• Head injury. An impact to the head that causes brain injury has been linked to future risk of dementia.
• Heart health. Research shows a connection between brain health and heart health. The risk of developing Alzheimer’s may be increased by conditions that damage the heart and blood vessels, such as heart disease, diabetes, stroke, high blood pressure, and high cholesterol.

Can drugs help?

There are two types of drugs on the market at this time that focus on enhancing memory and cognitive function.

Fillit says cholinesterase inhibitors are modestly effective in treating the symptoms of Alzheimer’s, while memantine drugs help improve memory and cognitive function in people with moderate to severe dementia.

Rebecca Edelmayer, PhD, director of scientific engagement at the Alzheimer’s Association, says that while there are several FDA-approved prescription medications to treat the cognitive symptoms of Alzheimer’s disease, many are most beneficial in the earliest stages of the disease.

“But we know there are some individuals who are not benefiting from these medicines, and we need to improve upon the medicines that are available, so there are many clinical trials underway today… looking at ways to better treat both the cognitive and behavioral symptoms of Alzheimer’s disease and other dementia,” Edelmayer told Healthline.

Fillit agrees, noting that the ADDF supports programs working to find Alzheimer’s medications, particularly those focused on APOE.

“I think we’ve come up with what’s looking like a promising answer. We haven’t figured it out yet, probably because the APOE is so complicated. We think fixing it with gene therapy is the way to go, so we’ve been supporting a gene therapy program at Weill Cornell here in New York, and that program has progressed into clinical trial,” he said.

The idea behind the research is to take the APOE2 gene and put it inside a noninfectious virus, which is then injected into the brain.

“The virus would make the APOE2, and the APOE would offset the APOE4 risk. It’s a strategy that is FDA approved. We’re in phase I to see about the safety,” Fillit said.

He adds that there are many drugs close to development for Alzheimer’s symptoms, such as agitation and psychosis.

“What we really want are drugs that are going to treat the cause of Alzheimer’s disease or the factors that make it progress,” he said. “There are over 100 drugs right now in development that are directed in many different ways to treat the underlying pathways that cause Alzheimer’s disease.”

He says the drugs focus on a variety of contributors to the disease, including the protein beta-amyloid, the molecule tau, inflammation that occurs in the brain, genetics, and metabolic disorders.