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What Causes Dementia?

There’s still much to learn about why dementia happens, and the list of risk factors is long

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Dementia develops over time as brain cells die, although scientists can’t point to one single cause for this. Many factors appear to be at work.

In Alzheimer’s disease, the most common disease that leads to dementia, naturally occurring proteins, called beta-amyloid and tau, build up in the brain. They clump together to form plaques and tangles that disrupt cell function. Neurons, or nerve cells, lose their connections with each other, unable to send messages to other regions of the brain. But there’s more going on.

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​​“We have known for more than 25 years that it takes more than just an elevated level of amyloid protein in the brain to cause Alzheimer’s disease. Brain inflammation must also be present,” says Andrew Budson, M.D., chief of Cognitive & Behavioral Neurology, VA Boston Healthcare System. Scientists are also studying other possible factors, including the death of microglia, cells in the brain involved in the immune response.  

There are many factors that can influence a person’s risk of developing dementia. Some you can’t change — age, sex, family history. Others, including lifestyle behaviors, you can do something about. Here are some of the major risk factors associated with Alzheimer’s and other types of dementia:

Age, sex and family history

Age. The older you are, the higher the risk for Alzheimer’s, especially after age 65. About 5 percent of people 65 to 74 have the disease. Slightly more than 13 percent of people 75 to 84 do, and a third of people 85 and older have Alzheimer’s disease, according to the Alzheimer’s Association. It’s important to remember that although age raises the risk, Alzheimer’s and other forms of dementia are not a normal part of getting older.

Sex. Two-thirds of U.S. adults who have Alzheimer’s disease are women. Part of the reason is that women live longer than men, which leaves them more years to develop the disease. But women’s longevity doesn’t explain all of the disparity. Budson suggests that women’s stronger immune systems may work harder to fight infection, which may lead to more amyloid plaque buildup. Menopausal changes and genetics may be at play as well.

Family history. People with a parent or sibling with Alzheimer’s are more likely to develop the disease. The average 65-year-old has a 2 percent annual risk for dementia. With a close family relative, that risk goes up to 2.6 percent. This risk rises higher if there are multiple family members with the disease. But family history is not as big a risk factor as age. Many people with a family history do not develop dementia, and many people who develop dementia have no family history of it.

Scientists have identified many genes that put people at risk of developing Alzheimer’s. One gene variant, called APOE-e4, was the first identified and remains “the most important known to raise the risk of Alzheimer’s,” Budson says. Forty to 65 percent of those with Alzheimer’s have the APOE-e4 gene variant, according to the Alzheimer’s Association. But having APOE-e4 does not mean dementia is guaranteed.

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Those who inherit one copy of APOE-e4 from one parent have a greater risk of developing Alzheimer’s. Risk rises further for those who inherit a copy from both parents. Twenty to 30 percent of people in the United States have at least one copy of APOE-e4, while an estimated 2 percent have two copies.

Other gene variants increase the risk for early onset Alzheimer’s disease dementia. These include the amyloid precursor protein (APP), presenilin-1 (PSEN1) and presenilin-2 (PSEN2) mutations. “People with these [gene variants] always develop dementia, and they typically get dementia before age 65,” says Melinda Power, director of the George Washington University Institute for Brain Health and Dementia.


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​In total, scientists have identified at least 30 other gene variants linked to dementia, each with about a 1 percent risk, says Paul E. Schulz, M.D., director of the Neurocognitive Disorders Center at the UTHealth Houston McGovern Medical School. Still, “some patients may have 20 of them, which raises their risk to 20 percent,” he says. “These are minor mutations which, by themselves, don’t do it, but when you get a bunch of them, the risk goes up.”​​

Down syndrome. Many people with Down syndrome will develop early-onset Alzheimer’s disease by middle age. Down syndrome occurs when a person has an extra copy of chromosome 21. That chromosome carries the APP gene. Too much of the protein that APP produces leads to those beta-amyloid plaques in the brain. ​

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Environmental and lifestyle risk factors

Air pollution. Scientists have long suspected that environmental factors play a role in dementia, but research into several suspected culprits — toxic metals, for example — has failed to prove a link. There is growing evidence that exposure to air pollution, including the smoke spreading from long-lasting wildfires, is a factor. A recent analysis of 16 observational studies by Harvard scientists, published in 2023 in The BMJ, concluded that breathing in microscopic particles of pollutants may raise the risk of dementia even when a person’s annual exposure is less than the standards set by the U.S. Environmental Protection Agency.​

“Despite being so small you can’t see them, they easily get into your lungs and into your brain,” says Marc Weisskopf, Cecil K. and Philip Drinker professor of environmental epidemiology and physiology at Harvard T.H. Chan School of Public Health. “Dementia is a massive problem worldwide. If we can reduce exposure to these particles, we can reduce the burden of dementia.”​

Traumatic brain injuries. Also known as a TBI, a traumatic brain injury is caused by an external force strong enough to move the brain within the skull. TBIs can result from falls — older adults are especially vulnerable — or being struck by an object or car crashes. Studies suggest that experiencing a moderate to severe traumatic brain injury anytime in life increases the chances of developing dementia later. In a study of more than 14,300 people ages 45 to 65 and followed for 25 years, those who had at least one head injury in that time had a higher risk of dementia. Risk was higher among women and those who had two or more head injuries, researchers reported in 2021 in the journal Alzheimer’s & Dementia.

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Years ago, Schulz studied a pair of identical twin sisters. One developed Alzheimer’s at 65, the other did not and lived into her 90s. “They had identical genes, so I asked them both if they’d ever had a head trauma,” he says. “The one with Alzheimer’s had been in four accidents where her head had been hit. The other one, never.”

There are steps you can take to prevent falls — both by working on your balance and reducing risks at home.

Stroke. Having one or a series of strokes or any other type of bleed that disrupts blood flow to the brain can result in vascular dementia. You can take several steps to reduce your risk for stroke, such as controlling your blood pressure and cholesterol levels by getting regular exercise, not smoking, eating healthy and managing stress.

Hearing loss and social isolation. These often go together. Social isolation contributes to dementia, and hearing loss can contribute to social isolation. “If we don’t use our brains, they deteriorate, just like our muscles deteriorate when we don’t use them,” Budson says. “Our brains are highly active when we are interacting with other people, which helps keep them strong.”

Some experts aren’t convinced. “There is a link between hearing loss and dementia, but [we] don’t know whether hearing loss leads to dementia or dementia leads to hearing loss,” says Christine E. Kistler, M.D., associate professor of geriatric medicine at the University of Pittsburgh. 

The good news is that people with hearing loss who wear hearing aids had the same risk of dementia as people with no hearing loss, and that risk was lower than for people with hearing loss who didn’t wear hearing aids, according to a study of more than 437,700 people ages 40-69 reported in 2023 in The Lancet Public Health.

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