The leading risk factor for Alzheimer's disease in the United States appears to have shifted over the past decade.
Back in 2011, the most prominent, modifiable risk factor for Alzheimer's disease was physical inactivity, followed by depression and smoking.
According to a recent cross-sectional analysis, however, physical inactivity is now second to obesity when it comes to developing dementia.
Today, Alzheimer's disease is the most common form of dementia and a leading cause of death in the US. Yet despite much research, no one knows how the disease starts or how to stop it from progressing.
Research suggests there's a strong genetic component at play, but there are also numerous environmental factors coming to light that may contribute to the disease, including poor diet, high blood pressure, depression, smoking, and gum infections.
The good news is that these factors can be managed by patients and clinicians to mitigate disease risk. The bad news is that the impact of these risk factors is constantly changing, year by year, nation to nation.
Why that is remains unclear, but it may be due to a combination of shifting health concerns among the public and improved research methods.
In the most recent analysis from the US, for instance, hearing loss was added as a modifiable risk factor for Alzheimer's, even though it previously hasn't been considered in estimates.
What's more, the rate of midlife obesity experienced in the US has more than doubled since 2010. The prevalence of physical inactivity and smoking, meanwhile, has somewhat declined over the past few years.
Given these key changes, researchers conducted an updated risk assessment for Alzheimer's disease using US Behavioral Risk Factor Surveillance Survey data from 2018.
Among 378,615 individuals included, just over a third of all Alzheimer's cases were associated with one of the eight risk factors. These risk factors were self-reported, which means they aren't perfect measurements, but, they do point toward a general trend.
The most common risk factor identified in the nationwide analysis was midlife obesity, followed by physical inactivity, and low educational attainment.
"Notably," the author of the recent estimate writes, "the change in midlife obesity prevalence appeared to be the largest compared with other factors evaluated in this study, which potentially propelled midlife obesity to become the most prominent risk factor associated with [Alzheimer disease and related dementias] nearly a decade later."
This isn't the first time that midlife obesity has been tied to Alzheimer's onset.
A study in 2020 found evidence that excess body weight might make neural tissue more vulnerable to brain damage or cellular loss. These changes also seem to occur in parts of the brain that are closely associated with memories.
That doesn't mean midlife obesity is a direct cause of Alzheimer's, but it does suggest that maintaining a healthy weight can reduce the chances of the disease developing – at least to a certain extent.
Similar studies have also shown that when weight is lost later in life, the brain's cortex does not thin out nearly as much as it would in cases of obesity.
There are a bunch of hypotheses as to why that is. Some researchers suspect that obesity can affect blood circulation in the brain, causing decreased oxygen in some areas.
Other researchers suspect obesity can lead to chronic inflammation in the brain, which can degrade white matter and impair neural connections.
Figuring out who in the population is most susceptible to Alzheimer's could one day help scientists hone future research and assist doctors with better treatment options.
In the 2018 analysis, for instance, when researchers split up survey participants by sex, race, and ethnicity, they noticed some key differences in the data.
Cases of Alzheimer's disease that were associated with at least one of the eight modifiable risk factors were more common among men than women. They were also more common among older Black people, American Indian and Alaska Native people, and Hispanic individuals compared to White people.
The findings suggest that some groups of people are more at risk of developing Alzheimer's than others, possibly because of socioeconomic, cultural, or environmental factors that limit access to healthcare, physical exercise, or healthy, affordable foods.
Culture certainly seems to play a strong role. Apart from Australia and Latin America, the US is one of the only nations where midlife obesity is a leading risk factor for Alzheimer's.
In China and Europe, low education and physical inactivity are the two leading risk factors. Obesity doesn't rank in the top three.
The authors of the US analysis argue that policymakers and clinicians should increase their efforts to prevent Alzheimer's disease by focusing not only on midlife obesity, but also on physical inactivity and low education, especially among high-risk groups.
A different strategy may be necessary in other parts of the world.
Alzheimer's is not a simple disease, and the way that we go about tackling it will no doubt require great complexity.
The study was published in JAMA.