How Do You Stop or Slow Alzheimer’s Disease? Start Early.
How Do You Stop or Slow Alzheimer’s Disease? Start Early.
SPH researchers are at the forefront of determining the risk factors, treatments, and behavioral and environmental changes that may help alleviate the effects of Alzheimer’s disease and other related dementias.
Alzheimer’s disease (AD) is a uniquely challenging and distressing experience for the people living with this neurodegenerative condition, as well as for their family, friends, and other people in their lives. The progressive deterioration of this disease—the most common form of dementia, marked by memory loss, behavior and cognitive changes, and eventually a loss of independence and identity—can take a physical, mental, emotional, and financial toll on the diagnosed person and their caregivers.
Increased federal funding for research on Alzheimer’s and related dementias (ADRD) has propelled advancements in understanding the risk factors, prevalence, and medications, but there is still no known definitive test, exact cause, or cure for the disease. Even diagnosing dementia and determining the underlying biological processes driving disease progression remains challenging. There are promising drug treatments approved by the US Food and Drug Administration (FDA) that can help slow Alzheimer’s disease progression or mitigate symptoms to some degree, but no medication can reverse the AD diagnosis that more than seven million Americans currently experience, including 1 in 9 people ages 65 and older.
At age 45, the current lifetime risk for AD is 1 in 5 for women and 1 in 10 for men. As the population with ADRD is expected to soar to 13 million in the US and 150+ million worldwide by 2050, researchers are turning their attention to preventative measures that individuals can adopt earlier in life to possibly delay or entirely prevent an ADRD diagnosis in older age.
The good news is that we are finding there is probably a very long period of slowly developing disease between the very earliest subtle signs and major clinical impairment.
Several School of Public Health researchers studying the risk factors that may contribute to a person’s likelihood of developing AD are shedding light on the modifiable lifestyle changes people can make in younger years to lower their chances for developing this condition. Importantly, their work also highlights the policy changes needed to mitigate the structural inequities that place certain populations at disproportionate risk of progressive brain disorders.
“The good news is that we are finding there is probably a very long period of slowly developing disease between the very earliest subtle signs and major clinical impairment,” says Maria Glymour, chair and professor of epidemiology. “This suggests we may have important opportunities to slow or fully stop disease progression during those decades of middle age and into old age.”
In the absence of definitive causes, the general medical consensus is that ADRD is broadly caused by a combination of genetic, environmental, and lifestyle factors, along with age-related changes to the brain.
Building upon research that suggests up to 45 percent of ADRD diagnoses could be prevented by modifiable risk factors, Glymour is co-leading a $29 million project funded by the National Institutes of Health (NIH) to develop more reliable evidence that will guide ADRD prevention and treatment strategies. In the Triangulation of Innovative Methods to End Alzheimer’s Disease project, her team utilizes large datasets to investigate four major modifiable ADRD risk factors: lifetime alcohol use, depression, vision and hearing impairments, and social isolation.
In other SPH work, Marcia Pescador Jimenez, associate professor of epidemiology, and Glymour have highlighted disparities in midlife depressive symptoms and cognitive decline later in life. Their results in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association found that depression spurs faster cognitive decline among Black and Latino older adults.
Another study by Pescador Jimenez, published in Environmental Health Perspectives, emphasizes potential environmental effects on dementia risk, finding that greenspace exposure during midlife may slow a person’s annual rate of cognitive decline by 66 percent—with even larger effects among people of low socioeconomic status and among carriers of the APOE-ɛ4 allele, a genetic variant of the APOE gene that is a major risk factor for AD.
“These results shed light into the cognitive benefits of increasing green space exposure at a population level, particularly among vulnerable subgroups of the population,” Pescador Jimenez says.
Air pollution may be another significant environmental contributor to ADRD risk later in life, according to research by Jennifer Weuve, professor of epidemiology. A study she coauthored in JAMA Internal Medicine found that harmful emissions, specifically fine particulate matter (PM2.5), may increase one’s risk of developing dementia—and this risk increases based on the emissions source. Exposure to PM2.5 from auto vehicles and coal-burning, as well as agriculture and wildfires, was associated with higher risk of dementia in older age.
This information is especially informative as worsening climate change created conditions for historic wildfires from California to New Jersey this year, and triggered a record number of air quality alerts across the nation in 2024.
“Our findings, if supported by other evidence, raise the possibility that if we seek to reduce the population’s dementia risk by acting on PM2.5 air pollution, we might consider approaches that go beyond smokestacks and tailpipes,” says Weuve.
Collectively, this body of SPH research underscores the numerous ways in which racial and socioeconomic inequities shape ADRD risk in the US. Older Black Americans and Latino Americans are twice as likely and 1.5 times as likely, respectively, to develop ADRD than their White counterparts. People of color are more likely to develop many of the chronic conditions that are ADRD risk factors, less likely to have access to adequate healthcare, and more likely to experience biases within the healthcare system, including missed ADRD diagnoses. They are also less likely to have access to greenspace and more likely to be exposed to air pollution.
The genetic discoveries in [Alzheimer’s disease] in the past 10 to 15 years point to new biological pathways that may be important for the development of therapeutics,
Despite these inequities, Black and Latino people are also less likely to be represented in ADRD clinical trials. The Alzheimer’s Disease Sequencing Project (ADSP) aims to close this gap, says Anita DeStefano, professor of biostatistics and principal investigator of this genetics initiative that the NIH developed in 2012 as part of the National Alzheimer’s Project Act’s goal to treat and prevent the disease. It includes thousands of diverse participants and, among many goals, aims to understand whether genetic variation and AD risk with specific variants differ by ancestry.
“The genetic discoveries in Alzheimer’s disease in the past 10 to 15 years point to new biological pathways that may be important for the development of therapeutics,” DeStefano says.
Over the last several years, she and Gina Peloso, associate professor of biostatistics, have identified several new genes and gene variants linked to AD, including 17 significant variants among 5,000 individuals in a 2024 study in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association, and an expanded analysis among more than 13,000 people in Alzheimer’s & Dementia later that year that identified rare, non-coding variants.
In a Neurology study, they found that genetic risk and unfavorable cardiovascular health additively heighten dementia risk. “Individuals with a high genetic risk of ADRD may benefit from controlling their cardiovascular risk factors,” Peloso says.
According to findings by Phillip Hwang, assistant professor of epidemiology, in The Journal of Prevention of Alzheimer’s Disease, these health-protective actions should include consumption of flavonoid-rich fruit. Middle-aged adults who consumed apples and pears in midlife, or oranges, grapefruit, and blueberries in late-life, reduced their chances of developing all-cause dementia by 44 percent, compared to middle-aged adults who consume a low amount of these fruits.
“Healthy dietary patterns and other evidence have created a strong case that midlife is a critical window to influence vulnerability to developing dementia as a person ages,” Hwang says. “The factors that build cognitive reserve can help an individual be more resilient to the disease processes that ultimately lead to dementia later in life.”