Bottom-row, from left to right: Rebecca Graff, ScD; Fei Jiang, PhD, MS; Suzanna Martinez, PhD, MS; and Fan Xia, PhD
An ambitious new study examining strategies to prevent Alzheimer’s disease and other related dementias, led in part by Jacqueline Torres of UCSF, has received $28.8 million from the National Institutes of Health.
Torres, PhD, MA, MPH, an associate professor in the UCSF Department of Epidemiology and Biostatistics, is one of three principal investigators leading the study, along with Maria Glymour, SD, chair and professor of epidemiology at Boston University School of Public Health, and Paola Gilsanz, ScD, research scientist II at the Kaiser Permanente Northern California Division of Research.
“Alzheimer’s disease is a leading cause of mortality for older adults and is a devastating neurodegenerative disease that causes tremendous heartache and health challenges for people living with the disease and their family members,” Torres said. “There's a lot that's not known about what causes dementia, but there's increasingly a lot of observational evidence about what might prevent dementia.”
More than 55 million people worldwide are diagnosed with a form of dementia each year, more than half with Alzheimer’s disease. An estimated one in four people think they can’t do anything to prevent dementia, but a growing body of information suggests otherwise.
The Triangulation of Innovative Methods to End Alzheimer’s Disease (TIME-AD) project aims to build on the work in the 2024 Lancet Commission on Dementia, which found that up to 45 percent of Alzheimer’s disease and related dementia cases could be prevented by modifiable risk factors. Current research, however, is limited to observational studies that make it difficult to establish definitive cause-effect relationships.
Overcoming Limitations
The researchers will use cutting-edge methods to glean information from huge data sets, including electronic health records and surveys, to address limitations in the observational studies. The project will focus on a subset of modifiable risk factors: alcohol use, depression and chronic pain, hearing and vision impairment, and social isolation.
Studies have shown that these factors can predict future dementia risk, Torres said. But because Alzheimer’s and other dementias unfold over many decades, researchers are not able to conduct truly randomized studies.
“The impacts of these lifestyle modifications may not happen for many, many years,” Torres said.
In addition, the underlying data has its own imperfections and biases, Torres said. For instance, if someone reports social isolation, is that something changeable that may have caused their dementia? Or was it simply an early warning sign of the presence of dementia that doctors did not discover until much later? The same goes for people who report changes in memory and executive function. Torres said researchers’ term for this phenomenon is “reverse causation.”
“We’re proposing to improve the evidence base that underlies all of those recommendations, guidelines and high-level reports on dementia prevention—as well as how that's implemented, communicated and disseminated through a range of stakeholders—by triangulating across lots of different data sources,” Torres said.
For instance, when one study suggests a correlation between decreasing alcohol use and dementia prevention, the researchers will put that finding into the mix with other data, such as from electronic health records. Then they can see, Torres said, “are we getting the same association when we look at another data set that might have other limitations and strengths—and overcome some of the challenges of the diagnostic outcome assessment?”
They also plan to use quasi-experimental methods, such as analyzing changes in alcohol taxation, to mitigate bias. Did someone stop drinking because they were in an early stage of dementia? Or was it merely because they live in a state that raised alcohol taxes, which tends to reduce alcohol consumption in general?
Addressing Inequities
The investigators aim to also address inequities in Alzheimer’s disease prevention. The grant includes an "equity and dissemination" core that specifically focuses on ensuring the project incorporates an equity lens and disseminates the results at the community level and to national stakeholders, funders, and policymakers.
Dementia risk is disproportionately influenced by socioeconomic status, race, and ethnicity in both the United States and globally,” explained Yulin Hswen, ScD, MPH, assistant professor of epidemiology and biostatistics at UCSF and leader of the equity and dissemination core. "For instance, African-American and Latino individuals face a higher likelihood of developing Alzheimer’s disease compared to white individuals, yet they are significantly less likely to receive timely diagnoses.
“We will calculate the potential impacts of modifying those risk factors not just on dementia risk overall, but on dementia inequities,” Hswen said.
In addition to serving as one of the multiple principal investigators (MPIs) of the overall project, Torres is the MPI for the project’s administrative core, the Cognition, Exposure and Covariates Core, and the project focused on social isolation. Torres’ and Hswen’s colleagues from UCSF’s Department of Epidemiology and Biostatistics (DEB) also serving in MPI roles are Tom Hoffman, PhD, MA, leading the genetics and policy core; and Chiung-Yu Huang, PhD, MS, leading the analytics core.
Other researchers from UCSF’s DEB participating in the project include Rebecca Graff, ScD; Fei Jiang, PhD, MS; Suzanna Martinez, PhD, MS; and Fan Xia, PhD.
Others from UCSF participating in the project include Kaitlin Casaletto, PhD (MPI, Cognition, Exposure and Covariates Core); Ashwin Kotwal, MD (MPI, Social Isolation Project); Ulrike Muench, RN, PhD, FAAN (MPI, Depression and Chronic Pain Project); Irena Cenzer, PhD, MA; Jessica de Leon, MD; Tanisha Hill-Jarrett, PhD; Mark Kvale, PhD; Carla Perissinotto, MD, MHS; Laura Schmidt, PhD, MSW, MPH; Anusha Vable, ScD, MPH; and Kristine Yaffe, MD.
Thumbnail photo credit: National Institute on Aging, NIH