Researchers to analyze large group of statin users along with genetic, socioeconomic, and behavioral data
The potential for statins — a widely prescribed class of cholesterol-lowering medication — to reduce the risk of Alzheimer’s disease and related dementias (ADRD) will be explored in a 4-year study led by Kaiser Permanente Division of Research (DOR) investigator Catherine Schaefer, PhD.
Schaefer and colleagues received a $3 million grant from the National Institute on Aging (NIA) to use the large population of Kaiser Permanente Northern California (KPNC) members who have used statins over the past 24 years to explore any potential association with risk of ADRD.
“There is some evidence that statins may be protective against the development of Alzheimer’s and related dementias, but the evidence comes largely from observational studies that are potentially subject to a range of confounding factors and other sources of bias,” Schaefer said, noting that It is difficult to conduct an observational study to avoid those design problems.
This retrospective study avoids those obstacles. “We’re able to use the very powerful data resources of Kaiser Permanente, including data collected as part of the Research Program on Genes, Environment and Health (RPGEH), to provide a careful and systematic evaluation of statin treatment and other factors that could increase or decrease risk,“ Schaefer said. The RPGEH sample collection and survey data are now part of the Kaiser Permanente Research Bank.
Schaefer is working with DOR Research Scientist Paola Gilsanz, ScD, and DOR Adjunct Investigator Rachel Whitmer, PhD, a professor of epidemiology at the University of California, Davis and the associate director of its Alzheimer’s Disease Center. Schaefer also shares principal investigator duties with Ronald Krauss, MD, who studies pharmacogenetics of lipids at the University of California, San Francisco (UCSF), and Maria Glymour, ScD, a social epidemiologist at UCSF who uses causal inference methods to study risk factors for dementia.
Other UCSF researchers participating are Neil Risch, PhD, founding director of UCSF’s Institute for Human Genetics, Thomas Hoffmann, PhD, a statistical geneticist and associate professor of epidemiology and biostatistics, and Akinyemi Oni-Orisan, PharmD, PhD, assistant professor of pharmaceutical sciences.
The holy grail of epidemiology is prevention. And here you have something — statins — that could reduce risk of dementias.
The collaborators will analyze various populations of KPNC members, starting with the 1.4 million who are age 65 and older, about a third of whom use statins. The project will also use data from a subgroup of more than 380,000 KPNC members who completed the RPGEH survey on sociodemographic and behavioral factors between 2007 and 2010, and a subset of 100,000 KPNC members who volunteered their genetic information through the RPGEH.
The researchers will use these data to learn any benefits or risks of initiating statins on risk of ADRD and whether risk differs based on social, demographic, clinical, or genetic background. “It could be that in some groups of people, the benefit could be greater, while other people wouldn’t benefit from this at all because their dementia is related to other factors,” Schaefer said.
The researchers will also attempt to identify potential mediating factors involved in any relationship between statins and ADRD, such as changes in cholesterol levels or existing cerebrovascular disease.
While this analysis proceeds over the next 4 years, the NIA is pursuing a separate, large prospective study — a randomized, controlled trial over 7 years — to determine whether a statin can help prevent dementia and disability in people age 75 and older (the Pragmatic Evaluation of Events and Benefits of Lipid-Lowering in Older Adults, or PREVENTABLE trial).
The Kaiser Permanente study is complementary to the NIA trial and allows for a broader view of the evidence, Schaefer said. The trial population is narrower (including only people aged 75 and older) and excludes many factors that may influence the effects of statins on risk of ADRD.
“Previous evidence developed by Dr. Whitmer while she was at DOR showed that factors such as blood pressure, diabetes, and obesity in middle age are strongly predictive of dementia,” Schaefer said. “It’s quite important to be able to understand the role of midlife factors in contributing risk of Alzheimer’s disease so it’s possible to intervene with medication if that turns out to reduce risk.”
“Our longitudinal, comprehensive data resources in KPNC make it possible to study the long-term effects of statin treatment in a real-world environment,” she added.
This project is exciting for an epidemiologist because it involves a potential remedy already widely used with limited and well-known adverse effects. “The holy grail of epidemiology is prevention,” she said. “And here you have something — statins — that could reduce risk of dementias. Given that Alzheimer’s disease and dementia are a huge and growing problem with the aging of the population, it is exciting to think we could identify a common medication that could reduce the risk for some people.”