A recent study found a connection between rising dementia rates and fluctuating cholesterol levels.
Blood tests provide great snapshots of a person’s health status. Medical providers regularly use them to assess a person’s risk of chronic diseases. High levels of triglycerides and low-density lipoprotein (LDL) cholesterol, for instance, are both well-known risk factors for cardiovascular disease. But studies have also linked them to dementia and a growing risk of cognitive decline — especially when those levels fluctuate.
Blood lipid levels, of course, do fluctuate, year-over-year, and to some extent, even day-to-day. “Variation can be caused by factors like diet, physical activity, stress, hormonal changes, and aging,” Zhen Zhou, a research fellow at Monash University, wrote in an email to Being Patient. But as a person ages, variations in blood lipid levels can become even more extreme, potentially as a result of underlying health conditions, medication changes, or significant lifestyle changes. Zhou wondered: Could these year-to-year fluctuations in a person’s lipid panel shed light on their brain health?
Zhou’s research group had previously amassed thousands of blood test results in a study on the effects of daily aspirin use. She analyzed this group of blood test results, this time looking for links between fluctuations and brain health. What she found was that, indeed, people with more variable total cholesterol and LDL cholesterol levels were, in fact, at a greater risk for developing dementia or experiencing cognitive decline. The research was published in January in the journal Neurology.
New insights from existing data
Back when Zhou and colleagues were originally collecting these blood tests for their aspirin study, in 2010, they had set out to monitor nearly 20,000 adults (at least 65 years old) in Australia and the United States. During a three-year clinical trial, the researchers monitored the participants for different outcomes and collected detailed health information, including yearly lipid panels. They found that daily aspirin use had no effect on dementia and cognitive decline, and did not reduce the risk of cardiovascular disease. In fact, it actually increased the risk of mortality. The scientists also tested participants for dementia and cognitive decline at the time and found that aspirin had no effect on these outcomes.
A decade later, however, it became clear to researchers that there was more information to be gleaned.
After the aspirin clinical trial period ended, researchers at Monash University continued to monitor the participants. By 2021, they had accumulated 11 years of follow-up data, which offered insights into how the participants had fared after the trial ended. With previous findings already challenging the health benefits of daily aspirin use, the scientists explored additional questions they might be able to answer with the dataset — including Zhou’s questions about blood lipid level information.
In reanalyzing the data, Zhou had to exclude patients who stopped or started using lipid-lowering medications, like statins, during the initial clinical trial. But that still left her with blood test data from nearly 10,000 study participants.
At first, Zhou was interested to see whether there was a link between participants’ blood lipid levels at the start of the study and their risk of mortality. When she ran the numbers, she found a more complicated relationship: Participants with either high or low LDL cholesterol levels at the beginning of the study were more likely to have died. That motivated her to investigate how the participants’ blood lipid levels had changed over the course of the three-year clinical trial.
That’s when she focused more directly on the brain. Zhou found that the risk of dementia went up if their annual total cholesterol and LDL cholesterol levels fluctuated more. Participants with higher variability in their total cholesterol and LDL cholesterol levels were also more likely to experience cognitive decline unrelated to dementia.
At the moment, it’s not entirely clear what these results will mean for medical providers and patients. Zhou also cautioned that lipid levels may vary for a variety of reasons.
“It is unknown whether the predictive value of lipid variability changes when the underlying reasons differ,” she wrote to Being Patient. More research is needed to find out if reducing lipid level variability is always beneficial for brain health, or if it is most useful when the variability is linked to certain health conditions.
To be fair, it’s not yet fully understood how brain health and blood lipid levels are related. On the one hand, age-related health issues may make it harder for the body to control cholesterol levels. “This instability might harm brain blood vessels by destabilizing plaque buildup, making it more likely to rupture or block blood flow, which could further increase the risk of dementia,” wrote Zhou. However, fluctuating cholesterol levels could also just be an indicator of other health conditions ultimately responsible for declining brain health.
Zhou and her colleagues are still working out those finer details. But they already know what actions people can take on their own to reduce lipid variability. As it turns out, getting regular exercise, maintaining a balanced diet, and avoiding smoking — along with other science-backed lifestyle changes — could play significant roles in lowering the risk of dementia.
“The lifestyle behavioral interventions,” Zhou added, “are important across the lifespan, and should start as early as possible.” That means these guidelines are not just for older adults, but for people of all ages.
