Cholesterol can contribute to narrowing of the arteries, as seen in this illustration. (Illustration courtesy of the American Heart Association)

MARQUETTE — Older adults whose cholesterol levels fluctuate from year to year may face an increased risk of dementia and cognitive decline compared with people whose cholesterol levels remain more stable, new research shows.

The risk was greatest among people whose cholesterol became increasingly unstable as it rose than among those whose fluctuations steadily declined, the study showed. The findings are being presented Sunday at the American Heart Association Scientific Sessions in Chicago and are considered preliminary until the full results are published in a peer-reviewed journal.

The findings suggest “a large drop or rise in cholesterol levels in an older person could serve as an early warning sign of potential cognitive problems and early-stage dementia.” said the study’s lead researcher, Dr. Zhen Zhou, a researcher in the School of Public Health and Preventive Medicine at Monash University in Melbourne, Australia. “Monitoring changes in cholesterol over time in older people could be useful when it comes to implementing targeted prevention strategies at an early stage.”

However, the results should not be misinterpreted to suggest people avoid lowering their cholesterol levels too high, Zhou said. “Lowering cholesterol is a well-established way to reduce the risk of cardiovascular disease.”

Cholesterol is a waxy, fat-like substance in the blood that is produced by the liver, but also comes from food, mainly animal products such as meat, eggs, cheese and milk. It is measured as total cholesterol and also by its components – low-density lipoprotein or LDL, which is considered “river” cholesterol, because too much causes plaque in the arteries and high-density lipoproteins, or HDL, considered “good” cholesterol, as it helps reduce the risk of heart disease and stroke. Triglycerides are another type of fat that can contribute to unhealthy cholesterol buildup.

In addition to contributing to cardiovascular disease, high cholesterol has been shown to increase the risk of dementia. Millions of US adults have cholesterol levels outside the healthy range, which studies suggest is about 150 milligrams per deciliter for total cholesterol and at or below 100 mg/dL for LDL. It can be reduced by eating a healthier diet, being more physically active and taking drugs such as statins, which are prescribed by a healthcare professional.

In the study, the researchers wanted to see if unintended fluctuations in cholesterol from year to year were linked to faster cognitive decline or the development of dementia than stable cholesterol levels.

The analysis used data on 9,846 adults in the US and Australia enrolled in the Aspirin in Reducing Events in the Elderly, or ASPREE, trial, which investigated whether low-dose aspirin could help prevent age-related diseases such as dementia and by heart

The study, which also measured the participants’ cholesterol levels, was expanded into an observational study.

Total cholesterol, LDL, HDL, and triglycerides were measured at the beginning of the study and during each annual visit during the first three years of the study. Individuals who started or discontinued lipid-lowering medications during the study measurement period were excluded from the analysis. Participants were at least 65 years old, with no history of cardiovascular events, dementia or cognitive problems.

The participants were divided into four groups based on how much their total cholesterol and LDL changed over the three-year period. After more than five years of follow-up, people with the most variation in total cholesterol were 60 percent more likely to develop dementia and 23 percent more likely to experience cognitive decline than those with the least variation.

Those with the most variability in LDL cholesterol were 48 percent more likely to develop dementia and 27 percent more likely to experience cognitive decline than their peers with the least variability.

There was no association between HDL or triglycerides with dementia or cognitive decline. There was also no substantial difference between people who used lipid-lowering drugs and those who did not.

Dr. Sudha Seshadri, founding director of the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at UT Health San Antonio, emphasized that the observational study could not show that cholesterol fluctuations caused dementia, only that the two conditions were linked.

“It may not mean that the fluctuation leads to dementia,” she said. “It could be a sign of something else. For example, do they detect inconsistencies in lifestyle behaviors and are they occurring because a person is beginning to experience cognitive decline? We need to understand whether it is causal or indicative of something else.”

In recent years, there has been increasing interest among researchers in the role that fluctuations in cardiovascular risk factors may play in heart and brain health. But most studies have focused on blood pressure, heart rate or blood sugar, Zhou said.

She said future studies need to explore what causes the fluctuations and whether dementia began to develop before or as a result of the changes in cholesterol. She also questioned whether other chronic conditions might play a role.

“One possible explanation is that significant fluctuations in cholesterol levels (total and LDL) can destabilize the atherosclerotic plaque, which is mainly composed of LDL cholesterol.” Zhou said. This destabilization of plaque in the arteries can increase the risk of plaque growth, rupture and subsequent obstruction of blood flow to the brain, she said.

Seshadri, who was not involved in the research, stressed that anyone with high cholesterol should continue to take steps to lower it.

“Please follow any lipid-lowering regimens recommended by your doctor.” Seshadri said. “Don’t stop taking statins. Or if you eat well for a week, don’t exfoliate for two. Consistency is something doctors would advise anyway, and that might be a message we take from this.”