Fluctuating cholesterol in older adults tied to increased dementia risk

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Older adults whose cholesterol levels fluctuate from year to year may face an increased risk for dementia and cognitive decline compared to people whose cholesterol levels remain more stable, new research finds.

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

The findings suggest "a big drop or rise in cholesterol levels in an older person might 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 cholesterol change over time in older people might be useful when it comes to the implementation of targeted preventive strategies at an early stage."

However, the findings should not be misread to suggest people avoid lowering cholesterol levels that are too high, Zhou said. "Lowering cholesterol levels is a well-established way to reduce the risk of cardiovascular diseases."

Cholesterol is a waxy, fat-like substance in the blood that is produced by the liver but also comes from food, primarily from 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 "bad" cholesterol because too much causes plaque in the arteries, and high-density lipoprotein, or HDL, considered "good" cholesterol because it helps reduce the risk of heart disease and stroke. Triglycerides are another kind of fat that can contribute to unhealthy cholesterol buildup.

In addition to contributing to cardiovascular disease, high cholesterol has been shown to raise the risk for dementia. Millions of U.S. 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 lowered by eating a healthier diet, being more physically active and taking medications like statins that are prescribed by a health care professional.

In the study, researchers wanted to see if unintentional 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 for 9,846 adults in the U.S. and Australia enrolled in the Aspirin in Reducing Events in the Elderly trial, or ASPREE, which investigated whether low-dose aspirin could help prevent age-related illnesses such as dementia and heart disease. The trial, which also measured participants' cholesterol levels, was extended into an observational study.

Total cholesterol, LDL, HDL and triglycerides were measured at the start of the study and during each annual visit for the first three years of the study. People who began or discontinued lipid-lowering medications during the trial's measurement period were excluded from the analysis. Participants were at least 65 years old with no prior history of cardiovascular events, dementia or cognitive issues.

Participants were divided into four groups based on how much their total cholesterol and LDL varied over the three-year period. After more than five years of follow-up, people with the largest variation in total cholesterol were 60% more likely to develop dementia and 23% more likely to show cognitive decline than those with the least variability. Those with the greatest variability in LDL cholesterol were 48% more likely to develop dementia and 27% more likely to show cognitive decline than their peers with the least variability.

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

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

"It may not mean the fluctuation leads to dementia," she said. "It may be a marker of something else. For example, is it picking up inconsistencies in lifestyle behaviors and are those occurring because a person is beginning to have cognitive declines? We need to understand if it is causal or indicative of something else."

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

She said future studies need to explore what's causing the fluctuations and whether dementia had begun to develop prior to or as a result of the changes in cholesterol. She also questioned whether other chronic conditions could be playing a role.

"One possible explanation is that significant fluctuations in (total and LDL) cholesterol levels may destabilize atherosclerotic plaque, which is primarily 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, emphasized that anyone with high cholesterol should continue to take steps to lower it.

"Please adhere to whatever lipid-lowering regimens have been advised by your doctor," Seshadri said. "Don't just stop taking statins. Or if you eat well for one week, don't binge for two. Consistency is something that doctors would advise anyway, and that could be a message one takes from this."

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