Older adults whose cholesterol changes over time may be more likely to develop dementia than people whose cholesterol is stable, regardless of the actual cholesterol level, according to a study published in the January 29, 2025, online issue of Neurology®, the medical journal of the American Academy of Neurology.
The study does not prove that changing cholesterol causes dementia; it only shows an association.
“These results suggest that fluctuating cholesterol, measured annually, may be a new biomarker for identifying people at risk of dementia, providing more information than the actual cholesterol levels measured at a single time point,” said study author Zhen Zhou, PhD, of Monash University in Melbourne, Australia.
The study involved 9,846 people with an average age of 74 who did not have dementia or other memory problems. Cholesterol levels were measured at the beginning of the study and at three following annual visits. Participants were followed for an average of 5.5 years after the third visit. They took tests of memory skills annually.
Participants taking cholesterol medications, called statins, were allowed in the study unless they stopped or started taking the drugs during the measurement period for cholesterol.
The participants were divided into four equal groups based on the amount of change between their first and fourth cholesterol measurements. The difference between consecutive yearly measurements was 91 mg/dL on average in the group with the largest amount of change in total cholesterol and 22 mg/dL in the group with the smallest amount of change.
During the study, 509 people developed dementia. A total of 147 of the 2,408 people in the group with the largest amount of change in total cholesterol developed dementia, a rate of 11.3 per 1,000 person-years. In the group with the lowest amount of change in total cholesterol, 98 of 2,437 people developed dementia, a rate of 7.1 per 1,000 person-years. Person-years represent both the number of people in the study and the amount of time each person spends in the study.
After adjusting for other factors that could affect the risk of dementia, such as age, smoking status and high blood pressure, researchers found that those in the high change group were 60% more likely to develop dementia than those in the low change group.
The study also found a link between changing cholesterol levels and cognitive impairment or memory problems that did not meet the criteria for dementia.
Looking at the various types of cholesterol, researchers found a link between fluctuating LDL cholesterol, or “bad” cholesterol, and risk of dementia and cognitive impairment. They did not find that association with HDL, or “good” cholesterol, or triglycerides.
“Older people’s cholesterol should be monitored for changes over time to help identify people who may be at risk of cognitive impairment or dementia and could benefit from interventions, which could include lifestyle changes or making sure they start or keep taking statin to prevent fluctuations in their cholesterol and potentially reduce the risk of dementia,” Zhou said.
A limitation of the study is that while people who started or stopped taking cholesterol drugs were not included in the study to eliminate the medication-induced fluctuations in cholesterol, researchers did not have information on any changes in dosage or people who did not take their medication as prescribed, which could affect cholesterol changes.
The study is supported by the National Heart Foundation of Australia.