Fluctuating Cholesterol Levels Linked to 60% Higher Dementia Risk

Could changes in cholesterol be a warning sign of dementia?

A new study suggests that older adults whose cholesterol fluctuates significantly over time are more likely to develop dementia than those with stable levels.

Fluctuating Cholesterol and Dementia Risk

Older adults whose cholesterol levels fluctuate over time may have a higher risk of developing dementia compared to those with stable cholesterol, regardless of their actual cholesterol levels. This finding comes from a study published today (January 29, 2025) in Neurology, the medical journal of the American Academy of Neurology.

Note that the study does not prove that cholesterol changes cause dementia — only that there is a connection between the two.

“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.

Tracking Cholesterol Over Time

The study tracked 9,846 participants with an average age of 74, all of whom were free of dementia or other memory issues at the start. Researchers measured cholesterol levels at the beginning of the study and during three annual follow-ups. Participants were then monitored for an average of 5.5 years after the final cholesterol check, with yearly memory tests conducted to assess cognitive function.

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.

Higher Fluctuations, Higher Dementia Risk

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.

The Role of LDL vs. HDL

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.

Study Limitations and Considerations

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.

Reference: “Association of Year-to-Year Lipid Variability With Risk of Cognitive Decline and Dementia in Community-Dwelling Older Adults” by Zhen Zhou, Chris Moran, Anne M. Murray, Sophia Zoungas, Costan Magnussen, Trevor T.-J. Chong, Raj C. Shah, Kerry M. Sheets, Mark Nelson, Chao Zhu, Andrew M. Tonkin, Stella Talic, Michael E. Ernst, Suzanne G. Orchard, John J. McNeil, Rory Wolfe, Robyn L. Woods, Johannes T. Neumann, Peng Qiu and Joanne Ryan, 29 January 2025, Neurology.
DOI: 10.1212/WNL.0000000000210247

The study is supported by the National Heart Foundation of Australia.

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