Fluctuating Cholesterol Tied to Higher Dementia Risk

Year-to-year fluctuations in total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels were tied to higher risks of cognitive decline and dementia, a study of nearly 10,000 older adults showed.

Participants with the highest variability in total cholesterol had a 60% higher risk of incident dementia (HR 1.60, 95% CI 1.23-2.08) and a 23% higher risk of cognitive decline without dementia (HR 1.23, 95% CI 1.08-1.41), reported Zhen Zhou, PhD, of Monash University in Melbourne, Australia, and co-authors in Neurology.

Those with the highest fluctuations in LDL-C had a 48% higher risk of incident dementia (HR 1.48, 95% CI 1.15-1.91) and a 27% higher risk of cognitive decline (HR 1.27, 95% CI 1.11-1.46).

Greater variability in total cholesterol and LDL-C was associated with faster declines in global cognition, episodic memory, psychomotor speed, and a composite cognition score (all P<0.001), but not in language or executive function.

Higher variability in total cholesterol or LDL-C was associated with a greater risk of dementia regardless of the trend (up or down) and baseline values, the researchers noted. No significant association emerged between fluctuations in high-density lipoprotein cholesterol (HDL-C) or triglyceride levels and cognitive change.

“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,” Zhou said in a statement.

The findings suggest an “intriguing new dimension to the role of cholesterol and LDL-C in the development of dementia,” observed Ronald Krauss, MD, of the University of California San Francisco, and co-authors in an accompanying editorial.

“They present the opportunity for research aimed at determining whether and how fluctuations in these measures may directly affect the disease process,” Krauss and co-authors noted. Establishing a causal mechanism would support using cholesterol variability to assess dementia risk and may lead to targeted interventions, they added.

Previous studies have linked fluctuations in total cholesterol and triglyceride levels with higher risks of incident dementia, including Alzheimer’s disease. But the relationship between cholesterol changes and cognition is unclear: “Lipid metabolism in older adults is affected by various factors including biological aging, functional decline, reduced physiologic reserve, and nutrient intake,” Zhou and colleagues pointed out.

The researchers studied 9,846 people who had participated in the ASPREE trial of aspirin and its extension study in the U.S. and Australia. Participants were initially healthy older adults free of dementia and major cognitive impairment. Their mean age was 73.9 years and 54.9% were women.

The analysis included people who had lipid levels measured at baseline and in years 1, 2, and 3. Year-to-year variability in total cholesterol, LDL-C, HDL-C, and triglycerides over the first 3 years was quantified using variability independent of the mean.

People who initiated or discontinued lipid-lowering therapy during the measurement period were excluded from the analysis. The highest quartile of total cholesterol variability had a total average change of 42.3 mg/dL over 3 years. The highest quartile of LDL-C variability corresponded to a total average change of 37.3 mg/dL.

Cognitive tests were administered at baseline and at years 1, 3, and 5, at a final trial visit, and at four subsequent annual visits in the extension study. In total, 509 events of incident dementia and 1,760 events of cognitive impairment without dementia were recorded over a median follow-up of 5.8 and 5.4 years, respectively, after lipid variability assessment.

While participants who started or stopped lipid-lowering agents during the measurement period were not included in the study, the researchers did not have information about dose changes or people who didn’t take treatment as prescribed. In addition, clinical trials like ASPREE are likely to enroll healthier participants than the general population, Zhou and co-authors acknowledged.

Please enable JavaScript to view the

comments powered by Disqus.