A new study found that greater variability in total cholesterol and low-density lipoprotein cholesterol levels over time may be associated with increased risk of dementia and cognitive decline in older adults, independent of mean cholesterol values.
In the study, published in Neurology, investigators analyzed data from 9,846 participants (median age = 73.9 years, 54.9% female) in the ASPirin in Reducing Events in the Elderly (ASPREE) trial and its extension study. Over a median follow-up of 5.8 years, the investigators documented 509 incident dementia cases and 1,760 cases of cognitive impairment with no dementia (CIND).
Comparing the highest vs lowest quartiles of total cholesterol (TC) variability, the hazard ratio (HR) for dementia was 1.60. For low-density lipoprotein cholesterol (LDL-c) variability, the HR was 1.48. Similar associations were found for CIND, with HRs of 1.23 for TC and 1.27 for LDL-c variability.
"Monitoring cholesterol fluctuations through repeated measurements could provide complementary risk information on dementia and cognitive decline, particularly in older [patients]," the study authors wrote.
The study found higher TC and LDL-c variability was also associated with faster decline in global cognition, episodic memory, and psychomotor speed. No strong evidence emerged for an association between HDL-c and triglyceride variability with dementia and cognitive changes.
Notably, the associations remained significant after adjusting for multiple factors including age, sex, education, blood pressure, diabetes, kidney disease, and use of lipid-lowering medications. The findings persisted even after accounting for mean cholesterol levels during the measurement period.
"Tracking variability of TC and LDL-c may serve as a novel biomarker of incident dementia and cognitive decline in older [patients]," the study authors concluded.
The study suggested several possible mechanisms for the association, including that cholesterol fluctuations might destabilize atherosclerotic plaques, alter their composition, and increase the likelihood of rupture and growth. This process could lead to narrowing or obstruction of cerebral blood vessels.
The investigators noted some limitations, including that the study enrolled generally healthy older adults, so findings may not generalize to all populations. Additionally, they could not account for all factors that might influence lipid variability, such as dietary patterns and physical activity.
The findings have potential clinical implications, as routine lipid screening is common in many countries. The investigators suggested that monitoring cholesterol changes over time could help identify high-risk individuals who might benefit from early intervention, though they emphasized that further research is needed to verify the results and explore whether lipid variability directly contributes to dementia risk.
The study was supported by funding from the National Heart Foundation of Australia and the National Health and Medical Research Council. Full disclosures can be found in the study.
