Older adults with significant fluctuations in their cholesterol levels may face an increased risk of developing dementia, according to a recent study presented at the American Heart Association (AHA) 2024 Scientific Sessions. The research, which analyzed data from nearly 10,000 participants, suggests that variability in total cholesterol and low-density lipoprotein cholesterol (LDL-C) is associated with cognitive decline, independent of cholesterol-lowering medication use.
The study utilized data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial, which examined the effects of low-dose aspirin on heart disease risk. Participants, primarily from Australia and the United States, had their cholesterol levels monitored annually. Researchers assessed the association between cholesterol variability and the development of dementia or cognitive decline over a six-year follow-up period.
The findings revealed that individuals with the highest fluctuations in total cholesterol (top 25%) experienced a 60% increased risk of dementia and a 23% increased risk of cognitive decline compared to those with the most stable cholesterol levels. Furthermore, fluctuations in LDL-C and total cholesterol were linked to faster declines in cognitive test scores, particularly in areas of memory and reaction speed.
Cholesterol Variability and Cognitive Health
"This study adds an important piece to the puzzle of preserving brain health by providing evidence that increasing variability in cholesterol levels is associated with cognitive decline," said Fernando D. Testai, MD, PhD, FAHA, a neurology professor at the University of Illinois Chicago and AHA volunteer expert. He emphasized that the results were not influenced by statin use, as the study excluded participants who started or stopped lipid-lowering medications during the study period.
The study's retrospective analysis included relatively healthy adults without dementia who had been monitoring their cholesterol levels annually. The first three cholesterol measurements taken in the ASPREE study were used to determine how much each participant’s lipid levels varied from year to year. During almost 6 years of follow-up after the annual assessments, 509 participants developed dementia and another 1760 developed cognitive decline without dementia.
Implications for Prevention
The research underscores the potential importance of maintaining stable cholesterol levels through lifestyle interventions such as a healthy diet and regular exercise. While previous studies have focused on the link between high cholesterol levels and dementia risk, this study highlights the significance of cholesterol variability as an independent risk factor.
Study Limitations
The authors acknowledged several limitations, including the observational nature of the study, which prevents establishing a cause-and-effect relationship. Additionally, the study population was predominantly white (96%), limiting the generalizability of the findings to other ethnic groups. The study also notes that cholesterol readings can vary for many reasons and the connection between cholesterol variability and dementia risk may be affected by those unanalyzed factors.
Contextualizing the Findings
According to the CDC, approximately 7 million adults aged 65 years or older had dementia in 2014, and this number is projected to nearly double by 2060. Given the growing burden of dementia, identifying modifiable risk factors is crucial for developing effective prevention strategies. The Alzheimer’s Society has previously suggested a link between high cholesterol and increased dementia risk, with some research indicating that statins may help mitigate this risk. This new study expands on this knowledge by highlighting the role of cholesterol variability in cognitive decline.
