AHA 2024: Unexplained Changes in Cholesterol Could Help Identify Adults At Risk of Dementia

Results from a study of older adults in Australia and the US suggest that fluctuation of cholesterol levels from year to year without a change in medication could help identify individuals with a higher risk of developing dementia.¹

According to data from 2017 to 2020, 25.5% of US adults had high levels of low-density lipoprotein cholesterol (LDL-C), defined as 130 mg/dL or higher. Globally, in 2021, 3.72 million deaths were attributed to excessive LDL-C levels, according to the American Heart Association (AHA) Heart Disease and Stroke Statistics 2024 Update.²

Cholesterol in the heart | Image credit: © Rasi | stock.adobe.com

“In the past, studies have focused on the connection between individual vascular risk factors and cognitive decline. However, there is evidence that an increase in the variability of certain functions in the body, such as blood pressure or blood sugar levels, can be harmful to both the heart and the brain,” said AHA volunteer expert Fernando D. Testai, MD, PhD, FAHA, a professor of neurology and rehabilitation at the University of Illinois Chicago, in a news release.¹

Like high cholesterol levels, dementia is also a widespread concern. CDC data show that there were an estimated 7 million adults aged 65 years or older with dementia in 2014, and that population is projected to grow to nearly 14 million by 2060.¹

According to the Alzheimer’s Society, research has suggested that high cholesterol is linked to increased risk of dementia, and statin medications may help mediate that risk. Although the connection between statins and dementia is complex, researchers have found that statins reduced the risk of Alzheimer disease by about 30% and reduced the risk of vascular dementia by about 7%.³ This research has primarily focused on high cholesterol levels, however, as opposed to cholesterol variability.

The new study findings, presented at the AHA 2024 Scientific Sessions, utilized the in-trial and post-trial data of participants enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial, which determined that low-dose aspirin was ineffective for reducing heart disease risk in Australian and American adults. Although one-third of participants were taking cholesterol-lowering medication, none of the almost 10,000 participants started, stopped, or changed lipid-lowering medication during the follow-up period.¹

According to the news release, 87% of participants lived in Australia and 13% lived in the US between 2010 and 2014, at the time of enrollment in the ASPREE trial. This retrospective study using the ASPREE data started in early 2024. Participants were excluded from the analysis if they started, stopped, or changed cholesterol-lowering medications during the study period.¹

All participants were relatively healthy adults without dementia who had been monitoring their cholesterol levels annually. The first 3 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.¹

Compared with those who had the most stable cholesterol levels, researchers found that high fluctuations (in the top 25%) in total cholesterol were associated with a 60% increase in dementia and a 23% increase in cognitive decline. Additionally, LDL-C and total cholesterol fluctuations were associated with significantly faster declines in overall cognitive health test scores and tests involving memory and reaction speed.¹

Finally, high fluctuations in triglycerides or high-density lipoprotein cholesterol (HDL-C), commonly called “good” cholesterol, were not associated with dementia or cognitive decline. Triglycerides are the most common type of fat in the body, storing excess energy from food.¹

“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,” Testai said. “The study did not include people who started or stopped taking lipid-lowering medications during the study period. So, the results cannot be explained by the effect of statins. From a practical standpoint, not sticking to strategies that improve the lipid profile, such as following a healthy diet and exercising, can worsen the negative impact of harmful lipids on the brain.”¹

The study authors noted that there were some limitations, including the fact that cholesterol readings can vary for many reasons and the connection between cholesterol variability and dementia risk may be affected by those unanalyzed factors. Additionally, study participants were mostly white adults (96%), so the findings may not apply to individuals in other population groups. As an observational study, it cannot prove a cause-and-effect relationship.¹

REFERENCES

1. Unexplained changes in cholesterol may help identify older adults at risk for dementia. News release. American Heart Association. November 11, 2024. Accessed November 16, 2024. https://newsroom.heart.org/news/unexplained-changes-in-cholesterol-may-help-identify-older-adults-at-risk-for-dementia?preview=070d&preview_mode=True

2. 2024 Heart Disease and Stroke Statistics Update Fact Sheet. American Heart Association. 2024. Accessed November 16, 2024. https://www.heart.org/-/media/PHD-Files-2/Science-News/2/2024-Heart-and-Stroke-Stat-Update/2024-Statistics-At-A-Glance-final_2024.pdf?sc_lang=en

3. Cholesterol and the risk of dementia. Alzheimer’s Society. Updated August 2024. Accessed November 16, 2024. https://www.alzheimers.org.uk/about-dementia/managing-the-risk-of-dementia/possible-risks-of-dementia/cholesterol