When older adults have significant year-to-year fluctuations in their cholesterol levels without changes in medication, it could indicate an increased risk of developing dementia or cognitive decline, according to a preliminary study.
The current project used the in-trial and post-trial data of participants enrolled in a randomised clinical trial called ASPirin in Reducing Events in the Elderly (ASPREE) that determined low-dose aspirin was not effective for reducing heart disease risk in Australian and American adults.
While one-third were taking cholesterol-lowering medication, none of the almost 10,000 participants started, stopped or changed lipid-lowering medication during the follow-up period.
All participants were relatively healthy adults without dementia who had been having their cholesterol levels monitored annually.
The first three cholesterol measurements taken in the ASPREE study were used to determine how much each person’s lipid levels varied from year to year.
During almost six years of follow-up after the yearly assessments, 509 participants developed dementia and another 1,760 developed cognitive decline without dementia.
Lead author Zhen Zhou, Ph.D. is a postdoctoral research fellow in the School of Public Health and Preventive Medicine at Monash University in Melbourne, Australia.
The researcher said: “Older people with fluctuating cholesterol levels unrelated to whether they were taking lipid-lowering medications – particularly those experiencing big year-to-year variations — may warrant closer monitoring and proactive preventive interventions.”
Compared with those who had the most stable cholesterol levels, the study found:
- High fluctuations (in the top 25 per cent) in total cholesterol were associated with a 60 per cent increase in dementia and a 23 per cent increase in cognitive decline.
- Low-density lipoprotein cholesterol (LDL cholesterol or “bad” cholesterol) and total cholesterol fluctuations were associated with significantly faster declines in overall cognitive health test scores and tests involving memory and reaction speed.
- High fluctuations in high-density lipoproteins (HDL “good” cholesterol) or triglycerides were not associated with dementia or cognitive decline. Triglycerides are the most common type of fat in the body, storing excess energy from food.
Zhou said: “We need future studies to help us understand the relationship between cholesterol variability and dementia risk.
“Are cholesterol variability levels a real risk factor, a precursor or a biomarker of dementia risk?
“One possible explanation is that significant fluctuations in total and LDL cholesterol levels may destabilise atherosclerotic plaques, which are mostly composed of LDL cholesterol.
“This destabilisation can raise the risk of plaque growth, rupture and subsequent obstruction of blood flow in the brain, which may therefore impact brain function.”
The study had some limitations, including that cholesterol readings can vary for many reasons, and the connection between cholesterol variability and dementia risk may be affected by these unanalysed factors.
In addition, the study participants were mostly white adults (96 per cent), so, the findings may not apply to people in other population groups.
As an observational study, it cannot prove a cause-and-effect relationship between cholesterol fluctuations and dementia risk.
Zhou said: “If future research confirms a cause-and-effect relationship, reducing cholesterol variability could potentially be a promising therapeutic target for dementia.
“Importantly, our results should not be misinterpreted as suggesting that lowering cholesterol through lifestyle modification or lipid-lowering medications is harmful for brain health.”
