Cholesterol fluctuations may indicate increased dementia risk: study

By Stephen Beech

People at risk of dementia could be identified earlier by regular cholesterol checks, suggests new research.

Scientists found that when older people have "significant" year-to-year fluctuations in their cholesterol levels without changes in medication, it could indicate an increased danger of developing the debilitating condition.

The six-year study of more than 9,800 American and Australian adults in their 70s showed that those with stable cholesterol levels had a "significantly lower" risk of developing dementia or showing cognitive decline.

Researchers say their preliminary findings suggest that fluctuations in routine cholesterol screening might eventually be used to help identify people with a higher risk of developing dementia.

Study lead author Doctor Zhen Zhou 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.”

The study involved mostly white adults, with an average age of 74, enrolled in a randomized 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 a third were taking cholesterol-lowering medication such as statins, none of the 9,846 participants started, stopped or changed lipid-lowering medication such as statins during the study 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.

They were then monitored for signs of dementia for a further six years.

A total of 509 participants developed dementia while another 1,760 developed cognitive decline, but not dementia, during the six-year follow-up period after the annual assessments.

Compared with those who had the most stable cholesterol levels, the study found high fluctuations in total cholesterol were associated with a 60% increase in dementia and a 23% increase in cognitive decline.

Low-density lipoprotein cholesterol - LDL 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 or “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.

Dr. Zhou, of Monash University in Australia, 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 destabilize atherosclerotic plaques, which are mostly composed of LDL cholesterol.

"This destabilization can raise the risk of plaque growth, rupture and subsequent obstruction of blood flow in the brain, which may therefore impact brain function.”

She added: "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.”

The findings are due to be presented at the American Heart Association’s annual Scientific Sessions in Chicago later this week.

American Heart Association expert Professor Fernando Testai welcomed the findings.

Testai, of the University of Illinois, Chicago, said: “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.

“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."

He added: "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.”