Cholesterol and dementia: What is the link?
Cholesterol is a waxy, fat-like substance produced by the liver that is essential for making cell membranes, some hormones, and bile salts for fat digestion.
It can also be consumed in many foods, including meat, seafood, poultry, eggs, and dairy products. However, the Centers for Disease Control and Prevention (CDC) advise that people should avoid eating too much of foods high in cholesterol, as this can lead to health problems, such as heart attacks and strokes.
High cholesterol may develop as a result of dietary and lifestyle factors, but can also be a result of genetics, certain health conditions and some medications. The CDC states that around 25 million adults in the United States have high cholesterol — 240 milligrams per deciliter (mg/dL) or over.
There are two types of cholesterol , which have different health impacts:
New research suggests that it is not only high cholesterol but fluctuating levels of cholesterol that may influence health.
The study, presented at the American Heart Association's Scientific Sessions 2024 , and which is yet to undergo peer review, found that, in older adults, annual changes in cholesterol levels might increase the risk of dementia and cognitive decline.
Emer MacSweeney, MD , a consultant neuroradiologist at Re:Cognition Health, who was not involved in this research, explained why such changes could have that effect.
She told Medical News Today that:
"Cholesterol fluctuations, particularly in LDL cholesterol, may increase dementia risk due to their potential impact on atherosclerotic plaque stability. Plaque destabilization can lead to increased risk of plaque rupture and restricted blood flow, which affects brain function."
All participants to the current study were enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE project) , a large study run in Australia and the United States to investigate low-dose aspirin and health in older adults.
Of the 9,846 participants, all of whom were in their 70s, 87% lived in Australia and the rest in the U.S. All were free of dementia at the start of the study, and 32% were on cholesterol-lowering medications , which they remained on throughout the study.
For the 3 years of the study, participants underwent annual tests of their total cholesterol, LDL-C, HDL-C and triglycerides — another fatty substance that comes from diet and is found in the blood.
The researchers split them into four groups based on how much their cholesterol levels fluctuated, from highest to lowest fluctuations.
They then monitored the participants for 6 years for development of dementia and cognitive decline. An expert panel analysed the results of cognitive tests, self-reported cognitive problems, and medical reports of dementia diagnosis or prescription of dementia medication.
The researchers then compared the numbers with dementia and cognitive decline in the highest and lowest fluctuating cholesterol groups.
During the 6-year follow up, 509 people developed dementia and 1,760 developed cognitive decline without dementia.
The researchers found that there were associations between fluctuating levels of total cholesterol and LDL-C and dementia, but not with fluctuating HDL-C or triglycerides.
People with the highest fluctuations in total cholesterol levels had a 60% higher likelihood of dementia, and a 23% increase in cognitive decline, compared with those with the most stable cholesterol levels.
Those with the highest fluctuations in LDL-C had a 48% higher risk of dementia and a 27% higher risk of cognitive decline.
They also experienced more rapid declines in overall cognitive health, memory and reaction speed.
"Since the brain relies heavily on stable blood flow and oxygenation, interruptions can result in damage to neurons and other brain cells, possibly accelerating cognitive decline. LDL cholesterol is linked to inflammation, which may also contribute to neurological deterioration over time. Additionally, fluctuations in cholesterol levels may reflect underlying health instability or a dysregulated lipid metabolism, both of which could play roles in cognitive impairment."
– Emer MacSweeney, MD
Lead author Zhen Zhou, PhD , a postdoctoral research fellow in the School of Public Health and Preventive Medicine at Monash University in Melbourne, Australia, said in a press release that "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."
Zhou called for further studies. "We need future studies to help us understand the relationship between cholesterol variability and dementia risk," she said in the press release, wondering: "Are cholesterol variability levels a real risk factor, a precursor or a biomarker of dementia risk?"
MacSweeney also emphasized the need for more studies, particularly in more diverse populations, as 96% of those in this study were white, to investigate "how cholesterol fluctuations directly contribute to cognitive decline at a cellular or molecular level, particularly in the brain," and "whether cholesterol variability is linked with other biomarkers of dementia, potentially improving early diagnosis and intervention strategies."
In their study abstract, the authors suggested that "tracking the variability of TC [total cholesterol] and LDL-C measured annually may serve as a novel biomarker for higher risk of incident dementia and cognitive decline in older adults."
However, Clifford Segil, DO , a neurologist at Providence Saint John's Health Center in Santa Monica, CA, who was not involved in the study, was not fully persuaded by the findings.
He told MNT that: "Monitoring annual cholesterol levels is part of annual physical exams and lipids are directly related to the risk of having a heart attack and stroke. It does not seem after reading this [that] it will be useful in clinical practice any time soon, to monitor annual lipid profiles or cholesterol levels, with regard to assessing the risk for a patient to develop dementia."
