Fluctuating cholesterol, triglyceride levels may influence dementia risk

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Fluctuating levels of blood lipids may impact a person’s dementia risk. Image credit: BONNINSTUDIO/Getty Images.
  • Researchers investigated how fluctuating cholesterol and triglyceride levels affect dementia risk.
  • They found that fluctuating cholesterol and triglyceride levels increase dementia risk by 19% and 23%, respectively.
  • Further research is needed to understand how these findings may affect patient care.

Over 55 million people have dementia globally. By 2050, this figure is expected to almost triple to 152 million as the global population ages.

Prevention strategies for dementia are crucial for preserving health. One way to develop these strategies is to examine potential risk factors that increase dementia risk, and then find ways to mitigate them.

Screenings for cholesterol and triglyceride levels are a part of routine medical care. Cholesterol is a type of fat produced by the liver that is used to build cells and hormones. Triglycerides are a type of fat used for energy.

Investigating the link between blood lipids and dementia risk could provide an easy way for clinicians to screen for dementia risk and potentially prevent or delay its onset.

While studies have produced mixed results on whether high cholesterol levels increase dementia risk, some research indicates a link between cholesterol variation and dementia.

Further understanding of which lipid components increase dementia risk could provide insights for future screening options and treatments for dementia.

Recently, researchers analyzed health records to determine whether a link exists between cholesterol levels and dementia risk.

They found that participants in the top 20% of cholesterol and triglyceride variability were significantly more likely to develop dementia than those in the bottom 20%.

“While not necessarily practice-changing, this study emphasizes that we should pay particular attention to those with variable cholesterol levels. Further studies will be necessary to determine whether this variation is a true contributor to development of Alzheimer’s disease or simply a byproduct of dementia,” Dr. Dmitriy Nevelev, associate director of Cardiology at Staten Island University Hospital, not involved in the study, told Medical News Today.

The study was published in Neurology.

For the study, the researchers recruited 11, 571 participants with a mean age of 71 years. None of the participants had previously been diagnosed with Alzheimer’s disease or other forms of dementia, and 54% were female.

All of the participants had been assessed for multiple measures of blood lipids on at least three occasions within the 5 years prior to the study. These included:

The participants were followed for an average of 12.9 years. During this period, 2,473 participants developed some form of dementia.

The researchers split the participants into five groups based on how much their blood lipid measures fluctuated.

Ultimately, they found that participants in the highest 20% band of total cholesterol variability were 19% more likely to develop dementia than those in the bottom 20%.

Meanwhile, the group in the top 20% band of variation in triglycerides was 23% more likely to develop dementia than those in the bottom 20%.

The researchers noted that the results remained after adjusting for possible confounding factors including education, baseline cholesterol levels, and adherence to lipid-lowering treatments. They further found that variations in LDL and HDL were not linked to an increased risk of dementia.

MNT spoke with Dr. James Giordano, Pellegrino Center professor of neurology and biochemistry at Georgetown University Medical Center, not involved in the study, about how fluctuating cholesterol and triglyceride levels may increase dementia risk.

He noted that it is unclear how and if fluctuating cholesterol levels contribute to dementia risk. He nevertheless discussed potential mechanisms from his own research.

“In our own work, we have shown that a number of blood-borne factors may prompt shifts in inflammatory mediators that influence both the cerebral blood vessels, as well as nerve and glial cells of the brain [cells that clean up debris from the brain and transport nutrients to neurons],” said Dr. Giordano.

“This shift to a pro-inflammatory phenotype might interact with existing genetic predispositions in certain individuals [which may increase] risk of a number of neurodegenerative diseases, including some types of dementia,” he explained.

Dr. Nevelev agreed that, as of yet, there is no clear explanation for why cholesterol variability may increase dementia risk.

Previous studies have shown that cholesterol variability can cause endothelial dysfunction, which is an impairment in the functioning of our blood vessel lining and thereby a contributor to abnormal blood flow. Cholesterol variability is also linked with [the] instability of blood vessel plaque, which can also impede blood flow and cause damage to brain matter,” noted Dr. Nevelev.

“Another possibility, which this study attempts to account for, is the effect of intermittent adherence with cholesterol-lowering medication,” he added.

MNT asked Dr. Howard Pratt, a board-certified psychiatrist and medical director at Community Health of South Florida, not involved in the study, to explain the study’s key limitations.

“The people that were included in the study had higher levels of comorbidity compared to the control group that did not. So, there may be confounding variables that are not as easily discerned. Another limitation of the study is that the studied group was drawn from a single region, and it remains uncertain whether these findings speak for the general population,” he noted.

Dr. Giordano added that the study did not account for genetic risk factors for dementia, such as the apolipoprotein-E (Apo-E) gene, which may have affected the results.

MNT also asked Dr. Nevelev about the study’s limitations. He noted that it is unknown whether triglyceride levels were measured in fasting or non-fasting samples and that this is important as triglyceride levels vary while fasting.

He added that triglyceride and cholesterol levels are linked to body weight, and that body weight variability is linked to negative health outcomes.

“It is possible that the observation in this study is reversed — perhaps those in the beginning stages of dementia have changes in behavior or changes in body weight that lead to significant variation in triglyceride levels,” he noted.

Dr. Paul E. Schulz, professor of neurology and director of the Neurocognitive Disorders Center with McGovern Medical School at UTHealth Houston, not involved in the study, told MNT:

“One big question is how to translate the results of this study into the real world. We have many medications that reduce cholesterol or triglycerides, but I am not aware of any that reduce its fluctuations. On the other hand, diabetic control depends very much on diet. So, I wonder whether dietary changes might also help reduce fluctuations in cholesterol or triglycerides, and therefore reduce dementia risk?”

“At the same time, since so much data suggests that lower cholesterol is associated with less Alzheimer’s disease, I would still recommend that people at risk for Alzheimer’s disease consider taking their statin if their doctor prescribes it to reduce their risk for developing Alzheimer’s disease,” he concluded.

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