Low-density lipoproteins, also known as “bad” cholesterol, have already been implicated in a number of negative health outcomes. A recent study investigates the role of cholesterol fluctuation in cognitive decline.

Despite its bad name, cholesterol is essential to the normal functioning of the human body.

Our cell membranes are composed of around 30 percent cholesterol. It plays a vital role in building, maintaining, and keeping membranes functional.

Cholesterol cannot be dissolved in the blood; it is lipoproteins that carry it to the areas of the body where it is needed.

There are two types of lipoproteins: low-density (LDL) and high-density (HDL).

LDL cholesterol is considered “bad” because it helps build a thick, hard plaque that can clog up arteries and stiffen them. This leads to an increased risk of heart attack and stroke.

HDL cholesterol is considered “good” because it helps ferry LDL cholesterol toward the liver where it is broken down.\
‘Bad’ cholesterol and the brain

Previous research into the relationship between cholesterol levels and cognitive (thinking) function in older adults has been inconclusive. The relationship appears to be a complex one.

A study, published this week in the journal Circulation, used a slightly different approach to investigate the interaction. Rather than the overall levels of LDL cholesterol, the team looked at the effects of cholesterol fluctuation on cognitive performance.

Cholesterol levels are not static in an individual; they can rise and fall, dependent on factors such as exercise, diet, drugs, and impaired homeostasis due to age or disease. Each individual’s cholesterol levels ebb and flow to different degrees; some people’s levels are relatively static, others are more erratic.

A team of investigators from Leiden University Medical Center in Leiden, Netherlands, set out to see if LDL cholesterol fluctuations had a measurable impact on the brain.

The study used 4,428 participants, aged 70-82, taken from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). The individuals were from Scotland, the Netherlands, and Ireland.

PROSPER participants are all either at high risk of developing vascular disease or already had a vascular disease diagnosis.

Researchers, led by Dr. Roelof Smit, assessed the individual’s LDL cholesterol variability before putting them through a raft of cognitive tests.

These cognitive tests involved a measure of attention that used colored words – an individual is asked to read the word of a color, written in a different color, for instance, the word “red” written in the color blue. They also used an assessment of information processing speed and two verbal memory tests measuring recall and delayed recall after 20 minutes.
Cholesterol fluctuation slows thinking

Once the results had been analyzed, the team observed that participants with the highest cholesterol variability needed 2.7 seconds longer to finish the colored word test when compared with individuals with the lowest fluctuations.

This link was still significant when factors were taken into account, such as overall high LDL levels and the use of statin drugs, which lower cholesterol.

Although the effect size might seem small, as Dr. Smit says, it is “significant at a population level.”

Individuals with highest LDL cholesterol variability also showed lower brain blood flow and higher levels of white matter hyperintensity (WMH). WMH are areas that show as bright marks on MRI scans. They are associated with the normal aging process and are considered a marker of cognitive decline.

“Our findings suggest, for the first time, that it’s not just the average level of your LDL cholesterol that is related to brain health, but also how much your levels vary from one measurement to another.”

Dr. Roelof Smit, lead author

Although the results come from a European population, they are, most likely, applicable to American populations, too. However, because the study sample used older adults, the findings cannot be extrapolated to the population at large.

This study is the first step to understanding the relationship between LDL cholesterol, cognitive performance, and aging. As Dr. Smit says: “Our study is just the first exciting step. Further studies are needed to examine whether these findings could truly influence clinical practice.”

Learn about more about cholesterol here.

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