LDL Cholesterol: Too Many Ultra-Small Particles and the Risk of Alzheimer's Increases

Cholesterol: the lower the better. Not only for heart health and the risk of heart attack and stroke, but also for brain health. If this is the general theory we must rely on, we must then understand that not all cholesterol travels in the blood bound to the same transporters. In this sense, there would be some lipoproteins (precisely cholesterol transporters) that would be more easily associated with a greater probability of developing Alzheimer's disease. In practice, the higher these LDLs (i.e. the so-called "bad" cholesterol) are, the greater the probability of experiencing cognitive decline in old age.

A study published in Neurology and conducted by experts from the University of Texas at San Antonio (first author Sokratis Charisis ), together with experts from Boston University, the University of Texas Rio Grande Valley and the Framingham Heart Study, has defined this and other associations, always recommending monitoring the lipid profile of subjects at risk of heart attack and stroke, also to protect them from potential cognitive deficits.

Which lipids under examination

The starting point is simple. Those who present a higher cardiovascular risk are somehow more exposed to developing Alzheimer's and other forms of cognitive decline. But the research goes further, thanks to the analysis of more than 822 elderly people who participated in the Framingham Heart Study , started in 1948 in the town of the same name in Massachusetts. The evaluation in this case included participants from the original cohort aged 60 or older and without any cognitive problems in the late 80s, then following their cognitive levels and blood tests for lipid parameters. In particular, the values ​​of "good" cholesterol or LDL, cholesterol bound to low-density lipoproteins (LDL-C), or "bad cholesterol", a "superbad" cholesterol with small and dense particles (sdLDL-C) as well as other types of lipoproteins somehow associated with cardiovascular risk were considered. Over the entire observation period, up to 2020, 128 cases of Alzheimer's disease were observed in the population.

What damages and what protects

Researchers have discovered that an increase of 1 standard deviation unit (a parameter that measures the distribution of a series of data values) in the concentration of small, dense LDL cholesterol (sdLDL-C) is associated with a 21% increase in the risk of developing Alzheimer's disease. But that's not all. There are also protective aspects hidden in lipids. With an increase of 1 standard deviation unit in the concentration of ApoB48, a lipoprotein that transports dietary fat from the intestine to the blood, a 22% reduction in the risk of Alzheimer's is observed. In short: lower concentrations of bad low-density cholesterol (sdLDL-C) and higher concentrations of ApoB48 are associated with a lower risk of Alzheimer's. With a curiosity: people with lower values ​​of HDL cholesterol, the "good" one, still showed a lower probability of developing Alzheimer's compared to the sample. Which is to say that, in the end, the more we reduce total cholesterol with an eye on LDL, the more we preserve the heart, circulation and brain. "These results underscore the links between lipoprotein metabolism pathways and Alzheimer's risk, emphasizing the potential role of blood lipoprotein markers in Alzheimer's risk stratification and lipid modification strategies in dementia prevention," the researchers write in the study.

What factors to act on

In Italy, people are living longer and are getting sick less at the same age than 30 years ago. Due to the rapid aging of the population in Italy, the number of people with dementia is expected to almost triple by 2050, from 1.2 million in 2019 to over 3 million, with estimated direct and indirect costs of 23 billion to more than 60 billion euros. The increase in life expectancy will also lead to an increase in people with dementia in low-income and poverty-stricken countries. But be careful: the trend can be modulated by counteracting the elements that can increase the risks.

The list has grown recently, as high levels of low-density lipoprotein (LDL) or “bad” cholesterol in middle age and untreated vision loss in later life take their toll. These add to those identified by the Lancet Commission in 2020, many of which are the same as those seen with cardiovascular disease. We’re talking about low levels of education, hearing problems, high blood pressure, smoking, obesity, depression, physical inactivity, insulin resistance and diabetes, heavy alcohol consumption, head trauma, air pollution and social isolation, which are linked to around four in ten cases of dementia.

What to do

“Lowering cholesterol and especially LDL is very good for the heart,” recalls Stefano Carugo , Director of the Cardio-thoracic-vascular Department of the IRCCS Policlinico in Milan. “This has been a fact that has been consolidated for years and lipid-lowering therapies guarantee very effective cardioprotection.” But there is a question that still remains implicit today in the international scientific community: is lowering it too much bad for the brain? “The brain is "full" of cholesterol, its membranes have a lot of it,” the expert emphasizes. “However, this interesting research seems to indicate a new path: lowering LDL is also good for the brain. Cerebral protection against certain pathologies is of fundamental importance and research itself seems to be going in this direction. Further studies will be necessary but the path is marked.”