Could there be a link between dementia and cholesterol treatments?

THE ESSENTIAL

  • Hypercholesterolemia promotes the development of vascular dementia.
  • This could be due to drug-related disturbances in the conversion of cholesterol to bile acids.

Almost 20% of the adult population suffers from hypercholesterolemia, that is to say an abnormal increase in their cholesterol level in the blood, according to the French Federation of Cardiology. Statistically, people with it are more likely to develop vascular dementia, which is a loss of cognitive function related to the destruction of brain tissue due to reduced or blocked blood supply. But, until now, how cholesterol increases this risk has been unknown because the blood-brain barrier is impermeable to cholesterol. It is a physiological barrier between the central nervous system and the blood circulation which prevents, among other things, the intrusion of cholesterol into the brain. A recent study, published in the journal PLOS Medicine maybe offer an explanation. According to the authors, this is due to disturbances – induced by taking certain drugs – during the conversion of cholesterol into bile acids, a natural phenomenon called cholesterol catabolism. Bile acids are secreted by the liver (in particular thanks to cholesterol) in the digestive tract and contained in the bile. These help in the digestion of fats.

A three-phase study

To reach this conclusion, the researchers first looked at data from more than 1,800 people who took part in two previous studies. Their purpose of this first analysis was to determine whether cholesterol catabolism was associated with brain abnormalities linked to vascular dementia. Next, they tested whether the administration of cholesterol-lowering drugs – those that block the absorption of bile acids into the bloodstream – was associated with an increased risk of dementia in more than 26,000 patients in general medicine clinics located in the UK. Finally, they examined 29 autopsy samples to determine whether people with Alzheimer’s disease had abnormal levels of bile acids in their brains.

Men are more at risk than women

Through these three phases of studies, the authors found that the longer the prescription of these drugs, the higher the risk of vascular dementia in men, but not in women. Thus, scientists believe that disruption of cholesterol catabolism could impact the development of dementia based on gender. โ€œTo extend these results further, we will test whether drugs approved for other diseases that can correct abnormal bile acid conversion in the brain could be new treatments for Alzheimer’s disease and associated dementias.โ€, Emphasizes Madhav Thambisetty, one of the authors of the study. Scientists would like to better understand the role of cholesterol conversion in vascular dementia and determine whether the impact of the conversion of cholesterol to amino acids in the brain could be a new therapeutic target in dementia.


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