Reduced cholesterol breakdown may accelerate dementia in males

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THERE is a well-established connection between high cholesterol levels in the blood and dementia. However, cholesterol cannot cross the blood-brain barrier, so its link with dementia is hard to explain.

A new study suggests that bile acids, the breakdown products of cholesterol, are detectable in the brain and play a vital role in healthy brain function.

The research found that low levels of these molecules in the brain were associated with a more rapid progression of dementia in males.

The study also found evidence that males who take drugs to lower the concentration of bile acids in their blood have a higher risk of dementia.

Raised serum cholesterol levels are known to increase a person’s risk of developing vascular dementia and Alzheimer’s disease, but researchers have been at a loss to explain why.

The problem with any explanation is that cholesterol is a large molecule that cannot cross the blood-brain barrier.

According to new research, the solution to the mystery may lie in the breakdown, or “catabolism,” of cholesterol into molecules called oxysterols.

These chemicals are small enough to enter the brain, where they break down further into other molecules called bile acids.

Researchers at the National Institute on Aging (NIA), part of the National Institutes of Health (NIH), in Bethesda, MD, found an association between low serum levels of oxysterols and the progression of dementia in males, though not in females.

Oxysterols are essential for the brain to synthesize bile acids, which in turn may be needed to maintain healthy nerves and brain function.

The researchers went on to find a link between drugs that lower the absorption of bile acids from the gut and a higher risk of vascular dementia, once again only in males.
Their study has been published in the journal PLOS Medicine.

The relationship between blood cholesterol, bile acids, and dementia is complex. First author Vijay Varma, Ph.D., a staff scientist at the NIA, told Medical News Today, “While our results suggest that dysregulation in cholesterol breakdown and bile acid synthesis may impact dementia pathogenesis, the conversion of cholesterol into bile acids is only one of several mechanisms that regulate blood cholesterol levels.”