Scientists have found that high blood cholesterol is associated with the risk of developing vascular dementia, which leads to the development of Alzheimer’s disease and other forms of dementia, and this is typical mainly for men. The results of the study are published in the journal PLOS Medicine.
Doctors know that neurodegenerative diseases are often accompanied by high levels of cholesterol in the blood of patients, but how these two factors are related to each other has not yet been known.
Cholesterol cannot directly affect the brain, as the blood-brain barrier is impervious to it. To find out how high cholesterol is linked to the accelerated development of dementia, researchers from the United States, the United Kingdom, and the Netherlands analyzed data from more than 1,800 participants in two large prospective studies: the Baltimore Longitudinal Study of Aging (BLSA), launched in the United States in 1958, and the Alzheimer’s Disease Neuroimaging Initiative (ADNI), implemented since 2003.
At the first stage, the authors found that a key role in the development of dementia is played by violations of the so-called catabolism of cholesterol-its conversion into bile acids. Such disorders are typical for patients with Alzheimer’s disease and vascular dementia. The researchers then tested more than 26,000 general practice patients in the UK to see if exposure to cholesterol drugs that block the absorption of bile acids into the bloodstream was associated with the primary symptoms of dementia.
The researchers found that with high doses of drugs that block bile acids, the risk of developing vascular dementia increases, but only in men. The researchers suggest that cholesterol catabolism and bile acid synthesis influence the progression of dementia through gender-specific brain signaling pathways.
Their findings that people with Alzheimer’s disease tend to increase bile acids in the brain, the authors confirmed on 29 samples obtained from autopsies of deceased patients in the BLSA study.
“To further consolidate the results, we are now testing whether approved drugs for other diseases that correct bile acid signaling disorders in the brain can become new treatments for Alzheimer’s disease and related dementia,” PLOS senior author Dr. Madhav Thambisetty, head of the Department of Clinical and Translational neuroscience at the Behavioral Neuroscience Laboratory at the National Institute of Aging, said in a press release.
This work is carried out within the framework of the project “Repurposing drugs for the effective treatment of Alzheimer’s disease” (DREAM). The authors hope that the results will lay the groundwork for the development of new therapeutics, but note that before that, additional experimental studies are needed to better understand the role of cholesterol breakdown in dementia.