Cholesterol contributes to brain and vascular health, but excessive levels can cause blockages that limit blood flow and increase dementia risk. Some people possess genetic variants that lower cholesterol by affecting the same proteins targeted by common drugs like statins and ezetimibe.
Using a method called Mendelian Randomization, which mimics natural randomized trials using genetic data, researchers compared individuals with and without these cholesterol-lowering variants. This technique minimizes confounding lifestyle factors and isolates the genetic influence on brain health.
The study revealed that a modest reduction-about one millimole per litre-was linked to up to an 80% lower dementia risk for certain cholesterol-related gene targets. Importantly, these findings suggest that long-term cholesterol control, beginning early in life, might be one of the most effective prevention strategies against dementia. However, the study cannot yet confirm whether cholesterol-lowering medications directly prevent the disease.
Lead author Dr. Liv Tybjærg Nordestgaard explained that high cholesterol likely contributes to atherosclerosis, a buildup of fatty deposits in blood vessels that can restrict brain blood flow. She emphasized the need for decades-long clinical trials to explore whether cholesterol-lowering treatments truly protect the brain—potentially opening new preventive approaches to one of the world’s fastest-growing health challenges.
Reference: Liv Tybjærg Nordestgaard, Aimee Hanson, Eleanor Sanderson, Emma Anderson, Venexia Walker, Anne Tybjærg‐Hansen, George Davey Smith, Børge G. Nordestgaard. Cholesterol‐lowering drug targets reduce risk of dementia: Mendelian randomization and meta‐analyses of 1 million individuals. Alzheimer\'s, 2025; 21 (10) DOI: 10.1002/alz.70638
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