Common cholesterol medications may help prevent dementia

This work was supervised by Dr Liv Tyberg Nordestgaard during her time at the University of Bristol and in the Department of Clinical Biochemistry at Copenhagen University Hospital – Herlev and Gentofte. The results were published in Alzheimer’s disease and dementia: Journal of the Alzheimer’s Association.

Genetic clues and cholesterol-lowering effects

Some individuals are born with genetic variants that affect the same proteins targeted by cholesterol-lowering drugs such as statins and ezetimibe. To explore whether these medications might affect dementia risk, the team used a technique called Mendelian randomization. This method allows scientists to study how specific genetic variants mimic the effects of treatment while minimizing the influence of external factors such as weight, diet, or lifestyle.

By comparing people who had these cholesterol-lowering gene variants and those who did not, the researchers observed a clear difference in the risk of developing dementia. A small reduction in cholesterol levels (about 1 mmol per liter) was associated with an up to 80% reduction in dementia risk for some drug-linked genetic targets.

Lower cholesterol, lower risk of dementia

“What our study suggests is that if you have these variants that lower your cholesterol, you seem to have a much lower risk of developing dementia,” said Dr. Nordestgaard, who now works in the Department of Clinical Biochemistry at Copenhagen University Hospital – Bispebjerg and Frederiksberg Hospital.

The findings suggest that maintaining low cholesterol levels – whether through genetics or medical treatment – ​​may protect against dementia. However, research has not yet confirmed that statins themselves directly prevent the disease.

Why is studying dementia so difficult?

Because dementia often develops late in life, studying its causes requires tracking participants for decades. This makes it difficult to determine cause and effect in traditional clinical trials.

It is also still unclear why high blood cholesterol increases the risk of dementia. One explanation, according to Dr. Nordestgaard, is that high cholesterol contributes to atherosclerosis — the buildup of fatty deposits in blood vessels.

How can cholesterol harm the brain?

“Atherosclerosis is the result of cholesterol buildup in the blood vessels,” Dr. Nordestgaard said. “It can be in both the body and brain and increases the risk of small blood clots forming – one of the causes of dementia.

“A really good next step would be to do randomized clinical trials over, say, 10 or 30 years, where participants are given cholesterol-lowering medications and then look at their risk of dementia,” Dr. Nordestgaard added.

Global cooperation and financing

The study used data from the UK Biobank, the Copenhagen General Population Study, the Copenhagen City Heart Study, the VINGEN study, and the World Lipid Genetics Consortium.

Funding was provided by the Medical Research Council, the Independent Research Fund of Denmark, and the Research Council of the Capital Region of Denmark (LTN).