Having lower cholesterol levels may help protect against dementia, according to a large-scale international study led by the University of Bristol. The research, involving data from more than one million participants, found that people with genetic traits that naturally reduce cholesterol are less likely to develop dementia.
The work was led by Dr. Liv Tybjærg Nordestgaard during her time at the University of Bristol and at the Department of Clinical Biochemistry at Copenhagen University Hospital — Herlev and Gentofte. The findings were published in Alzheimer’s & Dementia: The 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 medications such as statins and ezetimibe. To explore whether these drugs might influence dementia risk, the team used a technique called Mendelian Randomization. This method allows scientists to study how specific genetic variants mimic the effects of a treatment while minimizing the influence of outside factors like weight, diet, or lifestyle.
By comparing people with and without these cholesterol-lowering genetic variants, the researchers observed a clear difference in dementia risk. A small decrease in cholesterol levels (about one millimole per liter) was associated with up to an 80% reduction in dementia risk for certain drug-related genetic targets.
Lower Cholesterol, Lower Dementia Risk
“What our study indicates is that if you have these variants that lower your cholesterol, it looks like you have a significantly 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 results suggest that keeping cholesterol levels low — whether through genetics or medical treatment — may protect against dementia. However, the research does not yet confirm that cholesterol-lowering drugs themselves directly prevent the disease.
Why Studying Dementia Is So Challenging
Because dementia often develops late in life, studying its causes requires tracking participants for decades. This makes it difficult to establish cause and effect in traditional clinical trials.
It also remains unclear why high cholesterol raises dementia risk. One explanation, according to Dr. Nordestgaard, is that high cholesterol contributes to atherosclerosis — the buildup of fatty deposits in blood vessels.
How Cholesterol May Harm the Brain
“Atherosclerosis is a result of the accumulation of cholesterol in your blood vessels,” Dr. Nordestgaard said. “It can be in both the body and the brain and increases the risk of forming small blood clots — one of the causes of dementia.
“It would be a really good next step to carry out randomised clinical trials over 10 or 30 years, for example, where you give the participants cholesterol-lowering medication and then look at the risk of developing dementia,” Dr. Nordestgaard added.
Global Collaboration and Funding
The study used data from the UK Biobank, the Copenhagen General Population Study, the Copenhagen City Heart Study, the FinnGen study, and the Global Lipids Genetics Consortium.
Funding was provided by the Medical Research Council, Independent Research Fund Denmark, and Research Council at the Capital Region of Denmark (LTN).
