A new study led by the University of Bristol, involving more than one million participants, has found that having lower cholesterol levels may reduce the risk of developing dementia.
The study, led by Dr. Liv Tybjærg Nordestgaard during her time at the University of Bristol and the Department of Clinical Biochemistry at Copenhagen University Hospital (Herlev and Gentofte), found that individuals with specific genetic variants that naturally lower cholesterol levels have a reduced likelihood of developing dementia.
Drawing on data from more than one million participants across Denmark, England, and Finland, the research was published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Using genetics to mimic cholesterol-lowering drugs
Some people inherit genetic variants that influence the same proteins targeted by cholesterol-lowering medications such as statins and ezetimibe. To examine how these medications might impact dementia risk, the researchers applied a method called Mendelian Randomization. This genetic analysis approach enabled them to simulate the effects of cholesterol-lowering treatments and determine their influence on dementia risk, while minimizing the effects of external factors like body weight, diet, and lifestyle.
When comparing people with these variants to those without them, the researchers found that lowering blood cholesterol by even a small amount (one millimole per liter) was linked to as much as an 80% reduction in dementia risk for certain drug targets.
Genetic evidence supports lower cholesterol protection
“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 having low cholesterol, whether due to genes or medical treatment, can help reduce the risk of dementia. However, the study does not say anything definitive about the effect of the medicine itself.
Unraveling the connection between cholesterol and dementia
One of the challenges is that dementia typically does not appear until late in life, and therefore, research in the area typically requires a very long period of follow-up.
It is still not known exactly why high cholesterol can increase the risk of dementia, but one possible explanation proposed by Dr. Nordestgaard is that high cholesterol can lead to atherosclerosis.
“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 randomized 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.
Reference: “Cholesterol-lowering drug targets reduce risk of dementia: Mendelian randomization and meta-analyses of 1 million individuals” by Liv Tybjærg Nordestgaard, Aimee Hanson, Eleanor Sanderson, Emma Anderson, Venexia Walker, Anne Tybjærg-Hansen, George Davey Smith and Børge G. Nordestgaard, 8 October 2025, Alzheimer’s & Dementia.
DOI: 10.1002/alz.70638
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).
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