Low cholesterol may protect your brain from dementia

People often think cholesterol only affects the heart. Yet new research shows it might shape the brain’s future too.

A study from the University of Bristol, working with Copenhagen University Hospital, found that people with naturally lower cholesterol face a smaller risk of dementia.

The study involved more than a million people from Denmark, England, and Finland, making it one of the largest of its kind.

Cholesterol genes hold answers

Some people are born with genetic variants that keep cholesterol low without any medication. Dr. Liv Tybjærg Nordestgaard and her team used these genes to understand how cholesterol lowering might protect the brain.

The method they used, called Mendelian randomization, mimics what happens when someone takes drugs like statins or ezetimibe – but without lifestyle confounders. There’s no need to factor in diet, exercise, or weight.

The results were striking. Lowering cholesterol by just one millimole per liter (mmol/L) could reduce dementia risk by up to 80 percent for certain genetic targets.

“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, now based at Copenhagen University Hospital.

Cholesterol’s toll on the brain

Non-HDL cholesterol includes all the harmful types – those that clog arteries and restrict blood flow. When it builds up, arteries narrow, and small clots can form.

Those clots may cut off oxygen to parts of the brain, causing tiny, repeated injuries that slowly erode memory.

“Atherosclerosis is a result of the accumulation of cholesterol in your blood vessels. 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,” said Dr. Nordestgaard.

Her words highlight a simple truth: what harms the heart can also harm the brain. The study suggests that lifelong control of cholesterol, whether through genes or treatment, can make a real difference to how the brain ages.

Data from a million lives

The researchers analyzed six cholesterol-related genes, including HMGCR, NPC1L1, and CETP. These genes regulate proteins that drugs like statins and ezetimibe target. When these genes naturally lower cholesterol, dementia risk drops too.

This research used information from the UK Biobank, the Copenhagen General Population Study, the Copenhagen City Heart Study, the FinnGen study, and the Global Lipids Genetics Consortium. Together, these datasets showed consistent results across different populations and ages.

The analysis also revealed that genetic lowering of cholesterol affected all forms of dementia—vascular, unspecified, and Alzheimer’s – but most strongly for vascular and unspecified dementia. These forms are linked more directly to blood vessel health.

Beyond the usual drugs

Statins dominate cholesterol treatment today, but other drugs may join the fight. PCSK9 inhibitors, for instance, already protect the heart by helping the body clear LDL cholesterol. CETP inhibitors and drugs targeting ANGPTL4 are also being studied.

Some of these drugs showed weaker results in the current analysis, yet the general pattern held: lower cholesterol meant lower dementia risk. The research suggests that brain protection may depend on how early cholesterol control begins.

“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,” said Dr. Nordestgaard.

Protection beyond genetic risk

One big question was whether this benefit depends on the APOE ɛ4 gene, a well-known risk factor for Alzheimer’s disease.

The study found that lower cholesterol helped even those who carried APOE ɛ4. That means the protective effect works independently of that genetic risk.

This finding strengthens the idea that cholesterol control is a lifelong safeguard, not just a midlife concern. It also explains why studies on statins in older adults often show mixed results. Starting treatment late might be too little, too late.

Cholesterol control prevents dementia

The takeaway from this research feels refreshingly clear. Keep cholesterol low – not just for the heart but for the brain.

The benefits likely begin decades before memory loss appears. Early and steady control may delay or even prevent dementia altogether.

The study doesn’t claim that cholesterol-lowering drugs cure dementia, but it shows that maintaining healthy cholesterol levels could change how we age. The next challenge is proving it through long-term trials that follow people across their lives.

Brain health starts young

The message for public health is simple: brain health starts long before the first signs of decline. The same choices that protect arteries – balanced diet, exercise, and medical management – may protect neurons too.

As Dr. Nordestgaard and her team concluded, lifelong low cholesterol might be one of the strongest defenses against dementia.

The heart and brain, long studied apart, seem to tell one shared story – protect one, and you just might save the other.

The study is published in the journal Alzheimer’s & Dementia.

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