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A large genetic study found people with gene variants that lower certain cholesterol pathways had a markedly lower chance of developing dementia.
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The research method mimicked lifelong effects of cholesterol-lowering drugs on dementia risk, drawing on data from over one million people across three countries.
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The strongest associations were seen for gene targets tied to widely used cholesterol-lowering pathways suggesting potential brain-health benefits.
Dementia is a major public-health concern — as our population ages, any clue toward prevention draws attention.
Now, a recent study from the University of Bristol suggests that the same biological mechanisms that control cholesterol might also influence our likelihood of developing dementia.
While we’ve long known that high cholesterol affects heart health, this research opens the door to thinking about brain health too — and raises the question: could keeping cholesterol low help preserve memory and cognitive function down the road?
“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,” researcher Dr. Liv Tybjærg Nordestgaard said in a news release.
The study
Instead of running a long clinical trial, the researchers used people’s genes to understand how cholesterol might affect dementia. Our genes can naturally raise or lower cholesterol throughout our entire lives. Because genes are set at birth, they aren’t influenced by things like diet, income, or other health conditions.
The team looked at over one million people from several large population studies. They focused on certain gene variants linked to six different cholesterol pathways — the same pathways targeted by common cholesterol-lowering medications.
By comparing people with genetic traits that naturally lower non-HDL cholesterol (a type of unhealthy cholesterol) to those without them, the researchers could estimate what lifelong lower cholesterol might do to dementia risk.
The results
The results were striking: people who had genetic traits that lowered non-HDL cholesterol through specific pathways had a much lower chance of developing dementia.
The strongest effects were seen for three key cholesterol-related genes:
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HMGCR – linked to statins
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NPC1L1 – linked to ezetimibe
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CETP – a target of another group of cholesterol drugs
For these pathways, having genes that lowered unhealthy cholesterol was linked to a substantially lower risk of dementia over time.
For the other cholesterol pathways the team studied, the genes did not show a clear effect on dementia risk. This means how cholesterol is lowered — not just how much — may matter.
It’s important to note what the researchers didn’t conclude: They did not say that taking cholesterol-lowering drugs will definitely prevent dementia. Their study only shows what happens when cholesterol is lower throughout a person’s entire life due to genetics. But the findings suggest that the biological pathways targeted by some cholesterol drugs could have protective effects on the brain — something future clinical trials will need to test directly.
“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 said.