Longevity

Longevity Briefs: Can Keeping Your Cholesterol Low Protect You Against Dementia?

Posted on 26 July 2021

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Cholesterol and the way in which it is processed is important for the health of brain cells, and may be linked to dementia. For example, the the ε4 allele of the gene coding for apolipoprotein E (a protein involved in the metabolism of cholesterol and other fats) is one of the common genetic factors that increases the risk of late-onset Alzheimer’s disease. However, changes in cholesterol processing in the brain are not necessarily related to the levels of cholesterol in the blood. Some previous studies have suggested a link between blood cholesterol and dementia risk, but findings have been mixed and uncertainty around this relationship remains.

What did the researchers do: Here, researchers performed a retrospective analysis of data from over 1.8 million individuals aged 40+ from the UK Clinical Practice Research Datalink (CPRD), who were followed up for over two decades. Data included measurements of total cholesterol, LDL cholesterol measured, HDL cholesterol and triglycerides. Researchers investigated whether there was a relationship between these measurements and subsequent occurrence of dementia during the follow up period.

Shown here is the risk of of developing dementia relative to someone with an LDL cholesterol of less than 2.59, broken down by age and by follow up period. The top right graph shows risk of dementia after more than 10 years according to LDL cholesterol measured before age 65. According to this graph, someone with an LDL of more than 4.92 is about 50% more at risk of dementia after 10 years than someone with an LDL cholesterol of 2.59.
Source

Key takeaway(s) from this research: After controlling for confounding factors, there was a modest association between dementia risk after 10 years of follow-up and both total cholesterol and LDL cholesterol, with the association being stronger for LDL cholesterol. The association was also stronger for measurements in those below the age of 65. There was almost no association between HDL cholesterol or triglycerides and dementia.

This is the largest study to date investigating the link between blood cholesterol and dementia risk, and suggests that LDL cholesterol in particular is associated with dementia, though it cannot prove that LDL cholesterol causes dementia. LDL cholesterol can be reduced through lifestyle choices and with drugs like statins, potentially making it a valuable modifiable risk factor for dementia. Previous randomised trials have found no evidence that statins can prevent cognitive decline or dementia. However, these trials have had follow-up periods of less than 5 years, which according to this study might not be long enough to observe significant benefits.


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References

Blood cholesterol and risk of dementia in more than 1·8 million people over two decades: a retrospective cohort study: https://doi.org/10.1016/S2666-7568(21)00150-1

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