An estimated one in four adults worldwide has metabolic syndrome. While metabolic syndrome is most often thought of as a warning sign that diabetes or cardiovascular disease may be on the horizon, my team’s new study suggests that its consequences reach further – and it actually may be accelerating the ageing of the brain.
Metabolic syndrome is not a single disease. Rather, it’s a cluster of interrelated risk factors, including high blood sugar, high blood pressure, excess belly fat, low levels of HDL (“good”) cholesterol and high triglycerides (blood fats). A diagnosis of metabolic syndrome means having at least three of the five components. Each of these risk factors raises health risks on its own, but together they compound one another.
Previous studies have linked metabolic syndrome to increased risk of neurological disorders such as stroke, dementia and even Parkinson’s disease. But what metabolic syndrome actually does to the brain, and how, has remained unclear.
My colleagues and I set out to answer this using data from 27,375 study participants from the UK Biobank, a large research database that tracks the health of UK adults between the ages of 40 and 70 as they age. At the centre of our analysis was a concept called the brain-age gap.
This concept reflects the idea that while we all grow older at the same pace, our brains can age faster or slower than the years alone would suggest. Advances in brain imaging and artificial intelligence now allow researchers to estimate how old a person’s brain looks based on patterns in magnetic resonance imaging (MRI) scans – including loss of brain tissue, deterioration of the fibres that connect different brain regions and damage to blood vessels.
In our study, brain age was estimated using more than 1,000 different imaging markers from brain MRI scans. We first trained a machine learning model on the scans of the healthiest participants, whose brain age should have closely matched their chronological (actual) age. After the model “learned” what healthy brain ageing looks like, we applied it to the full study population.
The results were striking. People with metabolic syndrome had brains that appeared significantly older than expected. The more metabolic syndrome components a person had, the larger the gap.
Those with three metabolic syndrome components had brains that looked one year older than their actual age on average. This rose to 1.7 years with four components and 2.3 years with all five. Each of the metabolic syndrome components were also individually linked to an older-looking brain.
A year or two may not sound alarming, but in terms of brain health it matters. Having an older brain age in relation to chronological age signals a departure from healthy ageing. Over time, this can raise the risk of cognitive decline and dementia.
Our study was also able to probe how exactly metabolic syndrome leads to poorer brain health.
We examined data from blood samples collected from participants at the beginning of the study. Blood contains information on hundreds of different metabolites – small molecules, such as sugars and fats, produced by the body’s chemical reactions – offering a snapshot of a person’s health.
Three metabolites appeared to partially explain the link between metabolic syndrome and accelerated brain ageing.
The first was GlycA, a marker of chronic, low-grade inflammation. Our findings indicate that people with metabolic syndrome have higher levels of inflammation, which could in turn damage blood vessels, trigger the buildup of harmful proteins in the brain and speed up the death of brain cells.
The second was the ratio of apolipoproteins ApoB and ApoA1. These are markers of atherosclerosis – a sign of the narrowing and hardening of blood vessels. People with metabolic syndrome tended to have higher levels of atherosclerosis in our study. The resulting reduction in blood flow could leave brain tissue starved of the oxygen it needs.
The third was fatty acids, including omega-6 and other polyunsaturated fats. These molecules are highly abundant in the brain and play an important role in maintaining the structure and function of brain cells.
The good news is that all five components of metabolic syndrome are modifiable, meaning they can be improved through everyday lifestyle choices. Regular exercise, eating well and prioritising quality sleep are all proven ways to combat metabolic syndrome and, by extension, protect the brain along the way.
Even partial improvements may help. Because our study showed that the presence of each additional metabolic syndrome component was linked to a progressively older brain, bringing even just one under control could meaningfully slow brain ageing.
Brain ageing is inevitable, but the pace at which it unfolds is not. The implications of our research are clear: keeping metabolic syndrome under control matters not only for cardiovascular and metabolic health, but also for the brain.
