OXFORD, UNITED KINGDOM: Diabetes, traffic-related air pollution and alcohol intake frequency have emerged as the three strongest modifiable factors associated with changes in brain regions vulnerable to ageing, according to research from the University of Oxford.
The researchers examined 161 individual risk factors using brain scans from nearly 40,000 UK Biobank participants. Their findings highlight how metabolic health, environmental exposure and lifestyle habits may influence brain ageing and long-term cognitive health.
What the Oxford Study Revealed About Brain Ageing
The research, published in Nature Communications on 27 March 2024, examined how genetic and modifiable risk factors relate to a specific network of brain regions that show early signs of degeneration during ageing.
The researchers analyzed brain imaging data from 39,676 UK Biobank participants. They examined 161 individual modifiable risk factor variables across 15 categories, including diabetes, blood pressure, cholesterol, weight, alcohol consumption, smoking, sleep, pollution, physical activity, diet and education.
Rather than assessing each risk factor in isolation, the researchers used a two-stage analysis.
First, they examined the 161 variables and identified 12 leading modifiable risk factors associated with changes in the vulnerable brain network.
Next, they assessed these 12 factors together in a statistical model. This helped identify which factors had an independent association after accounting for other variables, including age, sex and head size.
Three factors remained statistically significant in the combined analysis:
- Diabetes diagnosed by a doctor.
- Nitrogen dioxide exposure linked to traffic-related air pollution.
- Alcohol intake frequency.
The findings were also highlighted in a HuffPost UK report, which drew attention to these three leading factors. (Manuello et al., 2024)
Why Some Brain Regions Age Faster
The researchers focused on a network of higher-order brain regions known as the Last-In, First-Out (LIFO) network.
These regions develop relatively late during adolescence. They also show earlier signs of degeneration during old age compared with other brain regions.
The LIFO network supports several important mental functions, including:
- Executive function and decision-making.
- Working memory and information processing.
- Attention and concentration.
Previous research has also linked these regions to increased vulnerability to Alzheimer’s disease and schizophrenia.
This makes the network an important area of investigation when studying brain ageing and neurological conditions. However, changes in this network do not automatically indicate that someone has dementia or another neurological disorder. (Oxford Research Team, 2024)
3 Major Risk Factors Linked to Brain Ageing
1. Diabetes
Diabetes emerged as the strongest modifiable risk factor associated with changes in the vulnerable brain network.
The researchers specifically examined whether participants had received a medical diagnosis of diabetes. They did not directly compare different levels of blood glucose control or diabetes severity.
Diabetes affects the body’s ability to regulate blood sugar. Persistently high blood glucose can damage blood vessels and increase the risk of cardiovascular complications, including stroke.
These complications can also affect the brain. Poorly managed diabetes has been associated with problems involving memory, attention and other cognitive functions.
The study strengthens the evidence linking diabetes with changes in brain regions vulnerable to ageing. It also highlights the importance of early diagnosis and appropriate disease management.
Regular blood glucose monitoring, prescribed treatment, physical activity and a balanced diet can help people manage diabetes and reduce the risk of complications.
The US Centers for Disease Control and Prevention (CDC) also identifies uncontrolled diabetes as an important modifiable risk factor for dementia. (CDC, 2024)
2. Traffic-Related Air Pollution
Traffic-related air pollution emerged as the second major factor associated with changes in the vulnerable brain network.
The researchers specifically examined nitrogen dioxide (NO₂), a pollutant mainly produced by fuel combustion. Road traffic is an important source, particularly in busy urban areas.
An important detail is that the study used nitrogen dioxide exposure estimates from 2005. It treated this measurement as an indicator of traffic-related pollution rather than assessing every type of air pollution separately.
Long-term exposure to air pollution has been associated with several health problems, including cardiovascular and respiratory conditions. Research also suggests that exposure to polluted air may affect brain health.
Potential biological pathways include inflammation, oxidative stress and damage to blood vessels. However, the Oxford study did not directly investigate these mechanisms or establish that nitrogen dioxide alone caused the observed brain changes.
The findings add to growing evidence that environmental conditions may influence long-term cognitive health.
Reducing vehicle emissions, improving urban air quality and limiting exposure to heavily polluted environments are important public health measures. (Manuello et al., 2024)
3. Alcohol Consumption
Alcohol intake frequency was the third strongest modifiable factor associated with changes in vulnerable brain regions.
The researchers examined how frequently participants consumed alcohol. This measurement is important because it differs from total alcohol consumption, the number of units consumed or the presence of alcohol use disorder.
Alcohol affects the central nervous system, which includes the brain and spinal cord. Excessive alcohol consumption can interfere with brain function and affect memory, attention and decision-making.
Long-term harmful drinking can also increase the risk of conditions such as high blood pressure, stroke and nutritional deficiencies.
The Oxford findings highlight alcohol intake frequency as an important variable in research on brain ageing.
However, the study does not establish a specific drinking frequency or quantity that causes faster brain ageing. It also does not prove that frequency alone caused the observed changes.
Reducing harmful alcohol consumption can support overall health. People who regularly drink heavily should seek medical advice before stopping suddenly, as withdrawal can be dangerous.
Other Risk Factors That May Influence Brain Health
Although diabetes, nitrogen dioxide exposure and alcohol intake frequency emerged as the three leading factors, the researchers also identified other variables associated with the vulnerable brain network.
The next four in the research team’s ranking were:
- Sleep duration.
- Waist circumference.
- Past tobacco smoking.
- Medication for blood pressure.
The wider analysis also considered cholesterol, hearing, inflammation, exercise, socialization and other lifestyle factors.
This highlights an important point about brain ageing: several biological, behavioral and environmental factors may contribute to changes in brain structure.
It is therefore important to consider overall health rather than focusing on only one lifestyle habit.
Genetic Factors Also Influence Brain Vulnerability
Alongside modifiable risk factors, the researchers investigated the genetic influences associated with the vulnerable brain network.
They identified seven genetic clusters linked to conditions and outcomes such as Alzheimer’s disease, Parkinson’s disease, schizophrenia and cardiovascular deaths.
Two particularly interesting genetic findings involved the XG blood group system, located in a relatively little-studied region shared by the X and Y chromosomes.
These findings provide additional information about the genetic factors associated with brain vulnerability.
Unlike diabetes, alcohol consumption and environmental pollution, genetic factors cannot generally be changed through lifestyle interventions. Further research is needed to understand their role in brain ageing and disease development. (Manuello et al., 2024)
What the Study Does Not Prove
Although the findings are significant, they require careful interpretation.
The study identified associations between certain risk factors and changes in a specific network of vulnerable brain regions. It did not prove that these factors directly cause faster brain ageing or dementia.
The strength of the statistical associations was also relatively modest. In the combined analysis, the reported correlations were approximately -0.05 for diabetes, -0.05 for nitrogen dioxide exposure and -0.04 for alcohol intake frequency.
The researchers also reported that the 12 selected modifiable factors together explained approximately 1.5% of the effect measured on the vulnerable brain network in their model. Age and sex remained important influences.
There are also limitations concerning the study population. Participants were aged between 44 and 83 years and were generally healthier than the wider population. Only a small number had received a dementia diagnosis before their brain scans.
The findings also need replication in other large datasets.
Most importantly, the researchers specifically stated that these three factors should not be interpreted as the three biggest risk factors for dementia overall. Their ranking applies to the particular brain network examined in this research. (Manuello et al., 2024)
How to Support Long-Term Brain Health
The findings highlight the importance of managing preventable health and environmental risks throughout life.
Several practical measures can help support general brain health:
Manage diabetes and blood pressure: Regular health assessments, blood glucose monitoring and appropriate medical treatment can help reduce complications that affect cardiovascular and brain health.
Stay physically active: Regular walking, cycling, swimming and strength exercises support cardiovascular health and overall physical function.
Reduce harmful alcohol consumption: Limiting alcohol intake can help reduce the risk of several conditions that affect the nervous system and cardiovascular system.
Avoid tobacco: Smoking cessation supports blood vessel health and reduces several risk factors associated with dementia.
Reduce exposure to air pollution: Checking local air quality reports and avoiding outdoor exercise beside heavily congested roads during periods of high pollution can help limit exposure.
Maintain a balanced lifestyle: Adequate sleep, a nutritious diet, social interaction and mentally stimulating activities can contribute to long-term wellbeing.
The World Health Organization’s updated 2026 guidelines on reducing cognitive decline and dementia also recommend managing conditions such as diabetes and high blood pressure, increasing physical activity, reducing harmful alcohol consumption and limiting exposure to air pollution. (WHO, 2026)
Conclusion
The University of Oxford study identified diabetes, traffic-related nitrogen dioxide pollution and alcohol intake frequency as the three strongest modifiable factors associated with changes in brain regions vulnerable to ageing.
The findings provide further insight into how metabolic health, environmental exposure and lifestyle habits may influence brain structure. However, they do not establish that these factors directly cause dementia or determine an individual’s future cognitive health.
Managing chronic conditions, reducing harmful lifestyle exposures and maintaining overall physical health remain important steps towards healthier ageing and long-term brain health.
