The most harmful modifiable risk factors for dementia have been identified in new research, with diabetes, traffic-related pollution and alcohol having the biggest impact on brain aging.

Researchers from the University of Oxford had previously identified a ‘weak spot’ in the brain, fragile regions which show earlier degeneration as we get older and are more vulnerable to schizophrenia and Alzheimer’s disease.

More recently, the team looked at the genetic and modifiable influences on these vulnerable areas of the brain by evaluating 40,000 brain scans from people aged over 45.

They looked at 161 risk factors for dementia and listed them in order of how much impact they have on these areas of the brain, after the natural effects of aging has been taken into account.

Modifiable risk factors are those which could be altered to cut the risk. The researchers grouped these risk factors into 15 areas, including blood pressure, cholesterol, diabetes, weight, alcohol consumption, smoking, inflammation, pollution, sleep, diet, physical activity, and education.

Co-author Professor Anderson Winkler, from the National Institutes of Health and The University of Texas Rio Grande Valley, said: “What makes this study special is that we examined the unique contribution of each modifiable risk factor by looking at all of them together to assess the resulting degeneration of this particular brain ‘weak spot’.

“It is with this kind of comprehensive, holistic approach – and once we had taken into account the effects of age and sex – that three emerged as the most harmful: diabetes, air pollution, and alcohol.”

Stud lead Professor Gwenaëlle Douaud said: “We know that a constellation of brain regions degenerates earlier in aging, and in this new study we have shown that these specific parts of the brain are most vulnerable to diabetes, traffic-related air pollution – increasingly a major player in dementia – and alcohol, of all the common risk factors for dementia.

“We have found that several variations in the genome influence this brain network, and they are implicated in cardiovascular deaths, schizophrenia, Alzheimer’s and Parkinson’s diseases, as well as with the two antigens of a little-known blood group, the elusive XG antigen system, which was an entirely new and unexpected finding.”

Co-author Professor Lloyd Elliott added: “In fact, two of our seven genetic findings are located in this particular region containing the genes of the XG blood group, and that region is highly atypical because it is shared by both X and Y sex chromosomes.

“This is really quite intriguing as we do not know much about these parts of the genome; our work shows there is benefit in exploring further this genetic terra incognita.”

Read the study in full in Nature Communications.

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