By Chris McIntyre, Communications Manager (Research and Innovation), University of Oxford.
The researchers had previously identified a ‘weak spot’ in the brain, which is a specific network of
higher-order regions that not only develop later during adolescence, but also show earlier
degeneration in old age. They showed that this brain network is also particularly vulnerable to
schizophrenia and Alzheimer’s disease.
In this new study, published in Nature Communications, they investigated the genetic and modifiable
influences on these fragile brain regions by looking at the brain scans of 40,000 UK Biobank
participants aged over 45.
The researchers examined 161 risk factors for dementia, and ranked their impact on this vulnerable
brain network, over and above the natural effects of age. They classified these so-called ‘modifiable’
risk factors − as they can potentially be changed throughout life to reduce the risk of dementia − into
15 broad categories: blood pressure, cholesterol, diabetes, weight, alcohol consumption, smoking,
depressive mood, inflammation, pollution, hearing, sleep, socialisation, diet, physical activity, and
education.
Prof. Gwenaëlle Douaud, who led this study, 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.’
Prof. Lloyd Elliott, a co-author from Simon Fraser University in Canada, concurs: ‘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.’
Importantly, as Prof. Anderson Winkler, a co-author from the National Institutes of Health and The
University of Texas Rio Grande Valley in the US, points out: ‘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.’
This research sheds light on some of the most critical risk factors for dementia, and provides novel
information that can contribute to prevention and future strategies for targeted intervention.
The research has attracted much media attention