Neurodegeneration: new findings

In the largest study of its kind, researchers have found a specific network of brain regions that is not only more vulnerable to unhealthy ageing – for example, Alzheimer’s disease – but also to disorders that emerge in young people, such as schizophrenia.

The international team, led by Medical Research Council (MRC) funded researcher Dr Gwenaëlle Douaud, at the Oxford University Functional MRI of the Brain (FMRIB) Centre, also discovered that, in healthy people, these parts of the brain are the last to develop and the first to show signs of neurodegeneration. The research has been published in the journal Proceedings of the National Academy of Sciences. 

The network of nerve cells in the brain (grey matter), consisting of mainly ‘higherorder’ regions that coordinate information coming from different senses, doesn’t develop until late adolescence or early adulthood and is associated with both intellectual ability and long-term memory. These mental abilities become significantly impaired in, respectively, people with schizophrenia or those with Alzheimer’s. 

The University of Oxford team used MRI scans to look at changes in the brain structure of 484 healthy people, ranging in age from 8 to 85 years. Uniquely, the researchers used a ‘datadriven’ approach to study these age-related changes. This means that, instead of looking for a particular pattern of brain change over the lifespan in a specific location of the brain, they analysed all the imaging data to see what patterns were revealed. 

The imaging data showed a specific network within the grey matter linking mostly higher order regions of the brain. In addition, this network was found to develop later than the rest of the brain, and was the first to degenerate in older age. 

The findings fit with a ‘last in, first out’ or ‘retrogenesis’ theory of brain change across the lifespan which dates back to the 1880s. It proposes that brain capacity declines in reverse order to the way in which it develops both in human developmental terms – e.g. from children to adults – but also in evolutionary terms – e.g. evolving from chimpanzees to humans. This study is the first to demonstrate this theory in the grey matter on a large scale using complex, ‘data-driven’ image analysis techniques. 

Although it has been known for some time that grey matter declines with age, this study revealed one specific network that was more vulnerable to age-related neurodegeneration, in that it degenerated earlier than other parts of the brain. The researchers compared this network, identified from MRI data of healthy subjects’ brains, with the pattern of grey matter damage observed in the scans of people suffering from Alzheimer’s and from schizophrenia. The researchers found striking similarities between the three, and could relate the network to key symptoms of both diseases, suggesting that these areas of the brain are likely play a crucial role in the emergence of these two very different disorders. 

Research has shown previously that these higher-order regions are not as developed in the brains of chimpanzees and other primates. In addition, because these animals appear not to suffer from schizophrenia or Alzheimer’s, some scientists have suggested that these diseases might be the high price humans pay for both our highly-evolved brains and our extended lifespan. 

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