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 funded researcher Gwenaëlle Douaud, at the Oxford University Functional MRI of the Brain 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, consisting of mainly higher-order regions that coordinate information coming from different senses, develops in 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 data-driven approach to study these age-related changes, in which 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. 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 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 and in evolutionary terms. 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. 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. As the researchers found striking similarities between the three, and could relate the network to key symptoms of both diseases, they suggest that these areas of the brain 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 a result of humans’ highly-evolved brains and extended lifespan.
The study was the result of an international collaboration between the University of Oxford neuroscience imaging team, neuroscience researchers from the University of Oslo and research clinicians from the University Hospital Basel, Imperial College London and the University of Oxford’s Department of Psychiatry.
Douaud explains: “Our results show that the same specific parts of the brain not only develop more slowly, but also degenerate faster than other parts. These complex regions, which combine information coming from various senses, seem to be more vulnerable than the rest of the brain to both schizophrenia and Alzheimer’s. These results, which might seem surprising at first, are really exciting as they actually reconcile two historical hypotheses – until now presented completely separately in the scientific literature – that the brain damage observed in Alzheimer’s and schizophrenia is related to these higher order regions of the brain.”
Hugh Perry, chairman of the MRC’s Neurosciences and Mental Health Board, which funded the work, says: “Early doctors called schizophrenia ‘premature dementia’ but until now we had no clear evidence that the same parts of the brain might be associated with two such different diseases. This large-scale and detailed study provides an important, and previously missing, link between development, ageing and disease processes in the brain.”