The ability to study the structure of the brain in living people has yielded new insights disease, and provided a crucial platform for clinical trials.
Although post-mortem analysis long ago revealed the brain abnormalities associated with Alzheimer's disease, only with the imaging techniques of CT and, in particular, MRI have changes in living brain tissue been visualised. Professor Nick Fox has pioneered studies to characterise brain pathology in dementia, and in individuals in advance of disease. His work has not only established that brain changes occur well in advance of clinical disease, but has also provided a platform for reliably assessing the impact of interventions in clinical trials.
In the mid-1990s, Professor Fox and Professor Martin Rossor realised that advances in MRI were providing opportunities to characterise the brains of dementia patients, and to distinguish pathological effects from those seen in normal ageing. Furthermore, they recognised that families with inherited forms of the disease, although rare, provided unique opportunities to study the onset of disease. Because dementia was far more likely to develop in this group than in the general population, and at earlier ages, it was practical to study them intensively in advance of disease onset.
Over the next 20 years, Professor Fox and colleagues conducted multiple studies to track brain atrophy in Alzheimer's disease and other dementias. One of the most profound conclusions was that loss of brain tissue was occurring before cognitive symptoms are apparent. This influential discovery has driven a radical reappraisal of Alzheimer's disease, to encompass both a 'pre-dementia' phase, with minor cognitive deterioration, and a 'pre-clinical phase' - potentially decades long - when the pathology of Alzheimer's is accumulating in advance of symptoms of cognitive decline.
Furthermore, this idea has emphasised the need to treat Alzheimer's disease as early as possible. By the time serious symptoms are apparent, the brain may already be beyond repair. This emphasis on early intervention is a central principle of the new Leonard Wolfson Experimental Neurology Centre.
Significantly, thanks to the exquisite sensitivity with which brain imaging can track changes in brain structure, clinical trials are now feasible on relatively small numbers of patients. Nevertheless, Professor Fox is continuing to characterise patterns of tissue loss and other changes, such as the build up of β-amyloid using PET imaging, for example in groups showing early onset of disease. This deep understanding will reveal more about the biology of disease, but will also be a critical way to stratify patients in trials.