Nick Fox: aiming to prevent Alzheimer's disease

Abstract

The frantic existence that Nick Fox leads as a Professor at University College London's Institute of Neurology and a Consultant Neurologist at the UK's National Hospital for Neurology and Neurosurgery (NHNN) is a far cry from his relaxed upbringing in Jamaica. His parents moved to the Caribbean to teach when he was a baby, and the young Fox enjoyed a laid-back education system based on short school days and long holidays. Fox always leaned towards maths and sciences, “probably because it was easier than writing essays”, he tells The Lancet Neurology. After returning to the UK aged 15 years to escape Jamaica's rapidly escalating violence in the late 1970s, he went on to study natural sciences at Cambridge University (Cambridge, UK). After graduation, Fox worked briefly in the Foreign Office before embarking on a degree in medicine at St Thomas' Hospital (University of London, London, UK). Fox had to finance this degree himself, which he did with a number of entrepreneurial ventures, including bulk-buying 1000 red roses to sell with his fellow medical students on St Valentine's day. “I did not have a burning fixed view of what I would specialise in, but eventually I leaned towards neurology because the brain seemed the most interesting part of the body”, explains Fox. During Fox's junior doctor training, he was fortunate to meet Martin Rossor, one of the few neurologists researching cognitive neurology and dementia, at the NHNN. The timing was key, because the Alzheimer's Society had just launched clinical fellowships and Rossor wanted to use MRI to study familial Alzheimer's disease. Rossor thought Fox's background in physics would strengthen the application. The pair aimed to assess hippocampal volume changes over time using manual measurements from brain scans, but these measures were labour intensive and prone to error. In 1994 Fox had a “eureka” moment. Fox explains: “Rather than try and match up slices of brain, I realised it was better to think of the whole brain as a volume, and get the computer to match the images: superimposing an individual's later brain scan on top of an earlier one to see what had changed.” Imaging experts told him this would be too difficult, but Fox got PhD student Peter Freeborough to write the code for the process, termed co-registration. Alignment of serial scans with tremendous precision was then possible, revealing changes in volume not only in the hippocampus, but also in other brain regions. “This meant we could then pick up and measure presymptomatic changes in Alzheimer's disease, and we were amazed to see that subtle changes were occurring years before symptoms emerged”, says Fox. The technique has since been used in many trials to measure atrophy progression and assess therapies. Fox believes early identification of Alzheimer's disease and intervention will be the keys to provision of maximum benefit. Fox hopes to be working long enough to see a ‘statin for the brain’ emerge (ie, a drug that slows or prevents Alzheimer's disease). He draws an apt parallel with statins for heart disease, the early work for which was done in patients with familial hypercholesterolaemia. Much of Fox's research is done in the less than 1% of people with the familial form of Alzheimer's disease, which manifests very early. “These families are humbling, with selfless caring and amazing commitment to research, knowing that taking part will not help them but might help someone else”, Fox says. In addition to his development of atrophy measures from registration of serial imaging, Fox's career includes working on the Dominantly Inherited Alzheimer's Network (DIAN; an international consortium studying familial Alzheimer's disease) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). In DIAN, pharmaceutical companies are putting forward their best candidate drugs so that they can be tested in people at risk of familial Alzheimer's disease to see whether the disease can be prevented. Fox recently helped to put together University College London's successful bid to establish the Leonard Wolfson Experimental Neurology Centre, which will be dedicated to finding treatments and preventive therapies for neurodegenerative diseases. Another area of Fox's research is early onset and unusual dementias, including posterior cortical atrophy (PCA), a relatively rare form of Alzheimer's disease that mainly affects the back of the brain: patients experience a decline in their visual function but have little memory loss at first. The author Terry Pratchett brought prominence to PCA by declaring that he had the condition. “Alzheimer's disease is not a single entity”, says Fox. “We are trying to find out why different parts of the brain are more vulnerable in different patients.” “Nick's background in both basic sciences and neurology make him uniquely placed to understand the physics underpinning MR and its clinical application to dementia in equal measure”, says John O'Brien, who leads the Dementias and Neurodegenerative Disease Research Group at Newcastle University (Newcastle, UK). “He is a highly esteemed and generous collaborator, a superb champion of charities like the Alzheimer's Society and a great ambassador for our field.” “Nick's basic approach has become the mainstay of change-over-time measurement on MRI throughout the field of neurodegenerative brain disease—both for clinical trials and observational research studies”, says Clifford R Jack, The Alexander Family Professor of Alzheimer's Disease Research at the Mayo Clinic, Rochester, MN, USA. “The same rigorous, analytic approach that characterised his initial studies has been in evidence throughout his career.” Posterior cortical atrophyPosterior cortical atrophy (PCA) is a neurodegenerative syndrome that is characterised by progressive decline in visuospatial, visuoperceptual, literacy, and praxic skills. The progressive neurodegeneration affecting parietal, occipital, and occipitotemporal cortices that underlies PCA is attributable to Alzheimer's disease in most patients. However, alternative underlying causes, including dementia with Lewy bodies, corticobasal degeneration, and prion disease, have also been identified, and not all patients with PCA have atrophy on clinical imaging. Full-Text PDF Open Access