We must make the most of Alzheimer’s disease research
We recently wrote about the challenge for dementia clinical services if immunotherapy for Alzheimer’s disease proves to be successful.
It is important to plan for the future but there is some thinking and planning to be done before we arrive there.
The focus of research has shifted significantly away from established and moderately severe Alzheimer’s disease to the much earlier stages of the illness and in some cases when symptoms are very mild or even absent. People have called this “Prodromal” Alzheimer’s disease or “Asymptomatic” Alzheimer’s disease.
For technocrats like us, of course, dementia is defined as a clinical syndrome and by definition has to have symptoms. So one would not talk about pre symptomatic dementia (that would include everybody who did not have dementia, a bit like the club of which we are members ie people who have not yet won the Nobel Prize for medicine). As Alzheimer’s disease is largely defined in terms of the brain deposition of amyloid plaques and abnormal tangles of nerve fibres (due to the deposition of tau protein), you can certainly have these in the absence of symptoms.
In some situations, probably less than 1% of the total number, Alzheimer’s disease is passed on by a familial gene (APP and presenilin) for which testing is available. Since these rare gene mutations lead to disease with consistent ages at onset within families, there is a unique opportunity to study the earliest development of the changes in the brain such as amyloid deposition. In addition there is an opportunity to intervene before symptoms develop.
There are two major examples of this approach. The Alzheimer’s Prevention Initiative study, taking place in Medellin, Colombia involves about 300 participants from local families that can be traced to a common descendant who had a rare genetic mutation. The second is the DIAN TU study which is looking to determine the safety, tolerability, and effectiveness of two potentially disease modifying therapies in individuals who carry one of the gene mutation that causes dominantly inherited Alzheimer’s disease. Individuals in the UK are participating in the DIAN TU study at the UCL centre.
It is likely that disease modifying treatments will be based on their ability to tackle amyloid deposition in the brain. Amyloid is detected using a positron emission tomography scan, which currently costs about £1,400. There are three tracers available which use fluorine 18 to bind the tracer approved by the USA Food and Drug Administration in 2012, 2013 and 2014 respectively – they are: florbetapir, trade name Amyvid from Eli Lilly flutemetamol, trade name Vizamyl from GE Healthcare and florbetaben, trade name Neuraceq from Piramal Imaging). Amyloid can be detected before there are any symptoms and there are studies being developed of people who have positive amyloid scans but no symptoms.
The A4 study is the first trial designed to prevent memory loss by identifying individuals who have the earliest changes of Alzheimer’s disease but are asymptomatic. Tau can be detected using similar techniques but the technology is less well advanced.
At the same time as all this excitement in dementia, the 100,000 genome project has been established in the NHS. Facilitated by 13 genomic medical centres across England, the aims include increasing discovery of pathogenic variants leading to new treatments, devices and diagnostics and to advance genomic practice into the NHS.
The opportunities for Alzheimer’s disease are significant in terms of potentially identifying people at risk, elucidating pathological mechanisms, perhaps helping predict who may respond to treatment allowing us to target interventions.
What are the implications for us? First, what we need is a collective and agreed view on the different ways of investigating people in the early stages of Alzheimer’s disease. Who should get an amyloid scan and when? More and closer working between clinical disciplines involved in memory assessments is crucial here.
Second, If and when one of the monoclonal antibodies is shown to have an effect in slowing the progression of Alzheimer’s disease then it will be one of the most significant events in the unfolding of the dementia story, we must be ready for it and in the sense of there being no surprises we must prepare the ground, working with colleagues across the system and reflecting work done by organisations such as Alzheimer’s Research UK and the Alzheimer’s Society is key. We are aware that there are similar protocols that have been developed for monoclonal antibody work in conditions such as rheumatoid arthritis.
Third, we need to harness the power of genomics and specifically the 100,000 genomes project to mainstream dementia in general and Alzheimer’s disease in particular.
The field of dementia is on the threshold of change which will benefit people with the condition, their families and carers. We all have a responsibility to make the most of the opportunities.
For further reading, go to:
Alistair Burns, CBE FRCP, FRCPsych, MD, MPhil
Alistair Burns is Professor of Old Age Psychiatry at The University of Manchester and an Honorary Consultant Old Age Psychiatrist in the Greater Manchester Mental Health NHS Foundation Trust. He is the National Clinical Director for Dementia and Older People’s Mental Health at NHS England and NHS Improvement.
He graduated in medicine from Glasgow University in 1980, training in psychiatry at the Maudsley Hospital and Institute of Psychiatry in London. He became the Foundation Chair of Old Age Psychiatry in The University of Manchester in 1992, where he has variously been Head of the Division of Psychiatry and a Vice Dean in the Faculty of Medical and Human Sciences, with responsibility for liaison within the NHS. He set up the Memory Clinic in Manchester and helped establish the old age liaison psychiatry service at Wythenshawe Hospital. He is a Past President of the International Psychogeriatric Association.
He was Editor of the International Journal of Geriatric Psychiatry for twenty years, (retiring in 2017) and is on the Editorial Boards of the British Journal of Psychiatry and International Psychogeriatrics. His research and clinical interests are in mental health problems of older people, particularly dementia and Alzheimer’s disease. He has published over 300 papers and 25 books.
He was made an honorary fellow of the Royal College of Psychiatrists in 2016, received the lifetime achievement award from their old age Faculty in 2015 and was awarded the CBE in 2016 for contributions to health and social care, in particular dementia.
Professor Martin Rossor
Martin Rossor is the NIHR National Director for Dementia Research, Professor Emeritus, and Principal Research Associate at the UCL Queen Square Institute of Neurology. He has been a leading figure in the field of dementia for over twenty years.
Following his training in clinical neurology at the National Hospital, Queen Square, Martin undertook primary research on the neurochemistry of degenerative dementia at the MRC Neurochemical Pharmacology Unit, Cambridge, before being appointed as Consultant Neurologist at St. Mary’s Hospital London and the National Hospital in 1986. Martin was appointed as the Chairman of the Division of Neurology in 2002, after becoming Professor of Clinical Neurology. He established a specialist cognitive disorders clinic, which acts as a tertiary referral service for young onset and rare dementias.
Martin’s clinical research interests are in the degenerative dementias, particularly familial disease, and more recently in general cognitive impairment in systemic disease and multimorbidity. He established the Queen Square Dementia Research Centre and has served as the editor of the Journal of Neurology, Neurosurgery and Psychiatry, President of the Association of British Neurologists, Director of the NIHR Clinical Research Network for Dementia and Neurodegenerative diseases (DeNDRoN), and Director of the NIHR Queen Square Dementia Biomedical Research Unit. As part of the activities of DeNDRoN he established Join Dementia Research (JDR), a national system for linking patients and public to research studies.
He has served on numerous advisory boards and is currently a member of the NIHR Strategy Board, associate member of the World Dementia Council, member of the 2020 Dementia Programme Board, and Chairman of the Senate for the German Centre for Neurodegenerative Diseases (DZNE).
Martin has authored and co-authored numerous articles and textbooks in dementia and general neurology. You can find a complete list of his publications using the following link: https://orcid.org/0000-0001-8215-3120