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Britain must make the most of Alzheimer’s disease research
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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.
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Alistair Burns
Professor Alistair Burns is Professor of Old Age Psychiatry and Vice Dean for the Faculty of Medical and Human Sciences at The University of Manchester.
He is an Honorary Consultant Old Age Psychiatrist in the Manchester Mental Health and Social Care Trust (MMHSCT) and is the NHS England’s National Clinical Director for Dementia and Older Peoples’ Mental Health.
He graduated in medicine from Glasgow University in 1980 and trained 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 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 MMHSCT and helped establish the old age liaison psychiatry service in UHSMT. He is a Past President of the International Psychogeriatric Association.
He is Editor of the International Journal of Geriatric Psychiatry 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.
Prof Alistair Burns
Professor (Ben and Marianne Porges)
Affiliations:
Division of Neuroscience & Experimental Psychology (L5)Division of Neuroscience & Experimental Psychology
Manchester Institute for Collaborative Research on AgeingSchool of Social Sciences
Email: alistair.burns@manchester.ac.uk
gillian.burns@manchester.ac.uk
Phone: +44 (0)161 306 7942
Professor Martin Rossor
Professor Martin Rossor trained in Neurology at the National Hospital, Queen Square and undertook research into the neurochemistry of degenerative dementia at the MRC Neurochemical Pharmacology Unit, Cambridge.
He is honorary consultant neurologist at the National Hospital for Neurology and Neurosurgery where he established the specialist cognitive disorders clinic which acts as a tertiary referral service for young onset and rare dementias. Clinical research interests are in neurodegenerative disease and particularly in familial disease.
He is the NIHR National Director for Dementia Research, Director of the NIHR Queen Square Dementia Biomedical Research Unit and a NIHR Senior Investigator.
He was Director of the NIHR Dementia and Neurodegenerative Disease Research Network (DeNDRoN) from 2005-2014, Editor of the Journal of Neurology, Neurosurgery and Psychiatry 2004-2009 and President of the Association of British Neurologists 2011-2013.
Prof Martin Rossor
Tel: 020 3448 3171
Fax: 020 3448 3104
Email: m.rossor@ucl.ac.uk
Location:
National Hospital for Neurology and Neurosurgery
Specialities:
Cognitive disorders clinic, Neurology and neurosurgery
Location: Specialities: |
Professional background
Professor Rossor graduated from Jesus College, Cambridge and Kings College Hospital Medical School London. He trained in Neurology at the National Hospital, Queen Square and undertook research into the neurochemistry of degenerative disease at the MRC neurochemical pharmacology unit in Cambridge.
He is the NIHR National Director for Dementia Research, Director of the NIHR Queen Square Dementia Biomedical Research Unit and a NIHR Senior Investigator.
He is honorary consultant neurologist at the National Hospital for Neurology and Neurosurgery where he established the specialist cognitive disorders clinic which acts as a tertiary referral service for young onset and rare dementias. Clinical research interests are in neurodegenerative disease and particularly in familial disease.
Professor Rossor graduated from Jesus College, Cambridge and Kings College Hospital Medical School London. He trained in Neurology at the National Hospital, Queen Square and undertook research into the neurochemistry of degenerative disease at the MRC neurochemical pharmacology unit in Cambridge.
He is the NIHR National Director for Dementia Research, Director of the NIHR Queen Square Dementia Biomedical Research Unit and a NIHR Senior Investigator.
He is honorary consultant neurologist at the National Hospital for Neurology and Neurosurgery where he established the specialist cognitive disorders clinic which acts as a tertiary referral service for young onset and rare dementias. Clinical research interests are in neurodegenerative disease and particularly in familial disease.
Research interests
- Neurodegenerative Diseases
- Young onset dementias
- Neurodegenerative Diseases
- Young onset dementias
Is this a new era for dementia?
Now, rarely does a week go by without a news story concerning dementia – a research breakthrough, a new technique of care, a human interest story and, unfortunately, an example of where care has fallen below an acceptable standard.
The overarching tale is that this is an illness for which there is no effective treatment. Some drugs are available for Alzheimer’s disease, the commonest cause of dementia, which are of benefit but there is still significant therapeutic nihilism around.
The news a few weeks ago of the putative efficacy of a disease modifying treatment for Alzheimer’s disease has ignited widespread public, professional and political interest and enthusiasm.
Solanezumab (Sola or Solab for short) is a monoclonal antibody directed at the amyloid protein that is regarded by many as being the core pathological abnormality causing cell death, brain shrinkage and ultimately clinical symptoms. Current treatments ameliorate the downstream effects by modulating neurotransmitters and offer symptomatic benefit. Changes to amyloid offer a more fundamental approach in altering the progression of the illness (stabilisation).
The results from a clinical trial were presented at a major international meeting of an open label extension of two double blind placebo controlled trials in patients with mild to moderate Alzheimer’s disease. Although these were negative a further analysis showed that people with mild Alzheimer’s disease had significantly slower progression of their symptoms compared to placebo.
The open label extension publicised gave a total of three and a half years’ worth of observation and showed a reduction of about one third in the expected decline in memory. Another phase three trial in people with mild Alzheimer’s disease is expected to report at the end of 2016 which will give a more definitive answer as to the efficacy of the treatment.
Should we feel the hand of history on our shoulders?
Considering the lack of efficacy of existing treatments for Alzheimer’s disease anything that shows evidence of potential benefit such as this is to be applauded. Testimonials from individuals anxious to be started on treatment are pre-emptive and realistically the availability of the treatment will be some years away.
If further trials prove positive it is likely to benefit a defined group of people with mild Alzheimer’s disease, probably those with evidence of amyloid abnormalities (detected by brain scans or lumbar puncture).
The challenge for the NHS and for professionals involved in the assessment, diagnosis and treatment of people with Alzheimer’s disease is to think ahead by gearing up for a fundamental change in the way the disorder is approached. Solanezumab is given as a monthly infusion, a simple invasive procedure compared to others in neurology but a new venture for many old age psychiatrists. The opportunities and challenges are threefold.
First, it takes the practice of dementia to another level with a potential treatment that could change the way we think of and consider disease. How did it feel when the first drugs to treat cancer were introduced, or the antipsychotics or the first antidepressants?
Second, there is a professional challenge for practitioners involved in dementia to work closely together – specifically psychiatry and neurology – which does not sound a lot to ask in view of the shared interest in brain function of the two disciplines. The relationship should be raised above those personal associations which so often make big changes to practice.
Third, people in the public eye driving interest and awareness of dementia have a responsibility to take a measured approach, this is not to dampen enthusiasm or to curb hope but it will be a long time before a readily available treatment will even halt let alone improve the symptoms of many people who have dementia.
The one simple message is we should be gearing ourselves up for a change – and not before time.
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