Research in Dementia

Transcription

1 Research in Dementia Tom Dening 7 th November 2013 November 7th 2013 Dementia Congress, Nottingham 1

2 Professor of Dementia Research, Institute of Mental Health, University of Nottingham post funded by Notts Healthcare & Barchester Honorary Consultant Psychiatrist, Notts Healthcare NHS Trust Chair of Dementia Evidence Group, NHS England Formerly Consultant in Old Age Psychiatry, Cambridgeshire & Peterborough NHS Foundation Trust ( ) No payments from PLCs All views expressed are my own

3 What this lecture covers and what it doesn t! Yes The research agenda Diagnosis in dementia and why that matters to everyone No A comprehensive review of all areas of dementia research

4 Research matters Why s research important? Who does it? Who uses it? Who benefits? Who pays for it? What do we need to know?

5 Why it matters We all use research Examples include: person centred care drugs for treating Alzheimer s disease mental capacity and decision making There s a pathway of research from laboratories to clinics to people s homes

6 Why it matters 2 range of research related activities producing research, e.g. lab scientists, experiments, drug trials, new therapies participating in research, e.g. surveys reviewing research implementing research research into policy, e.g. National Dementia Strategy using research in teaching & practice consuming research, e.g. using equipment end users, i.e. people with dementia & their families

7 Why research matters 3 Who benefits? main beneficiaries must be people with dementia and their families practitioners in health & social care commissioners & politicians the public and society in general Who pays for it? mainly Government, through NIHR, MRC etc charitable sources, e.g. Alzheimer s Society, Alzheimer s Research UK, many other smaller bodies

8 What do we need to know? The blind men and the elephant

9 What do we need to know? the blind men and the elephant that is, it depends on your perspective sometimes simplified into Cause, Cure, Care Cause = biological research into brain (e.g. imaging, neuropathology), genetics, effects of physical diseases Cure = treatments not many of these but usually includes drug treatments

10 Prospects for Cause and Cure 90% of research money spent in these areas >20 genes associated with Alzheimer s disease now known understanding of processes of amyloid deposition its distribution in the brain sequence of changes over time appears to start 20+ years before clinical dementia develops current Alzheimer s drugs symptomatic at best do they slow down course of disease? hard to tell upcoming new drugs drugs used in other conditions (minocycline, pioglitazone) monoclonal antibodies nutraceuticals inhibition of cell death (years off!)

11 Research on Care traditionally underfunded however, if dementia has up to 10-year history most people aren t in contact with many services especially health most of the time so, what you do the rest of the time is at least as important!!

12 Research on Care: what we know general health is really important early life factors such as deprivation also important carers provide most of the care, often at a personal cost it s easy to use too much medication for people s behaviour social environments are important adequate stimulation & activity participation in normal things being able to go out care homes are complex places but important for research

13 Research strategy Is research a priority? What priorities do we have? What s already out there? What needs more attention? Who decides? How do we influence the agenda?

14 Existing priorities for research different approaches: Ministerial Advisory Group 2011 NIHR dementia themed call 2011 ESRC dementia call 2012 PM s Challenge, May 2013 Alzheimer s-james Lind priority setting partnership, August 2013 overseas initiatives, e.g. EU, Canada, Australia

15 Ministerial Advisory Group on Dementia Research 15 point plan under 5 headings: strengthen collaboration & co-ordination embed research in treatment & care grow capacity and capability harness existing resources engage the public

16 PM Challenge (2013 progress report) patients and their data discovery science translational research, inc NIHR BMUs clinical research (trials, diagnosis, data sharing/ consent) living well with dementia Sets out goals for 2015 and 2025 for each area

17 Alzheimer s-james Lind alliance Independence Care Diagnosis Challenging behaviour Hospitals Nutrition Carers End of life Care homes Dementia friendly environments

18 Examples from abroad Canadian Dementia Action Network proposal 2010 Canadian Consortium on Neurodegeneration and Aging 2013 Australian Govt Dementia Research Map 2011 ALCOVE (EU) 2013

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20 Dementia Research Map (Brodaty et al, 2011) development and validation of rigorous diagnostic tests standardised diagnostic criteria for causes of non-ad dementia rates of and times to diagnosis of dementia in Australia new pharmacological treatments for dementia symptoms non-pharmacological approaches to managing BPSD identification and treatment of risk factors for dementia dementia and other chronic diseases in primary care psychosocial interventions to improve cognition, health and wellbeing of people with dementia and their carers cost-effective models of care for people with dementia and their carers in the primary care system

21 ALCOVE Alzheimer Cooperative Valuation in Europe (Dawn Brooker & colleagues) epidemiology timely diagnosis support systems for BPSD rights, autonomy, dignity antipsychotics limitation

22 Therefore: plenty of research agendas most have themes in common vary from high level strategy (MAGDR) to lists of topics (JLA) weaknesses: reflect the interests of their authors if comprehensive, they lack much detail no guidance about the balance of funding probably don t need another one

23 Anything missing? not much about social care, organisation of services, how people actually spend their time nor on knowledge translation and knowledge exchange [putting it into practice] dementia and creative arts participation application of technology in dementia many devices, little evaluation, unproven benefit potential mismatch between research outputs and affordable practice readiness of staff to implement findings

24 Suggestions discuss how research agenda is set what is the role of expert consensus v public consultation? more consideration of world context of dementia better knowledge translation

25 Interlude IDEA Atdementia Fishbowl

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28 Coming soon!

29 Why talk about diagnosis at Congress? I want to persuade you that this matters, that it is not just arcane medical stuff

30 Because Diagnosis affects the language we use the numbers of people who have a condition people s expectations And therefore our perception of a disease what happens to people with the condition our practice and the money!

31 Why do we make diagnoses? summarise features that people may have in common may share the same causes and pathology implications for choices of treatment some predictive value for prognosis

32 Downside labelling, stigma may not be a true biological entity illness related, so doesn t concentrate either on current problems or on individual strengths and resources often suggested that we should concentrate on symptoms not disorders

33 Dementia a clinical syndrome usually memory loss + other cognitive domain + psychosocial impairment ICD10 & DSMIV criteria has various causes, e.g. Alzheimer s disease, vascular, Dementia with Lewy bodies etc

34 Shortcomings heterogeneity diagnosis requires clinical judgement has been a stigmatising label, hence rise of Alzheimer s BUT dementia now back in fashion to describe the public issue cases that fall short of diagnostic threshold

35 Sub-dementia long history of competing terms for memory loss without significant psychosocial impairment OR memory loss greater than expected for age but not much else wrong current favoured term: mild cognitive impairment (MCI)

36 MCI better than some of the alternatives face validity is good heterogeneous not everyone gets dementia treatment trials are negative because of this correctly regarded as an at-risk state rather than a disease

37 DSM5 (American Psychiatric Association, 2013) major and minor neurocognitive disorder dementia can still be used as an alternative NCD: significant cognitive disorder interferes with independence not due to delirium not due to other mental disorder moves spectrum to disorders occurring in younger people

38 DSM5 neurocognitive disorders for major NCD, specify due to which underlying disease, e.g. Alzheimer s, brain injury etc major NCD can be a single domain, e.g. amnestic mild NCD = moderate cognitive decline, not interfering with independence, therefore resembles MCI

39 Presymptomatic diagnosis that is, MCI or mild NCD Biomarkers: brain imaging CSF proteins blood tests genetic risk profiling neuropsychology combinations

40 Brain imaging 1. Structural (CT, MRI) loss of brain tissue evident in cases who go on to develop AD however lack of precision to make this diagnostic serial imaging in people at risk may be more accurate

41 Brain imaging 2 2. Functional conventional, e.g. fmri, PET scans molecular e.g. PIB (Pittsburgh compound B) and florbetapir highlight areas of amyloid deposition considerable cost

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43 Brain imaging 3 amyloid starts to accumulate up to 20 years before disorder is clinically manifest (Villemagne et al, 2013) whereas hippocampal atrophy appears about 4 years and memory loss on average up to 3 years before onset of dementia

44 Protein biomarkers in general, changes in amyloid or tau proteins measured in CSF, blood or elsewhere, e.g. eye technical issues in measurement CSF requires lumbar puncture not ready as diagnostic tests may help predict progression from MCI to dementia (NB molecular fingerprints PAPA chip proposal O Shea et al)

45 Genetic risk profiling individual mutations causing AD APP gene, presenilins 1 and 2 very rare, early onset, autosomal dominant genes of increased risk ApoE-e4 (?earlier age of onset rather than risk) TREM2 approx 20 others

46 Genetics 2 clinically, people with AD have slightly more relatives with AD but not in a predictable Mendelian pattern in most cases, genetic advice not warranted genetic focus now turning to gene action, e.g. inflammatory processes rather than simple genotype studies

47 Neuropsychology certain tests, e.g. CANTAB paired associate learning test, show impairment preceding clinical dementia by several years licence holders of tests promote use, including self testing however, problems with specificity

48 Biomarkers and Alzheimer's disease: proposed changes in biomarkers in relation to the time course of pathological and clinical stages. From: Multimodal techniques for diagnosis and prognosis of Alzheimer's disease Richard J. Perrin, Anne M. Fagan & David M. Holtzman Nature 461, (15 October 2009) doi: /nature08538

49 A sobering fact By far the biggest risk factor for AD is age: therefore you can say it is the most potent biomarker of the lot!

50 Screening, early diagnosis, timely diagnosis A topic of current debate! Population screening or early diagnosis? are we talking about the same thing? screening is a seductive word sounds precise, decisive & implies action

51 Good screening tests require good sensitivity & specificity can t prevent the problem but should reduce risk DH programme emphasises risk reduction public expectations need to be reasonable minimal adverse effects, e.g. overdiagnosis misdiagnosis false sense of security

52 Dementia suitability for screening WHO criteria, important? definitely 2. treatment? supportive, palliative 3. facilities for Δ & treatment? variable 4. latent stage? do we mean MCI? 5. specific tests? accuracy of tests imprecise 6. acceptable? not known 7. natural history understood? no 8. whom to treat? not agreed 9. proportionate cost? not known 10. case finding continuous? could be

53 Big unknowns/big problems limitations of tests diagnostic test accuracy [Cochrane] limitations of available biomarkers harder to interpret in asymptomatic population acceptability to population lack of robust research [systematic review: Brayne & colleagues] existing studies suggest that participants are self selecting implications for population unclear issues of consent and trust in GP-patient interaction public expectations are not well understood

54 Big unknowns/big problems 2 when should treatment start? natural history heterogeneity of MCI variability of progression benefits v harms of treatment for asymptomatic people no evidence that treatment this early affects LT outcomes, indeed ve drug trials in MCI no evidence that risks are reduced at this stage risk of overdiagnosis

55 NHS England/BMA consensus meeting July 2013 timely not early diagnosis or screening reduce variation services need to be responsive & fit for purpose set up 5 groups review Dementia Enhanced Service (DES) dementia information prescriptions dementia diagnosis national reference group evidence base for dementia diagnosis (TD chairing) vascular dementia

56 Policy & commissioning improving care for people with dementia (Gov.uk, April 2013): diagnosis rates health & care services dementia friendly communities dementia research incentives for CCGs and primary care

57 Diagnosis rates said to be about 45% in England, NB higher rates in Scotland and Northern Ireland subject of much political and media attention in my view, suspect, as based on figures that probably include MCI as well as dementia, plus based on projections from MRC CFAS data from 1980s CFAS2 estimate is significantly lower

58 Help for GPs and CCGs Dementia Quality Outcomes Framework (QOF) Dementia enhanced service payment (DES) identify people at risk, offer assessments of (a) memory and (b) dementia, memory clinic referral, carer health check Dementia Prevalence Calculator Dementia Road Map Dementia CQUIN (acute care) Dementia self-assessment framework (acute care)

59 Healthy scepticism

60 What do people want? A systematic review of screening for dementia in the older population (Brayne, Dening, Fox, Katona, Lafortune, Rait, funding Alzheimer s Society, final report August 2013) 1. What are the clinical and psychosocial harms and benefits of population screening for dementia? 2. What are the economic implications of population screening for dementia? 3. What tools are available for population screening of dementia and how suitable are they? 4. What views and attitudes do people with dementia, their carers and healthcare professionals have about population screening for dementia?

61 Review 1: clinical & psychosocial impact of screening Key findings: We found no papers reporting primary data on the positive or negative clinical and psychosocial impacts of screening for dementia. None of the suggested benefits of screening has been empirically tested and there is no high quality evidence for benefit in diagnosing patients before the usual point of presentation.

62 Review 4: PPI event (July 2013) factors such as personal beliefs, experiences and attitudes to health impact upon decisions to screen main themes: low levels of understanding and awareness around the disease acceptability and validity of the test costs to NHS; their existing health state financial/profit motive for screening inability to change prognosis importance and availability of support.

63 Where does that leave us?

64 Timely diagnosis public have got the message about memory problems and present earlier than they did dementia QOF and other pressures have increased referrals for diagnosis potential benefits in terms of helping pts/carers understand their experiences making advance choices discussion about drug treatments/social care but little evidence that these make a difference and beware vested interests purveyors of tests, treatments etc

65 Current limitations rate of diagnosis remains apparently low rates based on a questionable denominator but nonetheless variation seems too great ability of memory assessment services to cope with referrals already stretched often precludes providing ongoing support what s the most appropriate thing for them to offer?

66 What would I want for myself? 1. I wouldn t want to undergo cognitive testing every time I see my GP about an unrelated problem just because I m a certain age I would get pretty irritated! 2. I would want a serious assessment and referral to a specialist if I was getting forgetful or muddled - Whether I d want neuroimaging would depend on various other factors, but that s for another day!!

67 In summary research in dementia is really important for us all with regard to diagnosis/screening issues, debate is good, but let s see what the public thinks too we must ensure we present sensible information responsibly population screening of asymptomatic older people for dementia is misguided timely diagnosis is potentially beneficial however, and we can improve what we currently deliver

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