Medical and scientific advances in prevention and treatment of dementia

Transcription

1 Medical and scientific advances in prevention and treatment of dementia 12 th UK Dementia Congress Doncaster Prof Craig Ritchie Centre for Dementia Prevention Centre for Clinical Brain Sciences University of

2 Talk Summary The emerging reality of prevention Principles into practice Progress to date Research into Practice

3 Focus of Funding Research and Practice 2010

4 Focus of Funding Research and Practice 2010 Research Practice

5 Focus of Funding Research and Practice 2015 Research Practice

6 Focus of Funding Research and Practice 2020 Research Practice

7 Focus of Funding Research and Practice 2025 Research Practice

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9 Alzheimer s Dementia? A B C D

10 Alzheimer s Disease? A B C D

11 Alzheimer s Disease (Pathology/Biomarkers)

12 Alzheimer s Dementia (Pathology/Biomarkers) Amyloid Pathology Tau Pathology Cerebrovascular Changes a-synuclein Blood Brain Barrier Integrity Glial activation and inflammation Oxidative stress Mitochondrial dysfunction Synaptic dysfunction Metal dyshomeostasis Apoptosis Insulin resistance mtor signalling b-hsd function

13 Different Profiles (Normal Ageing) ABeta Cortl* Inflm* Vasc Tau Mito Oxdn* asyn Aging Processes

14 Different Profiles (Alzheimer s disease/dementia) ABeta Cortl* Inflm* Vasc Tau Mito Oxdn* asyn Aging Processes Specific interventions at a critical (early) time point on background of general approach to modification of risk

15 Different Profiles: Highlights Distinction ABeta Alzheimer s Disease Cortl* Inflm* 1. More specific pathology Vasc present 2. Biomarkers Tau to diagnose Mito 3. Asymptomatic Oxdn* 4. Modifiable stage for disease asyn Aging Processes Specific interventions at a critical (early) time point on background of general approach to modification of risk

16 Different Profiles: Highlights Distinction ABeta Alzheimer s Disease Cortl* Inflm* 1. More specific pathology Vasc present 2. Biomarkers Tau to diagnose Mito 3. Asymptomatic Oxdn* 4. Modifiable stage for disease asyn Aging Alzheimer s Dementia 1. Multiple pathologies present 2. Biomarkers not needed for diagnosis 3. Symptoms and functional decline 4. Greater benefit from symptomatic treatments Processes Specific interventions at a critical (early) time point on background of general approach to modification of risk

17 Across the lifespan Risk factors Risk factors APOE, other genes Unhealthy diet Alcohol overuse Obesity Smoking Diabetes Familial aggregation Hypertension Dyslipidemia Neuronal damage Vascular insults 0 20 Adult life 60 Mid-life Education Cognitive and social activity Physical activity Protective factors 75 Late-life Dementia Brain reserve Cognitive reserve Figure adapted from Sindi S, et al. F1000Prime Rep. 2015;7:50.

18 4-factor modelling RISKS TIME (Changes in other 3 factors) DISEASE (Biomarkers) DISEASE (Cognition et al)

19 High probability Moderate probability Low probability The Vision That any given individual from birth onwards can be given an accurate probability of a neurodegenerative event Dementia Cognitive decline Biomarker change We will be making a prognosis not a diagnosis

20 Secondary Prevention of Dementia The three steps to achieve secondary prevention: STEP 1: Identifying the at risk person Risk factors (fixed and modifiable) Cognitive profile (not symptoms ) Biomarker evidence of disease Changes in these over time Can we develop an accurate prediction algorithm/score?

21 Secondary Prevention of Dementia The three steps to achieve secondary prevention: STEP 2: Tailoring treatment Reducing modifiable risk factors Enhancing resilience Disease course modification through specific drug intervention(s)

22 Secondary Prevention of Dementia The three steps to achieve secondary prevention: STEP 3: Measuring success Individual s probability status reduces Cognition improves Biomarkers normalise Risk of dementia decreases

23 Tailoring prevention Risks: Diet Weight Smoker Alcohol Risks: Head Injury Genetics Family History Cognition Biomarkers

24 Tailoring prevention Risks: Diet Weight Smoker Alcohol Risks: Head Injury Genetics Family History Cognition Biomarkers Individualised profile which maps onto individualised/tailored intervention

25 Inadvertent Success? 20% reduction in expected incidence over 20 year period between CFAS1 and CFAS 2

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27 What about interventions: The Sad Truth

28 Ongoing clinical trials in Alzheimer disease (AD) β amyloid Tau More than 200 drug development failures in the last 30 years Aß production Schneider Aß aggregation Mangialasche Kivipelto Aß clearance et al., JIM 2014 Currently approved for AD treatment Cholinergics Others Mangialasche, Kivipelto et al, modified 2013 from Lancet Neurology, 2010

29 PREVENTION PREMISED ON UNDERSTANDING DISEASE BEFORE DEMENTIA Develop and apply modeling strategies Understand Biology Deep and accurate clinical phenotyping Find Huge Numbers Participants Communicate before, during & after results PRIMARY PREVENTION SECONDARY PREVENTION

30 PREVENTION PREMISED ON UNDERSTANDING DISEASE BEFORE DEMENTIA EPAD* PreClinical PRIMARY PREVENTION SECONDARY PREVENTION

31 The EPAD Consortium AMYPAD UCL GE Piramal

32 The EPAD Project Structure WP2 WP4/ 8 WP1 WP2/ 4 WP4/ 8 WP3/ 8 The EPAD Delivery Cluster WP 5-8: Supporting Work Packages 32

33 The EPAD Flow Enrichment Journey 33

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35 Academic Progress to Date Numerous Peer Reviewed Outputs Supporting about 10 PhD/MD Students Two videos 1,700 Twitter Followers

36 How I Got Here

37 The Edinburgh Consensus: Preparing for the advent of disease modifying therapies for Alzheimer s disease Background, recommendations and plans Authors*: Banerjee, Barber, Boaden, Burns, Fox, Holmes, Isaacs, Leroi, Lovestone, Norton, O Brien, Pearson, Perry, Pickett, Ritchie, Rossor, Russ, Waldman and Wong. *Alphabetical order #edinburghconsensus

38 Rapidly developing understanding of Alzheimer s disease in phase before dementia develops. Heavily reliant on biomarkers Anticipated progress with disease modifying drugs against better refined/defined strata of patients with MCI Right of patients presenting with clinical problems to know what is wrong with them Urgent need to enhance services from a memory clinic paradigm for care to a Brain Health Clinic modus for care AND prevention.

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40 The Consensus Focused on 4 Key Areas Biomarkers for assessment and diagnosis Policy and professional development The optimal care pathway Communication

41 Biomarkers for assessment and diagnosis Four conclusions Disease modifying therapies most likely to be effective in earliest stages of disease Being able to measure markers of cortical amyloidosis are fundamental Biomarkers can be used for personalizing intervention Require establishment of a Phase IV testing environment ahead of marketing

42 Policy and professional development Three conclusions Equity of Access is Key Numerous professional groups will need training An opportunity to reconfigure services Brain Health Clinics

43 The optimal care pathway Three questions Who should be referred? What would optimal services require? How many people would be eligible? Primary Triage and Referral Secondary Assessment and Diagnosis Tertiary Confirmation and Therapeutics

44 Communication Disease before dementia Optimism of new message on prevention Agreement on message Consistency of communication (GP, Specialist, Public, Media and Academic) Accuracy of conclusions Credibility of those drafting communication strategy Powerful Mechanisms The Societies zz2ng

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46 Summary Global increase in numbers of people with dementia Care and practice can shift to prevention and delay to reduce burden of illness Massive research programmes are making this possible There will never be a cure for dementia but there can be a cure for the diseases leading to dementia The public, politicians and practitioners need to understand and embrace the plausibility of prevention!

47 Acknowledgment The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n , resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/ ) and EFPIA companies in kind contribution.