Craig Ritchie
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Transcript of Craig Ritchie
Research: risk reduction & prevention, cognitive testing and dementia in the workplace
Prof Craig RitchieCentre for Dementia Prevention
University of Edinburgh
www.centrefordementiaprevention.com
Overview• Why Prevention?
• What is secondary prevention?
• What is EPAD?
Why Prevention?
Age
60 65 70 75 80 85 900
10
20
30
40
50
60
70
Current Incidence5-year delay
Ritchie et al. 2015 Lancet Psychiatry (In Press)
Biomarkers and Alzheimer’s Dementia
• 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
SECONDARY PREVENTIONPRIMARYPREVENTION
PREVENTION PREMISED ON UNDERSTANDING DISEASE BEFORE DEMENTIA
Risk factors
Dementia
Familial aggregation
APOE, other genes
DyslipidemiaHypertension
Obesity
Cognitive reserve
Neuronal damage
0 20Adult life
60Mid-life
75Late-lifeA
cros
s th
e lif
espa
n
Vascular insults
Brain reserveEducation
Physical activity
Cognitive and social activity
Unhealthy diet
Alcohol overuse
Smoking
Diabetes
Protective factors
Risk factors
Figure adapted from Sindi S , et al. F1000Prime Rep. 2015;7:50.
Secondary Prevention
The three steps to achieve secondary prevention:
STEP 1: Identifying the ‘at risk’ person1. Risk factors (fixed and modifiable)2. Cognitive profile (not ‘symptoms’)3. Biomarker evidence of disease4. Changes in these over time
Can we develop an accurate prediction algorithm/score?
Secondary Prevention
The three steps to achieve secondary prevention:
STEP 2: Tailoring treatment1. Reducing modifiable risk factors2. Enhancing resilience3. Disease course modification through specific drug
intervention(s)
Secondary Prevention
The three steps to achieve secondary prevention:
STEP 3: Measuring success1. Individual’s risk status reduces
1. Cognition improves** (Karen Ritchie)2. Biomarkers normalise3. Risk of dementia decreases
2. Population level success1. Incidence decreases2. Trajectory of decline at early stage ameliorated
The European Prevention of Alzheimer's Dementia (EPAD) project aims to develop an infrastructure that efficiently enables the undertaking of adaptive, multi-arm Proof of Concept studies for early and accurate decisions on the ongoing development of drug candidates or drug combinations for the prevention of AD dementia.
European Prevention of Alzheimer’s Dementia (EPAD) Goal
EPAD Consortium
Current Grant Funding from IMI = €64M until end 2019
EPAD funnell
The EPAD Longitudinal Cohort Study
14
Loss to Follow Up
Maintained at N=6,000
Data
EPAD Cohort Baseline• Clinical• Biomarker• Imaging
Data
Data
1st Follow Up 2nd Follow Up
?
Enter Other Clinical Trial
Enter EPAD Trial
Replenishment from Virtual EPAD Register
The EPAD PoC Trial (n=1,500)
15
Allows early decisions on progression to longer term clinical outcomes by impact on pre-defined and target-specific intermediary phenotype.
2016 2023
Memantine, AChEIs, combination
Improved and earlier risk prediction
Precision Medicine
Other cognitive enhancers
Disease-modifying therapies
Community-wide prevention initiatives (diet, exercise…)
Alzheimer’s Disease treatment 2016 and beyond
2016 2023
Memantine, AChEIs, combination
Improved and earlier risk prediction
Precision Medicine
Other cognitive enhancers
Secondary Prevention therapies
Community-wide prevention initiatives (diet, exercise…)
Alzheimer’s Disease treatment 2016 and beyond (with EPAD)
National LeadsRitchie/Gallacher - UK & IrelandMiia Kivipelto - Scandinavia José Luis Molinuevo – Spain/Portugal Philip Scheltens - Benelux Giovanni Frisoni - Switzerland/Italy Bruno Vellas - France
AcknowledgementsWork Package LeadsWP1Simon Lovestone (UOXF) Andrew Satlin (Eisai) Gary Romano (JPNV)WP2Adrian Mander (MRC) Shobha Dhadda (Eisai) Scott Berry (BERRY) Kristian Windfeld (Lundbeck) WP3Pieter Jelle Visser (VU-VUmc) Gerald Luscan (Pfizer) WP4Craig Ritchie (UEDIN) Catherine Debove (BI) Miia Kivipelto (KI) Mila Etropolski (JPNV)
WP5Carlos Díaz (SYNAPSE) Serge Van der Geyten (JPNV) WP6Jean Georges (AE) Sean Knox (NOV) WP7José Luis Molinuevo (BBRC) Frank Tennigkeit (UCB) Saira Ramasastry (SYNAPSE)WP8Edo Richard (RUMC) Luc Truyen (JPNV) Carol Brayne (UCAM) Shirlene Badger (UCAM
Executive Committee & PMOSerge Van der Geyten (JPNV)Luc Truyen (JPNV)Andrew Satlin (Eisai)Craig Ritchie (UEDIN)Simon Lovestone (UOXF)José Luis Molinuevo (BBRC)Carlos Díaz (Project Manager)
Sandra Pla (member of PMO) Lennert Steukers (member of PMO) Mila Eltropolski (JPNV – member of PMO)Judi Syson (UEDIN – member of PMO)
The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n° 115736, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution.
Acknowledgment