Cognitive Health in Ageing Reflecting On Learning From the CHARIOT Register (Cognitive Health in Ageing Register: Investigational, Observational and Trial studies in dementia research) Emily Pickering and Elliott Smith
Neuroepidemiology and Ageing Research Unit • Part of the School of Public Health. Based across Charing Cross Hospital and White City. • To better understand risk and protective factors • Inform methods for early prediction and prevention • Facilitating this through building of a register of “cognitively healthy” individuals aged 50-85 and Professor Lefkos T Middleton Chair of Neuroepidemiology and Ageing Research at the interested in ageing research School of Public Health
Ageing Epidemiology Research Unit (AGE) • Part of the School of Public Health. Based across Charing Cross Hospital and White City. • To better understand risk and protective factors • Inform methods for early prediction and prevention • Facilitating this through building of a register of “cognitively healthy” Professor Miia Kivipelto individuals aged 50-85 and Director of the Ageing Epidemiology Research Unit at the interested in ageing research School of Public Health “Lifestyle interventions to prevent cognitive impairment, dementia and Alzheimer disease” – Nature 2018
Alzheimer’s Disease (AD) • Most common cause of dementia. Occurs in those age 65 and older • Proteins build up in the brain in the form of plaques and tangles up to 20+ years before clinical symptoms • Current treatments involve trying to address a shortage of important chemicals in the brain – Supportive or palliative rather than curative or disease-modifying
Prevalence Rates for Dementia • 50 million people with dementia globally. Projected to double by 2040, and triple before 2050 • 850,000 people with dementia in the UK. Also predicted to double by 2040 World Health Organisation (2017); Prince et al. (2015); Prince et al. (2014)
Ageing London • 2.2 million aged over 50 in 2014 • 980,000 aged over 65 in 2014 – 1.2 million expected by 2024 • 130,000 aged over 85 in 2014 – 180,000 expected by 2024 Age UK London
London BoroughPopulation Population London Borough Population Population %50+ %65+ %50+ %65+ 50+ 65+ 50+ 65+ Hillingdon 78,000 29% 35,200 13% Barking and Hounslow 64,500 25% 26,900 10% 43,700 24% 19,200 11% Dagenham Islington 43,400 21% 18,100 9% Kensington and Barnet 102,700 29% 47,400 13% 44,700 28% 19,300 12% Chelsea Bexley 77,800 34% 47,900 21% Brent 77,800 25% 32,600 10% Kingston upon 45,800 29% 20,300 13% Thames Bromley 108,200 35% 51,900 17% Camden 53,500 24% 24,100 11% 59,000 20% 23,100 8% Lambeth Lewisham 63,300 23% 26,200 10% City of London 2,400 32% 1,000 13% Merton 52,600 26% 23,200 11% Newham 54,500 18% 20,400 7% Croydon 103,500 29% 44,500 12% Redbridge 76,400 27% 33,400 12% Ealing 86,100 25% 36,300 11% Enfield 86,600 28% 39,000 13% Richmond upon 57,100 31% 25,200 14% Greenwich 61,300 24% 26,000 10% Thames Hackney 44,800 18% 17,300 7% Southwark 58,500 20% 22,400 8% Sutton 60,000 32% 27,300 15% Hammersmith 38,900 21% 16,400 9% and Fulham Tower Hamlets 39,100 15% 15,800 6% Haringey 55,900 22% 22,500 9% Waltham Forest 61,100 24% 25,600 10% Harrow 73,900 31% 33,600 14% Wandsworth 63,200 21% 27,100 9% Havering 87,000 37% 42,400 18% Westminster 55,100 25% 24,400 11% Census 2011
Why has therapy development for dementia failed in the last 2 decades? • 3 main challenges: – Significant gaps in knowledge in nosology & complexity of biological mechanisms of commonest, non-familial forms of late-onset dementias – Low signal-to-noise ratio, notwithstanding lack of validated biomarkers as entry and/or end point criteria – Recruitment & retention, particularly in the asymptomatic and early disease stages Gauthier et al. (2016) – Alzheimers Dement
Late-onset dementias (LODs) • Heterogenous, complex and poorly understood • Co-existing pathologies • RCTs in high-risk individuals
Low signal-to-noise ratio • RCTs traditionally tested in established dementia patients, with control groups using standard dementia drugs • General overall and associated health better than 20 years ago • Biomarkers becoming part of inclusion criteria have increased costs and contributed to longer enrolment periods
Recruitment and retention • Frequent early termination of studies due to difficulties finding and retaining study participants
CHARIOT Register • Collaboration between GPs and the School of Public Health at Imperial College London • Main Objective: to build a register of “cognitively healthy” volunteers between the ages of 50-85 who are interested in taking part in Principal Investigators of the CHARIOT Register research to prevent age-related Professor Lefkos Middleton, Professor Azeem Majeed disease and Dr Josip Car
Pilot Study – Background and Method • Success of dementia prevention research dependent on having access to well-characterized, representative and sufficiently large population of individuals • Identifying cognitively healthy people at high risk of developing dementia • Invitations posted and demographics and contact details extracted from electronic health records of those who consented
Pilot Study - Results
Cognitive Health in Ageing Register: Investigational, Observational, and Trial studies in dementia research (CHARIOT): Prospective Readiness cOhort study (PRO) Cohort target - asymptomatic , healthy older adults CHARIOT-PRO Sperling R et al. (2011) Alzheimers Dement 7, 280-282
Findings from the CHARIOT Register so far
Table 1: Characteristics of study population. Predominantly Table 2: Variables computed in calculation of Reitz risk score white cohort with 1:4 APOE ε 4 allele carrier categories, with recommended points ascribed to each variable
Figure 5 : Categorisation of neurocognitive abilities of CPRO study cohort Figure 6 : Associations between LOAD predictive risk categories and based on predictive risk for LOAD. Low risk subjects perform significantly better longitudinal neurocognitive test performance. Significant associations observed than medium or high risk individuals. Neurocognitive test data are represented across statistical tests employed. Increasing risk significantly associated with as mean +- SEM. A one way ANOVA followed by multiple comparison poorer performance over time. procedure (Tukey post-hoc test) was applied to determine statistical differences in baseline cognitive performance across risk groups
Current clinical trials: Generation • Phase II trial of two medications (an injection and a tablet) that prevent build up of amyloid in the brain • Participants must be aged 60-75 years, cognitively healthy, APOEe4 homozygote carriers • Objective: to test the effectiveness of CNP520 and CAD106 at preventing or delaying the onset of Alzheimer’s disease symptoms
Current Status of the CHARIOT Register Register statistics by age 2500 2000 1500 1000 500 0 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94
Current Status of the CHARIOT Register Register by Gender 18000 17500 17000 16500 16000 15500 15000 14500 14000 13500 F M
Current Status of the CHARIOT Register Number of people joining the register each year 14000 12000 10000 8000 6000 4000 2000 0 2012 2013 2014 2015 2016 2017 2018
Recruiting to the CHARIOT Register Events Advertising General Practice Local Voluntary Secondary Care Organisations Eligible, Consenting Patients Chariot Register Study Study Study A B C
Recruiting to the Register through primary care
Recruiting onto the Register
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