Cognitive Health in Ageing Reflecting On Learning From the CHARIOT - - PowerPoint PPT Presentation

Reflecting On Learning From the CHARIOT Register (Cognitive Health in Ageing Register: Investigational, Observational and Trial studies in dementia research)

Cognitive Health in Ageing

Emily Pickering and Elliott Smith

• 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 interested in ageing research

Neuroepidemiology and Ageing Research Unit

Professor Lefkos T Middleton Chair of Neuroepidemiology and Ageing Research at the School of Public Health

• 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 interested in ageing research

Ageing Epidemiology Research Unit (AGE)

Professor Miia Kivipelto Director of the Ageing Epidemiology Research Unit at the School of Public Health “Lifestyle interventions to prevent cognitive impairment, dementia and Alzheimer disease” – Nature 2018

• 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

Alzheimer’s Disease (AD)

• 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)

Prevalence Rates for Dementia

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

Census 2011

London BoroughPopulation 50+ %50+ Population 65+ %65+ Barking and Dagenham 43,700 24% 19,200 11% Barnet 102,700 29% 47,400 13% Bexley 77,800 34% 47,900 21% Brent 77,800 25% 32,600 10% Bromley 108,200 35% 51,900 17% Camden 53,500 24% 24,100 11% City of London 2,400 32% 1,000 13% Croydon 103,500 29% 44,500 12% Ealing 86,100 25% 36,300 11% Enfield 86,600 28% 39,000 13% Greenwich 61,300 24% 26,000 10% Hackney 44,800 18% 17,300 7% Hammersmith and Fulham 38,900 21% 16,400 9% Haringey 55,900 22% 22,500 9% Harrow 73,900 31% 33,600 14% Havering 87,000 37% 42,400 18% London BoroughPopulation 50+ %50+ Population 65+ %65+

Hillingdon

78,000 29% 35,200 13%

Hounslow

64,500 25% 26,900 10%

Islington

43,400 21% 18,100 9%

Kensington and Chelsea

44,700 28% 19,300 12%

Kingston upon Thames

45,800 29% 20,300 13%

Lambeth

59,000 20% 23,100 8%

Lewisham

63,300 23% 26,200 10%

Merton

52,600 26% 23,200 11%

Newham

54,500 18% 20,400 7%

Redbridge

76,400 27% 33,400 12%

Richmond upon Thames

57,100 31% 25,200 14%

Southwark

58,500 20% 22,400 8%

Sutton

60,000 32% 27,300 15%

Tower Hamlets

39,100 15% 15,800 6%

Waltham Forest

61,100 24% 25,600 10%

Wandsworth

63,200 21% 27,100 9%

Westminster

55,100 25% 24,400 11%

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
• f “cognitively healthy” volunteers

between the ages of 50-85 who are interested in taking part in research to prevent age-related disease

Principal Investigators of the CHARIOT Register Professor Lefkos Middleton, Professor Azeem Majeed 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)

CHARIOT-PRO

Sperling R et al. (2011) Alzheimers Dement 7, 280-282

Cohort target - asymptomatic, healthy older adults

Findings from the CHARIOT Register so far

Table 1: Characteristics of study population. Predominantly white cohort with 1:4 APOEε4 allele carrier Table 2: Variables computed in calculation of Reitz risk score categories, with recommended points ascribed to each variable

Figure 5: Categorisation of neurocognitive abilities of CPRO study cohort based on predictive risk for LOAD. Low risk subjects perform significantly better than medium or high risk individuals. Neurocognitive test data are represented as mean +- SEM. A one way ANOVA followed by multiple comparison procedure (Tukey post-hoc test) was applied to determine statistical differences in baseline cognitive performance across risk groups Figure 6: Associations between LOAD predictive risk categories and longitudinal neurocognitive test performance. Significant associations observed across statistical tests employed. Increasing risk significantly associated with poorer performance over time.

• 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
• r delaying the onset of Alzheimer’s disease symptoms

Current clinical trials: Generation

500 1000 1500 2000 2500 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

Register statistics by age

Current Status of the CHARIOT Register

Current Status of the CHARIOT Register

13500 14000 14500 15000 15500 16000 16500 17000 17500 18000 F M

Register by Gender

Current Status of the CHARIOT Register

2000 4000 6000 8000 10000 12000 14000 2012 2013 2014 2015 2016 2017 2018

Number of people joining the register each year

Chariot Register General Practice

Eligible, Consenting Patients Study A Study C Study B

Secondary Care Local Voluntary Organisations Events Advertising

Recruiting to the CHARIOT Register

Recruiting to the Register through primary care

Recruiting onto the Register