Protocol of the Cognitive Health in Ageing Register: Investigational, Observational and Trial Studies in Dementia Research (CHARIOT): Prospective Readiness cOhort (PRO) SubStudy

Abstract

Introduction: The Cognitive Health in Ageing Register: Investigational, Observational and Trial Studies in Dementia Research (CHARIOT): Prospective Readiness cOhort (PRO) SubStudy (CPSS), sponsored by Janssen Pharmaceutical Research & Development LLC, is an Alzheimer's disease (AD) biomarker enriched observational study that began 3 July 2015 CPSS aims to identify and validate determinants of AD, alongside cognitive, functional and biological changes in older adults with or without detectable evidence of AD pathology at baseline.

Methods and analysis: CPSS is a dual-site longitudinal cohort (3.5 years) assessed quarterly. Cognitively normal participants (60-85 years) were recruited across Greater London and Edinburgh. Participants are classified as high, medium (amnestic or non-amnestic) or low risk for developing mild cognitive impairment-Alzheimer's disease based on their Repeatable Battery for the Assessment of Neuropsychological Status performance at screening. Additional AD-related assessments include: a novel cognitive composite, the Global Preclinical Alzheimer's Cognitive Composite, brain MRI and positron emission tomography and cerebrospinal fluid analysis. Lifestyle, other cognitive and functional data, as well as biosamples (blood, urine, and saliva) are collected. Primarily, study analyses will evaluate longitudinal change in cognitive and functional outcomes. Annual interim analyses for descriptive data occur throughout the course of the study, although inferential statistics are conducted as required.

Ethics and dissemination: CPSS received ethical approvals from the London-Central Research Ethics Committee (15/LO/0711) and the Administration of Radioactive Substances Advisory Committee (RPC 630/3764/33110) The study is at the forefront of global AD prevention efforts, with frequent and robust sampling of the well-characterised cohort, allowing for detection of incipient pathophysiological, cognitive and functional changes that could inform therapeutic strategies to prevent and/or delay cognitive impairment and dementia. Dissemination of results will target the scientific community, research participants, volunteer community, public, industry, regulatory authorities and policymakers. On study completion, and following a predetermined embargo period, CPSS data are planned to be made accessible for analysis to facilitate further research into the determinants of AD pathology, onset of symptomatology and progression.

Trial registration number: The CHARIOT:PRO SubStudy is registered with clinicaltrials.gov (NCT02114372). Notices of protocol modifications will be made available through this trial registry.

Keywords: dementia; epidemiology; old age psychiatry; preventive medicine.

Conflict of interest statement

Competing interests: MTR was formerly employee of Janssen and is an industry consultant. GN, SB, HMA, MF, KK, ZS and NR are employees of Janssen Research & Development, LLC and own stock/stock options in the company. NK and HRB are former employees of Janssen Research & Development, LLC and both own stock/stock options in the company. JD is an employee of Janssen China Research and Development Center and owns stock/stock options in the company. LM served as principal study investigator at Imperial College of London (ICL) abd has held consultancy agreements, in the last five years, with Eli Lilly, Astra Zeneca and Takeda and is National Coordinator for the TOMMORROW, Amaranth and Generation Clinical Studies; and does not hold any agreement with any of the funders in relation to patents, products in development relevant to this study or marketed products. CR served as principal study investigator at Edinburgh University (EDI), and has served as a consultant in the last five years for: Actinogen, Biogen, Roche Pharmaceuticals and Roche Diagnostics, Eisai, Abbott Pharmaceuticals, Eli Lilly, Kyowa Kirin, Signant Health, Merck and Nutricia. He is also the Chief Investigator and Co-coordinator of IMI-EPAD which is a public-private partnership of 39 partners www.ep-ad.org. CU-M, JC, RP, GP, Cd-JL, HW and MK served as co-principal study investigators at ICL for Janssen Research & Development, LLC and all declare no conflict of interest. JC's and AM’s posts at ICL are in part supported by the NIHR NW London Applied Research Collaboration. CR, DB, MC, PG, DK, YC-S, DP, LC, KL, HM-Y, JC and AM were study investigators at ICL and declare no conflict of interest. KR served as co-principal study investigator at EDI for Janssen Research & Development, LLC and declares no conflict of interest. TW and NR-M were study investigators at EDI and declare no conflict of interest. DS and LB are employees of Bioclinica Inc. and declare no competing interests.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

The Cognitive Health in Ageing Register: Investigational, Observational and Trial Studies in Dementia Research (CHARIOT): Prospective Readiness cOhort (PRO) Substudy Recruitment Pathway. aJoin Dementia Research. bScottish Primary Care Research Network. cFormerly Centre for Dementia Prevention. dCHARIOT:PRO Main Study. eFormerly Neuroepidemiology and Ageing (NEA) Research Unit.

Figure 2

Screening and baseline assessment schedule. CDR, Clinical Dementia Rating; CSF, cerebrospinal fluid; PACC, Preclinical Alzheimer Cognitive Composite; PET, positron emission tomography; RBANS, Repeatable Battery for the Assessment of Neuropsychological Status; CFI, Cognitive Function Index; ADCS-ADL-PI, ADCS-Activities of Daily Living—Prevention Instrument; NAB, Neuropsychological Assessment Battery; NART, National Adult Reading Test; GDS, Geriatric Depression Scale; STAI, State Trait Anxiety Inventory.

Figure 3

Positron emission tomography (PET) amyloid-β (Aβ) status reading workflow. SUVR, Standardised Uptake Value Ratio; Q, quantification of SUVR; FS, parcellation of cerebral structures based on Freesurfer imaging pipeline; QC, quality control assessment; VIS, result of visual assessment of amyloid PET; Aβ+, assessed as Aβ positive based on visual and/or quantitative (SUVR) analysis of amyloid PET.