Prospective Evaluation of Cognitive Health and Related Factors in Elderly at Risk for Developing Alzheimer’s Dementia: A Longitudinal Cohort Study
The CHARIOT PRO Main study is a prospective, non-interventional study evaluating cognitive trajectories in participants at the preclinical stage of Alzheimer’s disease (AD) classified by risk levels for developing mild cognitive impairment due to AD (MCI-AD).
The study aimed to characterize factors and markers influencing cognitive and functional progression among individuals at-risk for developing MCI-AD, and examine data for more precise predictors of cognitive change, particularly in relation to APOE ε4 subgroup.
This single-site study was conducted at the Imperial College London (ICL) in the United Kingdom. Participants 60 to 85 years of age were classified as high, medium (amnestic or non-amnestic) or low risk for developing MCI-AD based on RBANS z-scores. A series of clinical outcome assessments (COAs) on factors influencing baseline cognitive changes were collected in each of the instrument categories of cognition, lifestyle exposure, mood, and sleep. Data collection was planned to occur every 6 months for 48 months, however the median follow-up time was 18.1 months due to early termination of study by the sponsor.
987 participants were screened, among them 690 participants were actively followed-up post baseline, of whom 165 (23.9%) were APOE ε4 carriers; with at least one copy of the allele. The mean age was 68.73 years, 94.6% were white, 57.4% were female, and 34.8% had a Family History of Dementia with a somewhat larger percentage in the APOE ε4 carrier group (42.4%) compared to the non-carrier group (32.4%). Over half of the participants were married and 53% had a Bachelor’s or higher degree. Most frequently, safety events typical for this population consisted of upper respiratory tract infection (10.4%), falls (5.2%), hypertension (3.5%) and back pain (3.0%).
Conclusion (clinical relevance)
AD-related measures collected during the CHARIOT PRO Main study will allow identification and evaluation of AD risk factors and markers associated with cognitive performance from the pre-clinical stage. Evaluating the psycho-biological characteristics of these pre-symptomatic individuals in relation to their natural neurocognitive trajectories will enhance current understanding on determinants of the initial signs of cognitive changes linked to AD.
Key wordsCHARIOT aging registry cognitive health pre-clinical Alzheimer Disease
The authors are most grateful to the study participants for their contributions and the investigational site staff for their work on the study. The authors acknowledge Bradford Challis (Janssen Research & Development, LLC) for assistance in preparation and editorial support of this manuscript.
Study funding: Funded by Janssen Research & Development, LLC. The sponsor also provided a formal review of this manuscript.
Conflict of interest/disclosures: Janssen Research & Development, LLC, funded the study. Michael T. Ropacki was formerly an employee of Janssen and is an industry consultant. Gerald. Novak, H. Michael Arrighi, and Nandini Raghavan are employees of Janssen Research & Development, LLC and own stock/stock options in the company. Nzeera Ketter is a former employee, and H. Robert Brashear is an employee of Janssen AI Research & Development, LLC and both own stock/stock options in the company. Jianing Di is an employee of Janssen China Research and Development Center and owns stock/stock options in the company. Lefkos Middleton served as principal study investigator at Imperial College of London (ICL), has a consultancy agreement 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. Chinedu Udeh-Momoh, Josip Car, Robert Perneczky, Geraint Price, Tresa Andrews and Heather Ward served as co-principal study investigators at ICL for Janssen Research & Development, LLC and all declare no conflict of interest. Catherine Robb, Darina Bassil, Martin Cohn, Parthenia Giannakopoulou, Dinithi Perera, Lisa Curry and Bowen Su were study investigators at ICL and declare no conflict of interest.
Ethical standards: To ensure the quality and integrity of the research, this study was conducted in accordance with Good Clinical Practice (GCP) Guidelines, Good Pharmacoepidemiology Practices (GPPs) issued by the International Society for pharmaceutical Engineering (ISPE), applicable national guidelines, and to the Declaration of Helsinki 2013, as modified by the 52nd World Medical Assembly, Edinburgh, Scotland, 2000, and clarified by the World Medical Assembly (WMA) General Assembly, Washington 2002 and Tokyo 2004. The Chariot-Pro Main study has received National Research Ethics Services approval (15/L0/0711) and internal Imperial College London (ICL) Research Ethics, Joint Research Compliance Office approval (JRCO:15/1C/2791). Prior to consenting onto the Chariot-Pro Main study, participants were provided with a detailed study information sheet outlining study procedures, as well as risks and benefits associated with participation. Participants were provided with a minimum of 48-hours to consider the information provided, and fully understand the study requirements prior to discussing further with study staff, where necessary; after which signed informed consent was obtained prior to undertaking any study procedures at the screening visit.
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