Cognitive Health in Ageing Register: Investigational, Observational and Trial Studies in Dementia Research (CHARIOT): Prospective Readiness Cohort Study (PRO)
Overview
- Phase
- N/A
- Intervention
- Not specified
- Conditions
- Alzheimer's Disease
- Sponsor
- Janssen Research & Development, LLC
- Enrollment
- 1136
- Primary Endpoint
- SubStudy: Change From Baseline on Preclinical Alzheimer Cognitive Composite (PACC) Component Score
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The purpose of this study is to prospectively investigate the longitudinal change of the components of the Preclinical Alzheimer Cognitive Composite (PACC) and the components (index scores) of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in asymptomatic at risk for Alzheimer's disease (ARAD) individuals.
Detailed Description
This is a prospective, non-interventional study that will enroll participants without dementia who are considered at high, medium, and low risk for developing AD from a community based register (referred to as the CHARIOT registry) in the United Kingdom. Participants will undergo a series of neuropsychological evaluations to characterize the patterns of cognitive change and their inter-relationship in the earliest stages of cognitive impairment. In addition, how such changes relate to the clinical presentation of cognitive impairment of the Alzheimer's type may be evaluated over time. The SubStudy will investigate the longitudinal change of components of the PACC and RBANS in ARAD individuals who have demonstrable amyloid in the brain by either PET or CSF compared with individuals not classified as ARAD. SubStudy participants will be followed every 6 months throughout the SubStudy and will alternate between completing the alternative forms of the PACC and RBANS for a period of up to 4.5 years (54 months). Blood, urine, and saliva samples will be collected from participants during the study for biomarker analyses to assess risk factors for dementia, Alzheimer's disease or confounding factors of dementia risk. Adverse events experienced by the participants during their participation in the study will be monitored.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Completed Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Preclinical Alzheimer Cognitive Composite (PACC) neurocognitive testing at least once during the SubStudy screening visits
- •Have a global Clinical Dementia Rating (CDR) score of 0 at screening
- •Be fluent in and able to read and write in English; be willing and able to give written informed consent; and have adequate hearing and visual acuity to complete the required psychometric tests
- •Have evidence of amyloid pathology by means of low cerebrospinal fluid (CSF) beta amyloid protein (ABeta42) concentrations at screenings (for amyloid positive cohort only) or have no evidence of amyloid pathology by this criterion (for amyloid negative cohort only) and are selected for inclusion in Cognitive Health in Ageing Register: Investigational, Observational, and Trial studies in dementia research: Prospective Readiness cohort study (CHARIOT-PRO) as per the interactive web response decision algorithm
- •Be otherwise in satisfactory health and medically stable on the basis of medical history, vital signs, and physical exam. Any abnormalities must not be the cause or be associated with cognitive impairment
Exclusion Criteria
- •Meets clinical criteria for Alzheimer's disease (AD) dementia, Mild Cognitive Impairment (MCI) diagnosis, or has any degenerative brain disorder that is associated with dementia, such as Parkinson's disease
- •Participants whose age- and education-adjusted cognitive performance is more than 1.5 standard deviation (SD) below normal on any of the RBANS Index scores at the first RBANS administration
- •Any known history of familial autosomal dominant AD or other familial dementing diseases
- •History of or current thyroid disease or thyroid dysfunction, which is currently uncontrolled or untreated, or clinically significant abnormal thyroid function tests. Participants treated for thyroid disease may be enrolled following review of their records of thyroid function, laboratory tests at screening, diagnosis and treatment history by the Investigator or designee
- •Any contraindications for magnetic resonance imaging (MRI) (example, pacemaker, metal prostheses, implants, claustrophobia, pacemakers etc) unless MRI compatible
Outcomes
Primary Outcomes
SubStudy: Change From Baseline on Preclinical Alzheimer Cognitive Composite (PACC) Component Score
Time Frame: Baseline and Month 42 (Year 3.5)
The PACC is a retrospectively validated measure that is weighted towards episodic memory, and also includes a timed executive function test and a global cognitive screening test. The PACC includes: 1. Total Recall score from the Free and Cued Selective Reminding Test - Immediate Recall \[FCSRT-IR\] (0-48 words); 2. Delayed Paragraph Recall total score on single administration of the Logical Memory story from the Wechsler Memory Scale \[WMS\]-Revised (0-25 story units); 3. Digit Symbol Substitution Test score from the Wechsler Adult Intelligence Scale \[WAIS\]-Revised (0-135 symbols), and 4. MMSE score (0-30 points). The component scores are transformed using an established normalization method into z-scores. Each of the 4 component change scores is divided by the baseline sample standard deviation of that component. Z-score implies how many standard deviations higher or lower the score is compared with the baseline score.
Main Study: Change From Baseline Cognition
Time Frame: Up to 4 years
Cognition will be evaluated at baseline and longitudinally with the Mini-Mental State Examination (MMSE), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Neuropsychological Assessment Battery (NAB)-Executive Function module, NAB-Memory module, CogState Brief Battery (CBB), Cognitive Drug Research Assessment System (CDR-AS), and Delis Kaplan Executive Function System (DKEFS), as well as the Clinical Dementia Rating Scale.
SubStudy: Change From Baseline in RBANS Index Scores
Time Frame: Baseline and Month 42 (Year 3.5)
This brief test is for cognitive assessment, detection, and characterization of dementia in the elderly as well as neuropsychological screening for younger patients. The RBANS Index scores include Immediate Memory Index, Visuospatial/Construction Index, Language Index, Attention Index and the Delayed Memory Index. The sum of these 5 Index scores is converted to a Total Scale value via a mapping table. The Total Scale is a norm-based t score based on a distribution with a mean of 100 and standard deviation of 15.
Secondary Outcomes
- SubStudy: Change From Baseline on the RBANS Total Scale(Baseline and Month 42 (Year 3.5))
- SubStudy: Change From Baseline on the PACC Composite Score(Baseline and Month 42 (Year 3.5))