Cohort Descriptives

Variable Response
Cohort Name Cognitive Health in Ageing Register: Investigational, Observational, and Trial studies in dementia research (CHARIOT): Prospective Readiness cOhort Study (PRO)
Cohort Acronym CHARIOT: PRO Sub Study
Study Overview There is limited information on people with minimal cognitive changes who are likely to progress to both the earliest stage of cognitive impairment due to Alzheimer’s disease (AD) and then clinically evident dementia of the Alzheimer’s type. Characterizing change in cognition is essential to identify opportunity for intervention at the earliest stage of disease. Participants in both the Main Study and the Substudy 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. An opportunity is possible to identify and characterize individuals with different likelihoods of progressing along different clinical paths, which may form a framework for the evaluation of interventions.
#Subjects at Baseline 225
Institution Name Imperial College London
Department Name Neuroepidemiology and Ageing Research Unit
City London
Principal Investigator (PI) Professor Lefkos Middleton
Population Based Study? Yes
Family Based Study? No
Clinical based sample? No
Is there follow-up data available? Yes
Were participants included prior to development of dementia (may refer to controls only)? Yes
Were participants included prior to development of MCI (may refer to controls only)? Yes
How is data collected? In person: 90 day screening period with at least 4 study visits, followed by 3-monthly visits to ICL site post-baseline
Who carries out data collection? Clinicians. Clinical staff: Research nurses, Assistant Psychologists, Clinical Psychologists, Research Lab Technicians, Research Phlebotomists and Clinical Research Fellows
Does this take place in participants' homes or at a central location? Central: Charing Cross Hospital, Hammersmith, London
Do participants take part individually or are families/partners involved? Individually: Participants take part with a study partner
Dementia cases ascertained as part of study: No
Diagnosis based on review of existing clinical data No
How many times followed up? Every 3 months for a period of up to 3.5 years
Study start date 1/22/2015 12:00:00 AM
Is study ongoing? Yes
Is study still recruiting? Yes
Inclusion criteria "1. Criterion modified per Amendment 7 1.1 Between 60 and 85 years of age, inclusive, and meets all Main Study inclusion/exclusion criteria 2. Criterion modified per Amendment 6 2.1. Completed RBANS and ADCS-PACC neurocognitive testing at least once during the SubStudy screening visits 3. Have a global CDR score of 0 at screening 4. Criterion modified per Amendment 8 4.1. Have had a history of educational and/or work experience to ensure that congenital learning disabilities are highly unlikely as determined by the Principal Investigator. 5. Be able to read and write and must have adequate hearing and visual acuity to complete the required psychometric tests 6. Have evidence of amyloid pathology by means of either criterion listed below (for amyloid positive cohort only) or have no evidence of amyloid pathology by these criteria (for amyloid negative cohort only): a. Low CSF A42 concentrations at screeninga b. Evidence of increased amyloid deposition on a PET scan at screeningb aCut off value for CSF Aβ42 will be based on the value established by the central CSF screening laboratory and specified in a separate laboratory manual bAmyloid status by PET scans will be assessed centrally by qualified readers for inclusion based on predefined criteria specified in the imaging manual 7. Criterion deleted per Amendment 8 8. Criterion modified per Amendment 9 8.1. Be otherwise healthy 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. The Sponsor's Medical Monitor may review selected screening data prior to participant enrollment in the SubStudy to confirm eligibility 9. Clinical and neurological examinations and laboratory tests performed during SubStudy screening to confirm participants are healthy and medically stable. If the results of the hematology, serum chemistry, C-reactive protein, coagulation panel, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant, to be appropriate and reasonable for the population under study, and not to be a potential cause of cognitive impairment, with written concurrence from the Sponsor's Medical Monitor obtained prior to participant enrollment. The Sponsor's Medical Monitor will review all screening data prior to participant enrollment in the SubStudy to confirm eligibility
Exclusion criteria "1. Met clinical criteria for AD dementia or has any degenerative brain disorder that is associated with dementia 2. Criterion modified per Amendment 7 2.1 Criterion modified per Amendment 8 2.2 Criterion modified per Amendment 9 2.3 Screening age- and education-adjusted baseline cognitive performance is more than 1.5 SD below normal on any of the RBANS Index scores (note: when any screening RBANS Index scores are more than 1.5 SD below normal, the Sponsor’s Medical Monitor and/or designee(s) will adjudicate and approve enrollment, and if participants are enrolled, they will be assigned to the appropriate risk group) 3. Clinical evidence of any other brain disease 4. Criterion modified per Amendment 7 4.1 MRI evidence of abnormalities, as interpreted by the central radiologist, other than mild mediotemporal atrophy (eg, brain edema such as vasogenic edema including amyloid-related imaging abnormalities ARIA-E91, hydrocephalus, >25% age related white matter disease, frontal or temporal atrophy not typical of AD), history or evidence of a single prior hemorrhage >1 cm3, multiple lacunar infarcts (2 or more), or evidence of a single prior infarct >1 cm3, evidence of a cerebral contusion, encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space occupying lesions (eg, abscess or brain tumors such as meningioma >1cm), or MRI features atypical of AD dementia. Evidence of brain edema (eg, ARIA-E, vasogenic edema, hemosiderin deposits HD ≥10 mm in size or HD <10 mm in size but >10 in number will be reviewed by the Sponsor’s Medical Monitor to address plans for clinical evaluation and follow up as well as for potential inclusion/exclusion in the study. 5. Have ever received cholinesterase inhibitors (ChEI) and/or memantine 6. Receiving daily medications with the potential to affect cognition such as sedatives (eg, benzodiazepines), pain medications (eg, narcotic analgesics), or anticonvulsants (eg, barbiturates, valproic acid and congeners, phenytoin, carbamazepine) within the last 30 days prior to screening 7. Any known history of familial autosomal dominant Alzheimer’s disease or other familial dementing diseases 8. 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, and with written concurrence by the Sponsor's Medical Monitor. 9. Criterion modified per Amendment 9 9.1 Clinically significant vitamin B12 or folic acid deficiency. Abnormal B12 or folate levels performed at screening require assessment of homocysteine and methylmalonic acid to assess physiologic significance. Participants with abnormally low B12 or folate levels but normal methylmalonic acid or homocysteine levels may be eligible but must be reviewed and approved by the Sponsor’s Medical Monitor prior to enrollment. Participants treated with oral vitamin B12 or folic acid may be enrolled following review of their screening laboratory values and review of their records of diagnosis and treatment history by the investigator and with written concurrence by the Sponsor's Medical Monitor prior to randomization. Intramuscular B12 is not permitted. 10. Chromosome 21 trisomy (Down Syndrome)

Administration

Variable type Variables generally collected
Study ID Y
Age Y
Sex Y

Sociodemographic

Variable type Variables generally collected
Age Y
Sex Y
Ethnicity Y
Years of education Y
Level of education Y
Employment status Y
Demographics Y
Occupation Y
Income Y

Physical Health Status

Variable type Variables generally collected
Cardiovascular disease Y
Myocardial infarction Y
Medication use for CVD Y
Hypertension Y
Hypotension Y
Hypercholesterolemia Y
Cancer Y
Diabetic Status Y

Health Care Utilisation

Variable type Variables generally collected
Medication use Y
Medication use for CVD Y

Life Functionality

Variable type Variables generally collected
ADCS-ADL (Prevention Instrument used) Y
Lawton IADL (Incorporated into the CHARIOT:PRO Health and Lifestyle questionnaire) Y
Work Productivity and Activity Impairment Y

Psychological Status

Variable type Variables generally collected
Health Utilities Index 1,2 or 3 Y
CHARIOT:PRO Health and Lifestyle Questionnaire Y
Berlin Questionnaire Y
Pittsburgh Sleep Quality Index Y
Technology Readiness Questionnaire Y
Actigraphy to measure sleep patterns Y

Mental Health Status

Variable type Variables generally collected
Geriatric Depression Scale (GDS) Y
Speilberger State Anxiety Scale Y
State-Trait Anxiety Scale Y

Cognitive Status

Variable type Variables generally collected
Subjective complaint Y
Clinical Dementia Rating Scale (CDR) Y
Revised Perceived Deficits Questionnaire Y
Cognitive Function Index Y
Technology Readiness Questionnaire Y

Lifestyle

Variable type Variables generally collected
CHARIOT:PRO Health and Lifestyle Questionnaire Y
Scottish Collaborative Group Food Frequency Questionnaire Y
International Physical Activity Questionnaire Y
Berlin Questionnaire Y
Pittsburgh Sleep Quality Index Y
Smoking Y
Pack years Y
Passive smoking Y
Current smoking Y
Former smoking Y
Alcohol Y
Specified beverage type (wine, spirits, beers) Y
Physical activity and exercise Y
Exercise duration Y
Objective measures of activity Y
Diet Y
Carbs, protein, fats, fish oil Y
Anti-oxidants Y
Vegetarian? Y
Coffee and caffeine Y
Vitamin A,B and E Y
Food questionnaires (SFFQ) Y
Other dietary items listed in SFFQ Y
Sleep assessment Questionnaires Y

Physical Environment

Variable type Variables generally collected
Living situation Y

Physical Examination

Variable type Variables generally collected
Blood pressure Y
Weight Y
Height Y
Neurological examination Y
BMI Y

Biosample Assays

Variable type Variables generally collected
Plasma Y
Serum Y
RNA Y
DNA Y
Abeta 1-40 (Data blinded until end of study) Y
Abeta 1-42 (Data blinded until end of study) Y
Urine collection Y
Saliva Y
Cortisol Y
CSF collected Y

Digital Phenotyping

Variable type Variables generally collected
Verbal memory Y
Language Y
Vigilance Y
Latent memory Y
IQ data Y
NART Y
MMSE Y
RBANS Y
DKEFS Y
Clinical Drug Research Assessment System Y
CogState Y
Neuropsychological Assessment Battery - Memory and Executive function modules Y
Clinical Dementia Rating Scale Y
ADCS-PACC Y

Imaging

Variable type Variables generally collected
Structural T1 Y
Fluid attenuation inversion recovery (FLAIR) Y
Diffusion imaging (DTI/DWI) Y
f-MRI (rest) Y
PET (Amyloid (blinded data until end of study)) Y
Retinal Imaging (under Neurovision Ancillary Study) Y

Genomics

Variable type Variables generally collected
APOE gene screening (Blinded data until end of study) Y

Metabolomics

Variable type Variables generally collected
CRP (c-reactive protein) Y
eGFR (estimated Glomular Filtration Rate) Y
Glucose Y
HbA1c Y
Lipids Y
Liver Function Tests Y
Serum creatinine Y
Homocysteine Y
Folate Y