Cohort Descriptives

Variable Response
Cohort name CHARIOT: PRO Main Study
Cohort acronym CHARIOT: PRO
General 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.
Number of subjects at baseline 712
Institution name Imperial College London
Department name Neuroepidemiology and Ageing Research Unit
City London
Principal Investigator (PI): Name Prof Lefkos Middleton
PI: Address Neuroepidemiology and Ageing Research Unit, Imperial College London, Room 10L05, 10th Floor Laboratory Block, Charing Cross Hospital, St Dunstan's Road, London W6 8RP
PI: email

l.middleton@imperial.ac.uk

PI: phone 0203 311 0215
Administrative Contact (AC): Name Dr Chi Udeh-Momoh
AC: Address Neuroepidemiology and Ageing Research Unit, Imperial College London, Room 10L05, 10th Floor Laboratory Block, Charing Cross Hospital, St Dunstan's Road, London W6 8RP
AC: email C.udeh@imperial.ac.uk
AC: phone 0203 311 0320
Technical Contact/Data manager (TC): Name Dr Chi Udeh-Momoh
TC: Address Neuroepidemiology and Ageing Research Unit, Imperial College London, Room 10L05, 10th Floor Laboratory Block, Charing Cross Hospital, St Dunstan's Road, London W6 8RP
TC: email

c.udeh@imperial.ac.uk

TC: phone 0203 311 0320
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: 6-monthly visits to ICL site
Who carries out data collection? Interviewers
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
Dementia cases ascertained as part of study: No
Diagnosis based on review of existing clinical data No
Was diagnosis/primary outcomes made blind to exposure variables? No
How regular is follow-up? Every 6 months until December 2016
Study start date 19/11/2013
Is study ongoing? No
Is study still recruiting? No
Inclusion criteria "1) Participants aged from 60 to 85 years inclusive
2) Willing and able to give written informed consent
3) Criterion modified per Amendment 6
3.1) Criterion modified per Amendment 7
3.2) Criterion modified per Amendment 9
3.3) Meets the definition of one of the following groups:
• High risk: The high risk group is operationally defined as participants whose age and education-adjusted baseline cognitive performance is 0.6 to 1.5 standard deviation (SD) (inclusive) below normal on the RBANS Immediate and/or Delayed
Memory Index, and 0.6 to 1.5 SD (inclusive) below normal on at least one other nonmemory RBANS cognitive domain.
• Medium risk (amnestic): The medium risk amnestic group is operationally defined as participants whose age- and education-adjusted baseline cognitive performance is 0.6 to 1.5 SD (inclusive) below normal only on the RBANS Immediate and/or
Delayed Memory Index, and all other RBANS nonmemory domains within normal limits operationally defined as better than 0.6 SD below normal.
• Medium risk (nonamnestic): The medium risk nonamnestic group is operationally defined as participants whose age- and education-adjusted baseline cognitive performance is better than 0.6 SD below normal on the RBANS Immediate and
Delayed Memory Index, and one or more other RBANS domains are 0.6 to 1.5 SD (inclusive) below normal.
• Low risk: The low risk group is operationally defined as participants whose ageand education-adjusted baseline cognitive performance on the RBANS is within normal limits, as defined for this study as all RBANS domains better than 0.6 SD below normal.
• Participants for whom an age- and education-adjusted baseline RBANS domain index score is more than 1.5 SD below normal will be adjudicated for inclusion.
4) Be willing and able to adhere to the prohibitions and restrictions specified in this protocol
5) Fluent in English
"
Exclusion criteria "1) Criterion modified per Amendment 6
1.1) Criterion modified per Amendment 7
1.2) Concurrent participation in an interventional trial. Enrollment in noninterventional trials is permitted only if the safety of the participant and integrity of the CHARIOT-PRO study data are not compromised by any of the following:
• High participant burden through enrollment in multiple studies
• Blood draw requirements beyond the permissible amount according to local recommended blood donation limits
• Cumulative exposure to radiation that exceeds local recommended exposure limits
• Exposure to the neuropsychological measures in CHARIOT-PRO that may impact participant performance (eg, learning effects)
2) Dementia or MCI diagnosis
3) Past or current use of memantine or cholinesterase inhibitors
4) Criterion modified per Amendment 6
4.1) Diagnosis of other neurologic disease or conditions known to cause or be associated with dementia, such as Parkinson’s disease
5) A history of traumatic brain injury with residual neurological deficit
6) Criterion modified per Amendment 7
6.1) History of stroke or diagnosis of transient ischemic attack (TIA)
7) History of seizures, excluding febrile seizures in childhood
8) Criterion modified per Amendment 6
8.1) Current diagnosis of significant psychiatric illness, as per the Diagnostic &
Statistical Manual of Mental Disorders, 4th Edition - Text Revision (DSM-IVTR) (including but not limited to major depressive disorders and anxiety disorders) and is currently in an acute phase/episode, or the participant has a current diagnosis or history of schizophrenia or bipolar disorder
9) Reversible causes of dementia such as B12 deficiency, metabolic problems and/or nutritional deficiencies (eg, folic acid)
10) History of hydrocephalus at any time
11) Uncontrolled hypo- or hyperthyroidism at enrollment
12) Criterion modified per Amendment 6
12.1) Chronic use of medications known to impair cognition such as sedatives, pain medications or anticonvulsants. Additionally, use within 48 hours or 4 times the half-life, whichever is longer, before the baseline cognitive assessments is prohibited.
13) At baseline, any clinically significant unstable illness, for example, hepatic impairment or renal insufficiency, or cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, infectious skin and subcutaneous tissue disorders, or metabolic disturbance that is likely to result in rapid deterioration of the participant’s condition or affect their safety during the study
14) Clinically significant infection within 30 days (eg, persistent or acute infection such as a urinary tract infection or upper respiratory infection) at study entry
15) Self-reported HIV infection
16) History of alcohol or drug dependence or abuse as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV-TR) criteria within the last 3 years
17) Criterion modified per Amendment 6
17.1) Any disability that would prevent completion of study procedures or assessments (eg, blindness or significant visual impairment, deafness or significant hearing impairment, speech impairment, or sensory or motor dysfunction)
18) Criterion modified per Amendment 6
18.1) Criterion modified per Amendment 7
18.2) Criterion modified per Amendment 8
18.3) Criterion modified per Amendment 9
18.4) Participants whose 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 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)
"

Demographic and Clinical Information

Variable Response
Demographics
Age Yes
Sex Yes
Ethnicity Yes
Education Yes
Physical examinations
Any physical examination performed? Yes
Blood pressure Data available
Weight Data available
Height Data available
Medical conditions
Cardiovascular disease data Yes
Myocardial infarction Data available
Medication use for CVD Data available
Hypertension Data available
Systolic/diastolic BP Data available
Hypotension Data available
Hypercholesterolemia Yes
Medication use Yes
Cancer Data available
Diabetic Status Data available

Cognitive Outcomes

Variable Response
Any domain-specific cognitive test performed? Yes
Verbal Memory Data available
Data available
Language Data available
Data available
Vigilance Data available
Data available
Latent memory Data available
Data available
IQ data available? Yes
NART Yes
Cognitive background? Yes
Years of education Yes
Level of education Yes
Parental education No
Standard dementia global cognition scales? Yes
MMSE Yes
MoCA No
ADAS-Cog No
Addenbrooke's Cognitive Exam No
3MS No
GPCOG No
Other assessments of global cognition RBANS, DKEFS, Clinical Drug Research Assessment System, CogState, Neuropsychological Assessment Battery- Memory and Executive function modules, Clinical Dementia Rating Scale - Sum of boxes

Non-Cognitive Clinical Outcomes

Variable Response
Dementia diagnosis
Subjective complaint Yes
Dementia diagnosis (Other comments) Study makes no dementia diagnosis of individual participants
Functional rating scales
Any information on dementia rating collected? Yes
ADCS-ADL No
ADCS-ADL-MCI No
Blessed Dementia Scale No
Clinical dementia rating scale (CDR) Yes
Complex Activities of Daily Living No
Dependence Scale No
Functional Assessment Questionniare (FAQ) No
FAST No
Global Deterioration Scale (GDS) No
Katz ADL No
Lawton IADL Yes
Comments: incorporated into the CHARIOT:PRO Health and Lifestyle questionnaire
PDQ39 (PD specific) No
UPDRS (PD specific) No
Hoehn and Yahr (PD specific) No
Schwab and England (PD specific) No
UHDRS (HD specific) No
Any information on subjective complaints collected? Yes
Any neuropsychiatric rating scale administered? Yes
Aggression Scale No
Beck Depression Inventory No
Behave-AD No
Center for Epidemiologic Studies Depression scale (CES-D) No
Connor-Davidson Resilience Scale No
Cornell depression Scale No
Geriatric Depression Scale (GDS) Yes
Hamilton depression rating scale (HDRS) No
Montgomery-Asberg depression scale (MADRS) No
NPI No
NPI-Q No
Speilberger State Anxiety Scale Yes
Hospital anxiety depression scale/psychiatry (HADS) No
Any Quality of Life Data Colllected? Yes
Dementia Quality of Life Instrument (DEMQOL) No
Discomfort Scale for Dementia of Alzheimers Type (DS-DAT) No
Progressive Deterioration Scale (PDS) No
Quality of Life in Late-Stage Dementia Scale (QUALID) No
Bedfords Alzheimers Nursing Severity Scale(BANS-S) No
EQ-5DVAS No
Short Form (SF) 36 No
Health Utilities Index 1, 2 or 3 Yes
Specify any other quality of life scales CHARIOT:PRO Health and Lifestyle Questionnaire, State-Trait Anxiety Index Scale, Revised Perceived Deficits Questionnaire, Work Productivity and Activity Impairment, Scottish Collaborative Group Food Frequency Questionnire, International Physical Activity Questionnaire, Berlin Questionnaire, Pittsburgh Sleep Quality Index
Any information on Caregivers and Caregiving Collected? No
Health service utilisation
Any Health Resource Utilisation Collected ? No
Hospital utilisation No
Costs of Visits to Specialists (out-patient) No
Other neurological or psychiatric measurements? Yes
Any stroke data? No
Stroke type No
Transient Ischemic Attack No
Carotid plaques No
Any head trauma data? No
Loss of consciousness No
Sports, soccer and boxing No
Head trauma severity No
BISQ or equivalent No
EEG No
Psychiatric evaluations Yes
CESD scale (depression) No
Personality evaluation No
Apathy evaluation No
Anxiety measure Yes
Resilience evaluation No

Imaging

Variable Response
For imaging data, what format(s) do you use for storing data? N/A

Genetics

Variable Response
Overview
Number Gwas subjects 800
N APOE genotyped 900
Gene screening
APOE Yes
Estimated N: 900

Biological samples

Variable Response
Blood collected Yes
Plasma Yes
Serum Yes
RNA Yes
DNA Yes
Blood Metabolic Analytes
CRP (c-reactive protein) No
eGFR (estimated Glomular Filtration Rate) No
Glucose No
HbA1c No
Lipids No
Liver Function Tests No
Serum creatinine No
Homocysteine No
Folate No
Other blood samples No
Are laboratory protocols and storage information available for bloods Yes
Urine collection
Urine Yes
Autopsy data
Autopsy No
Measurements already performed No
Saliva
Saliva collected Yes
Cortisol Yes: Data available January 2018
Are laboratory protocols and saliva storage information available? Yes
CSF
CSF collected No
CSF Abeta No
CSF tau No
No

Brain donation

Variable Response
Is brain donation part of the existing protocol? No
Are information sheets made available to representative or consultees? No
Are retrospective interviews carried out after the participant's death? No
Is there a procedure for declining donation/failed recruitment/project termination? No
Has an actuarial analysis been completed? No

Lifestyle

Variable Response
Smoking Yes
Pack years Data available
Passive smoking Data available
Current smoking Data available
Former smoking Data available
Alcohol Data available
Specified beverage type (wine, spirits, beers) Data available
Drugs of abuse assessment
Drugs of abuse assessment - Data available? Data available
Comments: Data collected as part of medical history
Obesity and associated risk factors
BMI Data available
Physical activity and exercise Yes
Type of exercise: heavy, light Data available
Exercise duration Data available
Occupation possible job matrices Data available
Diet Yes
Carbs, protein, fats, fish oil Data available
Anti-oxidants Data available
Vegetarian? Data available
Coffee and caffeine Data available
Vitamin A, B, E Data available
Food questionnaires Data available
Comments: SFFQ
Other dietary items Yes - listed in SFFQ
Employment status
Employment status Data available
Living situation
Living situation Data available
Socioeconomic status
Socioeconomic status measures Data available
Comments: Demographics, occupation & income
Sleep assessment
Questionnaires Data available
Comments: Yes - PSQl and BSQ

Ethics and Engagement

Variable Response
Participant engagement
Is there participant representation in the governance of the cohort? No
Do existing mechanisms for consulting/involving participants exist? No
Ethics
Is there an ethics advisory or ELSI group within the cohort governance? No
Does the cohort include participants who lack capacity? No
Is there a process in place for participants who lose capacity? Yes
Do participants provide contact information for a person to act as a potential consultee? No
Disclosure
Do procedures exist for the disclosure of incidental findings? Yes
What kinds of finding do these relate to? (imaging, genotyping, etc) Cognitive, Psychiatric and Medical abnormalities
Who is responsible for disclosing incidental findings? Study Investigators - Principal Investigator, Co-investigators, Sub-investigators (Clinical Research Fellows) and Clinical Research Psychologists
Do procedures exist for the disclosure of clinically relevant information identified as a direct focus of the study? (e.g. a diagnosis of dementia) No
Recruitment
How was the cohort recruited (NHS or not, primary or secondary care)? Either self-referred or from the CHARIOT: Cognitive Health in Ageing Register: Investigational, Observational and Trial studies in dementia research
Does the study involve ongoing connections with participants' own doctors (e.g. GPs)? Yes
Consent and recontact
Is there consent for recontact? No

Data Management

Variable Response
Consent for linkage to routine data