Cohort Descriptives

Variable Response
Cohort name Southall And Brent REvisited
Cohort acronym SABRE
General Study Overview The Southall And Brent REvisited Study (SABRE) is the largest tri-ethnic population-based cohort in the UK and investigates the causes of diabetes and disorders of the heart and circulation across ethnicities.
SABRE participants were aged 40-69 when first studied in 1988. In 2008 a comprehensive combined morbidity and mortality follow up was carried out, together with non-invasive clinical measurements. SABRE Visit 3 (25 year follow-up visit) collects data on participants and their partners. Changes in the health of the heart and circulation are measured, with focus on blood vessels of the brain, as well as diabetes.
More recently, the aims have increased to include:: 1.How large are ethnic /sex differences in cardiac function, cognitive function and hippocampal volumes in older age?
2. To what extent do cardiac function, cognitive function and hippocampal volumes change over a 5 year period in each ethnic group?
3. Which risk factors measured in mid-life and in early old age are most strongly associated with current cardiac and cognitive function and hippocampal volumes and with 5 year changes in these parameters? Can these risk factors explain ethnic differences in cardiac and cognitive function?
4. How large are gender differences in current disorders of cardiac and cognitive function and in their associations with current risk factors?
5. Do ethnic differences in incident cardiometabolic disorders persist into older age?
6. Which risk factors or risk factor profiles measured in mid-life and early old age are most strongly associated with incident cardiometabolic disorders and which best explain ethnic differences in incidence?
Number of subjects at baseline 4,858
Institution name University College London
Department name Institute of Cardiovascular Science
City London
Study or database website

http://www.sabrestudy.org/

Principal Investigator (PI): Name Prof Nish Chaturvedi
PI: Address UCL Institute of Cardiovascular Science, Gower Street, London, WC1E 6BT
PI: email

n.chaturvedi@ucl.ac.uk

PI: phone 02076799431
Administrative Contact (AC): Name Therese Tillin
AC: Address UCL Institute of Cardiovascular Science, Gower Street, London, WC1E 6BT
AC: email T.tillin@ucl.ac.uk
AC: phone +44 20 7679 9471
Technical Contact/Data manager (TC): Name Therese Tillin
TC: Address UCL Institute of Cardiovascular Science, Gower Street, London, WC1E 6BT
TC: email

t.tillin@ucl.ac.uk

TC: phone +44 20 7679 9471
Key study references

Open literature list

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
Who carries out data collection? Interviewers
Clinicians
Does this take place in participants' homes or at a central location? Home
Central: Homes if participants can't attend clinic.
Do participants take part individually or are families/partners involved? Individually
Family: Informants were asked to take part at Visit 2 only for the cognition section. Visit 3 will not involve informants.
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 many times followed up? 2
Study start date 1988-01-01
Study end date 2017-12-30
Is study ongoing? Yes
Is study still recruiting? Yes
Inclusion criteria Taken part in original study.
Age 40-69 in 1989-1991.
European, Indian Asian and African Caribbean men and women.
(Study partners and a new group of African Caribbeans have been added in V3).
Exclusion criteria Inability to give informed consent
Terminal illness, severe psychiatric or physical disorder, limited mobility.

Demographic and Clinical Information

Variable Response
Demographics
Age Yes
Age at time of diagnosis of dementia No
Age at last follow-up Yes
Age at time of death Yes
Sex Yes
Ethnicity Yes
Education Yes
Physical examinations
Any physical examination performed? Yes
Blood pressure Data available
Assessed before onset of dementia
Comments: Baseline: Resting brachial. V2: Resting ankle and brachial - average of second and third of three measurements in the sitting position using OMRON 705CP-II. 24 hour ambulatory BP Visits 1, 2 and 3 in a subset.
Weight Data available
Assessed before onset of dementia
Height Data available
Assessed before onset of dementia
Heart Rate Data available
Assessed before onset of dementia
Anthropometry Data available
Assessed before onset of dementia
Comments: Body fat estimation (bioimpedence) was carried out at Visit 2 and will also be included in Visit 3. A single slice CT of the abdomen at L4 level and a single slice CT across the mid thigh used to assess fat distribution. A DEXA scan has been added for Visit 3.
ECG Data available
Assessed before onset of dementia
Comments: 12 lead ECG was carried out at baseline, Visit 2 and Visit 3.
Cardiovascular examination Data available
Assessed before onset of dementia
Comments: 2D echocardiography (Visits 1, 2 and 3) and measures of left ventricular function and Doppler echocardiography as well as Coronary Artery Calcium scoring using multislice CT imaging at Visit 2. 3D echocardiography: used to provide estimates of cardiac structure and function. In addition, intra-ethnic validation of equations to calculate left ventricular mass using 2D echocardiography, using direct measurements on 3D echocardiography, (Phillips IE33).
Specific assessment of peripheral vascular disease Data available
Assessed before onset of dementia
Respiratory examination Data available
Assessed before onset of dementia
Comments: At Visit 3
PEFR Data available
Assessed before onset of dementia
Comments: At Visit 3
Spirometry Data available
Assessed before onset of dementia
Comments: At Visit 3: MicroQuark protocol available.
Gait assessment Data available
Assessed before onset of dementia
Comments: At Visit 3. DataGait monitor.
Opthalmic examination Data available
Assessed before onset of dementia
Comments: Lens photography (opacities and cataracts) was carried out at V2 as well as retinal photography (see Imaging) at Visit 1 (subset) and Visit 2, but not at Visit 3.
Acuity Data available
Assessed before onset of dementia
Comments: Visit 2 and Visit 3 http://www.neura.edu.au/research/facilities/falls-and-balance-research-group/quickscreen
Visual fields (direct/indirect) Data available
Comments: Visit 3
Specify any others Thigh circumference and leg length.
Long and short axis Tissue Doppler Imaging performed using an ATL HDI 5000 ultrasound system and digital cineloops recorded for offline analysis. Analysis of speckle tracking performed using an angle independendent non-Doppler 2D strain imaging method.
Carotid and femoral ultrasound.
Liver ultrasound examinations performed using an EPIQ7 ultrasound device equipped with a C5–1 convex transducer.
CT coronary artery calcification (CAC) scoring using a Philips Mx8000 IDT 64-detector multislice CT scanner at V2.
Grip strength.
Liver elastography to measure fibrosis (protocols available).
Medical conditions
Cardiovascular disease data Yes
Echography Data available
Comments: 2D and Doppler Echocardiography, 3D Echocardiography. Left ventricular volumes, wall masses, cavity dimensions, ventricular function and ventricular dyssynchrony.
Myocardial infarction Data available
Medication use for CVD Data available
Hypertension Data available
Systolic/diastolic BP Data available
Mean arterial pressure Data available
Hypercholesterolemia Yes
Virus testing No data available
Olfactory sensitivity No
Medication use Yes
Drug coding system: Coded as according to BNF.
Cancer Data available
Diabetic Status Data available

Cognitive Outcomes

Variable Response
Any domain-specific cognitive test performed? Yes
Visual Memory Data available
Data available
N (estimate) : 1490
List all tests: Reasoning and delayed visual recall: WHO gnostic assessments (1993)
Pen and paper
Verbal Memory Data available
Data available
N (estimate): 1490
Pen and paper: CERAD 10 word list learning with delayed recall (Morris et al., 1989)
Attention Data available
Data available
N (estimate): 1490
List all tests: Forward and backward digit span (Weschler, 1987)). Attention and mental flexibility: Colour Trailmaking test (Lee et al., 2000).
Language Data available
Data available
N (estimate): 1490
List all tests: Verbal fluency (animal naming, incorporated in the CSID). Boston Naming Test (Kaplan et al., 1983)
Pen and paper
IQ data available? No
Cognitive background? Yes
Years of education Yes
Level of education Yes
Parental education No
Standard dementia global cognition scales? No
MMSE No
MoCA No
ADAS-Cog No
Addenbrooke's Cognitive Exam No
3MS No
GPCOG No

Non-Cognitive Clinical Outcomes

Variable Response
Dementia diagnosis
Alzheimer's dementia No
Lewy Body Disease No
Huntingtons Disease No
Parkinsons Disease No
Frontotemporal dementia No
Vascular dementia No
MCI No
Subjective complaint No
Dementia diagnosis (Other comments) No
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) No
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 No
PDQ39 (PD specific) No
UPDRS (PD specific) No
Hoehn and Yahr (PD specific) No
Schwab and England (PD specific) No
UHDRS (HD specific) No
Specify any other dementia rating scales Global function: Community Screening Instrument for Dementia (CSID, Hall et al., 1993) plus the CSID informant interview.
Any information on subjective complaints collected? No
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 Yes
NPI-Q No
Speilberger State Anxiety Scale No
Hospital anxiety depression scale/psychiatry (HADS) No
Specify any other scales No
Any Quality of Life Data Colllected? Yes
Quality of Life-Alzheimers Disease (QOL-AD) No
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 Yes
Short Form (SF) 36 No
Health Utilities Index 1, 2 or 3 No
Specify any other quality of life scales Quality of life (EQ5D) for Visit 2 and 3 only.
Any information on Caregivers and Caregiving Collected? Yes
Caregivers for Alzheimers disease Problems Scale (CAPS) No
Community Dementia Quality of Life Profile (CDQLP) No
COQoL-AD No
Dementia Management Strategies Scale (DMSS) No
Caregiver Activity Survey (CAS) No
Quality of life of caregivers (CQOL) No
Screen for Caregiver Burden/Time Spent Caregiving (TSC) No
Work Productivity and Activity Impairment Questionnaire-dyad version (WPAI-DYAD) No
Zairit Burden No
Specify any other caregiver scales Visit 3 only: Caregiver participant questionnaire formed specific to SABRE. Some questions in this were lifted from other validated scales.
Health service utilisation
Any Health Resource Utilisation Collected ? Yes
Hospital utilisation Yes
Prescription Medicine Cost No
Over the Counter Drug Costs No
Nursing Home Costs No
Costs of Visits to Specialists (out-patient) No
Costs of Home-Care No
Admission to nursing home No
Admission to home care No
Day care at nursing home No
Day care at home for elderly No
Home care- domestic No
Home care- personal care No
Home care- nursing No
Physical therapist Yes
Care of community mental health team No
Permanent stay at nursing home No
Informal ADL care Yes
Informal iADL care Yes
Days of work absence if having a paid job Yes
Other neurological or psychiatric measurements? Yes
Any stroke data? Yes
Stroke type Yes
Transient Ischemic Attack Yes
Carotid plaques Yes
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 No
CESD scale (depression) No
Personality evaluation No
Apathy evaluation No
Anxiety measure No
Resilience evaluation No

Imaging

Variable Response
For imaging data, what format(s) do you use for storing data? The SABRE scans are stored in DICOM format. Most analysis is performed by the Centre for Medical Image Computing at UCL. They convert the DICOM images to Niftis for processing.
Structural T1 Acquired
Acquired: T1 3D TFE MPRAGE (isotropic). T2 FFE, T2 3D.
N controls: 1200+
Acquisition period: 2008-2011 and 2014-onwards
Manufacturer: GE
Field strength: 1.5
Fluid attenuation inversion recovery (FLAIR) Acquired
Acquired: FLAIR 3D. TSE (isotropic)
N controls: 1200+
Acquisition period: 2008-2011 and 2014-onwards
Manufacturer: GE
Field strength: 1.5
Diffusion imaging (DTI/DWI) Acquired
Acquired: b0,1000
N controls: 1200+
Acquisition period: 2008-2011 and 2014-onwards
Model: GE
Field strengths: 1.5
f-MRI (task) Not acquired
Not acquired
f-MRI (rest) Not acquired
Not acquired
PET Not acquired
Not acquired
SPECT Not acquired
Not acquired
MEG Not acquired
Not acquired
In vivo Spectroscopy Not acquired
Not acquired
Other (please specify) Carotid and femoral ultrasound.
Tissue Doppler Imaging.
CT coronary artery calcification (CAC) scoring using a Philips Mx8000 IDT 64-detector multislice CT scanner.
3D echocardiography: used to provide sensitive and unbiased estimates of cardiac structure and function. In addition, intra-ethnic validation of equations to calculate left ventricular mass using 2D echocardiography will be performed, using direct measurements on 3D echocardiography, (Phillips IE33) which is equivalent to cardiac MR.
Liver ultrasound examinations performed using an EPIQ7 ultrasound device equipped with a C5–1 convex transducer.
Kidney ultrasound.
Brain scan analyses:
Volumetric analysis for atrophy: tissue type segmentation of gray matter, white matter, structural segmentation.
Cerebral Microbleeds: number, location.
White matter hyperintensities: volume, location.
Stroke, lacunes, perivascular spaces: number, location.
Circle of Willis, variants.
Perfusion: cerebral blood flow measurements:
Do you use an imaging data management system (e.g. XNAT or LORIS)? Yes
If yes, which system do you use? XNAT
Primary contact for the technical aspects of the imaging data Lorna Smith, senior radiographer at UCL lorna.smith@ucl.ac.uk.
Retinal imaging Data available
Comments: Retinal photography at V1 and V2 (4 field stereo photographs of both eyes) to assess retinopathy, age related macular degeneration and retinal vascular geometry. Photography of the lens of both eyes in order to assess lens opacities and cataracts.
Macular degeneration Data available

Genetics

Variable Response
Overview
Number Gwas subjects Controls N
Controls N: Approx 3,300+
Controls % male: 80% male
Consortia: UCLEB
Comments: Planned. Newly developed chip.
Gwas platform Illumina: New chip Illumina Human Drug Target array, combining a standard range to be used
N imputed subjects Controls N
Controls N: Approx 3,300+
Controls % male: 80%
Consortia: UCLEB
Comments: Planned
Exome/Genome sequencing broad platform categories Illumina
N APOE genotyped Controls N
Controls N: 1200
Gene screening
APOE Yes
Subgroup
Estimated N: Done at Visit 2 for approx 1,200 people, mainly men.
TREM2 No
APP No
PSEN1 No
PSEN2 No
GRN No
MAPT No
C9ORF72 No
VCP No
CHMP2B No
TDP-43 No
PRNP No
SNCA No
LRRK2 No
PINK1 No
PARK2 No
PARK7 No
NOTCH3 No
CST3 No
TTR No
GSN No
ITM2B No
HTT No
NPC1 No
NPC2 No

Biological samples

Variable Response
Blood collected Yes
Plasma Yes
Repeated Collection
Serum Yes
Repeated Collection
RNA Yes
Comments: Planned for Visit 3
DNA Yes
Repeated Collection
Abeta 1-40 No
Abeta 1-42 No
Abeta x-40 No
Abeta x-42 No
Blood Metabolic Analytes
CRP (c-reactive protein) Yes
eGFR (estimated Glomular Filtration Rate) Yes
Glucose Yes
HbA1c Yes
Lipids Yes
Comments: Total cholesterol, triglycerides, HDL cholesterol.
Liver Function Tests Yes
Serum creatinine Yes
Homocysteine No
Folate No
Other blood samples Yes
Are laboratory protocols and storage information available for bloods Yes
Urine collection
Urine Yes
Repeated Collection
Details: Albumin creatinine ratio for Visit 1, 2 and 3.
Autopsy data
Autopsy No
Measurements already performed No
Saliva
Saliva collected Yes
Details: Visit 3 for cortisol and amylase
Cortisol Yes
Are laboratory protocols and saliva storage information available? Yes
CSF
CSF collected No
Are CSF laboratory protocols and storage information available? No
mtDNA abnormalities No
Oxidative stress 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
Current smoking Data available
Former smoking Data available
Alcohol Data available
Units per day/week vs weekend Data available
Specified beverage type (wine, spirits, beers) Data available
Abstainers/former users Data available
Drugs of abuse assessment
Obesity and associated risk factors
BMI Data available
Hip/waist circumference Data available
Fat percentage Data available: Bioimpedance and DEXA and the CT scan of abdomen and thigh
Dyslipidemia Data available
Blood lipids Data available
Metabolic syndrome Data available
Type of exercise: heavy, light Data available
Comments: Reported as MJ/week at Visit 1, 2 and 3.
Exercise duration Data available
Comments: Reported in a questionnaire in the first visits
Objective measures of activity Data available
Comments: Visit 3 actigraphy watch for 3 days
Objective measure of fitness (VO2) Data available
Comments: Visit 3: Six Minute Step Test (6MST) (Borel et al., 2010) plus the Borg scale. Protocol available.
Other measurements of activity Visit 3 TANGO M2 blood pressure (BP) monitor with a range of cuff sizes and ECG leads during exercise. Protocol available.
Diet Yes
Carbs, protein, fats, fish oil Data available
Anti-oxidants Data available
Shortage of food Data available
Vitamin A, B, E Data available
Fat intake MUFA, PUFA Data available
Food questionnaires Data available
Comments: Food Frequency Questionnaire for Visit 1 and Visit 3.
Other dietary items No
Employment status
Employment status Data available
Living situation
Living situation Data available
Socioeconomic status
Socioeconomic status measures Data available
Sleep assessment
Questionnaires Data available
Comments
Actigraphy to measure sleep patterns Data available
Comments: At Visit 3

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? Regular meetings held and participants asked to consult on documents and give feedback about details of the study.
If so, does this happen on an ongoing or an ad hoc basis? Ad hoc
Ethics
Is there an ethics advisory or ELSI group within the cohort governance? No
If yes, who is represented on it? N/A
Does the cohort include participants who lack capacity? No
Is there a process in place for participants who lose capacity? No
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) With consent, the participants and GP are sent the results of the routine tests:„„ routine blood tests (blood sugar, cholesterol and other fat levels and blood creatinine), urine tests, blood pressure.
For all the other tests, such as the ECG, ultrasound, DEXA and MRI scans, participants do not receive results, but participants and GPs are informed if there are any findings which need further investigation.
All MR scans reviewed by consultant radiologist. Anything sinister is reported to the GP and then followed up to check GP has actioned this.
A similar process happens with a consultant cardiologist with the cardiology scans. Anything sinister is reported to the GP and then followed up to check GP has actioned this.
Liver ultrasounds are reviewed by a liver specialist. Anything sinister is reported to the GP and then followed up to check GP has actioned this.
Who is responsible for disclosing incidental findings? Study clinician informs GP.
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)? GP lists for the majority and 800 people from local workplaces.
Does the study involve ongoing connections with participants' own doctors (e.g. GPs)? Yes
Consent and recontact
Is there consent for recontact? Yes
If so, under what conditions? "connected with SABRE"

Data Management

Variable Response
Consent for linkage to routine data
Which parts of the UK are represented by participants in your cohort? England
England