Cohort Descriptives

Variable Response
Cohort name Whitehall II
Cohort acronym Whitehall-II
General Study Overview The Whitehall II Study was established in 1985 to investigate the importance of socioeconomic circumstances for health by following a cohort of working men and women aged 35-55 at enrolment. Participants have taken part in eleven data collection phases, six of which have included a medical screening. The 12th is currently underway. The aim of the study is to understand the causes of age-related heterogeneity in health.
By combining the existing 28 years of data on social inequalities and chronic disease with new clinical measures of cognitive function, mental disorders and physical functioning, Whitehall II has been transformed interdisciplinary study of ageing. In addition to providing insights into individual and social differences in the development of frailty, disability, dependence, and dementia, the study will enable the determination of optimal time windows and targets for interventions that maximise the potential for healthy-ageing and independent living.
Number of subjects at baseline 10,308: 3413 women and 6895 men
Institution name University College London
Department name Department of Epidemiology & Public Health
City London
Study or database website

https://www.ucl.ac.uk/whitehallII

Principal Investigator (PI): Name Professor Mika Kivimaki
PI: Address Whitehall II Study, Department of Epidemiology & Public Health, University College London, 1-19 Torrington Place, London, WC1E 6BT
PI: email

m.kivimaki@ucl.ac.uk

PI: phone +44 2076798260
Administrative Contact (AC): Name Dr Tindie Kalsi
AC: Address Whitehall II Study, Department of Epidemiology & Public Health, University College London, 1-19 Torrington Place, London, WC1E 6BT
AC: email J.k.kalsi@ucl.ac.uk
Technical Contact/Data manager (TC): Name Ms Stephanie Smith
TC: Address Whitehall II Study, Department of Epidemiology & Public Health, University College London, 1-19 Torrington Place, London, WC1E 6BT
TC: email

shstudy@ucl.ac.uk or whitehall2@ucl.ac.uk

TC: phone 0800 068 1562 or 020 7679 5621
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
Clinical staff: Mix of nurses and technicians and trained interviewers. Data reviewed by clinicians.
Does this take place in participants' homes or at a central location? Central
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 many times followed up? 11
Study start date 1985-01-30
Study end date 2030-12-30
Is study ongoing? Yes
Is study still recruiting? No
Inclusion criteria Civil servant working in the London offices of 20 Whitehall departments in 1985–88
Aged 35-55
Capacity to consent

Demographic and Clinical Information

Variable Response
Demographics
Age Yes
Age at time of diagnosis of dementia Yes
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
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
ECG Data available
Assessed before onset of dementia
Comments: Minnesota coding.
Cardiovascular examination Data available
Assessed before onset of dementia
Respiratory examination Data available
Assessed before onset of dementia
Spirometry Data available
Assessed before onset of dementia
Gait assessment Data available
Assessed before onset of dementia
Comments: Walking speed
Specify any others Ultrasound measures of endothelial dysfunction in a subsample (Phase 5 onwards).
Carotid artery wall thickness/distensibility in a subsample (Phase 5 onwards).
Heart rate variability (Phase 5 onwards).
HPA axis measurements in a subsample (Phase 5).
Salivary cortisol diurnal rhythm (Phase 7).
Chair rises.
Pulse Wave Velocity.
Purdue Pegboard Task (N = 800 in Whitehall II Imaging Substudy).
Medical conditions
Cardiovascular disease data Yes
Echography Data available
Myocardial infarction Data available
Comments: Self-reported non-fatal coronary events and those identified by research clinic ECD and verified through primary care and hospital records.
Medication use for CVD Data available
Comments: Self-reported non-fatal coronary events and those identified by research clinic ECD and verified through primary care and hospital records.
Hypertension Data available
Systolic/diastolic BP Data available
Mean arterial pressure Data available
Hypotension Data available
Hypercholesterolemia Yes
Virus testing No data available
Olfactory sensitivity No
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
N (estimate): 7390 across whole sample and 800 in Imaging substudy.
List all tests: Main study: Short term verbal memory was assessed with a 20 word free recall test. Participants were presented a list of 20 one or two syllable words at two second intervals and were then asked to recall in writing as many of the words in any order within two minutes. Imaging Substudy: Hopkins Verbal Learning Test-Revised (HVLT-R).
Pen and paper
Visuospatial Function Data available
Data available
N (estimate): 800 in Whitehall II Imaging substudy
List all tests: Rey Complex Figure Test and Recognition Trial (also probes other domains)
Reaction time Data available
Data available
N (estimate): 800 in Whitehall II Imaging substudy
List all tests: CANTAB RTI 5 Choice
Computerised
Language Data available
Data available
N (estimate): 7390 in main study and 800 from Whitehall II Imaging substudy
List all tests: Main Study: Vocabulary was assessed with the Mill Hill vocabulary test used in its multiple choice format, consisting of a list of 33 stimulus words ordered by increasing difficulty and six response choices. Verbal fluency (phonemic, S and semantic, animals) was carried out, N=7390. Boston Naming Test (BNT-60) was carried out for Imaging Substudy, N=800.
Pen and paper
Working memory Data available
Data available
N (estimate): 800 from the Whitehall II imaging substudy
List all tests: Digit Span and Coding tests from the WAIS-IV
Pen and paper
Other cognitive tasks In the main study, N=7390, the cognitive test battery was administered at three clinical examinations over 10 years (phases 5, 7, and 9) and includes The Alice Heim 4-I (AH4-I), composed of a series of 65 verbal and mathematical reasoning items of increasing difficulty. It tests inductive reasoning, measuring the ability to identify patterns and infer principles and rules (Heim, 1970).
Imaging Substudy: Trail Making Test (A and B), Test of Premorbid Functioning (TOPF), CLOX clock drawing task, designed to assess executive impairment and non-executive failure.
IQ data available? Yes
NART No
IQ other (list) Test of Premorbid Functioning (TOPF) can be used to extract premorbid IQ.
Cognitive background? Yes
Years of education Yes
Level of education Yes
Parental education Yes
Standard dementia global cognition scales? Yes
MMSE Yes
Repeated Collection
Comments: Whole study.
MoCA Yes
Subgroup
Comments: Whitehall II Substudy (N=800)
ADAS-Cog No
Addenbrooke's Cognitive Exam Yes
Subgroup
Comments: Verbal Fluency test and Dots and Letters only (adapted from ACE-III) for Whitehall II Imaging Substudy.
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) Yes
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 Yes
Lawton IADL Yes
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? 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) Yes
Connor-Davidson Resilience Scale No
Cornell depression Scale No
Geriatric Depression Scale (GDS) No
Hamilton depression rating scale (HDRS) Yes
Montgomery-Asberg depression scale (MADRS) No
NPI No
NPI-Q No
Speilberger State Anxiety Scale 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 No
Short Form (SF) 36 Yes
Health Utilities Index 1, 2 or 3 No
Specify any other quality of life scales General Health Questionnaire (GHQ)
Any information on Caregivers and Caregiving Collected? No
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 No
Care of community mental health team No
Permanent stay at nursing home No
Informal ADL care No
Informal iADL care No
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 No
Any head trauma data? Yes
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) Yes
Personality evaluation No
Apathy evaluation Yes
Anxiety measure Yes
Resilience evaluation Yes

Imaging

Variable Response
Structural T1 Acquired
Acquired
N controls: 800
N patients: 30 participants with depressive symptoms based on previous study visit clinical examinations.
Manufacturer: Siemens
Model: Magnetom Verio
Scanner N: Single
Field strength: 3T
Fluid attenuation inversion recovery (FLAIR) Acquired
Acquired
N controls: 800
N patients: 30 participants with depressive symptoms based on previous study visit clinical examinations.
Manufacturer: Siemens
Model: Magnetom Verio
Scanner N: Single
Field strength: 3T
Diffusion imaging (DTI/DWI) Acquired
Acquired: dMRI
N controls: 800
N patients: 30 participants with depressive symptoms based on previous study visit clinical examinations.
Manufacturer: Siemens
Model: Magnetom Verio
Scanner N: Single
Field strengths: 3T
f-MRI (task) Not acquired
Not acquired
f-MRI (rest) Acquired
Acquired
N controls: 800
N patients: 30 participants with depressive symptoms based on previous study visit clinical examinations.
Manufacturer: Siemens
Model: Magnetom Verio
Scanner N: Single
Field strength: 3T
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) T2* (T2 Star)

Genetics

Variable Response
Overview
N Whole genome sequenced No
Gene screening
APOE No
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
Serum Yes
RNA No
DNA Yes
Abeta 1-40 No
Abeta 1-42 No
Abeta x-40 No
Abeta x-42 No
Blood Metabolic Analytes
eGFR (estimated Glomular Filtration Rate) No
Glucose Yes
Repeated Collection
HbA1c Yes
Repeated Collection
Comments
Lipids Yes
Repeated Collection
Liver Function Tests Yes
Comments: Stage 12 only so far.
Serum creatinine No
Homocysteine No
Folate No
Other blood samples Yes
Are laboratory protocols and storage information available for bloods Yes
Urine collection
Urine Yes
Repeated Collection: Collected at Stages 3 and 5.
Autopsy data
Autopsy No
Measurements already performed No
Saliva
Saliva collected Yes
Repeated Collection: Stage 7 and 9 for saliva only.
Cortisol Yes
Repeated Collection: Stage 7 and 9 for saliva only. Now collect hair for cortisol levels.
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? Yes
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
Units per day/week vs weekend Data available
Specified beverage type (wine, spirits, beers) Data available
Abstainers/former users Data available
Alcohol Use Disorders Identification Test (AUDIT) or other screen instrument (name) Data available
Comments: CAGE questionnaires part of the Whitehall II Imaging substudy. Family history of alcoholism also recorded.
Drugs of abuse assessment
Obesity and associated risk factors
BMI Data available
Hip/waist circumference Data available
Dyslipidemia Data available
Blood lipids Data available
Metabolic syndrome Data available
Type of exercise: heavy, light Data available
Exercise duration Data available
Other measurements of activity Imaging substudy: CHAMPS Physical Activity Questionnaire for Older Adults, Locus for Causality Exercise Questionnaire (LCE)
Diet Yes
Carbs, protein, fats, fish oil Data available
Vegetarian? Data available
Coffee and caffeine Data available
Vitamin A, B, E Data available
Fat intake MUFA, PUFA Data available
Food questionnaires Data available
Comments: Food Frequency Questionnaire (Phase 3, 5, 7 9), Body Image Questionnaire, and Three-Factor Eating questionnaire
Other dietary items Yes
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: Jenkins Sleep Questionnaire (JSQ) and Pittsburgh Sleep Quality Index (PSQI).
Other sleep recording (specify) Diurnal saliva cortisol levels (circadian).

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 but there is a researcher in the study who is a participant and provides insight into the participant experience.
Participants get feedback forms to fill out about their participant experience to improve eg catering and the clinical visit experience.
If so, does this happen on an ongoing or an ad hoc basis? Ongoing
Ethics
Is there an ethics advisory or ELSI group within the cohort governance? No
Does the cohort include participants who lack capacity? Yes
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? Yes
Disclosure
Do procedures exist for the disclosure of incidental findings? Yes
What kinds of finding do these relate to? (imaging, genotyping, etc) ECG and blood results. ECG looked at by a cardiologist. Compares to findings from previous phases.
Get a result letter 12 weeks to outline weight, cholesterol, ECG, BMI, insulin, glucose. One letter also gets sent to the GP if the participant consents.
Participants are required to write in to request cognitive tests or lung function results, and anything of non clinical value.
Who is responsible for disclosing incidental findings? If there is something that needs more urgent follow up than 12 weeks, clinic nurse phones them and suggests to go to the GP, and then its up to the participant to go through that with the 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)? Through Whitehall employer.
Does the study involve ongoing connections with participants' own doctors (e.g. GPs)? Yes
Consent and recontact
Is there consent for recontact? Yes

Data Management

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