Cohort Descriptives

Variable Response
Cohort name The PREVENT Research Programme
Cohort acronym PREVENT
General Study Overview The PREVENT Research Programme has established a cohort of individuals to explore differences in the brain and cognitive function in healthy people in mid-life (aged 40-59). People are grouped into high, mid and low risk based on their family history and APOE status (a well-known risk gene for Alzheimer’s disease).
Participants are assessed on biological indicators including markers in blood, saliva, urine and spinal fluid as well as direct imaging of the brain's structure and function. Changes in all of these markers will be monitored at 2 years to work out if risks that predict these changes. One of the main aims of the study is to identify the earliest signs of changes in the brain whilst people are still in good health.
Number of subjects at baseline 210 enrolled (target 750 across London and expansion sites in Edinburgh, Cambridge and Oxford).
Institution name West London Mental Health Trust, Imperial College London and University of Edinburgh
Department name West London Cognitive Disorders Treatment and Research Unit
City London
Study or database website

https://www.preventdementia.co.uk

Principal Investigator (PI): Name Prof Craig Ritchie
PI: Address Kennedy Tower, Royal Edinburgh Hospital, Morningside, Edinburgh, EH10
PI: email

craig.ritchie@ed.ac.uk

PI: phone 0131 537 6264
Administrative Contact (AC): Name Katie Wells
AC: Address West London Cognitive Disorders Treatment and Research Unit, Lakeside Mental Health Unit, West Middlesex Hospital site, Twickenham Road, Isleworth, London, TW7 6AF
AC: email Katie.wells@imperial.ac.uk
AC: phone 020 8483 1823 / 07714051464
Technical Contact/Data manager (TC): Name Isabel Carriere for data and Su Li for imaging
TC: Address U1061 Neuropsychiatry, Inserm, Montpellier, France
TC: email

Data: isabelle.carriere@inserm.fr, Imaging: ls514@cam.ac.uk

TC: phone 020 8483 1823
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
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: Yes
Diagnosis based on review of existing clinical data No
Was diagnosis/primary outcomes made blind to exposure variables? Yes
How many times followed up? 1
How regular is follow-up? Every 2-3 years
Every 2-3 years: Initially there will be a two year follow-up visit from baseline and the future aim is for participants to be followed up every 5 years.
Less often
Study start date 2014-02-28
Study end date 2017-12-31
Is study ongoing? Yes
Is study still recruiting? Yes
Inclusion criteria Age range 40-59.
Participants are stratified by APOE genotype, but only after they have completed the visit.
High risk group:
Apoe e4 allelic positive status
Parent with dementia: Middle risk group:
Parent with dementia
OR Apoe 4
Apoe e3 homozygous : Low risk group:
Apoe 2
no parent with dementia
Exclusion criteria Does not have dementia.
No metal contraindications or issues that would prevent having an MR scan, eg claustrophobia.
Haven't already had APOE genetic testing (for sake of blinding) before entering the study.

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 No
Sex Yes
Ethnicity No
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
Neurological examination Data available
Assessed before onset of dementia
Extrapyramidal symptoms Data available
Assessed before onset of dementia
Comments: Simpson and Angus Scale (1970).
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
Cardiovascular examination Data available
Assessed before onset of dementia
Comments: ECG.
Respiratory examination Data available
Assessed before onset of dementia
Comments: "Respiration rate should be recorded by counting the number of breaths they take in one minute"
PEFR Data available
Assessed before onset of dementia
Spirometry Data available
Assessed before onset of dementia
Gait assessment Data available
Assessed before onset of dementia
Opthalmic examination Data available
Comments: A retinal imaging substudy began in Edinburgh in 2015.
Acuity Data available
Assessed before onset of dementia
Comments: A retinal imaging substudy began in Edinburgh in 2015.
Visual fields (direct/indirect) Data available
Assessed before onset of dementia
Comments: A retinal imaging substudy began in Edinburgh in 2015.
Colour vision Data available
Assessed before onset of dementia
Comments: Visual short term memory binding test colour perception component. A retinal imaging substudy began in Edinburgh in 2015.
VER Data available
Assessed before onset of dementia
Comments: A retinal imaging substudy began in Edinburgh in 2015.
Nerve conduction Data available
Assessed before onset of dementia
Comments: A retinal imaging substudy began in Edinburgh in 2015.
Specify any others Body temperature: Taken using a Zeal Ezetemp disposable thermometer. The thermometer should be placed under the tongue and left for 2 minutes.
Pregnancy and menstruation scale.
Medical conditions
Cardiovascular disease data Yes: This is self-reported in the medical history.
Myocardial infarction Data available
Comments: This is self-reported in the medical history.
Medication use for CVD Data available
Age of onset (relative to dementia) known
Comments: This is self-reported in the medical history.
Hypertension Data available
Systolic/diastolic BP Data available
Hypotension Data available
Hypercholesterolemia Yes
Virus testing Data collected: Self reported medical history, specifically asked about hepatitis and STIs.
Olfactory sensitivity No
Medication use Yes
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) : 210
List all tests: Visual Short term memory binding test and COGNITO assessments. COGNITO examines both visual analysis (perception, localization and higher-level ordering of visual material) and visual performance (the capacity to carry out goal-oriented tasks within a spatial domain).
Computerised: COGNITO
Verbal Memory Data available
Data available
N (estimate): 210
List all tests: Delayed and Cued Verbal Recall
Computerised: COGNITO
Visuospatial Function Data available
Data available
N (estimate): 210
List all tests: COGNITO
Computerised: COGNITO
Attention Data available
Data available
N (estimate): 210
List all tests: Auditory and Visual Attention from COGNITO. COGNITO assesses auditory and visual attention modalities. In the first task the subject is asked to discriminate between long and short sounds and in the second to select a visual stimulus presented in an array of distractors. The two tasks are then performed together to constitute a complex task of divided and focused attention constituting working memory. Difficulties in allocating attentional resources due to inability to inhibit automatic responses to stimuli is also assessed by the Stroop test
Computerised: COGNITO
Reaction time Data available
Data available
N (estimate): 210
List all tests: Reaction Time
Computerised: COGNITO
Associative learning Data available
Data available
N (estimate): 210
List all tests: Visuospatial Associative Learning
Computerised: COGNITO
Language Data available
Data available
N (estimate): 210
List all tests: Reading and Comprehension of Phonemes and Syntax, Naming, Semantic Access, Immediate, Delayed and Cued Visual and Verbal Recall, Vocabulary. Phonology is assessed from a reading trial of the memory name list as the names have been chosen to cover the principal phonoarticulatory groups (occlusive, constrictive and nasal). Morphology is assessed by requesting the person to recognize the meaning of words by selection from multiple-choice arrays which include semantic, morphologic and phonetic distractors. Correct responses, error type and response latencies are then recorded. Syntax is evaluated by asking the person to read sentences of increasing syntactic complexity and then to carry out the command in the sentence in relation to an image. For example “Touch the clown who is in between the white dog and the other clown”. COGNITO also assesses morphological-lexical abilities by requesting the naming of common objects and the selection of an image which illustrates its use thus allowing differentiation of loss of name identifier from visual agnosia. The presence of simultanagnosia and use of category rather than specific names are also noted in the results as part of the qualitative features of performance. Metamorphological skills are assessed by verbal fluency tasks with a phonetic then a semantic prompt. Intrusions and perseverations are noted as qualitative errors. An estimate of verbal (crystallized) intelligence is derived from a multiple choice vocabulary test.
Computerised: COGNITO
Working memory Data available
Data available
N (estimate): 210
List all tests: Working Memory.
Computerised: COGNITO
Latent memory Data available
Data available
N (estimate): 210
List all tests: Delayed and Cued Visual and Verbal Recall
Computerised: COGNITO
Other cognitive tasks Implicit Memory and Conceptual Sequencing tasks from COGNITO. Implicit memory in COGNITO is measured through the fifteen-step reconstruction by pixels of the names learnt within the verbal learning tasks and distractor names, on the assumption that priming will have occurred if the previously learnt names are recognized with fewer reconstruction steps than the new names.
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? 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 Yes
Repeated Collection
Comments: Lawton and Brody, 1969.
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
Specify any other scales Asked if they have any memory problems.
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 Yes
Cornell depression Scale No
Geriatric Depression Scale (GDS) No
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
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 No
Short Form (SF) 36 No
Health Utilities Index 1, 2 or 3 No
Specify any other quality of life scales Life Stressor Checklist Revised, Wolfe, J., & Kimerling, R. (1997).
Lifetime of Experiences Scale, Valenzuela & Sachdev (2007).
Any information on Caregivers and Caregiving Collected? No
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
Health service utilisation
Any Health Resource Utilisation Collected ? No
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 No
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 Yes
Sports, soccer and boxing Yes
Head trauma severity Yes
BISQ or equivalent Yes
Intra-cranial hemorrhage Yes
EEG No
Psychiatric evaluations Yes
CESD scale (depression) Yes
Personality evaluation No
Apathy evaluation Yes
Anxiety measure Yes
Resilience evaluation Yes

Imaging

Variable Response
For imaging data, what format(s) do you use for storing data? London: All data from the Imaging study will be saved to the Imperial College Hammersmith CIF Cluster. The imaging lead for the study periodically transfers the imaging data to Cambridge and stores them at data servers in Wolfson Brain Imaging Centre for analysis.
Structural T1 Acquired
Acquired: 1x1x1mm – high resolution volumetric for structural 32 channel head coil for high SNR, use parallel factor of 2 for nearly the same homogeneity to the non-parallel approach. 5 minutes.
N controls: 210
N patients: 210, target 750
Manufacturer: Siemens
Model: MAGNETOM Verio
Scanner N: Single
Field strength: 3T
Fluid attenuation inversion recovery (FLAIR) Acquired
Acquired: TR = 7840ms, TE = 96ms, Flip Angle = 150 deg, IR =2500ms, SENSE = 1, Acquisition matrix = 320x256, FOV = 224x180mm, 27 4mm slices (with 1mm gap between slices), voxel size = 0.7x0.7x4mm, foldover = RL, Turbo SE factor = 17. 4:28 minutes
N controls: 210, target 750
N patients: 0
Manufacturer: Siemens
Model: MAGNETOM Verio
Scanner N: Single
Field strength: 3T
Diffusion imaging (DTI/DWI) Acquired
Acquired: DWI + B0 map scan: TR = 11700ms, TE = 106ms, SENSE = 2, Acquisition matrix = 96x96, FOV = 192x192mm, 63 2 mm slices, voxel size = 2x2x2mm, foldover = AP, EPI-TRSE (Siemens), epi factor = 96, b=0 (1 averages) b=1000 (63 directions) 13 :05 minutes
N controls: 210, target 750
N patients: 0
Manufacturer: Siemens
Model: MAGENTOM Verio
Scanner N: Single
Field strengths: 3T
f-MRI (task) Acquired
Acquired: About 37 indoor and 38 outdoor images (75 in total) in the study stage and 50 indoor and 50 outdoor images (100 in total with 75 from the study stage) in the test stage. In the study phase, presente each image for 3s and give another 2s to make an indoor/outdoor response. And in the test phase, present each image for 3s and give another 2s to make a new/old response. TR = 2000ms, TE = 30ms, 188 TRs visual display whole brain coverage focus on MTL and fusiform areas Rapid event related design =6 minutes. functional MRI Part II*- recall phase of the recognition memory task TR = 2000ms, TE = 30ms, 250TRs= 8:22 minutes.
N controls: 210, target 750
N patients: 0
Manufacturer: Siemens
Model: MAGNETOM Verio
Scanner N: Single
Field strength: 3T
f-MRI (rest) Acquired
Acquired: TR = 2430ms, TE1 = 13ms, TE2 = 31ms, TE3 = 48ms, Flip Angle = 90 deg, SENSE=2, Acquisition matrix = 64x64, FOV = 240x240mm, 34 3.8mm slices, voxel size = 3.8x3.8x3.8mm, foldover = AP. 11:05 minutes
N controls: 210, target 750
N patients: 0
Manufacturer: Siemens
Model: MAGENTOM Verio
Scanner N: Single
Not acquired
PET Not acquired
Not acquired
SPECT Not acquired
Not acquired
MEG Not acquired
Not acquired
In vivo Spectroscopy Acquired
Acquired: single midline voxel in grey matter of precuneus/posterior cingulate, for early metabolic changes including pre-shim and water suppression optimisation TE 30ms, TR 2s. 5 minutes .
N controls: 210, target 750
N patients: 0
N at-risk: stratified in low, middle and high risk groups, as yet to be decided.
Manufacturer: Siemens
Model: MAGNETOM Verio
Scanner N: Single
Field strength: 3T
Other (please specify) 1) SWI
TR = 35ms, TE = 20ms, Flip Angle = 17 deg, SENSE = 2, Acquisition matrix = 256x240, FOV = 256x240mm, 40 2mm slices, voxel size = 1x1x2mm, foldover = RL, recon at 0.87, Fat shift P
5:05 minutes: 2) hippocampal subfield sequence. Coronal T2
TR = 6420ms, TE = 11ms, Flip Angle = 160 deg, SENSE = 1, Acquisition matrix = 512x408, FOV = 210x167mm, 20 2mm slices, voxel size = 0.4x0.4x2mm, foldover = RL, 2 acquisitions
6:16 minutes.
3) ASL for blood flow
4:30 minutes:
Do you use an imaging data management system (e.g. XNAT or LORIS)? No
Primary contact for the technical aspects of the imaging data Dr Su Li
ls514@cam.ac.uk
Retinal imaging Data available
Comments: Retinal imaging substudy (N=50) beginning 2015. 5 scans: OCT, OCT Angiopathy, fundus scanning, biometry, ultra-wide SLO.
Macular degeneration Data available
Comments: Retinal imaging substudy (N=50) beginning 2015
OCT Data available
Comments: Retinal imaging substudy (N=50) beginning 2015. OCT, OCT Angiopathy.

Genetics

Variable Response
Overview
N APOE genotyped Controls N
Controls N: 210 approx planned from screening
Gene screening
APOE Yes
Estimated N: Entire group (approx 210 as of August 2015).

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
CRP (c-reactive protein) Yes
Repeated Collection
eGFR (estimated Glomular Filtration Rate) Yes
Repeated Collection
Glucose Yes
Repeated Collection
HbA1c No
Lipids Yes
Repeated Collection
Liver Function Tests Yes
Repeated Collection
Serum creatinine Yes
Repeated Collection
Homocysteine No
Folate Yes
Repeated Collection
Other blood samples Yes
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
Repeated Collection
Details: SOPs and storage information attached to Cohort Profile (Procedures library document).
Cortisol Yes
Are laboratory protocols and saliva storage information available? Yes
CSF
CSF collected Yes
Subgroup
Details: Consent has been granted by approximately 50 participants. The study team are waiting appointment of a clinician to do this.
Are CSF laboratory protocols and storage information available? Yes
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
Binge drinking Data available
Drugs of abuse assessment
Drugs of abuse assessment - Data available? Data available
Comments: Self reported medical history interview.
Obesity and associated risk factors
BMI Data available
Hip/waist circumference Data available
Blood lipids Data available
Metabolic syndrome Data available
Comments: Self reported medical history interview.
Type of exercise: heavy, light Data available
Comments: Self report
Exercise duration Data available
Comments: Self report
Diet Yes
Carbs, protein, fats, fish oil Data available
Comments: Inferred from food diary.
Anti-oxidants Data available
Comments: Inferred from food diary.
Vegetarian? Data available
Comments: Inferred from food diary.
Shortage of food Data available
Comments: Inferred from food diary.
Coffee and caffeine Data available
Comments: Inferred from food diary.
Vitamin A, B, E Data available
Comments: Inferred from food diary.
Fat intake MUFA, PUFA Data available
Comments: Inferred from food diary.
Food questionnaires Data available
Comments
Other dietary items Yes
Employment status
Employment status Data available
Living situation
Living situation Data available
Socioeconomic status
Socioeconomic status measures Data available
Comments: Classfied using http://www.neighbourhood.statistics.gov.uk/HTMLDocs/dev3/ONS_SOC_occupation _coding_tool.html
Sleep assessment
Questionnaires Data available
Comments: Pittsburgh Sleep Quality Index questionnaire.

Ethics and Engagement

Variable Response
Participant engagement
Is there participant representation in the governance of the cohort? Yes, there is a participant representative on the Steering Group
Do existing mechanisms for consulting/involving participants exist? Participant representative on the steering group who represents the Participant Panel.
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.
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? 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) Imaging and bloods
Who is responsible for disclosing incidental findings? Clinical team on the study
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)? 1. CRaFT team and study coordinator: Potential participants can be drawn from the DemReg research database and asked whether they would like to participate in the programme. They will also be approached when attending clinic appointments by these team members when consenting to be part of the DemReg register.
2. Clinicians: During clinical appointments clinicians will be asked to introduce the study to family members to see whether they would be interested in the study or know any other family members or friends who may want to participate.
3. Marketing materials: Participants may contact the research team directly if they have heard about the study through newspaper articles, the PREVENT Research Programme website or from seeing a PREVENT Research Programme information leaflet.
4. Join Dementia Research https://www.joindementiaresearch.nihr.ac.uk/
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? "I agree to be contacted by the Prevent Research team about studies related to Prevent".
Any contact would have to go through the main study team.

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