Cohort Descriptives

Variable Response
Cohort name Lothian Birth Cohort 1936
Cohort acronym LBC1936
General Study Overview The Lothian Birth Cohort of 1936 is a follow up study of the Scottish Mental Survey of 1947, which tested the intelligence of almost every child in Lothian born in 1936. The key aims are to examine the distribution and causes of cognitive ageing across most of the human life course and understand how childhood social background and intelligence contribute to physical and mental health in older age. This involves establishing 'determinants of normal cognitive ageing in survivors of the Scottish Mental Survey 1947', i.e. the ageing of cognitive functions largely in the normal range, and not principally dementia or other pathological cognitive disorders. Wave 2 was intended to identify the mechanisms that cause white matter damage and how this causes cognitive decline with ageing. Participants were recruited at mean age 70.
Number of subjects at baseline 1091 in Wave 1, 866 in Wave 2, 697 in Wave 3, Wave 4 underway (some may have dementia).
Institution name University of Edinburgh
Department name Department of Psychology
City Edinburgh
Study or database website

http://www.lothianbirthcohort.ed.ac.uk/

Principal Investigator (PI): Name Prof Ian Deary
PI: Address Centre for Cognitive Ageing and Cognitive Epidemiology, 7 George Square, University of Edinburgh, Edinburgh, EH8 9JZ
PI: email

i.deary@ed.ac.uk

PI: phone 0131 650 3452
Administrative Contact (AC): Name Paul Redmond
AC: Address Department of Psychology, Room F3, 7 George Square, Edinburgh, EH8 9JZ
AC: email Paul.redmond@ed.ac.uk
AC: phone 0131 651 1534
Technical Contact/Data manager (TC): Name Paul Redmond
TC: Address Department of Psychology, Room F3, 7 George Square, Edinburgh, EH8 9JZ
TC: email

paul.redmond@ed.ac.uk

TC: phone 0131 651 1534
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: Research nurses and psychology graduates and post docs.
Does this take place in participants' homes or at a central location? Home
Central: Questionnaires completed at home, scanning and physicals performed in centre
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 Yes
How many times followed up? 4
Study start date 2004-01-01
Is study ongoing? Yes
Is study still recruiting? No
Inclusion criteria Carried out the Scottish Mental Survey in 1947.
Exclusion criteria No neurodegenerative disease in Wave 1.

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
Comments: Systolic and diastolic sitting and standing using an Omron 705IT monitor.
Weight Data available
Assessed before onset of dementia
Height Data available
Assessed before onset of dementia
Anthropometry Data available
Assessed before onset of dementia: weight, height, head circumference
Respiratory examination Data available
Assessed before onset of dementia
Comments: PEFR, forced expiratory volume in 1s, and forced vital capacity (each as best of three).
PEFR Data available
Assessed before onset of dementia
Spirometry Data available
Assessed before onset of dementia
Comments
Opthalmic examination Data available
Assessed before onset of dementia: Retinal photographs taken.
Acuity Data available
Assessed before onset of dementia
Comments: Corrected and uncorrected in both eyes using a Snellen chart.
Specify any others Time taken to walk 6m.
Ability to stand from sitting.
Demi-span.
Head circumference.
Grip strength in the right and left hand using a North Coast Hydraulic Hand Dynamometer.
Date of menopause for women.
Bioelectrical impedence (Bodystat Quadscan 4000).
Medical conditions
Cardiovascular disease data Yes
Myocardial infarction Data available
Comments: Self reported medical history.
Medication use for CVD Data available
Hypertension Data available
Systolic/diastolic BP 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
Visual Memory Data available
Data available
N (estimate) : 1091 in Wave 1, 866 in Wave 2, 697 in Wave 3, Wave 4 underway.
List all tests: Spatial Span from the WMS-III (UK) Weschler, 1998.
Pen and paper
Verbal Memory Data available
Data available
N (estimate): 1091 in Wave 1, 866 in Wave 2, 697 in Wave 3, Wave 4 underway.
List all tests: Logical Memory I: Immediate verbal declarative memory test from the Weschler Memory Scale - III (UK, Weschler, 1998). Logical memory II: Remembering the stories read from Logical Memory I after a delay
Pen and paper
Visuospatial Function Data available
Data available
N (estimate): 1091 in Wave 1, 866 in Wave 2, 697 in Wave 3, Wave 4 underway.
List all tests: WAIS-III (UK) block design (Weschler et al., 1998) and Spatial Span from WMS-III (UK).
Attention Data available
Data available
N (estimate): 1091 in Wave 1, 866 in Wave 2, 697 in Wave 3, Wave 4 underway.
List all tests: WAIS-III (UK) Symbol search- used to assess speed of information processing. Each item requires the participant to detect a target symbols and to answer yes or no as quickly as possible.
Pen and paper
Reaction time Data available
Data available
N (estimate): 1091 in Wave 1, 866 in Wave 2, 697 in Wave 3, Wave 4 underway.
List all tests: Simple and four choice reaction time.
Computerised: LCD screen as outlined in Deary et al., 2001, constructed for the UK Health and Lifestyle Survey (Cox et al., 1993).
Associative learning Data available
Data available: Verbal
N (estimate): 1091 in Wave 1, 866 in Wave 2, 697 in Wave 3, Wave 4 underway.
List all tests: Weschler Memory Scale-III (UK) paired associates (Weschler, 1998). Immediate and delay.
Pen and paper
Language Data available
Data available
N (estimate): 1091 in Wave 1, 866 in Wave 2, 697 in Wave 3, Wave 4 underway.
Comments: Also completed a Bilingualism questionnaire in Wave 2.
List all tests: Verbal fluency one minute for as many words as possible for letters C/F/L.
Pen and paper
Working memory Data available
Data available
N (estimate): 1091 in Wave 1, 866 in Wave 2, 697 in Wave 3, Wave 4 underway.
Comments
List all tests: Backward Digit Span and Letter-Number sequencing tests of working memory from WMS-III (UK) and WAIS-III (UK) respectively. Trail making test B (Waves 3 and 4).
Pen and paper
Latent memory Data available
Data available
N (estimate): 1091 in Wave 1, 866 in Wave 2, 697 in Wave 3, Wave 4 underway.
List all tests: Delayed Logical Memory I/II and Verbal paired associates delay from WMS-III (UK) (Weschler, 1998).
Planning Data available
Data available
N (estimate): 697 in Wave 3, Wave 4 underway.
List all tests: Trail Making Test B
Pen and paper
Other cognitive tasks Digit symbol coding: subtest from Weschler Adult Intelligence Scale - III (UK, Weschler, 1998).
Constructional ability: WAIS-III (UK) block design (Weschler, 1998).
Matrix reasoning: non-verbal reasoning task from WAIS-III (UK) (Weschler, 1998).
Inspection time: forced choice visual discrimination task used to assess speed of elementary visual processing run through E-Prime (Psychology Software Tools, Pittsburgh, PA).
For all cognitive tests, see: Deary et al., 2007, BMC Geriatrics, attached to this profile.
IQ data available? Yes
NART Yes
IQ other (list) Moray House Test No 12 (first carried out by all participants in 1947). Data available from age 11 for N= 1028.
Weschler Test of Adult Reading (WTAR, Holdnack, 2001). Weschler Test of Premorbid Function from Wave 3.
Cognitive background? Yes
Years of education Yes
Level of education Yes
Parental education Yes
Standard dementia global cognition scales? Yes
MMSE Yes
Repeated Collection
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 Yes
Lewy Body Disease No
Huntingtons Disease No
Parkinsons Disease No
Frontotemporal dementia No
Vascular dementia Yes
MCI No
Subjective complaint No
Dementia diagnosis (Other comments) No
Functional rating scales
Any information on dementia rating collected? No
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
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) No
Hamilton depression rating scale (HDRS) No
Montgomery-Asberg depression scale (MADRS) No
NPI No
NPI-Q No
Speilberger State Anxiety Scale No
Hospital anxiety depression scale/psychiatry (HADS) Yes
Specify any other scales Yes
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 Nine Item Townsend Disability Scale Activities of Daily Living Scale (Townsend, 1979) was administered. In addition, the WHOQOL-BREF Quality of Life Assessment was also carried out. This produces scores for four domains related to quality of life: physical health, psychological, social relationships and environment as well as one facet on overall quality of life and general health (WHOQOL Group, 1998). All but one of the 26 questions was utilised as the question regarding participants' sex lives was not deemed appropriate for this age group.
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
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 No
Transient Ischemic Attack No
Carotid plaques Yes
Any head trauma data? No
Sports, soccer and boxing No
BISQ or equivalent No
EEG No
Psychiatric evaluations Yes
CESD scale (depression) No
Personality evaluation Yes
Personality evaluation comments Yes
Comments: IPIP Big Five Factor Markers (http://ipip.ori.org/) and NEO-Five Factor Inventory (Costa and McCrae, 1992).
Apathy evaluation No
Anxiety measure Yes
Resilience evaluation No

Imaging

Variable Response
For imaging data, what format(s) do you use for storing data? DICOM
Structural T1 Acquired
Acquired: Structural T1 and T2
N controls
Acquisition period: Wave 1 (2004-2007), Wave 2 (2007-2010), Wave 3 (2011-2013), Wave 4 (2014-2016)
Manufacturer: GE
Model: Signa Horizon
Scanner N: Single
Field strength: 1.5T
Fluid attenuation inversion recovery (FLAIR) Acquired
Acquired
N controls: 1091 in Wave 1.
N patients
Acquisition period: Wave 1 (2004-2007), Wave 2 (2007-2010), Wave 3 (2011-2013), Wave 4 (2014-2016)
Manufacturer: GE
Model: Signa Horizon
Scanner N: Single
Field strength: 1.5T
Diffusion imaging (DTI/DWI) Acquired
Acquired: DTI
N controls: 1091 in Wave 1.
Acquisition period: Wave 1 (2004-2007), Wave 2 (2007-2010), Wave 3 (2011-2013), Wave 4 (2014-2016)
Manufacturer: GE
Model: GE Signa Horizon
Scanner N: Single
Field strengths: 1.5T
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) The scans done were: structural MRI: T1, T2, FLAIR , GRE, MTR, MTI, DTI.
Carotid artery Doppler ultrasound on neck performed using a Siemens Antares Premium Colour Doppler scanner with 7.5Jz variable frequency probe (N=866). Planned for Wave 4.
Retinal imaging in Wave 2, N= 866.
Face photography in Wave 3, N= 697.
Do you use an imaging data management system (e.g. XNAT or LORIS)? Yes
If yes, which system do you use? The data are currently being put into an XNAT system, but this will not contain the MTR or MTI data, and is not yet complete.
Primary contact for the technical aspects of the imaging data Dominic Job: dominic.job@ed.ac.uk
Retinal imaging Data available
Comments: Retinal imaging in Wave 2, N= 866. Includes number of arterioles, venules, optic disc radius (see Data Dictionary).

Genetics

Variable Response
Overview
Number Gwas subjects Controls N
Controls N: Estimated 1091 (some may have a diagnosis, taken from general population study)
Controls % male: Approx 50%
Platform: Illumina
Consortia: ENIGMA
Comments: GWAS (Illumina Human 610-Quad and Illumina HumanExome Beadchip) and Illumina HM450 data are available for 1,091 individuals at multiple time points from the LBC1936. Specifically, after quality control, LBC1936: 920 at 70 years, 299 at 73 and 273 at 76 years. Participants with methylation measures at the second and third time points in both cohorts also had methylation measures at all preceding waves. These participants are all White British. DNA was derived from peripheral whole blood.
Gwas platform Illumina
Human610-Quad_v1: Illumina610-Quadv1 chip
N imputed subjects Controls N
Controls N: 1091
Controls % male: 50%
Consortia: ENIGMA
N Whole Exome sequenced Comments
Comments: Planned
N Whole genome sequenced No: Planned
N APOE genotyped Controls N
Controls N: 1028
Gene screening
APOE Yes
Estimated N: 1028 non-demented at Wave 1. For APOE, DNA was isolated from whole blood, and the target sequences for rs7412 and rs429358 were genotyped with TaqMan technology ( Invitrogen website, 2012). These 2 SNPs form the APOE ε2/ε3/ε4 haplotype (commonly and herein simply “genotype”).
TREM2 No
APP Yes
Estimated N: 1063
PSEN1 Yes
Estimated N: 1063
PSEN2 Yes
Estimated N: 1063
GRN No
MAPT Yes
Estimated N: 1063
C9ORF72 No
VCP No
CHMP2B No
TDP-43 No
PRNP Yes
Estimated N: 1063
SNCA No
LRRK2 No
PINK1 No
PARK2 Yes
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 No
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
Repeated Collection
eGFR (estimated Glomular Filtration Rate) Yes
Repeated Collection
Glucose No
HbA1c Yes
Repeated Collection
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
Repeated Collection
Autopsy data
Autopsy No
Measurements already performed No
Saliva
Saliva collected Yes
Cortisol Yes
CSF
CSF collected No
Are CSF laboratory protocols and storage information available? No
mtDNA abnormalities No
Oxidative stress Yes
Repeated Collection
Details: Blood markers

Brain donation

Variable Response
Is brain donation part of the existing protocol? Yes
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? Yes
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
Comments: From Wave 3 onwards
Abstainers/former users Data available
Binge drinking Data available
Comments
Drugs of abuse assessment
Obesity and associated risk factors
BMI Data available
Fat percentage Data available
Blood lipids Data available
Type of exercise: heavy, light Data available
Comments: Self report questionnaire - 6 item scale rating from chores to competitive sport (Hirvensalo et al., 1998)
Exercise duration Data available
Comments: How many days in an average month (more than 20 mins at a time) in exercise
Occupation possible job matrices Data available
Objective measures of activity Data available
Diet Yes
Carbs, protein, fats, fish oil Data available
Anti-oxidants Data available
Vegetarian? Data available
Shortage of food Data available
Coffee and caffeine Data available
Vitamin A, B, E Data available
Fat intake MUFA, PUFA Data available
Food questionnaires Data available
Comments: Scottish Collaborative Group Food Frequency Questionnaire Version 7.0 (Masson et al., 2003). Data were sent to the University of Aberdeen for nutrient extraction.
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
Actigraphy to measure sleep patterns Data available
Other sleep recording (specify) Self reported "How satisfied are you with your sleep?". Wave 4 includes a sleep and fatigue diary.

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.
If so, does this happen on an ongoing or an ad hoc basis? NA
Ethics
Is there an ethics advisory or ELSI group within the cohort governance? No
If yes, who is represented on it? 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) Imaging and anything of clinical value eg bloods.
Who is responsible for disclosing incidental findings? The study team informs a study doctor who weighs up its clinical relevance. If thought to be clinically relevant this is passed to the GP and the GP discloses this information. The study team informs the participant of ongoing relationship with 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) Yes
Recruitment
How was the cohort recruited (NHS or not, primary or secondary care)? The Lothian Health Board identified possible participants using a Community Health Index (CHI)- a list identifying people who are registered with a local GP and through advertisements in local media.
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? Wave 4 Consent form: "Being contacted in the future by the LBC1936 team to discuss my possible participation in further research arising directly from this study. I affirm that this will not commit me in any way to taking part in further research.":

Data Management

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