Cohort Descriptives

Variable Response
Cohort name Identifying Predictors of dementia with Lewy bodies in People with Mild Cognitive Impairment
Cohort acronym LewyPro
General Study Overview The aim of this LewyPro is to identify people who may be in the early stages of developing Dementia with Lewy Bodies (DLB). Participants have MCI and symptoms of Lew Body Disease (LBD) and undergo a clinical examination, tests of their cognitive function, a specialised brain scan (FP-CIT), blood samples and a lumbar puncture. These people are then followed-up over the course of two years to see who develops DLB and see what factors at baseline assessment were associated with the development of DLB.
Number of subjects at baseline Target 100
Institution name Newcastle University
Department name Clinical Ageing Research Unit
City Newcastle
Principal Investigator (PI): Name Prof Alan Thomas
PI: Address Biomedical Research Building, Campus for Ageing and Vitality, Newcastle, NE4 5PL
PI: email

alan.thomas@newcastle.ac.uk

PI: phone 0191 208 1341
Administrative Contact (AC): Name Prof Alan Thomas
AC: Address Biomedical Research Building, Campus for Ageing and Vitality, Newcastle, NE4 5PL
AC: email Alan.thomas@newcastle.ac.uk
AC: phone 0191 208 1341
Technical Contact/Data manager (TC): Name Clinical and cognitive data: Ms Nicky Barnett. For imaging data: Dr Sean Colloby
TC: Address Institute of Neuroscience, Newcastle University Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL
TC: email

n.a.barnett@newcastle.ac.uk. For for imaging data contact S.J.Colloby@ncl.ac.uk

TC: phone 0191 208 1322
Population based study? No
Family based study? No
Clinical based sample? Yes
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)? No
How is data collected? In person
Who carries out data collection? Interviewers
Clinicians: Study registrar and assistant psychologists.
Does this take place in participants' homes or at a central location? Home
Central
Do participants take part individually or are families/partners involved? Family: Partners only take part as informants.
Dementia cases ascertained as part of study: Yes
Diagnosis based on review of existing clinical data Yes
Was diagnosis/primary outcomes made blind to exposure variables? Unknown
How many times followed up? 2
Study start date 2013-01-01
Study end date 2016-02-21
Is study ongoing? Yes
Is study still recruiting? Yes
Inclusion criteria LewyPro will recruit older adults (≥60 years old) with prodromal DLB, that is, people who have cognitive and non-cognitive symptoms consistent with Lewy body disease but do not have dementia (including MMSE ≥20 and CDR 0 or 0.5). This means subjects will meet MCI criteria (Winblad et al., 2004) and only one symptom characteristic of Lewy body disease:: MCI Criteria (Winblad et al., 2004):
1. Clinical evidence of subjective and objective cognitive decline.
2. No dementia.
3. Preserved basic activities of daily living.
4. Instrumental activities of daily living are minimally impaired or intact.
Characteristic Symptoms of Lewy body disease:
1. Complex persistent visual hallucinations.
2. Spontaneous motor parkinsonism.
3. Cognitive fluctuations.
4. Severe neuroleptic sensitivity.
5. REM sleep behaviour disorder.
In addition to these prodromal DLB criteria:
Age ≥60.
Stable medically, e.g. no delirium or recent changes (within last month) in prescribed medication.
Mental Capacity to consent to research.
Has provided written informed consent for participation in the study prior to any study specific procedures.
Exclusion criteria Clinical evidence of dementia.
MMSE <20.
CDR >0.5.
Probable Dementia with Lewy Bodies.
Parkinson’s Disease according to Queen Square Brain Bank Criteria.
Probable Alzheimer’s disease (McKhann et al., 2011).
Possible or Probable Vascular Dementia (Roman et al., 1993).
Possible or Probable frontotemporal dementia (Rascovsky et al., 2011).
History or evidence from neurological examination of clinical stroke.
Diagnosis of a movement disorder or other serious neurological condition.
Severe mental illness (major depression (current episode), bipolar disorder, schizophrenia).
Pregnant or possibility of becoming pregnant.

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 No: Unless still in study.
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: UPDRS III (Goetz et al., 2008).
Heart Rate Data available
Assessed before onset of dementia
Gait assessment Data available
Assessed before onset of dementia
Comments: UPDRS III (Goetz et al., 2008).
Opthalmic examination Data available
Assessed before onset of dementia
Comments: Visual hallucinations are self reported in the clinician interview.
Specify any others Participants undergo a clinical history structured interview with the study doctor. Included in this interview is a subjective report of impairment of cognitive features and of visual hallucinations and parkinsonism and of sleep impairment.
Medical conditions
Cardiovascular disease data Yes: If self reported in clinical interview.
Myocardial infarction Data available
Comments: If self reported in clinical interview.
Medication use for CVD Data available
Comments: If self reported in clinical interview.
Hypertension Data available: If self reported in clinical interview.
Systolic/diastolic BP Data available
Hypotension Data available
Comments: If self reported in clinical interview.
Hypercholesterolemia Yes
No: If self reported in clinical interview.
Virus testing No data available
Olfactory sensitivity No
Medication use Yes
Drug coding system: If self reported in clinical interview. Equivalent dose of opioids is calculated.
Cancer Data available
Comments: If self reported in clinical interview.
Diabetic Status Data available
Comments: If self reported in clinical interview.

Cognitive Outcomes

Variable Response
Any domain-specific cognitive test performed? Yes
Verbal Memory Data available
Data available
N (estimate): 100 at study end
List all tests: Rey Auditory Verbal Learning
Pen and paper
Visuospatial Function Data available
Data available
N (estimate): 100 at study end
List all tests: David Salmon Motor Integration Test baseline version only
Computerised: Matlab
Attention Data available
Data available
N (estimate): Target 100
List all tests: Trails A & B
Pen and paper
Reaction time Data available
Data available
N (estimate): Target 100
Pen and paper
Computerised: Simple reaction time (V), choice reaction time (< or >), Matlab.
Language Data available
Data available
N (estimate): 100
List all tests: Graded Naming Test (McKenna and Warrington). FAS verbal fluency. Rey Auditory Verbal Learning (AVLT).
Pen and paper
Vigilance Data available
Data available
N (estimate): 100
List all tests: Digit vigilance
Computerised: Matlab
Working memory Data available
Data available
N (estimate): 100
Pen and paper: Trails B
Other cognitive tasks Angle discrimination test - computerised on Matlab.
David Salmon Motor Integration Test (baseline version only).
IQ data available? No
Cognitive background? Yes
Years of education Yes
Level of education Yes
Parental education No
Standard dementia global cognition scales? Yes
MMSE Yes
Repeated Collection
MoCA No
ADAS-Cog No
Addenbrooke's Cognitive Exam Yes
Repeated Collection
Comments: ACE-III (2012).
3MS No
GPCOG No
Other assessments of global cognition CDR.
Dementia Cognitive Fluctuation Scale (DCFS-R).
Clinician assessment of fluctuating confusion and quality of consciousness (Walker et al., 2000) carried out with informant.

Non-Cognitive Clinical Outcomes

Variable Response
Dementia diagnosis
Alzheimer's dementia No
Lewy Body Disease Yes
Huntingtons Disease No
Parkinsons Disease No
Frontotemporal dementia No
Vascular dementia No
MCI Yes
Subjective complaint Yes
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) 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
Repeated Collection
PDQ39 (PD specific) No
UPDRS (PD specific) Yes
Repeated Collection
Comments: UPDRS III (Goetz et al., 2008).
Hoehn and Yahr (PD specific) No
Schwab and England (PD specific) No
UHDRS (HD specific) No
Specify any other dementia rating scales Clinician Assessment of Flucting confusion and quality of consciousness (Walker et al., 2000) carried out with carer.
Dementia Cognitive Fluctuation Scale (DCFS-R).
Repeated collection.
Any information on subjective complaints collected? No
Specify any other scales Questionnaire for symptoms suggestive of Lewy Body disease.
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 No
Short Form (SF) 36 No
Health Utilities Index 1, 2 or 3 No
Specify any other quality of life scales Bristol Activities of Daily Living Scale (Bucks et al., 1996) carried out with study partner.
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
Health service utilisation
Any Health Resource Utilisation Collected ? No
Hospital utilisation 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? No
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
Intra-cranial hemorrhage No
EEG No
Psychiatric evaluations No
CESD scale (depression) No
Personality evaluation No
Personality evaluation comments Yes
No: Subjective report as part of screen
Apathy evaluation No
Anxiety measure No
Resilience evaluation No

Imaging

Variable Response
Structural T1 Not acquired
Not acquired
Fluid attenuation inversion recovery (FLAIR) Not acquired
Not acquired
Diffusion imaging (DTI/DWI) Not acquired
Not acquired
f-MRI (task) Not acquired
Not acquired
f-MRI (rest) Not acquired
Not acquired
PET Not acquired
Not acquired
SPECT Acquired
Acquired: FP-CIT DatSCAN. GE provide isotope and pay for scans.
N controls: 0
N patients: Target 100, approx 70 at May 2015
Acquisition period: 2013- study end.
Scanner N: Single scanner
MEG Not acquired
Not acquired
In vivo Spectroscopy Not acquired
Not acquired
Other (please specify) GE paid for scans and provided SPECT isotope.
Do you use an imaging data management system (e.g. XNAT or LORIS)? Unknown
Primary contact for the technical aspects of the imaging data Dr Sean Colloby:
S.J.Colloby@ncl.ac.uk
Tel 0191 208 1321

Genetics

Variable Response
Overview
N APOE genotyped Cases N
Cases N: Target 100
Gene screening
APOE Yes
Estimated N: Target 100.
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
Repeated Collection
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) No
Glucose Yes
Repeated Collection
HbA1c No
Lipids No
Liver Function Tests Yes
Repeated Collection
Serum creatinine No
Homocysteine No
Folate Yes
Repeated Collection
Comments
Other blood samples No
Are laboratory protocols and storage information available for bloods Yes
Urine collection
Urine No
Autopsy data
Autopsy No
Measurements already performed No
Saliva
Saliva collected No
Cortisol No
Are laboratory protocols and saliva storage information available? No
CSF
CSF collected Yes
Subgroup
Repeated Collection
Details: Optional additional measurement taken up by approximately 10% patients. CSF collection is carried out fasted.
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? 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
Abstainers/former users Data available
Drugs of abuse assessment
Drugs of abuse assessment - Data available? Data available
Obesity and associated risk factors
BMI Data available
Comments: Height and weight data are available.
Diet No
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: Epworth Sleepiness Scale, Mayo Sleep Questionnaire.

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? Ad hoc.
Ethics
Is there an ethics advisory or ELSI group within the cohort governance? No
If yes, who is represented on it? NA
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? 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 cognitive data, anything clinically relevant
Who is responsible for disclosing incidental findings? Information is passed to the participant's GP/consultant. Consent form: "I give permission for my GP will be informed of my participation in this study. I give my permission that in the unlikely event that an unexpected abnormality is discovered my GP and I will be informed."
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)? Secondary care. Letters to NHS memory clinics and psychiatrists.
Case note searching.
Treating consultants send letters to potential participants.
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
Which parts of the UK are represented by participants in your cohort? England
England