Cohort Descriptives

Variable Response
Cohort name The Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation-PD
Cohort acronym ICICLE-PD
General Study Overview The ICICLE-PD study aims to accurately characterise two independent cohorts of incident parkinsonism in Newcastle-Gateshead and Cambridgeshire. A key objective is to identify patients who develop PD Dementia and the factors that predict its evolution. From this information, a simplified panel of tests that can be used to predict PDD will be established. ICICLE-PD will therefore provide a platform for studies investigating agents designed to help treat this complication of PD.
Participants were recruited between June 2009 and March 2012. Longitudinal follow up is on-going with assessments at 18 month intervals.
Number of subjects at baseline 219 with PD and 99 controls (318 total)
Institution name Newcastle University
Department name Clinical Ageing Research Unit
City Newcastle
Study or database website

http://www.ncl.ac.uk/caru/research/project/2909

Principal Investigator (PI): Name Prof David Burn
PI: Address Clinical Ageing Research Unit, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL.
PI: email

david.burn@ncl.ac.uk

PI: phone 0191 208 1266
Administrative Contact (AC): Name Rachael Lawson
AC: Address Clinical Ageing Research Unit, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL.
AC: email Rachael.lawson@ncl.ac.uk
AC: phone 0191 208 1279
Technical Contact/Data manager (TC): Name Dr Alison Yarnall and Dr Michael Firbank (Imaging)
TC: Address Clinical Ageing Research Unit, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL.
TC: email

alison.yarnall@ncl.ac.uk

TC: phone 0191 208 1279
Key study references

Open literature list

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)? 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? 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 Yes
Was diagnosis/primary outcomes made blind to exposure variables? No
How many times followed up? 5
Study start date 2009-06-01
Study end date 2018-12-12
Is study ongoing? Yes
Is study still recruiting? No
Inclusion criteria Aged 18 plus.
PD: Newly diagnosed PD from community and outpatient clinics in Newcastle upon Tyne/Gateshead and Cambridgeshire.
Controls: age and sex matched controls from the same area.
Exclusion criteria PD: Atypical parkinsonian disorder, drug induced parkinsonism, vascular parkinsonism
No capacity to consent.
Controls: Dementia, movement disorder, major psychiatric disorder, carer or spouses of PD participants.

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 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
Heart Rate Data available
Assessed before onset of dementia
ECG Data available
Assessed before onset of dementia
Gait assessment Data available
Assessed before onset of dementia
Opthalmic examination Data available
Assessed before onset of dementia
Acuity Data available
Assessed before onset of dementia
Visual fields (direct/indirect) Data available
Assessed before onset of dementia
Colour vision Data available
Assessed before onset of dementia
Specify any others Transcranial magnetic stimulation substudy (short latency afferent inhibition) that investigated cholinergic function, N= approx 45 and 43 controls.
Medical conditions
Cardiovascular disease data No
Myocardial infarction Data available
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) : 219 PD, 99 controls.
List all tests: Pattern Recognition Memory and Spatial Recognition Memory.
Computerised: CANTAB
Visuospatial Function Data available
Data available
N (estimate): 219 PD, 99 controls.
List all tests: Pentagon copying item of the MMSE (graded score 0-2).
Pen and paper
Attention Data available
Data available
N (estimate): 219 PD, 99 controls
List all tests: Cognitive Drug Research computerised battery.
Computerised: Cognitive Drug Research computerised battery, Wesnes et al., 2002.
Reaction time Data available
Data available
N (estimate): 219 PD, 99 controls.
List all tests: Simple reaction time, Choice reaction time, Digit vigilance combined to make a Power of Attention score.
Computerised: Cognitive Drug Research computerised battery, Wesnes et al., 2002.
Associative learning Data available
Data available
N (estimate): 219 PD, 99 controls.
List all tests: Paired Associates Learning (PAL)
Computerised: CANTAB
Language Data available
Data available
N (estimate): 219 PD, 99 controls.
List all tests: Naming and Sentence subsets of the MoCA. Executive Function: Phonemic fluency (words beginning with ‘F’ in 1 min, a subset also had ‘A’ and ‘S’ in 1 minute) and semantic fluency (animals in 90 s).
Pen and paper
Vigilance Data available
Data available
N (estimate): 219 PD, 99 controls.
List all tests: Digit Vigilance, CDR
Computerised: CDR
Planning Data available
Data available
N (estimate): 219 PD, 99 controls.
List all tests: Listed as a measure of Executive function: One touch Stockings of Cambridge.
Computerised: CANTAB.
Other cognitive tasks The authors consider the following tests as measures of executive function: One touch Stockings of Cambridge (CANTAB), phonemic fluency (words beginning with ‘F’ in 1 min) and semantic fluency (animals in 90 s).
IQ data available? Yes
NART Yes
Cognitive background? Yes
Years of education Yes
Level of education No
Parental education No
Standard dementia global cognition scales? Yes
MMSE Yes
Repeated Collection
MoCA Yes
Repeated Collection
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 Yes
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) 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) Yes
Repeated Collection
UPDRS (PD specific) Yes
Repeated Collection
Comments: MDS-UPDRS Revised (2008) only Parts II and III.
Hoehn and Yahr (PD specific) Yes
Repeated Collection: MDS-UPDRS Revised (2008) only Parts II and III.
Schwab and England (PD specific) Yes
Repeated Collection
UHDRS (HD specific) No
Any information on subjective complaints collected? Yes
IQCODE Data available
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 PDQ39.
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) Yes
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 Scale of Quality of Life of Care-Givers (SQLC): Glozman et al., 1998). http://www.ncbi.nlm.nih.gov/pubmed/9617723
Health service utilisation
Any Health Resource Utilisation Collected ? Yes
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? Yes
Any stroke data? Yes
Stroke type No
Transient Ischemic Attack Yes
Carotid plaques No
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 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? MRI are stored as Philips PAR/REC files and NIfTI format.
Structural T1 Acquired
Acquired: Newcastle subjects were scanned using a 3T Philips Intera Achieva scanner with a magnetization-prepared rapid gradient echo sequence (MPRAGE), sagittal acquisition, echo time 4.6 milliseconds, repetition time 9.6 milliseconds, inversion time 1,250 milliseconds, flip angle = 8°, SENSE factor = 2, in-plane field of view 240 × 240 mm with slice thickness 1.2 mm, yielding a voxel size of 1.15 × 1.15 mm. In Cambridge, a 3T Siemens Trio scanner was used with MPRAGE, sagittal acquisition, echo time 2.98 milliseconds, repetition time 2,250 milliseconds, inversion time 900 milliseconds, flip angle = 9°, GRAPPA factor = 2, in-plane field of view 256 × 256 mm with slice thickness 1.0 mm yielding a voxel size of 1.0 × 1.0 mm.
N controls: 50
N patients: 148
Acquisition period: 2009-2012 and Repeat at 18 months follow up.
Manufacturer: Siemens and Philips
Model: Siemens Trio and Philips Intera Achieva
Scanner N: Two, one in Cambridge and one in Newcastle.
Field strength: 3T
Fluid attenuation inversion recovery (FLAIR) Acquired
Acquired
Diffusion imaging (DTI/DWI) Acquired
Acquired
f-MRI (task) Acquired
Acquired: Tower of London, Spatial Rotations, Episodic Memory Encoding Tasks
N controls: 85
N patients: 168
Scanner N: Two, one in Cambridge and one in Newcastle.
Field strength: 3T
f-MRI (rest) Acquired
Acquired
PET Acquired
Acquired: FDG-PET for glucose.
N controls: 20
N patients: 66
Acquisition period: 2009-2012 and not followed up.
Scanner N: Two, one in Cambridge and one in Newcastle.
SPECT Not acquired
Not acquired
MEG Not acquired
Not acquired
In vivo Spectroscopy Not acquired
Not acquired
Do you use an imaging data management system (e.g. XNAT or LORIS)? No
Primary contact for the technical aspects of the imaging data Michael Firbank michael.firbank@newcastle.ac.uk

Genetics

Variable Response
Overview
Gene screening
APOE Yes
Estimated N: 204 plus 95 controls.
TREM2 No
APP No
PSEN1 No
PSEN2 No
GRN No
MAPT Yes
Estimated N: 204 plus 95 controls.
C9ORF72 No
VCP No
CHMP2B No
TDP-43 No
PRNP No
SNCA Yes
Estimated N: 204 plus 95 controls.
LRRK2 Yes
Estimated N: 204 plus 95 controls.
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
Repeated Collection
Comments: Genetics and telomeres.
Abeta 1-40 No
Abeta 1-42 No
Abeta x-40 No
Abeta x-42 No
Blood Metabolic Analytes
CRP (c-reactive protein) No
eGFR (estimated Glomular Filtration Rate) No
Glucose Yes
Repeated Collection
HbA1c No
Lipids Yes
Repeated Collection
Liver Function Tests No
Serum creatinine No
Homocysteine Yes
Repeated Collection
Folate Yes
Repeated Collection
Other blood samples Yes
Are laboratory protocols and storage information available for bloods Yes
Urine collection
Urine No
Autopsy data
Autopsy Yes
Subgroup: Brain tissue.
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: Repeated 18 months and for PD participants only, N=67.
Are CSF laboratory protocols and storage information available? Yes
Other CSF Alpha-synuclein
Mitochondrial function Data available
mtDNA abnormalities Yes
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? Yes
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
Drugs of abuse assessment
Obesity and associated risk factors
BMI Data available
Dyslipidemia Data available
Blood lipids Data available
Objective measures of activity Data available
Comments: Subgroup in the study run by Lynn Rochester underwent an accelerometry study.
Diet No
Coffee and caffeine Data available
Other dietary items No
Employment status
Employment status Data available
Living situation
Living situation Data available
Socioeconomic status
Sleep assessment
Questionnaires Data available
Comments: Epworth and Pittsburgh sleep questionnaires.
Objective sleep staging (specify method) Data available
Comments: Overnight sleep assessment as part of an ICICLE sleep substudy, N=100. Kirsty Anderson is the PI on this study.

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? N/A.
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? 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, blood biomarkers, blood pressure, ECG or if for example, it is thought that a participant's Parkinson's is under-controlled. Concerns about cognition would also be flagged.
Who is responsible for disclosing incidental findings? The study team would inform the GP and secondary care team.
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)? Mainly through secondary care.
Does the study involve ongoing connections with participants' own doctors (e.g. GPs)? Yes
Consent and recontact
Is there consent for recontact? No
If so, under what conditions? The participants have been reconsented for the ICICLE follow ups if amendments have been made, but no specific consent for contact about other studies.

Data Management

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