Cohort Descriptives

Variable Response
Cohort name TRACK HD
Cohort acronym TRACK HD
General Study Overview TRACK HD is a prospective observational biomarker study in participants with premanifest and early Huntington's disease (HD). Track HD assessed longitudinal data collected at baseline, 12 months, 24 and 36 months at sites in Leiden (Netherlands), London (UK), Paris (France), and Vancouver (Canada). Participants were individuals without HD but carrying the mutant HTT gene (ie, premanifest HD), patients with early HD, and healthy control individuals matched by age and sex to the combined HD groups. Data were collected with 3T MRI, clinical, cognitive, quantitative motor, oculomotor, and neuropsychiatric assessments.
Number of subjects at baseline 123 controls, 120 premanifest gene carriers, and 123 early HD (Stage 1 or Stage 2).
Institution name University College London
Department name UCL Institute of Neurology
City London
Study or database website

http://hdresearch.ucl.ac.uk/completed-studies/track-hd/

Principal Investigator (PI): Name Prof Sarah Tabrizi
PI: Address Huntington’s Disease Research Centre, UCL Institute of Neurology, 2nd Floor Russell Square House, 10-12 Russell Square, London, WC1B 5EH
PI: email

s.tabrizi@ucl.ac.uk

PI: phone 0207 611 0121
Administrative Contact (AC): Name Dr Rachael Scahill
AC: Address Huntington’s Disease Research Centre, UCL Institute of Neurology, 2nd Floor Russell Square House, 10-12 Russell Square, London, WC1B 5EH
AC: email R.scahill@ucl.ac.uk
AC: phone 0207 611 0121
Technical Contact/Data manager (TC): Name Dr Rachael Scahill
TC: Address Huntington’s Disease Research Centre, UCL Institute of Neurology, 2nd Floor Russell Square House, 10-12 Russell Square, London, WC1B 5EH
TC: email

r.scahill@ucl.ac.uk

TC: phone 0207 611 0121
Key study references

Open literature list

Population based study? No
Family based study? Yes
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: Control participants were purposefully selected if they were gene negative or partners of people with HD.
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? No
How many times followed up? 3
Study start date 2008-01-01
Study end date 2011-12-31
Is study ongoing? No
Is study still recruiting? No
Inclusion criteria Premanifest gene carriers required a burden of pathology score greater than 250, on the basis of their medical records at the time of recruitment, and a total motor score of 5 or less in the motor assessment of the United Huntington's Disease Rating Scale (UHDRS), indicating no substantial motor signs.
Aged between 18 and 65 years, ability to tolerate MRI and biosample collection.
CAG repeat length more or equal to 40.
HD groups had to have a total functional capacity of greater than 6 from the UHDRS.
Controls were age-matched and gender-matched to individuals in the combined preHD and HD groups.
Exclusion criteria Absence of major psychiatric disorder or history of significant head injury at time of enrolment.
Concomitant significant neurological disorder.
Significant medical illness.
MRI contraindications.
Predictable non-compliance.
Any significant hand injuries.
Taking part in any concurrent clinical trials.

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
Sex Yes
Ethnicity Yes
Education Yes
Physical examinations
Any physical examination performed? Yes
Weight Data available
Assessed before onset of dementia
Height Data available
Assessed before onset of dementia
Extrapyramidal symptoms Data available
Assessed before onset of dementia
Anthropometry Data available
Assessed before onset of dementia
Gait assessment Data available
Assessed before onset of dementia
Comments: First two years: Gait analysis was measured by asking subjects to walk barefoot on an automated gait analysis carpet (Platinum GAITRite, 4.27 m length, Gaitrite, USA). Six walks were recorded at normal speed. Subjects started their walks 3m in front of the carpet to ensure assessment of gait in regular motion. Later this was replaced by posturography.
Opthalmic examination Data available
Assessed before onset of dementia
Comments: The study team recorded horizontal eye position with the Saccadometer Advanced (Ober Consulting, Poznan, Poland) during a random, centrally cued mixed pro/anti saccade task (Hicks et al., 2008). This was carried out at all visits.
Acuity Data available
Assessed before onset of dementia
Comments: This was carried out at baseline only.
Colour vision Data available
Assessed before onset of dementia
Comments: A colour blindness test was carried out at baseline only.
Specify any others Grip strength.
Tongue force.
Speed of finger tapping.
Pace finger tapping.
Medical conditions
Cardiovascular disease data Yes
Myocardial infarction Data available
Medication use for CVD Data available
Comments: Participant reported medical history and updated at every visit and verified against medical notes where possible.
Hypertension Data available
Olfactory sensitivity Yes
Medication use Yes: Participant reported medical history and updated at every visit and verified against medical notes where possible.
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) : 123 control individuals, 120 premanifest gene carriers, and 123 participants with early HD (Stage 1 or Stage 2)
List all tests: 'Spot the change' (now part of HD-CAB). Map search test from the CANTAB.
Computerised: 'Spot the change' test designed specifically for HD. Map search taken from CANTAB.
Visuospatial Function Data available
Data available
N (estimate): 123 control individuals, 120 premanifest gene carriers, and 123 participants with early HD (Stage 1 or Stage 2)
Comments: Only done for the last two years.
List all tests: Mental rotation, map search from CANTAB. Circle tracing task carried out at all visits.
Pen and paper: Map search
Computerised: Mental rotation computerised. CANTAB.
Attention Data available
Data available
N (estimate): 123 control individuals, 120 premanifest gene carriers, and 123 participants with early HD (Stage 1 or Stage 2)
List all tests: Symbol digit modality test. Stroop word reading (not colour versions).
Pen and paper
Reaction time Data available
Data available
N (estimate): 123, 123, 120
List all tests: Stroop word reading (not colour versions).
Pen and paper
Other cognitive tasks There was an emotion recognition task, which took place on a computer.
There was also a finger tapping task, although this was more of a motor task. N= 123 control individuals, 120 premanifest gene carriers, and 123 participants with early HD (Stage 1 or Stage 2).
IQ data available? Yes
NART Yes
IQ other (list) Carried out NART in the first year, however, these were not felt to be validated enough across international sites. N= 123 control individuals, 120 premanifest gene carriers, and 123 participants with early HD (Stage 1 or Stage 2).
Trail making A&B was also completed for first 3 years.
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 Yes
Parkinsons Disease No
Frontotemporal dementia No
Vascular dementia No
MCI No
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) No
UPDRS (PD specific) No
Hoehn and Yahr (PD specific) No
Schwab and England (PD specific) No
UHDRS (HD specific) Yes
Repeated Collection
Comments: UHDRS-99
Any information on subjective complaints collected? Yes
Specify any other scales Frontal Systems Behaviour (FrSBe) carried out at all 4 time points.
Any neuropsychiatric rating scale administered? Yes
Aggression Scale No
Beck Depression Inventory Yes
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 Yes
Health Utilities Index 1, 2 or 3 No
Specify any other quality of life scales UHDRS TFC scale.
Quality of life index QoLI, Ferrans and Powers, 1992 for 4 years.
SF-36 for 3 years.
HD specific QoL questionnaire (HDQ) carried out at the last visit
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 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 Yes
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 No
Carotid plaques No
Any head trauma data? Yes
Loss of consciousness Yes
Sports, soccer and boxing No
Head trauma severity Yes
BISQ or equivalent No
EEG No
Psychiatric evaluations Yes
CESD scale (depression) No
Personality evaluation Yes
Personality evaluation comments Comments: The short version of the Problem Behaviours Assessment (PBA-s) .
Apathy evaluation Yes
Anxiety measure Yes
Resilience evaluation No

Imaging

Variable Response
For imaging data, what format(s) do you use for storing data? Raw data are stored at LONI (http://www.loni.usc.edu/). Processed data are held and accessed via central coordination at the study (coordination@track-hd.net).
Structural T1 Acquired
Acquired
Model: Siemens in Paris and London, Vancouver and Netherlands= Philips.
Scanner N: Multiple
Field strength: 3T
Fluid attenuation inversion recovery (FLAIR) Not acquired
Not acquired
Diffusion imaging (DTI/DWI) Acquired
Acquired
N controls
Manufacturer: Siemens in Paris and London, Vancouver and Netherlands= Philips.
Scanner N
Field strengths: 3T
f-MRI (task) Not acquired
Not acquired
f-MRI (rest) Not acquired
Not acquired
PET Acquired
Acquired: Substudy with separate protocol
N patients: 10 early HD
SPECT Not acquired
Not acquired
MEG Not acquired
Not acquired
In vivo Spectroscopy Acquired
Acquired: NAA in HD patients, controls and pre-manifest HD. Eighty-four participants (30 controls, 25 pre-manifest HD, 29 early HD) were imaged at baseline, 12 months, and 24 months using 3T MRS of left putamen. Automated putaminal volume measurement was performed simultaneously. To quantify partial volume effects, spectroscopy was performed in a second, white matter voxel adjacent to putamen in six subjects.
N controls: 30
N patients: 29 HD
N at-risk: 25 HD premanifest
Scanner N: Single, at Vancouver only
Field strength: 3T
Do you use an imaging data management system (e.g. XNAT or LORIS)? Yes
If yes, which system do you use? XNAT
Primary contact for the technical aspects of the imaging data Coordination@track-hd.net

Genetics

Variable Response
Overview
Number Gwas subjects Comments
Comments: Planned
N Whole genome sequenced No
N not APOE genotyped Cases N
Cases N: 120 premanifest HD gene carriers and 123 participants with early HD (Stage 1 or Stage 2)
Controls N: 123
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 Yes
Subgroup
Estimated N: 223 including premanifest and early HD groups. CAG- expansion as well as definitive determination of expansion length was confirmed by analysis of a post-recruitment blood sample sent to Biorep® Technologies Inc (Milan)
NPC1 No
NPC2 No

Biological samples

Variable Response
Blood collected Yes
Plasma Yes
Comments: Plasma samples were collected in EDTA tubes (3 × 6ml) for proteomic, ELISA and meso-scale analysis, and lithium-heparin tubes (2 × 6ml) for metabolomic analysis.
Serum Yes
RNA Yes: Done at Year 1 and Year 4. Two PAXgene RNA blood tubes (2.5ml) were collected for the isolation of RNA for microarray or other RNA biomarker analysis.
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) No
eGFR (estimated Glomular Filtration Rate) No
Glucose No
HbA1c No
Lipids No
Liver Function Tests No
Serum creatinine No
Homocysteine No
Folate No
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 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? 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
Current smoking Data available
Former smoking Data available
Alcohol Data available
Units per day/week vs weekend Data available
Comments: Units per week
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
Other measurements of activity Study specific questionnaire about exercise and physical activity across the lifespan
Diet No
Employment status
Employment status Data available
Living situation
Living situation Data available
Comments: Part of the UHDRS
Socioeconomic status
Sleep assessment
Questionnaires Data available
Comments: Pittsburgh Sleep Quality Index carried out at Visits 3 and 4 only.

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, see below re PPI body in Wales
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? Ethics expert in the Institute of Neurology
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? No
What kinds of finding do these relate to? (imaging, genotyping, etc) Clinical and genetic data.
Who is responsible for disclosing incidental findings? Radiographer reviews the scans and reports to the site PI. The site PI was always a clinician running an HD clinic and would report to the GP if it was thought that this might be clinically relevant.
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 their HD specialist clinics. In the UK, this was NHS. Expressed interest in research at clinic previously.
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? Participants have signed up to "Enrol HD" to indicate that they would be happy to be contacted for 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