Cohort Descriptives

Variable Response
Cohort name Neuroimaging of Inflammation in MemoRy and Other Disorders (the NIMROD Study)
Cohort acronym NIMROD
General Study Overview The NIMROD (Neuroimaging of Inflammation in Memory and Other Disorders) study aims to understand the role of inflammation in several forms of dementia, memory loss and depression (Alzheimer's disease, AD, dementia with Lewy bodies, DLB, progressive supranuclear palsy, PSP, frontotemporal dementia, FTD, late life depression, LLD, vascular dementia, VaD, mild cognitive impairment, MCI). The study has been set up to investigate the extent and pattern of neuroinflammation in these disorders in relation to: key clinical symptoms, including cognitive impairment, peripheral markers of neuroinflammation, including cytokine levels and state-of-the-art immunoprofiling, structural changes on MRI, including atrophy and vascular (white matter lesion) changes, the extent and pattern of brain amyloid deposition as assessed with amyloid PET imaging, the extent and pattern of tau deposition as revealed with PET. A further aim is to investigate if neuroinflammation can predict subsequent clinical course, including cognitive and functional decline.
Number of subjects at baseline Currently 145: 13 controls, 12 controls for AV-1451 imaging, 22 MCI, 19 AD, 18 DLB, 6 LLD, 6 FTD, 2 VaD, 19 PSP, 1 unconfirmed (MCI) and 27 who have withdrawn but whose data remains in the study.
Institution name University of Cambridge
Department name Department of Psychiatry
City Cambridge
Principal Investigator (PI): Name Prof John O'Brien
PI: Address Prof O'Brien: Department of Psychiatry, University of Cambridge, Level E4, Box 189, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ
PI: email

john.obrien@medschl.cam.ac.uk

PI: phone Tel: +44 (0)1223 760682
Administrative Contact (AC): Name Prof John O'Brien
AC: Address Department of Psychiatry, University of Cambridge, Herchel Smith Building, Robinson Way, Cambridge, CB2 0SZ
AC: email John.obrien@medschl.cam.ac.uk
AC: phone Tel: +44 (0)1223 760682
Technical Contact/Data manager (TC): Name Robert Arnold
TC: Address Department of Psychiatry, University of Cambridge, Herchel Smith Building, Robinson Way, Cambridge, CB2 0SZ
TC: email

robert.arnold@medschl.cam.ac.uk

TC: phone 01223 768003
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
Does this take place in participants' homes or at a central location? Home
Central: Home for cognitive tests, scans at Wolfson Brain Imaging Centre, Cambridge
Do participants take part individually or are families/partners involved? Individually
Family: Only as informants, and only for patients, not for controls
Dementia cases ascertained as part of study: No
Diagnosis based on review of existing clinical data No
Was diagnosis/primary outcomes made blind to exposure variables? No
How many times followed up? 2
Study start date 2013-09-01
Study end date 2017-12-12
Is study ongoing? Yes
Is study still recruiting? Yes
Inclusion criteria Over 50 years old,
Grasp of English,
MMSE>12 for patients,
MMSE>26 for controls.
AD: meet diagnostic criteria for probable AD (McKhann et al., 2011),
MCI: MMSE >24 but with memory impairment beyond that expected for age and education (Petersen et al., 1999),
Lewy Body Dementia: criteria for dementia with LB and those with PD (McKeith et al., 2005),
PSP: Litvan et al., 1996 clinical diagnostic criteria with the relaxation of the falls criterion to falls within 3 years rather than 1 year, as suggested by the NNIPPS-PSP study group),
Later life depression: DSM-IV crietria,
FTD: Clinical criteria (according to Rascovsky et al., 2011 and Gorno-Tempini et al., 2011),
Vascular Dementia: diagnosed with vascular dementia.
Exclusion criteria Concurrent major psychiatric disorder,
Severe dementia, MMSE <12,
Severe physical illness or co-morbidity,
Prostheses or other implants that would limit the safety or value of scanning,
Past diagnosis with PD (unless in the Progressive Supranuclear Palsy or Lewy Body Dementia cohort),
Pregnant or breastfeeding,
History of or current consumption of excessive alcohol and or recreational drugs.

Demographic and Clinical Information

Variable Response
Demographics
Age Yes
Age at time of diagnosis of dementia Yes
Age at last follow-up Yes
Sex Yes
Ethnicity No
Education Yes
Physical examinations
Any physical examination performed? Yes
Neurological examination Data available
Gait assessment Data available
Comments: UPDRS III Motor evaluation
Opthalmic examination Data available
Specify any others Praxis battery completed
Medical conditions
Cardiovascular disease data Yes: Recorded in medical history
Medication use for CVD Data available
Systolic/diastolic BP Data available
Comments: Standing and lying
Hypercholesterolemia Yes: Recorded in medical history
Virus testing No data available
Olfactory sensitivity No
Medication use Yes
Diabetic Status Data available
Comments: Recorded in medical history

Cognitive Outcomes

Variable Response
Any domain-specific cognitive test performed? Yes
Verbal Memory Data available
Data available
N (estimate): 145
List all tests: Rey Auditory Visual Learning Test Learning and Recall/Recognition
Visuospatial Function Data available
Data available
Attention Data available
Data available
Reaction time Data available
Data available
N (estimate): 145
List all tests: CANTAB Simple Choice Reaction Time
Computerised: CANTAB
Associative learning Data available
Data available
N (estimate): 145 (although some PSP patients may not have done this)
List all tests: Paired Associates Learning (PAL), 3 and 6 Boxes
Computerised: CANTAB
Language Data available
Data available
N (estimate): 145
List all tests: Rey Auditory Visual Learning Test Learning and Recall/Recognition
Planning Data available
Data available
N (estimate): 145
List all tests: Stockings of Cambridge
Computerised: CANTAB
Other cognitive tasks INECO Frontal Screening (Torralva et al., 2009).
A cognitive section is included in the clinician assessment with participants, segregated into Attention, Language, Executive Function, Spatial Orientation, Memory.
IQ data available? No
Cognitive background? Yes
Years of education No
Level of education Yes
Parental education No
Standard dementia global cognition scales? Yes
MMSE Yes
Comments: Time orientation sections
MoCA No
ADAS-Cog No
Addenbrooke's Cognitive Exam Yes
Comments: ACE-R
3MS No
GPCOG No
Other assessments of global cognition Clinician Assessment of Fluctuating confusion and quality of consciousness from Walker et al., 2000.

Non-Cognitive Clinical Outcomes

Variable Response
Dementia diagnosis
Alzheimer's dementia Yes
Lewy Body Disease Yes
Huntingtons Disease No
Parkinsons Disease Yes
Frontotemporal dementia Yes
Vascular dementia Yes
MCI Yes
Subjective complaint No
Dementia diagnosis (Other comments) Yes
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
Subgroup
Comments: Informant section for clinical participants
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) Yes
Comments: UPDRS III Motor section carried out
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 Fluctuating confusion and quality of consciousness from Walker et al., 2000.
Any information on subjective complaints collected? Yes
Specify any other scales No scales included, however, a cognitive section is included in the clinician assessment with participants, segregated into Attention, Language, Executive Function, Spatial Orientation, Memory (attached to this Profile).
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) Yes
NPI Yes
NPI-Q No
Speilberger State Anxiety Scale No
Hospital anxiety depression scale/psychiatry (HADS) 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 Informants carry out The Bristol Activities of Daily Living Scale (BADLS).
Any information on Caregivers and Caregiving Collected? No
Health service utilisation
Any Health Resource Utilisation Collected ? No
Hospital utilisation 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? Yes
Loss of consciousness 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 Yes
Resilience evaluation No

Imaging

Variable Response
Structural T1 Acquired
Acquired: MR session to include sequences for volumetric T1 and T2, FLAIR, diffusion imaging, resting BOLD and blood flow (ASL) to assess structural, vascular and blood flow changes, and for use with co-registered PET data.
N controls: General control N= 16, Tau control N= 16.
N patients: MCI N= 24, AD, N=16, DLB, N= 16, Late Life Depression, N= 6, FTD N= 16, PSP N= 30.
Scanner N: Single
Field strength: 3T
Not acquired: MR session to include sequences for volumetric T1 and T2, FLAIR, diffusion imaging, resting BOLD and blood flow (ASL) to assess structural, vascular and blood flow changes, and for use with co-registered PET data.
Fluid attenuation inversion recovery (FLAIR) Acquired
Acquired
N controls: General control N= 16, Tau control N= 16.
N patients: MCI N= 24, AD, N=16, DLB, N= 16, Late Life Depression, N= 6, FTD N= 16, PSP N= 30.
Scanner N: Single
Field strength: 3T
Diffusion imaging (DTI/DWI) Acquired
Acquired: MR session to include sequences for volumetric T1 and T2, FLAIR, diffusion imaging, resting BOLD and blood flow (ASL) to assess structural, vascular and blood flow changes, and for use with co-registered PET data.
N controls: General control N= 16, Tau control N= 16.
N patients: MCI N= 24, AD, N=16, DLB, N= 16, Late Life Depression, N= 6, FTD N= 16, PSP N= 30.
Scanner N: Single
Field strengths: 3T
f-MRI (task) Not acquired
Not acquired
f-MRI (rest) Not acquired
Not acquired
PET Acquired
Acquired: (11C)PK11195, (18F)AV-1451 Tau and Pittsburgh Compound B Amyloid
N controls: General control, N=16, Tau control, N= 16. There is a separate AV-1451 control set to minimise total radiation dose for the control cohort
N patients: MCI N= 24: AD, N=16, DLB, N= 16, Late Life Depression, N= 6, FTD N= 16, N= 30.
Scanner N: Single
SPECT Not acquired
Not acquired
MEG Not acquired
Not acquired
In vivo Spectroscopy Not acquired
Not acquired
Primary contact for the technical aspects of the imaging data Robert Arnold robert.arnold@medschl.cam.ac.uk

Genetics

Variable Response
Overview
N Whole genome sequenced No
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 No
NPC1 No
NPC2 No

Biological samples

Variable Response
Blood collected Yes
Plasma Yes
Comments: Stored for future analyses, including markers of inflammation.
Serum Yes
Comments: Stored for future analyses, including immunoprofiling and markers of inflammation.
RNA Yes
Comments: Stored for future analyses.
DNA Yes
Comments: Stored for future analyses.
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
Are laboratory protocols and storage information available for bloods Yes
Urine collection
Urine No
Autopsy data
Autopsy No
Saliva
Saliva collected No
Cortisol No
CSF
CSF collected Subgroup
Details: Optional add on.
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
Alcohol Use Disorders Identification Test (AUDIT) or other screen instrument (name) Comments: Evidence for current or past dependence recorded
Drugs of abuse assessment
Obesity and associated risk factors
BMI Data available
Comments: Height and weight recorded
Blood lipids Data available
Comments: Hypercholesterolaemia recorded
Diet No
Employment status
Employment status Data available
Comments: 'What has been your main occupation?'
Living situation
Living situation Data available
Socioeconomic status
Sleep assessment
Other sleep recording (specify) Questioned in clinical interview specifically about REM sleep BD, EMW, excessive sleep etc.

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? PPI representatives in DeNDRoN and participants consulted for recruitment and dissemination issues.
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? 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.
Who is responsible for disclosing incidental findings? If clinically relevant or abnormal. Consented to have GP informed, PI informs the GP, GP informs patient.
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)? NHS secondary care. DeNDRoN (Dementias and Neurodegenerative Diseases Research Networks) Case Registers for potential participants in the North Thames and East Anglia regions fulfilling the study criteria were also consulted. Control subjects were recruited from friends and unrelated family of the patients, and from people who have previously indicated a willingness to participate in research.
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? This may be different from participants entering the study via Trusts other than CUH.

Data Management

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