Available via license: CC BY-NC 4.0
Content may be subject to copyright.
Uncorrected Author Proof
Journal of Parkinson’s Disease xx (20xx) x–xx
DOI 10.3233/JPD-161055
IOS Press
1
Research Report
1
A Consensus Set of Outcomes for
Parkinson’s Disease from the International
Consortium for Health Outcomes
Measurement
2
3
4
5
Paul de Roosa,c,∗, Bastiaan R. Bloemb, Thomas A. Kelleyc, Angelo Antoninid, Richard Dodele,
Peter Hagellf, Connie Marrasg, Pablo Martinez-Martinh, Shyamal H. Mehtai, Per Odinj,
Kallol Ray Chaudhurik, Daniel Weintraubl,m, Bil Wilsonnand Ryan J. Uittio
6
7
8
aDepartment of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden9
bRadboud university medical center; Donders Institute for Brain, Cognition and Behavior; Department of
Neurology, Nijmegen, The Netherlands
10
11
cInternational Consortium for Health Outcomes Measurement, Cambridge, USA12
dParkinson and Movement Disorders Unit IRCS Hospital San Camillo, Venice, Italy13
ePhilipps-Universitat, Marburg, Germany14
fThe PRO-CARE Group, School of Health and Society, Kristianstad University, Kristianstad, Sweden15
gMorton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson’s
disease, University of Toronto, Toronto, Canada
16
17
hNational Center of Epidemiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain18
iMayo Clinic, Scottsdale, USA19
jSk˚ane University Hospital, Lund, Sweden20
kKing’s College, London, UK21
lPerelman School of Medicine at the University of Pennsylvania, Philadelphia, USA22
mPhiladelphia Veterans Affairs Medical Center, Philadelphia, USA23
nICHOM Patient Representative, USA24
oMayo Clinic, Jacksonville, FL, USA25
Accepted 24 May 2017
Abstract.26
Background: Parkinson’s disease (PD) is a progressive neurodegenerative condition that is expected to double in prevalence
due to demographic shifts. Value-based healthcare is a proposed strategy to improve outcomes and decrease costs. To move
towards an actual value-based health care system, condition-specific outcomes that are meaningful to patients are essential.
27
28
29
Objective: Propose a global consensus standard set of outcome measures for PD.30
Methods: Established methods for outcome measure development were applied, as outlined and used previously by the
International Consortium for Health Outcomes Measurement (ICHOM). An international group, representing both patients
and experts from the fields of neurology, psychiatry, nursing, and existing outcome measurement efforts, was convened.
31
32
33
∗Correspondence to: Paul de Roos, Department of Neu-
roscience, Neurology, Uppsala University, 75185 Uppsala,
Sweden. Tel.: +46 186110000; Fax: +46 186115027; E-mail:
Paul.deroos@neuro.uu.se.
ISSN 1877-7171/17/$35.00 © 2017 – IOS Press and the authors. All rights reserved
This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC 4.0).
Uncorrected Author Proof
2P. de Roos et al. / Consensus Set Outcomes for Parkinson’s Disease
The group participated in six teleconferences over a six-month period, reviewed existing data and practices, and ultimately
proposed a standard set of measures by which patients should be tracked, and how often data should be collected.
34
35
Results: The standard set applies to all cases of idiopathic PD, and includes assessments of motor and non-motor symptoms,
ability to work, PD-related health status, and hospital admissions. Baseline demographic and clinical variables are included
to enable case mix adjustment.
36
37
38
Conclusions: The Standard Set is now ready for use and pilot testing in the clinical setting. Ultimately, we believe that using
the set of outcomes proposed here will allow clinicians and scientists across the world to document, report, and compare
PD-related outcomes in a standardized fashion. Such international benchmarks will improve our understanding of the disease
course and allow for identification of ‘best practices’, ultimately leading to better informed treatment decisions.
39
40
41
42
MESH terms: Delivery of Health Care∗/economics, Delivery of Health Care*/standards, Efficiency, Organizational, Inter-
national Cooperation, Health Care Costs Health Status, Health Surveys, Health Surveys/Health Status Indicators, Humans,
Outcome Assessment (Health Care), Quality of Health Care, Quality Indicators, Health Care/standards, Quality of Life, Aged,
Middle Aged, Disability Evaluation, Disease Progression, Female, Male, Parkinsonian Disorders, Parkinson Disease, Parkin-
son Disease/epidemiology, Parkinson Disease, Psychometrics, Activities of Daily Living, Outcome and Process Assessment
(Health Care)/standards, Parkinson Disease/therapy∗
43
44
45
46
47
48
INTRODUCTION34
Parkinson’s disease (PD) is a common and pro-
35
gressive neurodegenerative disease [1]. In the USA,
36
PD has an estimated prevalence of 0.3% and an esti-37
mated healthcare cost per patient of 10,000 USD/year38
[2]. Prevalence and costs are similar in Europe [3].
39
Due to the aging global population, the prevalence of
40
PD is expected to increase significantly [4], leading41
to greater disease-associated burden and higher care
42
expenditures. Optimizing the quality of PD care and43
minimizing the expense of care delivery are therefore
44
essential.45
Increasing value, defined as a patient’s outcomes46
divided by the cost to achieve those outcomes, has47
been proposed as a mechanism to improve the quality
48
of care [5]. A systematic measurement of outcomes49
can guide improvement and enable dissemination of
50
best practices. In order to move towards an actual51
value-based health care system, having condition-
52
specific outcomes that are meaningful to patients and53
their care providers is crucial. Transparency regard-
54
ing outcomes and costs is essential to help reduce
55
unwanted variations in healthcare delivery, and to56
increase the overall quality of care. This need has57
been recognized in the PD community for some time.58
Efforts to identify outcomes that are meaningful to59
patients and caregivers have led to the establishment
60
of various national assessment programs [6–9].
61
However, across the world, PD outcomes remain62
inconsistently defined, collected and reported. This
63
limits our ability to make reliable national and inter-
64
national comparisons, which in turn obscures our65
ability to learn from best practices, a necessary step66
to improve global healthcare.67
The International Consortium for Health Out- 68
comes Measurement (ICHOM) was formed to 69
develop global consensus sets of outcomes that 70
reflect patients’ concerns and experiences. ICHOM 71
has already developed international sets of outcomes 72
for 21 medical conditions [10]. We here report the 73
results of an ICHOM initiative to develop a simi- 74
lar set of outcomes for PD. To achieve this, ICHOM 75
brought together an International Working Group, 76
representing patients, neurology, psychiatry, nurs- 77
ing and existing outcome measurement efforts, to 78
develop a parsimonious standard set of outcome 79
indices for PD, with the aim of proposing the prod- 80
uct for international use. This paper describes the 81
development process and the resultant set. 82
METHODS 83
Working group 84
The formation of the Working Group was based 85
on the principles of previous ICHOM working 86
groups [11]. The PD Working Group consisted of 12 87
members from eight countries (USA, Canada, UK, 88
Spain, Italy, Germany, Netherlands, and Sweden) and 89
included expert neurologists (n= 9), a psychiatrist, 90
and a nurse specializing in PD, as well as an expe- 91
rienced patient advocate (Table 1). Working Group 92
members were identified by reviewing authors of 93
leading papers on PD care quality, and by identifying 94
members of international patient advocacy groups, 95
leading international PD scientific organizations, and 96
leading physicians in existing national and interna- 97
tional quality measurement efforts. 98
Uncorrected Author Proof
P. de Roos et al. / Consensus Set Outcomes for Parkinson’s Disease 3
Table 1
Working Group members
Working Group member Expertise
Bas Bloem Professor of Neurology, focusing on movement disorders.
Lead of National Parkinson’s Disease Registry in Netherlands.
Angelo Antonini Professor of Neurology, focusing on Parkinson’s disease and measurement of outcomes that matter to
patients.
Richard Dodel Professor of Neurology with interest in Parkinson’s disease and measurement of patient outcomes.
Member of MDS-UPDRS revision taskforce
Peter Hagell Professor of Neurological Caring Science, with a focus on outcomes measurement in Parkinson’s
disease.
Connie Marras Associate Professor of Neurology, focusing on Movement Disorders and the evaluation of clinical
assessment tools.
Pablo Martinez-Martin Neurologist, interest in Parkinson’s disease and development of clinical evaluation tools.
Shyamal Mehta Assistant Professor of Neurology, focusing on movement disorders and measuring outcomes in the
Parkinson’s disease clinic.
Per Odin Professor of Neurology, focusing on movement disorders.
Developed Swedish National Parkinson’s disease registry.
K Ray Chaudhuri Professor of Neurology, focusing on movement disorders.
Expertise in developing clinical evaluation tools.
Daniel Weintraub Professor of Psychiatry, with interest in psychiatric and cognitive complications of Parkinson’s
disease.
Bill Wilson Experienced Parkinson’s disease patient advocate. Part of the Parkinson’s Disease Foundation.
Ryan Uitti Professor of Neurology focusing on movement disorders with an academic interest in measuring
patient outcomes relative to cost.
Paul de Roos Neurology Resident. Research Fellow, providing literature review expertise.
Process
99
Following the process used in earlier ICHOM work100
[10, 11], a modified Delphi technique was employed101
to define the outcomes and case-mix variables. Case102
mix variables are defined as those variables that
103
capture the state of the patient independent of the104
medical condition for which they are being treated.
105
This includes demographic factors, health status (e.g.
106
co-morbidities) and treatments. The process is a
107
structured, consensus-driven approach, with telecon-
108
ferences and post-teleconference surveys to reach109
decisions. Proposals for each teleconference were110
generated in advance by a core ICHOM project team111
(RU, TAK, PdR). These were based on a literature112
review of existing guidelines and standards, as well113
as individual interviews with each Working Group
114
member.
115
The Working Group was officially announced in
116
December 2013 and launched with an in-person
117
meeting at the conference of the International118
Association of Parkinsonism and Related Disorders119
(IAPRD). This was followed by five 75-minute tele-
120
conferences, which took place every month between121
January and May 2014. All of these teleconferences122
were followed by a survey of the Working Group123
members to make decisions on key discussion areas.124
A 2/3 majority was required, being a commonly used125
threshold for Delphi and modified Delphi processes,126
on each survey question to reach consensus. Shifting 127
the threshold a bit did not have an impact on the selec- 128
tion process. When a 2/3 majority was not reached, 129
the topic was brought up for re-discussion at the fol- 130
lowing teleconference. The standard set of outcomes 131
was then launched at the International Parkinson and 132
Movement Disorder Society (MDS) Conference in 133
June 2014. 134
The process began with defining the scope of 135
the Working Group by deciding which causes of 136
parkinsonism to include in the set. Subsequently, 137
key outcome domains that are meaningful to patients 138
were identified based on relevant literature and out- 139
come measurement programmes [6–11]. These were 140
then reviewed with each Working Group member 141
individually to determine if additional domains, not 142
identified by the search, should be considered. The 143
resultant list of outcome domains was then organized 144
based on four criteria. Each criterion was rated on a 145
Likert scale of 1–4, where one was the lowest and 146
four was the highest score given: (1) Frequency of 147
the outcome domain in the patient population – an 148
important consideration for a set that aims to be par- 149
simonious; (2) Impact of the outcome domain on the 150
patient – an essential consideration for a set that aims 151
to reflect what is most meaningful to patients; (3) 152
Preventability/treatability of the outcome domain – a 153
necessary consideration for a set that aims to be used 154
in the clinic to generate meaningful data on which 155
Uncorrected Author Proof
4P. de Roos et al. / Consensus Set Outcomes for Parkinson’s Disease
clinicians can act to modify their practice; and (4)156
Feasibility to capture the outcome domain in clinical
157
practice – this is essential as the set is designed to158
be used in routine clinical practice. This formed the159
basis for the first teleconference discussion.160
Once the outcome domains were decided, the tools
161
for data collection were determined. Relevant scales162
or items were identified and prioritized using spe-163
cific criteria. Again, each criterion was rated on a164
Likert scale of 1–4, where one was the lowest and
165
four was the highest score given. The criteria were166
as follows: (1) Domain coverage – this set aims to be167
of minimal burden and complexity. Thus, tools that
168
cover many domains were preferable; (2) Psychome-169
tric properties – the data collected must be accurate,
170
and thus patient-reported tools were prioritized based171
on psychometric properties; (3) Feasibility to imple-172
ment – the tool must be practical for day-to-day use
173
in the clinic; and (4) Clinical interpretability – clini-174
cal teams must be able to understand the results. This175
formed the basis for the second teleconference dis-176
cussion. Finally, we sought to reach agreement on the177
frequency of data collection, balancing comprehen-178
siveness, practicalities for clinics, and what would be179
best for patients.
180
This was followed by identification of the base-
181
line case-mix variables, which are necessary to make182
meaningful comparisons between patients. Case-mix
183
variables to measure were prioritized based on three184
criteria. Each criterion was rated on a Likert scale of185
1–4, where one was the lowest score and four was
186
the highest score given. The criteria were as follows:187
(1) Relevance (strength of association between the
188
case-mix variable and the outcome) – we aimed to
189
identify case-mix variables that could strongly affect190
the outcome; (2) Case-mix variable independency –191
given the aim to collect a minimum set of case-mix192
variables, the aim was to identify variables that would193
independently affect the outcome; (3) Feasibility to194
collect – the set must be practical for use in the clinic.
195
This formed the basis for the third teleconference196
discussion.
197
The fourth teleconference focused on reaching198
agreement around internationally acceptable ways to199
measure case mix adjustment variables. The fifth tele-200
conference focused on reviewing the set prior to its201
launch to the international community.202
Literature search strategy203
The following PubMed MeSH terms and Boolean204
logic were used to perform a search to identify out-205
comes that matter to PD patients, as well as scales 206
to collect those outcomes: (“Parkinson’s disease” OR 207
“Parkinson disease” OR “Parkinsonism”) AND (“cri- 208
tique” OR “recommendation” OR “review”) AND 209
(“scale” OR “scales” OR “instrument” OR “instru- 210
ments” OR “questionnaire” OR “questionnaires”). 211
Limitations were applied, which included the need 212
to be review articles, written in the English language, 213
and published in the 10 years preceding January 2015. 214
From this search, article titles and abstracts were 215
reviewed to identify those that had a clear focus on 216
scales used in clinical practice. From these results, 217
references to scales were extracted and through tar- 218
geted searches, original validation studies and use of 219
the respective instruments were identified. 220
RESULTS 221
Scope 222
The set was designed to cover all cases of adult 223
(>18 years of age) idiopathic PD. Atypical parkin- 224
sonism was excluded, as the consensus was that 225
this would require different outcome measures. We 226
recommend that atypical causes of parkinsonism 227
be considered in future outcome sets. This set is 228
intended to be relevant to PD patients receiving all 229
common treatment options for motor and non-motor 230
symptoms, including pharmacotherapy (including 231
infusion or injection-based delivery), deep brain stim- 232
ulation, and rehabilitation-based therapy (including 233
allied health interventions, nursing, and behavioral 234
therapy). 235
Outcomes 236
A series of motor, non-motor and other outcomes 237
were agreed upon by the Working Group as essential 238
to collect. 239
Non-motor symptoms 240
Non-motor outcomes impact the ability of patients 241
with PD to carry out normal day-to-day activities 242
[12] and are key determinants of their perceived 243
health [13, 14]. Based on the current literature, non- 244
motor symptoms that are most important for PD 245
patients were listed [6, 7, 11, 15, 16]. As described 246
in Methods, the project team then prioritized this 247
list and suggested the following outcome domains 248
for inclusion in the standard set: depression, anxiety, 249
Uncorrected Author Proof
P. de Roos et al. / Consensus Set Outcomes for Parkinson’s Disease 5
cognitive function, urinary function, gastrointestinal250
function, pain, sleep, sexual function, treatment com-
251
plications (hemorrhage and behavior change). These252
were deemed frequent, of high impact on patients,253
treatable and feasible to capture in clinical practice.254
During the teleconference, the group agreed with
255
their inclusion but additionally felt that fatigue, hallu-256
cinations and sweating should also be included, due257
to their impact on patients. In the survey following258
the teleconference, the voting confirmed inclusion
259
of the aforementioned outcomes with the exception260
of treatment complications – specifically, hemor-261
rhage, as it is very uncommon, and behavior change,
262
as this is captured under the cognitive and psy-263
chiatric domains. Additionally, the survey revealed
264
that psychosis, apathy, impulse control disorder and265
dizziness/syncope were further domains deemed nec-266
essary to be part of the standard set, again due to their
267
impact on patients. These were reviewed at the next268
teleconference and agreed by all WG members to be269
included in the Set. (See Table 2 for the full list of270
outcome domains and suggested scales).271
A range of tools for data collection were identified.272
These included the Scale for Outcomes of Parkin-273
son’s disease (SCOPA-AUT) [17], the Non-Motor
274
Symptom Questionnaire (NMSQuest) [18], the Non-
275
Motor Symptoms Scale (NMSS) [19], the Movement276
Disorder Society – Unified Parkinson’s Disease Rat-
277
ing Scale (MDS-UPDRS) [20], as well as specific278
scales relating to depression [21, 22], anxiety [23],279
apathy [24], psychosis [25], fatigue [26], sleep [27]
280
and cognition [28, 29].281
It was felt that it would be simpler and less bur-
282
densome for patients and health systems to have a
283
single instrument rather than many individual patient-284
reported outcome measurements. A number of scales285
were considered, including NMSS [19], NMSQuest286
[19, 30], SCOPA-AUT [17] and MDS-UPDRS Part287
1 [31, 32]. Ultimately, the MDS-UPDRS part 1 was288
chosen, as it has the highest test-retest reliability
289
and internal consistency (as measured by Cronbach’s290
alpha), in comparison to the other tools, as well as
291
having acceptable construct validity. Additionally, it292
poses minimal burden on the health system, with the293
clinician-recorded component taking <10 minutes to294
complete and the rest being patient reported [32].295
Additionally, the MDS-UPDRS Part 2 (see below) is296
recommended for collection of the motor outcomes297
and thus it was felt simpler for clinics to use the MDS-
298
UPDRS for both motor and non-motor assessment.
299
Two of the selected domains (sweating and sex-
300
ual function) are not covered in the MDS-UPDRS
301
part 1 survey, so it was decided to use the questions 302
addressing these issues that are in the NMSQuest 303
[21]. While not a perfect solution, the Working Group 304
prioritized the selection of two simple, easy to admin- 305
ister, patient-reported questions. The Working Group 306
encourages the MDS to consider including questions 307
relating to sweating and sexual dysfunction in future 308
iterations of the MDS-UPDRS. 309
We initially considered using the MDS-UPDRS 310
part 1 as a screening tool for anxiety, depression 311
and cognitive symptoms, and to use domain specific 312
scales such as Beck Depression Inventory (depres- 313
sion) [33], State Trait Anxiety Inventory (anxiety) 314
[34] and Montreal Cognitive Assessment (cognition) 315
[35] to investigate these non-motor symptoms in 316
more detail. However, it was decided that this would 317
miss a key principle underpinning the work (i.e., to 318
produce a practical, minimum set of outcomes that is 319
of minimal burden to patients and staff). Therefore, 320
only the MDS-UPDRS part 1 was included as part of 321
the set. 322
Motor symptoms 323
Motor symptoms are an important problem in PD 324
and their presence is relied upon to make a clinical 325
diagnosis of PD. Motor features that were considered 326
to be most important to the PD patient were identi- 327
fied and listed [6, 7, 11]. The outcome domains that 328
the project team suggested including in the standard 329
set (following the process set out under the meth- 330
ods) included: mobility – ability to walk; activities 331
of daily living – living independently, handwriting 332
and keyboard capabilities; ability to self-care; tremor; 333
speech; swallowing; treatment complications (dysk- 334
inesia and dystonia). 335
During the teleconference (and confirmed by the 336
post-teleconference survey) it was agreed to include 337
these proposed outcome domains, and it was sug- 338
gested and agreed upon in the post-call survey to 339
include additional ones. The additional outcomes 340
included: leisure activities, saliva and drooling, and 341
ability to move in bed at night. These were agreed 342
upon as they are domains that can have a significant 343
impact on the patient’s quality of life. Ultimately, the 344
only outcome domains from the initial list not to be 345
included in the standard set were treatment compli- 346
cations – specifically, dyskinesia and dystonia – as it 347
was felt that we should focus on motor function, not 348
specific symptoms or side effects. 349
A wide variety of rating instruments were iden- 350
tified for different motor symptoms, including the 351
Uncorrected Author Proof
6P. de Roos et al. / Consensus Set Outcomes for Parkinson’s Disease
Table 2
Summary of the Parkinson’s disease Standard Set. Full set can be found: http://www.ichom.org/wp-content/uploads/2014/08/PD-Reference-
Guide-6.11.14-KL.pdf
Category Domain Tool Data source
Cognitive and psychiatric
symptoms/functioning
Cognitive impairment MDS-UPDRS Part 1 Physician reported
Hallucinations & psychosis
Depressed mood
Anxious mood
Apathy
Features of dopamine
dysregulation syndrome
(including impulse control
disorders)
Non-motor functioning Sleep problems MDS-UPDRS Part 1 – patient
questionnaire part 1
Patient and/or caregiver reported
Daytime sleepiness
Pain & other sensations
Urinary problems
Constipation problems
Light headedness on standing
Fatigue
Sexual function Non Motor Symptoms
Questionnaire
Patient and/or caregiver reported
Sweating
Motor functioning Speech MDS-UPDRS Part1–Patient
questionnaire part 2
Patient and/or caregiver reported
Saliva & drooling
Chewing & swallowing
Eating tasks
Dressing
Hygiene
Handwriting
Doing hobbies & other activities
Turning in bed
Tremor
Getting out of bed, a car, or a
deep chair
Walking & balance
Freezing
Additional health outcomes Ability to work Does your PD limit your ability
to work?
Patient reported
Hospital admissions 1. Admitted to hospital in last 12
months and how many times?
Patient and/or carer reported
2. Number of times related to
PD?
PD-related health status PDQ-8 Patient and/or carer reported
Falls Fall within last year and did it
cause a fracture?
Patient and/or carer reported
Case-mix variables Age In years Patient reported
Sex Male or female Patient reported
Level of education Defined using International
Standard Classification of
Education (ISCED)
Patient reported
Living status Who currently lives with you? Patient reported
Marital status Indication of marital status. Patient reported
Depression/anxiety/REM sleep
behavior disorder prior to PD?
Yes/No Patient reported
Age at PD diagnosis Age in years Patient reported
Age at onset of PD symptoms Age in years Patient reported
Comorbidities NHS comorbidity tool Patient reported
NB: All outcomes are collected annually.
Hoehn and Yahr staging [36, 37], the Schwab and352
England ADL scale [38], PD-related health sta-353
tus questionnaires [39] such as PDQ39 [40], the354
MDS-UPDRS, and scales which can be used to report 355
motor complications, such as “wearing off” [41], risk 356
of falling (including the Berg Balance Scale [42] 357
Uncorrected Author Proof
P. de Roos et al. / Consensus Set Outcomes for Parkinson’s Disease 7
and others [43, 44]) and mobility (Timed Get Up358
and Go Test) [45]. During the teleconference discus-
359
sions it was agreed that many domain-specific scales360
would be needed and that this would be too burden-361
some and complicated for patients and clinical teams.362
Therefore, the MDS-UPDRS and the PDQ-39 were
363
ultimately identified as the potential tools for data364
collection. The PDQ-39 is available in multiple lan-365
guages and is free to use, but only covers 6/10 motor366
domains that we identified as being important. In con-
367
trast, the MDS-UPDRS part 2 questionnaire is also368
available in multiple languages and is free to use clin-369
ically but covers 10/10 domains. MDS-UPDRS part
370
2 has excellent psychometric properties [20]. There-371
fore, the MDS-UPDRS part 2 was decided as the
372
motor tool of choice by the Working Group.373
Additional health outcomes
374
We identified four additional domains as impor-375
tant for patients with PD: ability to work, hospital
376
admissions, overall PD-related health status, and377
falls. These were selected by the group, particularly378
the patient representative, as important outcomes to
379
assess. To assess ability to work, hospital admissions,380
and falls, the questions currently used in the recently381
developed Dutch National Parkinson’s Disease Reg-382
istry (www.ParkinsonInzicht.nl), which cover these383
domains, were selected for use in the ICHOM set.
384
The Dutch registry uses the PDQ-39 to assess PD-385
related health status. The PDQ-8 and PDQ-39 are
386
comparable as health status indices, but the PDQ-8 is
387
significantly less burdensome to complete [46–48].
388
We recognize the value of having a single PD-related389
health status score and decided to include the PDQ-8.390
Finally, there was also a discussion around the391
assessment of cost of accessing care for the patient.392
While we agreed that cost is vitally important, it
393
was best included not as an outcome but rather394
the denominator of the value equation. Reporting
395
cost was therefore seen as out of the scope of this396
work.
397
Case-mix variables398
Patients with PD have a broad range of char-399
acteristics both related and unrelated to their
400
neurodegenerative disease that may influence their
401
outcomes. A parsimonious set of case-mix variables402
(Table 2) that were felt to strongly impact outcomes,403
based on existing literature [49, 50] and informal404
discussions, was proposed. For demographic vari-405
ables: age, gender, level of education, and living 406
status (i.e. whether the patient was living alone) were 407
proposed. Age and gender are associated with anxi- 408
ety, cognitive function, urinary function, GI function, 409
pain, sexual function and fatigue. Gender is associ- 410
ated with depression [51]. Level of education, gender 411
and living status are associated with cognitive func- 412
tion [49, 52]. For baseline health status: early age at 413
onset of PD, depression earlier in life, PD motor sub- 414
type, non-PD related cognitive dysfunction, non-PD 415
related co-morbidities, and non-PD related medica- 416
tion affecting sleep, sexual function, and dizziness 417
were proposed. During the teleconference it was sug- 418
gested and agreed upon to include marital status 419
as an additional demographic variable, as not being 420
married is known to be associated with the risk for 421
cognitive decline in the elderly general population 422
[53]. Other constructs such as loneliness and social 423
networks in late life also include marital status and 424
are known to be correlated to cognitive function [50]. 425
There was unanimous agreement to remove PD motor 426
subtype and all medication side effects due to the 427
difficulty of recording this information accurately. 428
There was agreement to change early age at diag- 429
nosis of PD to age at diagnosis of PD, as there are 430
conflicting views on the definition of “early”, while 431
age would provide a more specific time point assur- 432
ing less ambiguity in the data collected. For baseline 433
health status, the age of PD onset and diagnosis, the 434
diagnosis of depression, anxiety or rapid eye move- 435
ment (REM) sleep behavior disorder (RBD) before 436
PD diagnosis [53], and comorbidities were included. 437
We agreed on definitions for each of the case-mix 438
variables. For marital status and living status we 439
decided to use the widely accepted definitions devel- 440
oped by the European Social Survey [54]. For level of 441
education, the United Nations Educational, Scientific 442
and Cultural Organization (UNESCO) definitions of 443
education levels, which allow for international and 444
cross-cultural comparisons, were selected [55]. We 445
decided to change the term “tertiary” to “Univer- 446
sity or equivalent” as it was felt that this wording 447
would be easier for patients and care providers to 448
understand. For the case-mix variables, depression 449
and anxiety, we developed two new yes/no questions. 450
We agreed to include a single baseline patient- 451
reported question used to assess previous REM sleep 452
behavior disorder [53]. A validated patient-reported 453
Charlson Comorbidity Index currently in use by 454
the United Kingdom National Health Service [56] 455
was chosen to reduce data collection burden on 456
physicians.
Uncorrected Author Proof
8P. de Roos et al. / Consensus Set Outcomes for Parkinson’s Disease
Data collection457
In order to be able to easily compare between
458
providers, centers and countries, the use of estab-
459
lished instruments with multiple translations was460
prioritized and data collection methods that can be461
applied across different countries and settings were
462
proposed. We aimed to reduce the reporting burden on463
clinicians and as such the vast majority of outcomes464
in the set are patient-reported, with the exception of465
the cognitive and mental health outcomes. We rec-
466
ommend all outcomes to be recorded annually.467
DISCUSSION
468
We have produced a standard set of outcomes,469
intended for international use to monitor the quality470
of clinical management of patients with PD. The set471
includes validated indicators of motor and non-motor
472
symptoms and health status. Additional case-mix
473
variables have been included to enable case mix474
adjustment so that inter-center and international com-475
parisons can be performed. It aims to build on existing
476
outcome measurement work [6–10] and additionally477
brings the perspective of leading clinicians and a478
patient advocate from around the world to ensure a479
global perspective.480
The aim was parsimony, so more detailed481
symptom-specific scales (e.g., the Beck Depression
482
Inventory and the Montreal Cognitive Assessment)483
were not selected. Additionally, not all possible out-
484
come domains were included, but rather a focus on
485
those essential outcomes that really reflect what mat-
486
ters to most people with Parkinson’s disease in most487
places. For example, driving is key component of the488
patient’s independence, and a frequently volunteered489
priority in clinical practice [57]. The fact that driving490
was not mentioned suggests that not all elements that
491
matter to patients came to light in this project, and492
consequently did not make it to the final instrument.
493
We therefore encourage teams to use this dataset as494
the basis on which other outcome domains can be
495
added.496
Ultimately, the MDS-UPDRS parts 1 and 2, three497
questions from the NMSQuest, the PDQ-8, and six498
questions from the Dutch National PD registry were499
chosen, as their questions represent all of the domains500
that the Working Group identified as being important.501
We realize that some health care providers currently
502
use different scales and that there may be challenges
503
in switching to the present recommendation, but we
504
feel that the prospective benefit of being able to
505
perform cross-provider comparisons and to collabo- 506
ratively learn and improve patient care will encourage 507
universal adoption of this set over time. We also 508
recognize that computer-adaptive patient-reported 509
outcome measures are currently under investiga- 510
tion, and that they may eventually replace the scales 511
included in this set. To ensure continuity of the set 512
over time, a subset of Working Group members has 513
formed a Steering Committee to review and update 514
the set on an annual basis. 515
This set aims to be used on a day-to-day basis in the 516
clinic, as a useful tool to help guide management deci- 517
sions for clinicians and patients. It is also hoped that 518
it will be used to compare the quality of care provided 519
by different centers around the world, stimulating dis- 520
cussion and learning from those centers with the best 521
outcomes. For the MDS-UPDRS, the NMSQuest and 522
the questions from the Dutch registry, it is envisaged 523
that the results of each individual question will be the 524
unit of comparison. For the PDQ-8, an overall score 525
can be calculated, which will be used for comparison. 526
We are recommending existing validated instru- 527
ments, and as such this dataset can be used 528
immediately by teams across the world in pilot exper- 529
iments. Specifically, before this ICHOM approach 530
to outcome measurement can be recommended fully 531
to international communities of clinicians, we rec- 532
ommend that pilot experiments should be performed 533
in a cohort of individuals with PD. The results of 534
such pilot studies should be evaluated using estab- 535
lished psychometric approaches to further optimize 536
the question set. Accordingly, we actively seek such 537
feedback from teams to ensure that the set remains 538
practical and relevant for people living with Parkin- 539
son’s disease. For most institutions, implementation 540
into routine clinical practice may be challenging, not 541
in the least because it may require new resource com- 542
mitments and infrastructure development. ICHOM 543
has developed an expert implementation team to 544
assist institutions in figuring out how to overcome 545
these challenges. While we recognize the challenges, 546
we are encouraged by the increasing availability of 547
electronic health records and communication tech- 548
nologies that enable outcome reporting directly into 549
the patient’s medical record. We hope that this set will 550
further spur development in this area. We also recog- 551
nize that in some languages, validated translations of 552
the proposed scales do not yet exist and will need to be 553
undertaken. Finally, we note that valid comparisons 554
of outcomes across countries are in their infancy and 555
will require further methodological development to 556
ensure validity [58]. 557
Uncorrected Author Proof
P. de Roos et al. / Consensus Set Outcomes for Parkinson’s Disease 9
A methodological draw back to the project was the558
absence of physiotherapy and rehabilitation expertise
559
in the Working Group, as well as absence of represen-560
tation from Asia, Oceania and South America. This561
will be addressed by identifying appropriate exper-562
tise to join the steering committee, which is charged
563
with monitoring and updating the set on an ongoing564
basis.565
In summary, we have developed a simple, rela-566
tively easy to implement, set of outcome indices that
567
we believe should, after piloting testing, be collected568
and tracked for all patients with PD. This is an ini-569
tial step towards driving meaningful and significant
570
improvements in the care of patients with PD around571
the world.
572
ACKNOWLEDGMENTS573
We would like to thank all authors for the time and574
effort contributed without financial compensation.
575
SOURCES OF SUPPORT576
This project was funded by the International Con-577
sortium for Health Outcome Measurement.578
CONFLICT OF INTEREST
579
No conflicts of interest to report: De Roos,580
Martinez Martin, Antonini, Ray Chaudhuri, Uitti,
581
Wilson, Hagell, Weintraub, Mehta, Marras, Kelley.582
583
Per Odin has given lectures with honorarium584
and/or had expert advisor role for the following
585
companies: Abbott/AbbVie, Britannia, Bayer, Lund-586
beck, Orion Pharma, UCB.587
588
Bas Bloem589
See separate file attached.
590
591
Richard Dodel
592
See separate file attached.593
REFERENCES594
[1] Lees AJ, Hardy J, & Revesz T (2009) Parkinson’s disease.595
Lancet,373, 2055-2066.
596
[2] Kowal SL, Dall TM, Chakrabarti R, Storm MV, & Jain
597
A (2013) The current and projected economic burden of598
Parkinson’s disease in the United States. Mov. Disord,28,599
311-318.600
[3] Gustavsson A, Svensson M, Jacobi F, Allgulander C, Alonso601
J, Beghi E, Dodel R, Ekman M, Faravelli C, Fratiglioni
602
L, Gannon B, Jones DH, Jennum P, Jordanova A, J¨
onsson 603
L, Karampampa K, Knapp M, Kobelt G, Kurth T, Lieb R, 604
Linde M, Ljungcrantz C, Maercker A, Melin B, Moscarelli 605
M, Musayev A, Norwood F, Preisig M, Pugliatti M, Rehm 606
J, Salvador-Carulla L, Schlehofer B, Simon R, Steinhausen 607
H-C, Stovner LJ, Vallat J-M, Van den Bergh P, den Bergh 608
PV, van Os J, Vos P, Xu W, Wittchen H-U, J¨
onsson B, & 609
Olesen J (2011) Cost of disorders of the brain in Europe 610
2010. Eur Neuropsychopharmacol,21, 718-779. 611
[4] Dorsey ER, Constantinescu R, Thompson JP, Biglan KM, 612
Holloway RG, Kieburtz K, Marshall FJ, Ravina BM, Schi- 613
fitto G, Siderowf A, & Tanner CM (2007) Projected number 614
of people with Parkinson disease in the most populous 615
nations, 2005 through 2030. Neurology,68, 384-386. 616
[5] Porter ME (2010) What is value in health care? N Engl J 617
Med, 2477-2481. 618
[6] Cheng EM, Siderowf A, Swarztrauber K, Eisa M, Lee M, 619
& Vickrey BG (2004) Development of quality of care indi- 620
cators for Parkinson’s disease. Mov Disord,19, 136-150. 621
[7] Cheng EM, TonnS, Swain-Eng R, Factor SA, Weiner WJ, & 622
Bever CT (2010) Quality improvement in neurology: AAN 623
Parkinson disease quality measures: Report of the Quality 624
Measurement and Reporting Subcommittee of the American 625
Academy of Neurology. Neurology,75, 2021-2027. 626
[8] Nijkrake MJ, Keus SHJ, Ewalds H, Overeem S, Braspen- 627
ning JCC, Oostendorp RAB, Hendriks EJM, Bloem BR, & 628
Munneke M (2009) Quality indicators for physiotherapy in 629
Parkinson’s disease. Eur J Phys Rehabil Med,45, 239-245. 630
[9] National Parkinson Foundation (2012) Parkinson’s Out- 631
comes Project: Report to the Community. 632
[10] Our Standard Sets | ICHOM – International Consortium for 633
Health Outcomes Measurement. 634
[11] Martin NE, Massey L, Stowell C, Bangma C, Briganti A, 635
Bill-Axelson A, Blute M, Catto J, Chen RC, D’Amico AV, 636
Feick G, Fitzpatrick JM, Frank SJ, Froehner M, Frydenberg 637
M, Glaser A, Graefen M, Hamstra D, Kibel A, Mendenhall 638
N, Moretti K, Ramon J, Roos I, Sandler H, Sullivan FJ, 639
Swanson D, Tewari A, Vickers A, Wiegel T, & Huland H 640
(2015) Defining a standard set of patient-centered outcomes 641
for men with localized prostate cancer. Eur Urol,67, 460- 642
467. 643
[12] Chaudhuri KR, Prieto-Jurcynska C, Naidu Y, Mitra T, 644
Frades-Payo B, Tluk S, Ruessmann A, Odin P, Macphee G, 645
Stocchi F, Ondo W, Sethi K, Schapira AHV, Martinez Cas- 646
trillo JC, & Martinez-Martin P (2010) The nondeclaration of 647
nonmotor symptoms of Parkinson’s disease to health care 648
professionals: An international study using the nonmotor 649
symptoms questionnaire. Mov Disord,25, 704-709. 650
[13] Martinez-Martin P, Rodriguez-Blazquez C, Kurtis MM, & 651
Chaudhuri KR (2011) The impact of non-motor symptoms 652
on health-related quality of life of patients with Parkinson’s 653
disease. Mov Disord,26, 399-406. 654
[14] M¨
uller B, Assmus J, Herlofson K, Larsen JP, & Tysnes O-B 655
(2013) Importance of motor vs. non-motor symptoms for 656
health-related quality of life in early Parkinson’s disease. 657
Parkinsonism Relat Disord,19, 1027-1032. 658
[15] Chaudhuri KR, Odin P, Antonini A, & Martinez-Martin P 659
(2011) Parkinson’s disease: The non-motor issues. Parkin- 660
sonism Relat Disord,17, 717-723. 661
[16] van der Eijk M, Faber MJ, Al Shamma S, Munneke M, & 662
Bloem BR (2011) Moving towards patient-centered health- 663
care for patients with Parkinson’s disease. Parkinsonism 664
Relat Disord,17, 360-364. 665
[17] Visser M, Marinus J, Stiggelbout AM, & Van Hilten 666
JJ (2004) Assessment of autonomic dysfunction in 667
Uncorrected Author Proof
10 P. de Roos et al. / Consensus Set Outcomes for Parkinson’s Disease
Parkinson’s disease: The SCOPA-AUT. Mov Disord,19,
668
1306-1312.669
[18] Chaudhuri KR, Martinez-Martin P, Schapira AHV, Stoc-670
chi F, Sethi K, Odin P, Brown RG, Koller W, Barone P,671
MacPhee G, Kelly L, Rabey M, MacMahon D, Thomas S,672
Ondo W, Rye D, Forbes A, Tluk S, Dhawan V, Bowron
673
A, Williams AJ, & Olanow CW (2006) International674
multicenter pilot study of the first comprehensive675
self-completed nonmotor symptoms questionnaire for676
Parkinson’s disease: The NMSQuest study. Mov Disord,21,
677
916-923.678
[19] Chaudhuri KR, Martinez-Martin P, Brown RG, Sethi K,679
Stocchi F, Odin P, Ondo W, Abe K, Macphee G, Macmahon680
D, Barone P, Rabey M, Forbes A, Breen K, Tluk S, Naidu
681
Y, Olanow W, Williams AJ, Thomas S, Rye D, Tsuboi Y,682
Hand A, & Schapira AHV (2007) The metric properties of683
a novel non-motor symptoms scale for Parkinson’s disease:684
Results from an international pilot study. Mov Disord,22,
685
1901-1911.686
[20] Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn
687
S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB,688
Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky689
J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D,690
Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ,691
& LaPelle N (2008) Movement Disorder Society-sponsored
692
revision of the Unified Parkinson’s Disease Rating Scale
693
(MDS-UPDRS): Scale presentation and clinimetric testing
694
results. Mov Disord,23, 2129-2170.
695
[21] Schrag A, Barone P, Brown RG, Leentjens AFG, Mcdon-
696
ald WM, Starkstein S, Weintraub D, Poewe W, Rascol O,697
Sampaio C, Stebbins GT, & Goetz CG (2007) Depression698
rating scales in Parkinson’s disease: Critique and recom-699
mendations. Mov Disord,22, 1077-1092.700
[22] Williams JR, Hirsch ES, Anderson K, Bush AL, Gold-
701
stein SR, Grill S, Lehmann S, Little JT, Margolis RL,702
Palanci J, Pontone G, Weiss H, Rabins P, & Marsh L
703
(2012) A comparison of nine scales to detect depression
704
in Parkinson disease: Which scale to use?. Neurology,78,705
998-1006.706
[23] Leentjens AFG, Dujardin K, Marsh L, Martinez-Martin P,707
Richard IH, Starkstein SE, Weintraub D, Sampaio C, Poewe
708
W, Rascol O, Stebbins GT, & Goetz CG (2008) Anxiety
709
rating scales in Parkinson’s disease: Critique and recom-710
mendations. Mov Disord,23, 2015-2025.
711
[24] Leentjens AFG, Dujardin K, Marsh L, Martinez-Martin P,
712
Richard IH, Starkstein SE, Weintraub D, Sampaio C, Poewe713
W, Rascol O, Stebbins GT, & Goetz CG (2008) Apathy and714
anhedonia rating scales in Parkinson’s disease: Critique and
715
recommendations. Mov Disord,23, 2004-2014.
716
[25] Fernandez HH, Aarsland D, F´
enelon G, Friedman JH, Marsh
717
L, Tr¨
oster AI, Poewe W, Rascol O, Sampaio C, Stebbins GT,718
& Goetz CG (2008) Scales to assess psychosis in Parkin-719
son’s disease: Critique and recommendations. Mov Disord,720
23, 484-500.721
[26] Friedman JH, Alves G, Hagell P, Marinus J, Marsh L,722
Martinez-Martin P, Goetz CG, Poewe W, Rascol O, Sam-
723
paio C, Stebbins G, & Schrag A (2010) Fatigue rating scales
724
critique and recommendations by the Movement Disorders725
Society Task Force on rating scales for Parkinson’s disease.726
Mov Disord,25, 805-822.727
[27] H¨
ogl B, Arnulf I, Comella C, Ferreira J, Iranzo A, Tilley B,728
Trenkwalder C, Poewe W, Rascol O, Sampaio C, Stebbins
729
GT, Schrag A, & Goetz CG (2010) Scales to assess sleep730
impairment in Parkinson’s disease: Critique and recommen-731
dations. Mov Disord,25, 2704-2716.732
[28] Watson GS, Cholerton BA, Gross RG, Weintraub D, 733
Zabetian CP, Trojanowski JQ, Montine TJ, Siderowf A, 734
& Leverenz JB (2013) Neuropsychologic assessment in 735
collaborative Parkinson’s disease research: A proposal 736
from the National Institute of Neurological Disorders and 737
Stroke Morris K. Udall Centers of Excellence for Parkin- 738
son’s Disease Research at the University of Pennsylvania. 739
Alzheimers. Dement,9, 609-614. 740
[29] Kulisevsky J, & Pagonabarraga J (2009) Cognitive impair- 741
ment in Parkinson’s disease: Tools for diagnosis and 742
assessment. Mov Disord,24, 1103-1110. 743
[30] Evatt ML, Chaudhuri KR, Chou KL, Cubo E, Hinson V, 744
Kompoliti K, Yang C, Poewe W, Rascol O, Sampaio C, 745
Stebbins GT, & Goetz CG (2009) Dysautonomia rating 746
scales in Parkinson’s disease: Sialorrhea, dysphagia, and 747
constipation — critique and recommendations by Move- 748
ment Disorders Task Force on Rating Scales for Parkinson’s 749
Disease. 24 635-646. 750
[31] Martinez-Martin P, Rodriguez-Blazquez C, Alvarez- 751
Sanchez M, Arakaki T, Bergareche-Yarza A, Chade A, 752
Garretto N, Gershanik O, Kurtis MM, Martinez-Castrillo 753
JC, Mendoza-Rodriguez A, Moore HP, Rodriguez-Violante 754
M, Singer C, Tilley BC, Huang J, Stebbins GT, & 755
Goetz CG (2013) Expanded and independent validation 756
of the Movement Disorder Society-Unified Parkinson’s 757
Disease Rating Scale (MDS-UPDRS). J Neurol,260,758
228-236. 759
[32] Gallagher DA, Goetz CG, Stebbins G, Lees AJ, & Schrag A 760
(2012) Validation of the MDS-UPDRS Part I for nonmotor 761
symptoms in Parkinson’s disease. Mov Disord,27, 79-83. 762
[33] Beck AT, Steer RA, & Carbin MG (1988) Psychometric 763
properties of the Beck Depression Inventory: Twenty-five 764
years of evaluation. Clin Psychol Rev,8, 77-100. 765
[34] Spielberger CD, Gorsuch RL, & Lushene R (1983) Manual 766
for the state-trait anxiety inventory. Consulting Psycholo- 767
gists’ Press. 768
[35] Koski L, Xie H, & Finch L (2009) Measuring cognition 769
in a geriatric outpatient clinic: Rasch analysis of the Mon- 770
treal Cognitive Assessment. J Geriatr Psychiatry Neurol,771
22, 151-160. 772
[36] Goetz CG, Poewe W, Rascol O, Sampaio C, Stebbins GT, 773
Counsell C, Giladi N, Holloway RG, Moore CG, Wenning 774
GK, Yahr MD, & Seidl L (2004) Movement Disorder Soci- 775
ety Task Force report on the Hoehn and Yahr staging scale: 776
Status and recommendations. Mov Disord,19, 1020-1028. 777
[37] Hoehn MM, & Yahr MD (1967) Parkinsonism: Onset, pro- 778
gression and mortality. Neurology,17, 427-442. 779
[38] McRae C, Diem G, Vo A, O’Brien C, & Seeberger L 780
(2002) Reliability of measurements of patient health status: 781
A comparison of physician, patient, and caregiver ratings. 782
Parkinsonism Relat Disord,8, 187-192. 783
[39] Martinez-Martin P, Jeukens-Visser M, Lyons KE, Sampaio 784
C, Stebbins GT, Goetz CG, & Schrag A (2011) Health- 785
related quality-of-life scales in Parkinson’sdisease: Critique 786
and recommendations. Mov Disord,26, 2371-2380. 787
[40] Jenkinson C, Fitzpatrick R, Peto V, Greenhall R, & Hyman 788
N (1997) The Parkinson’s Disease Questionnaire (PDQ- 789
39): Development and validation of a Parkinson’s disease 790
summary index score. Age Ageing,26, 353-357. 791
[41] Antonini A, Martinez-Martin P, Chaudhuri RK, Merello 792
M, Hauser R, Katzenschlager R, Odin P, Stacy M, Stocchi 793
F, Poewe W, Rascol O, Sampaio C, Schrag A, Stebbins 794
GT, & Goetz CG (2011) Wearing-off scales in Parkinson’s 795
disease: Critique and recommendations. Mov Disord,26,796
2169-2175. 797
Uncorrected Author Proof
P. de Roos et al. / Consensus Set Outcomes for Parkinson’s Disease 11
[42] Qutubuddin AA, Pegg PO, Cifu DX, Brown R, McNamee
798
S, & Carne W (2005) Validating the Berg Balance Scale for799
patients with Parkinson’s disease: A key to rehabilitation800
evaluation. Arch Phys Med Rehabil,86, 789-792.801
[43] Schlenstedt C, Brombacher S, Hartwigsen G, Weisser B,802
M¨
oller B, & Deuschl G (2015) Comparing the Fuller-
803
ton Advanced Balance Scale with the Mini-BESTest and804
Berg Balance Scale to assess postural control in patients805
with Parkinson disease. Arch Phys Med Rehabil,96,806
218-225.
807
[44] Foreman KB, Addison O, Kim HS, & Dibble LE (2011)808
Testing balance and fall risk in persons with Parkinson809
disease, an argument for ecologically valid testing. Parkin-810
sonism Relat Disord,17, 166-171.
811
[45] Morris S, Morris ME, & Lansek R (2001) Reliability of812
measurements obtained with the Timed “Up & Go” test in813
people with Parkinson disease. Phys Ther,81, 810-818.814
[46] Jenkinson C, Fitzpatrick R, Peto V, Greenhall R, & Hyman N
815
(1997) The PDQ-8: Development and validation of a short-816
form Parkinson’s disease questionnaire. PsycholHealth,12,
817
805-814.818
[47] Peto V, Jenkinson C, & Fitzpatrick R (1998) PDQ-39:819
A review of the development, validation and applica-820
tion of a Parkinson’s disease quality of life questionnaire821
and its associated measures. J Neurol 245(Suppl 1),
822
S10-S14.
823
[48] Tan LCS, Luo N, Nazri M, Li SC, & Thumboo J (2004)
824
Validity and reliability of the PDQ-39 and the PDQ-8 in
825
English-speaking Parkinson’s disease patients in Singapore.
826
Parkinsonism Relat Disord,10, 493-499.827
[49] Poletti M, Emre M, & Bonuccelli U (2011) Mild cognitive828
impairment and cognitive reserve in Parkinson’s disease.829
Parkinsonism Relat Disord,17, 579-586.830
[50] Bennett DA, Arnold SE, Valenzuela MJ, Brayne C, &
831
Schneider JA (2014) Cognitive and social lifestyle: Links832
with neuropathology and cognition in late life. Acta Neu-
833
ropathol,127, 137-150.
834
[51] Guo X, Song W, Chen K, Chen X, Zheng Z, Cao B, Huang 835
R, Zhao B, Wu Y, & Shang H-F (2013) Gender and onset 836
age-related features of non-motor symptoms of patients with 837
Parkinson’sdisease - a study from Southwest China. Parkin- 838
sonism Relat Disord,19, 961-965. 839
[52] Lipnicki DM, Sachdev PS, Crawford J, Reppermund S, 840
Kochan NA, Trollor JN, Draper B, Slavin MJ, Kang K, Lux 841
O, Mather KA, & Brodaty H (2013) Risk factors for late- 842
life cognitive decline and variation with age and sex in the 843
Sydney Memory and Ageing Study. PLoS One,8, e65841. 844
[53] Postuma RB, Arnulf I, Hogl B, Iranzo A, Miyamoto T, 845
Dauvilliers Y, Oertel W, Ju Y-E, Puligheddu M, Jennum 846
P, Pelletier A, Wolfson C, Leu-Semenescu S, Frauscher B, 847
Miyamoto M, Cochen De Cock V, Unger MM, Stiasny- 848
Kolster K, Fantini ML, & Montplaisir JY (2012) A 849
single-question screen for rapid eye movement sleep behav- 850
ior disorder: A multicenter validation study.Mov Disord,27,851
913-916. 852
[54] European Social Survey (2012) APPENDIX A4 The mea- 853
surement of legal marital and relationship status in the ESS. 854
[55] UNESCO (2011) International Standard Classification of 855
Education (ISCED) 2011, UNESCO Institute for Statistics. 856
[56] (2012) Patient Reported Outcome Measures (PROMs) in 857
England: The case-mix adjustment methodology, Depart- 858
ment of Health, prepared by the PROMs team, Policy, 859
Strategy and Finance Directorate. 860
[57] Crizzle AM, Classen S, & Uc EY (2012) Parkinson dis- 861
ease and driving: An evidence-based review. Neurology,79,862
2067-2074. 863
[58] Tennant A, Penta M, Tesio L, Grimby G, Thonnard J-L, 864
Slade A, Lawton G, Simone A, Carter J, Lundgren-Nilsson 865
A, Tripolski M, Ring H, Biering-Sørensen F, Marincek C, 866
Burger H, & Phillips S (2004) Assessing and adjusting for 867
cross-cultural validity of impairment and activity limita- 868
tion scales through differential item functioning within the 869
framework of the Rasch model: The PRO-ESOR project. 870
Med Care,42, I37-I48. 871