Strategy-based Cognitive Intervention for Parkinson Disease: A Pilot Randomized Controlled Trial
Phase: NA
Conditions: Parkinson Disease
Sponsor: Washington University School of Medicine

 
 
 
 
 
MultiContext Approach for Parkinson Disease Pilot 
(MC4PD Pilot) 
  
Protocol Number: 201906062 
National Clinical Trial (NCT) Identified Number:  NCT04048122 
Principal Investigator: Erin R. Foster 
 
Grant Title: Strategy-based cognitive intervention for Parkinson disease: A pilot 
randomized controlled trial 
Grant Number: R21 AG063974 
Funded by: NIH NIA 
Version Number:  v.5 
Date: 2021.05.18 
 
 

NIH Protocol Template for Behavioral and Social Sciences Research Involving Humans 
CONFIDENTIALITY STATEMENT 
This document is confidential communication. Acceptance of this document constitutes agreement by the 
recipient that no unpublished information contained herein will be published or disclosed without prior 
approval of the Principal Investigator or other participating study leadership and as consistent with the 
NIH terms of award.  
 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences Research Involving Humans 
Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................. 1 
INVESTIGATOR’S SIGNATURE .............................................................................................................................. 2 
1 
PROTOCOL SUMMARY ............................................................................................................................... 3 
1.1 
Synopsis ................................................................................................................................................ 3 
1.2 
Schema ................................................................................................................................................. 4 
1.3 
Schedule of Activities .......................................................................................................................... 5 
2 
INTRODUCTION ............................................................................................................................................ 6 
2.1 
Study Rationale .................................................................................................................................... 6 
2.2 
Background........................................................................................................................................... 6 
2.3 
Risk/Benefit Assessment .................................................................................................................... 8 
3 
OBJECTIVES AND ENDPOINTS ................................................................................................................ 8 
4 
STUDY DESIGN ........................................................................................................................................... 10 
4.1 
Overall Design .................................................................................................................................... 10 
4.2 
Scientific Rationale for Study Design.............................................................................................. 10 
4.3 
Justification for Intervention ............................................................................................................. 10 
4.4 
End-of-Study Definition ..................................................................................................................... 10 
5 
STUDY POPULATION ................................................................................................................................ 11 
5.1 
Inclusion Criteria ................................................................................................................................ 11 
5.2 
Exclusion Criteria ............................................................................................................................... 11 
5.3 
Lifestyle Considerations .................................................................................................................... 11 
5.4 
Screen Failures .................................................................................................................................. 11 
5.5 
Strategies for Recruitment and Retention ...................................................................................... 12 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ............................................ 12 
6.1 
Study Intervention(s) or Experimental Manipulation(s) Administration ...................................... 12 
6.1.1 
Study Intervention or Experimental Manipulation Description ................................. 12 
6.1.2 
Administration and/or Dosing ....................................................................................... 13 
6.2 
Fidelity ................................................................................................................................................. 13 
6.2.1 
Interventionist Training and Tracking .......................................................................... 13 
6.3 
Measures to Minimize Bias: Randomization and Blinding ........................................................... 14 
6.4 
Study Intervention/Experimental Manipulation Adherence.......................................................... 14 
6.5 
Concomitant Therapy ........................................................................................................................ 15 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ......................................................................................... 15 
7.1 
Discontinuation of Study Intervention/Experimental Manipulation ............................................. 15 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................................................... 15 
7.3 
Lost to Follow-Up ............................................................................................................................... 15 
8 
STUDY ASSESSMENTS AND PROCEDURES ..................................................................................... 16 
8.1 
Endpoint and Other Non-Safety Assessments .............................................................................. 16 
8.2 
Safety Assessments .......................................................................................................................... 17 
8.3 
Adverse Events and Serious Adverse Events ............................................................................... 18 
8.4 
Unanticipated Problems .................................................................................................................... 18 
9 
STATISTICAL CONSIDERATIONS .......................................................................................................... 18 
9.1 
Statistical Hypotheses ....................................................................................................................... 18 
9.2 
Sample Size Determination .............................................................................................................. 18 
9.3 
Populations for Analyses .................................................................................................................. 19 
9.4 
Statistical Analyses............................................................................................................................ 19 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences Research Involving Humans 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 20 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ........................................................... 20 
10.1.1 
Informed Consent Process ........................................................................................... 20 
10.1.2 
Study Discontinuation and Closure ............................................................................. 20 
10.1.3 
Confidentiality and Privacy ........................................................................................... 21 
10.1.4 
Safety Oversight ............................................................................................................. 21 
10.1.5 
Data Handling and Record Keeping ............................................................................ 21 
10.1.6 
Publication and Data Sharing Policy ........................................................................... 22 
10.1.7 
Conflict of Interest Policy .............................................................................................. 22 
10.2 
Protocol Amendment History ........................................................................................................... 23 
11 
REFERENCES ............................................................................................................................................. 25 
 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
1 
STATEMENT OF COMPLIANCE 
 
The trial will be carried out in accordance with International Council on Harmonisation Good Clinical 
Practice (ICH GCP) and the following:  
 
• 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR Part 
46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812).  
 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are responsible for 
the conduct, management, or oversight of NIH-funded clinical trials have completed Human Subjects 
Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form(s) must 
be obtained before any participant is consented. Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study. All changes to the consent form(s) 
will be IRB approved; a determination will be made regarding whether a new consent needs to be 
obtained from participants who provided consent, using a previously approved consent form. 
 
 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
2 
INVESTIGATOR’S SIGNATURE 
The signature below constitutes the approval of this protocol and provides the necessary assurances 
that this study will be conducted according to all stipulations of the protocol, including all statements 
regarding confidentiality, and according to local legal and regulatory requirements and applicable US 
federal regulations and ICH guidelines, as described in the Statement of Compliance above. 
 
Principal Investigator or Clinical Site Investigator: 
Signed: 
 
Date: 
08/15/2019 
 
Name:  Erin Foster 
 
Title: 
Assistant Professor in Occupational Therapy, Neurology & Psychiatry 
 
Investigator Contact Information 
Affiliation: Washington University School of Medicine 
Address: MSC 8505-66-01|4444 Forest Park Avenue| St. Louis, MO 63108 
Telephone: (314) 286-1638 
Email: erfoster@wustl.edu  
 
 
 
 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
3 
1 
PROTOCOL SUMMARY 
 
1.1 
SYNOPSIS  
 
Title: 
Strategy-based cognitive intervention for Parkinson Disease: A pilot 
randomized controlled trial. 
Aka: MultiContext Approach for Parkinson Disease (MC4PD) Pilot  
Grant Number: 
R21 AG063974 
Study Description: 
We have developed a strategy-based cognitive intervention, based on 
the MultiContext (MC) approach, to enable people with PD to apply 
strategies in their everyday lives to cope with cognitive decline and 
improve or maintain daily function. We hypothesize that this 
intervention will produce better functional outcomes compared to 
cognitive process training. This project will assess feasibility and 
treatment fidelity and generate data in preparation for a definitive 
clinical trial by conducting a single-blind pilot randomized controlled 
trial comparing the MC approach to a standard-of-care treatment 
(Control). Participants with PD without dementia (N = 60) will 
complete pre-treatment testing, randomization to treatment group, 10 
treatment sessions, and immediate and 3 months post-treatment testing.  
Objectives: 
 
Aim 1: Examine the feasibility of the MC approach for people with PD 
within an RCT. 
Aim 2: Demonstrate adequate treatment fidelity to the MC approach. 
Aim 3: Obtain preliminary estimates of the MC approach’s effect on 
patient-reported functional cognition. 
Endpoints: 
Aim 1 Endpoints: Recruitment rate (#/month); retention rate; % of 
participants completing the intervention in 12 weeks 
Aim 2 Endpoints: Therapist adherence and competence scores; Client 
Satisfaction Questionnaire; Pittsburgh Rehabilitation Participation Scale 
Aim 3: Bangor Goal Setting Interview 
Study Population: 
60 males and females over age 40 who meet criteria for typical 
idiopathic PD, are stage I-III, and do not have dementia. 
Phase or Stage: 
Stage I (generation, refinement, modification, adaptation, pilot testing) 
Sites/Facilities Enrolling 
Participants: 
Washington University School of Medicine in St. Louis   
Description of Study 
Intervention/Experimental 
Manipulation: 
Both the MC and Control intervention will consist of 10 1-1.5 hour 
sessions over 12 weeks delivered in an individual, face-to-face format 
by trained licensed occupational therapists. Both interventions involve 
collaborative client-centered goal setting, practice of cognitively 
challenging functional activities, and home practice assignments. The 
MC intervention additionally incorporates strategy training, a 
metacognitive framework, therapist mediation, and action planning.  
Study Duration: 
24 months 
Participant Duration: 
14 weeks of in-person participation with a 3 month follow-up; 26 weeks 
in total  

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
4 
1.2 
SCHEMA  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The following target interval limits will be used, expressed as “target (window)”: 
• 
Pre assessment will occur ≤ 14 days of screening for eligibility. If more than 14 days have passed, 
participants will be re-screened before enrollment. 
• 
Treatment Session 1 will occur 7 (5-14) days after the Pre assessment. 
• 
Each subsequent treatment session will occur 7 (5-9) days after the prior treatment session. 
• 
Post assessment will occur 7 (5-14) days after Treatment Session 10. 
• 
Follow-up assessment will occur 3 months (-7 days/+14 days) after Treatment Session 10. 
Keep in mind that these are targets, and this study aims to determine whether these targets are feasible 
and/or how we can improve our processes to meet them in the future. Although we aim for participants 
to have a treatment session each calendar week, the stated goal of completing the intervention within 
12 weeks allows for up to 2 missed weeks due to practical circumstances (that would be present in real-
world clinical practice) such as participant or therapist illness, travel, inclement weather, holidays, etc.  
 
 
Screen for eligibility based on inclusion & exclusion criteria; schedule Visit 1 
Randomize 
Enroll (N = 60) 
Visit 1, Week 1: Pre-treatment assessment 
(In-person) 
MC (n = 30) 
Control (n = 30) 
Visit 12, Week 14: Post-treatment assessment 
(In-person) 
Visit 13, Week 26: Follow-up assessment 
(Questionnaires via mail or web) 
Visits 2-11, Weeks 2-13: Intervention sessions 
(In-person; Visit 2 & 3 = OT evaluation; Visits 4-11 = OT Treatment) 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
5 
1.3 
SCHEDULE OF ACTIVITIES  
Notes: * Completed by blind raters based on audiotape data (therapist adherence & competence; rehab participation) or 
homework worksheet. ^ Informants also complete these measures. # Collected by web or mailed questionnaires. + Phone/blind 
version. 
 
 
Pre-
screening 
(Pre-
consent) 
Visit 1: 
Pre-
treatment 
assessment 
Intervention Sessions 
Visit  12: 
Post-
Treatment 
Assessment 
Visit 13: 
Follow-up 
Assessment 
Visit 2-3:  
OT Eval 
Visits 4-11:  
OT Treatment 
Inclusion/Exclusion criteria 
X 
X 
 
 
 
 
Informed Consent 
 
X 
 
 
 
 
Baseline Characteristics 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
Clinical characteristics 
 
X 
 
 
 
 
UPDRS III 
 
X 
 
 
 
 
NIH Toolbox Cognitive Battery 
 
X 
 
 
 
 
MoCA 
X+ 
X 
 
 
 
 
Web or mailed 
questionnaires 
MDS-UPDRS II  
 
X 
 
 
 
 
Beck Depression Inventory-II 
 
X 
 
 
 
 
Parkinson Anxiety Scale 
 
X 
 
 
 
 
Apathy Scale 
 
X 
 
 
 
 
Parkinson Fatigue Scale 
 
X 
 
 
 
 
Randomization 
 
X 
 
 
 
 
Primary Outcomes 
 
 
 
 
 
 
2a. Therapist Adherence & Proficiency* 
 
 
X 
(random 30% of sessions rated) 
 
 
2b. Client Satisfaction Questionnaire 
 
 
 
 
X# 
 
2b. Pittsburgh Rehabilitation 
Participation Scale* 
 
 
 
X 
(3 sessions/pt) 
 
 
2b. Homework adherence* 
 
 
 
X 
 
 
3. Bangor Goal Setting Interview^ 
 
 
X 
 
X# 
X# 
Secondary/Exploratory Outcomes 
 
 
 
 
 
 
Weekly Calendar Planning Activity 
 
 
X 
 
X 
 
Self-Regulation Skills Inventory 
 
 
X 
 
X 
 
NeuroQOL Cognitive Function 
 
X 
 
 
X 
X# 
NeuroQOL Participation (Ability) 
 
X 
 
 
X 
X# 
Web or mailed 
questionnaires 
Global Rating of Change 
 
 
 
 
X 
X 
PD-Cognitive Functional Rating 
Scale^ 
 
X 
 
 
X 
X 
Cognitive Self-Efficacy Scale 
 
X 
 
 
X 
X 
General Self-Efficacy Scale 
 
X 
 
 
X 
X 
Credibility & Expectancy Questionnaire 
 
 
X 
X 
(in 4 and 7) 
X# 
 
Adverse Events Reporting 
 
 
X 
X 
X 
 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
6 
2 
 
INTRODUCTION 
 
2.1 
STUDY RATIONALE  
Parkinson disease (PD) affects over 1 million Americans and causes considerable personal and 
socioeconomic costs (>$34 billion/year in the US) that are expected to rise as the population ages1. 
Cognitive impairment produces disability and reduced quality of life among non-demented people with 
PD2-4. Surgical and pharmacologic treatments for PD do not prevent or treat cognitive impairment and 
may even exacerbate the problem5-8. As such, cognitive rehabilitation treatments that mitigate its 
negative functional consequences are a top research priority8-13. Unfortunately, existing cognitive 
rehabilitative programs for PD, which focus on restoring deficient cognitive processes through process 
training (repetitive practice of tasks that challenge specific cognitive processes), have had limited effect 
on daily function10. To overcome this limitation, we take a strategy training approach. We teach people 
targeted strategies to use in everyday life to circumvent cognitive deficits and accomplish meaningful daily 
activities. Contemporary cognitive rehabilitation evidence supports this approach for people with chronic 
neurocognitive dysfunction from stroke and brain injury14-16; however, it has not been studied in PD. By 
teaching strategies for everyday cognition and using training techniques to support transfer of learning 
beyond the training context, we hypothesize that our strategy training interventions will produce better 
functional outcomes for people with PD compared to process training. 
We adapted the MultiContext (MC) Approach to enable people with PD to apply strategies in their 
everyday lives to cope with cognitive decline and improve or maintain daily function). The MC Approach 
is an individualized, community-based intervention that focuses on the attainment of personally 
meaningful functional goals using training techniques known to enhance strategy learning and transfer. 
We hypothesize that the MC Approach can enable people with PD to manage everyday cognitive 
challenges so they can perform and participate in desired activities and roles. Such an intervention could 
improve function and quality of life, reduce caregiver burden, and enhance clinical care for this 
population. This specific study is part of a rigorous developmental process designed to optimize the MC 
Approach for clinical trials and eventual translation into clinical practice. It is significant because it will 
provide us with feasibility data, fidelity enhancements, clinical trials infrastructure, experience training 
and monitoring therapists, and an estimate of treatment effect—all essential elements for efficiency, 
rigor, reproducibility, and payoff in future clinical trials as well as for implementation and sustainability in 
real-world clinical practice. 
2.2 
BACKGROUND  
We need effective cognitive interventions for people with PD. About one third of people in the earliest 
stages of PD demonstrate mild cognitive deficits—typically in memory and executive control functions—
which are attributed to frontrostriatal circuitry dysfunction due to dopamine depletion in the basal ganglia 
and prefrontal cortex5,17,18. These deficits produce disability, reduced quality of life, and restricted 
participation early in the course of PD, potentially to a larger extent than motor impairment2-4,19,20. Due 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
7 
to its negative impact on daily function and the fact that it does not respond to existing medical 
treatments, cognitive impairment is considered a major unmet need and important target for treatment 
by patients, families, practitioners, and scientists in the PD community8,9. 
Cognitive process training interventions do not improve daily function in PD. Almost all cognitive 
interventions for PD to date have taken a restorative process training approach, attempting to enhance 
underlying neural physiology and improve specific cognitive processes through practice10,21-25. Although 
this approach has produced small, specific, and short-term improvements on cognitive tests, these 
benefits do not translate to daily function10. The goal of cognitive rehabilitation is to enable people with 
cognitive dysfunction to perform and participate in meaningful everyday activities and roles15,26. Clearly, 
cognitive process training falls short of this goal for people with PD, so we should pursue a different 
approach. 
Strategy training interventions may improve daily function in PD. A strategy training approach to 
cognitive intervention provides ways to maintain task performance despite the presence of cognitive 
deficits. It involves teaching people to use metacognitive, compensatory or adaptive techniques to bypass 
cognitive processing limitations and achieve task-related goals27. Strategy training is recommended for 
those with mild (vs. more severe) cognitive decline because it requires learning, capitalizes on existing 
cognitive resources, and aims to prevent or delay functional decline27,28. Although strategy training does 
not specifically target neurodegeneration or aim to improve cognition per se (which may be unrealistic in 
the context of neurodegeneration29), it can facilitate metacognitive control and continued activity 
engagement which may promote neuroplasticity, maintain cognition, or slow cognitive decline30-32. 
Strategy training is a Practice Standard for rehabilitation of mild memory and executive function deficits 
after stroke or brain injury14, and it has a larger impact on daily function than process training in older 
adults with MCI29,33. Because people with PD-MCI have similar cognitive problems and cognitive 
rehabilitation goals as these populations, strategy training may also be beneficial for them34,35; however, 
its application in PD is very limited to date10,13. Our prior work in prospective memory supports the value 
of strategy training for non-demented people with PD for improving objective laboratory performance36 
and maintaining reported everyday performance37.  
We adapted the MultiContext (MC) Approach to teach non-demented people with PD strategies in a 
way that promotes generalization to daily function. In contrast to process training, which can produce 
skills that are tightly tied to the training context, strategy training can produce flexible skills that people 
can apply across situations if it uses training techniques that foster transfer of learned strategies to real-
world activities and goals38,39. The MC Approach includes such techniques. First, it is client-directed in that 
the person identifies his or her own treatment priorities (goals), selects the treatment session focus, 
develops strategies to test, and is considered the expert in his or her own situation. Second, it uses a 
metacognitive framework to promote awareness of deficits and teach people to use structured and 
explicit methods to solve performance problems by anticipating challenges, generating and testing 
strategies or solutions, monitoring and evaluating their effectiveness during performance, and making 
connections between activity experiences and contexts (which facilitates generalization39-42). The 
therapist role within this client-directed metacognitive approach is to guide the process of self-awareness, 
strategy generation, and generalization. The therapist does not “tell” the person what to do, but instead 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
8 
uses mediation (e.g. systematic questioning, prompts) to facilitate reflection and discovery. The above 
techniques are rooted in constructivism theories that suggest learning and transfer are enhanced when 
the learner actively engages in the process of discovering, testing, and evaluating solutions to challenging 
experiences43-46. Emerging evidence in older adults27,47,48 and neurological conditions16,49,50 increasingly 
supports the superiority of this type of approach over more directed training approaches. Finally, the MC 
Approach uses homework with action plans, which are effective tools in promoting behavior change, self-
efficacy and daily function51,52, to support strategy application in everyday life38. Our preliminary study53 
found that the MC Approach is acceptable, engaging, and may address the functional cognitive problems 
of people with PD.  
Treatment fidelity is critical to complex behavioral interventions. Treatment fidelity—methods used to 
ensure interventions are implemented as intended—is increasingly recognized as essential to behavioral 
intervention development54,55. High treatment fidelity increases the ability to attribute change (or lack 
thereof) in outcomes to the intervention per se (rather than, e.g., implementation failure), facilitates 
theory testing, improves retention, is associated with better treatment outcomes, and enhances 
reproducibility and translation of interventions from research to real-world settings56. Therefore, in 
accordance with the NIH Behavioral Change Consortium Treatment Fidelity Workgroup guidelines54,57 we 
developed processes to enhance and monitor treatment fidelity, and we will assess and optimize their 
effectiveness in this study (Aim 2). 
 
2.3 
RISK/BENEFIT ASSESSMENT  
See the Data & Safety Monitoring Plan 
3 
OBJECTIVES AND ENDPOINTS  
   
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR ENDPOINTS 
Primary 
 
 
Aim 1. Examine the 
feasibility of the MC 
Approach for people with 
PD within an RCT. 
 
 
Recruitment, 
Retention, 
Intervention 
duration 
Understanding and optimizing the procedures of an 
RCT of a complex behavioral intervention is 
necessary before evaluating outcomes58-60. We will 
track recruitment, retention, and intervention 
duration to ensure we can maintain a productive 
flow of participants and complete treatment in a 
reasonable timeframe. We will record reasons for 
attrition and examine characteristics of those who 
drop out to inform retention-enhancing strategies 
for the definitive RCT.   
Aim 2. Demonstrate 
adequate treatment 
fidelity to the MC 
Approach. 
Therapist 
Adherence & 
Proficiency; 
Participant 
Acceptance, 
Appropriate delivery (Adherence & Proficiency) is 
the foundation of treatment fidelity55,61. To achieve 
the desired outcomes of any behavioral 
intervention, participants also must “buy into” its 
principles and practices (Acceptance), actively 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
9 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR ENDPOINTS 
Receipt, & 
Enactment 
engage with the content during treatment 
(Receipt), and apply the learned skills in relevant 
real-life settings (Enactment)54,55. 
Aim 3. Obtain preliminary 
estimates of effect on 
patient-reported functional 
cognition. 
Bangor Goal 
Setting Interview 
Functional cognition—how cognitive abilities 
enable/disable function in daily activities—is the 
primary target of cognitive rehabilitation and is 
now recognized as an important outcome in PD 
cognitive research62,63. Patient-reported outcomes 
are increasingly used to measure this type of 
construct since it is not directly observable in 
research or clinical settings and because the 
patient’s experience is a key determinant of 
treatment value64. In best practice cognitive 
rehabilitation, the therapist and client collaborate 
to identify problems with functional cognition and 
set related treatment goals15,28, and progress on 
those problems/goals determines treatment 
success. To be consistent with real-world practice 
and, therefore, to facilitate future clinical 
implementation, we will use this same process to 
determine treatment effect. 
Secondary 
 
 
To obtain preliminary 
estimates of effect on 
other measures of 
functional cognition. 
Weekly Calendar 
Planning Task, Self-
regulation Skills 
Inventory, 
NeuroQOL 
Cognitive Function, 
PD-Cognitive 
Functional Rating 
Scale 
 
To obtain preliminary 
estimates of effect on self-
efficacy. 
Cognitive Self-
efficacy Scale, 
General Self-
efficacy Scale 
 
Tertiary/Exploratory  
 
 
To obtain preliminary 
estimates of effect on 
participation. 
NeuroQOL Ability 
to Participate in 
Social Roles and 
Activities 
 
 
 
 
The following criteria will be used to declare failure: 
Aim 1: Feasibility 
• 
≤ 60% retention in the study intervention 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
10 
• 
≤ 75% retention in the study (80-85% is typically considered good in behavioral trials; e.g., Abshire et al., 
2017; Coday et al., 2005) 
• 
Note: Participants excluded post-Randomization count as failures in the above retention endpoints. 
Aim 2: Fidelity 
• 
Therapist adherence to protocol: Average ≤ 75% 
• 
Therapist competence in administration: Average < 2 
• 
Participant satisfaction: Average Client Satisfaction Questionnaire score ≤ 16 
• 
Participant engagement: Average Rehabilitation Participation Scale score ≤ 3 
Aim 3: Effect 
• 
Average Bangor Goal Setting Interview Goal Attainment change of ≤ 1 with lower 95% CB below 0. 
4 
STUDY DESIGN 
 
4.1 
OVERALL DESIGN 
We will conduct a single-site, single-blind pilot RCT. Participants will complete pre-treatment assessment 
and then will be randomized to treatment arm (stratified by sex and MoCA score [25/26]65). Both arms 
will consist of 10 individualized treatment sessions within a 12-week period. In-person post-treatment 
assessment will be 1 week after intervention completion, and questionnaire follow-up will be 3 months 
after. 
See also Sections 1.1, 1.2, 2.1, 2.2, 3 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
This project will build on our prior work to assess and optimize the feasibility of the MC Approach for 
people with PD in a pilot RCT and to generate data to power a definitive RCT. This Stage I study is part of 
a rigorous developmental process designed to optimize the intervention for future efficacy or 
effectiveness trials and eventual translation into clinical practice. It will provide us with feasibility data, 
fidelity enhancements, clinical trials infrastructure, experience training and monitoring therapists, and an 
estimate of treatment effect—all essential elements for efficiency, rigor, reproducibility, and payoff in 
future clinical trials as well as for implementation and sustainability in real-world clinical practice. 
See also Sections 1.1, 1.2, 2.1, 2.2, 3 
4.3 
JUSTIFICATION FOR INTERVENTION 
Both treatments consist of 10 ~1-1.5 hour sessions over 12 weeks delivered in an individual, face-to-face 
format in participants’ homes and/or communities by trained licensed occupational therapists (OTs). Both 
are realistic and reimbursable services within our current healthcare system. 
See also Sections 2.1, 2.2, 3, 6 
4.4 
END-OF-STUDY DEFINITION 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
11 
A participant is considered to have completed the intervention if he or she has completed the baseline 
assessment and 10 intervention sessions.  
Completion of the study is defined as completion of the 3-month follow-up assessment. 
5 
STUDY POPULATION 
 
5.1 
INCLUSION CRITERIA 
Males and females over age 40 who meet criteria for typical idiopathic PD66, are stage I-III67, have 
subjective cognitive decline (SCD)68 (as defined by a positive answer to either question: Do you feel like 
your thinking skills or memory are becoming worse? Do you have problems with your thinking skills or 
memory?), and can list ≥ 1 daily cognitive challenge they wish to address. Medications should be stable 
for 4 weeks prior with no changes planned during the study. 
Rationale for cognitive criteria for entry: We will include people with SCD regardless of whether they 
meet diagnostic criteria for PD-MCI. There is no gold standard assessment of SCD, so we are using a 
common method of ascertainment based on research criteria for SCD68,69. People with SCD are an 
important target for cognitive treatment because SCD may be a more sensitive measure of cognitive 
decline than cognitive tests in high functioning or at-risk individuals68 and, in the absence of objective 
deficits, SCD predicts future development of PD-MCI70,71. Because the MC approach is client-centered, 
we hypothesize that it can meet the needs of people with SCD with or without objective cognitive 
deficits. Our preliminary study53 supports this notion, as both kinds of participants (using MoCA cutoff 
25/26)65 reported improved functional cognition from the MC approach. To begin to explore this issue 
more thoroughly in the current study, we will recruit people with SCD and then use neuropsychological 
testing to characterize cognitive status (± PD-MCI) and assess it as a potential effect modifier. This study 
is not powered to detect significant effects of this factor, but our findings will guide sampling, inform 
hypotheses, and provide preliminary data for future trials. 
5.2 
EXCLUSION CRITERIA 
Dementia according to MDS criteria72 or MoCA score < 2165, other neurological disorders (e.g., stroke), 
brain surgery (e.g., STN DBS), history of psychotic disorder or any significant current psychiatric disorder, 
or any condition that would interfere with participation (e.g. non-English speaking). 
5.3 
LIFESTYLE CONSIDERATIONS 
 
During this study, participants are asked to: 
• 
Refrain from engaging in OT or other cognitive interventions. 
5.4 
SCREEN FAILURES 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
12 
Screen failures are defined as participants who do not meet eligibility criteria upon record or phone screen 
and are not enrolled in the study.  
Individuals who are ineligible to participate in the study because of not meeting criteria that could change 
over time may be rescreened. Examples include the development of SCD or emergence of functional 
cognitive goals. 
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
 
See Recruitment & Retention and Inclusion of Women & Minorities. 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) 
 
6.1 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ADMINISTRATION 
 
6.1.1 STUDY INTERVENTION OR EXPERIMENTAL MANIPULATION DESCRIPTION 
MultiContext Approach (MC): 
This treatment focuses on improving functional performance by enhancing the generation and use of 
strategies—which can be internal (e.g., self-talk, planning) or external (e.g., checklist, alarm)—to 
circumvent cognitive processing limitations caused by PD. It uses a standardized approach across and 
within sessions for all clients while being tailored to each client’s cognitive problems and goals. The first 
two session are OT evaluation sessions designed to (1) provide the OT with a comprehensive 
understanding of the client’s functional cognition, occupational performance and participation, (2) begin 
building the client’s awareness of cognitive strengths and limitations and how they may relate to daily 
function, and (3) inform individualized goal setting and treatment planning. They involve an explanation 
of MC’s purpose and process, OT functional cognitive “diagnostic” assessments (the WCPA, SRSI, 
structured treatment activity), review of pre-treatment assessments, collaborative goal setting (BGSI), and 
assignment and review of the cognitive log homework (record and reflect on daily cognitive lapses). All 
subsequent treatment sessions consist of a review of prior sessions and learning, homework review, 
treatment activities, homework provision, and session recap. Each session’s treatment activities are 
selected collaboratively based on the client’s goals and preferences and the OT’s assessment of the client’s 
cognitive and functional status. They involve the performance of simulated functional activities with OT 
mediation and a metacognitive framework to help the client anticipate performance problems, generate 
and use strategies to support performance, evaluate and modify performance and strategy use, and 
transfer these principles to other activities. The OT’s expertise in functional cognition, task and 
performance analysis, and task manipulation and grading guides this process. Treatment activities also 
involve in-depth discussion of these issues, including making explicit connections between the simulated 
functional activities, strategies, and the client’s real-life experiences, to promote generalization of 
learning40,41. Homework consists of action plans for using the strategies generated and practiced during 
the treatment session in specific everyday life situations. Clients record instances of strategy use (or 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
13 
missed opportunities) along with their evaluation of strategy effectiveness and potential modifications on 
a structured worksheet, which is reviewed collaboratively in the next session. In this way, homework not 
only supports real-life strategy application and practice, but it also reinforces self-monitoring, self-
evaluation, problem solving, strategy self-generation, and strategy optimization. Treatment progresses 
through three general phases (1: Understand and define problems and goals, 2: Generate, execute, and 
evaluate strategies, 3: Generalize and reinforce strategy use) and increases in difficulty, but progression 
is flexible depending on the client’s goals and abilities. 
Control: 
This treatment parallels the cognitive process training used in PD to-date but with simulated functional 
tasks (vs. computer or paper & pencil tasks). It has the same basic protocol as MC, but it is therapist-
directed, and the OT does not address strategies, metacognition, generalization, or use mediation or 
action plans. Therefore, this is a standard-of-care approach that includes all but the proposed critical 
elements of MC. The OT reviews pre-treatment cognitive test scores with the client but without discussion 
to build awareness. The OT selects treatment activities based on the client’s cognitive profile and goals 
from a published set of activities designed for use in cognitive interventions73. Graded task practice with 
OT feedback on performance accuracy is used to produce neurocognitive improvement (or possibly 
independent strategy development). The OT assigns practice of specific cognitively challenging everyday 
life activities for homework (but without action plans). 
6.1.2 ADMINISTRATION AND/OR DOSING 
Both interventions consist of 10 1-1.5 hour sessions over 12 weeks delivered in an individual, face-to-face 
format in participants’ homes and/or communities by trained licensed occupational therapists (OTs). Care 
partners are also invited to participate. 
A complete intervention is defined as completion of 10 OT sessions.  
6.2 
FIDELITY 
 
6.2.1 INTERVENTIONIST TRAINING AND TRACKING 
 
Training: MC training will consist of a 2-day PI and Co-I led workshop and regular meetings. Control 
training will consist of a 1-day PI led workshop and regular meetings. Both will involve reading, didactic 
instruction, interactive discussions and activities, role-playing, and videotaped examples. Each therapist 
will observe the PI conduct treatment with 1 participant and then will conduct treatment with 1-2 
participants under PI supervision. The Co-I has extensive experience training and supervising OTs in the 
MC Approach49,74,75, and the PI has extensive experience administering it. The study OTs will have requisite 
knowledge in metacognitive strategy training and task-oriented training and clinical experience with PD.  
Supervision: We will audiotape all treatment sessions, and the PI and Co-I will review the tapes and meet 
with the therapists to reinforce training, correct problems, and discuss issues. Initially, 50% of the tapes 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
14 
will be reviewed, and the teams will have weekly meetings; this will reduce to 20% review and fewer 
meetings when appropriate56. 
Assessment: Interventionist fidelity is a primary outcome of this study (Aim 2a) and thus will be formally 
assessed. See section 8.1. 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
Participants will be randomized to treatment arm (MC, Control)* stratified by sex and MoCA score 
[25/26]65. The study statistician created a randomization process that is implemented through REDCap by 
an independent person (Meghan Campbell, PhD). Immediately after a participant completes Pre 
assessment, the tester informs Dr. Campbell, via email, of their study ID, sex, and MoCA score 
(stratification variables). Within 2 days of being informed, Dr. Campbell will use the REDCap randomizer 
to assign treatment group and will inform the corresponding therapists, via email, that a participant has 
been assigned to their group. Only Dr. Campbell and the statistician can view the randomizer and its 
results. To maintain PI blinding during therapist supervision, the participants or treatment sessions under 
discussion will not be identified by study ID. 
Personnel collecting Pre, Post and Follow-up data, which includes the study coordinator, will remain blind 
to treatment arm throughout the entirety of the study. They will not know which therapists are 
administering which intervention. Inadvertent unblinding of testers will be documented (yes/no, notes). 
Most of the outcomes, including the primary efficacy outcome (BGSI, Aim 3), are collected via computer, 
so inadvertent unblinding should not bias the data. 
Personnel responsible for rating the audio files for fidelity (Aim 2) will be blind to study purpose. Due to 
the nature of their work, they will likely come to understand that there are two general intervention 
approaches being delivered and which therapists are delivering which approach; however, having no 
knowledge of the study aims and hypotheses and clear criteria for rating should reduce any associated 
biases in their ratings.  
Participants will be aware that they have been randomly assigned to one of two interventions, but they 
will be given no information on what the other intervention entails, nor will they be informed which is the 
hypothesized “active” (MC) or Control intervention. In the Follow-up assessment, participants will be 
asked if they think they received the active or control intervention (yes/no/I don’t know with an option 
to provide an open-ended response describing why).  
*Randomization ratios over the course of the study due to therapist availability: 
• 
November 2019-December 2020 = 2:1, MC:Control 
• 
January 2021- ~2021 = 1:2, MC:Control 
• 
~July 2021- = 1:1, MC:Control 
6.4 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION ADHERENCE 
Participant engagement in and adherence to the intervention are primary outcomes of this study (Aim 2b) 
and thus will be formally assessed. 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
15 
See section 8.1 
6.5 
CONCOMITANT THERAPY 
There are no medication exclusions for this protocol. Medication information will be obtained from 
electronic medical records and confirmed with the participant at the Pre-treatment assessment. Medical 
records will be reviewed after participation to determine whether there were any changes over the course 
of the study. If so, they will be documented and potentially accounted for in analyses (exploratory). 
 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
 
7.1 
DISCONTINUATION OF STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
Participants may discontinue the study intervention before receiving 10 treatment sessions for a variety 
of reasons (e.g., adverse events, no longer interested, other obligations taking precedence). Temporary 
discontinuation of the study intervention can also be considered; however, this should not last longer 
than 3 weeks unless absolutely necessary (i.e., the COVID-19 situation). When a participant permanently 
discontinues from the study intervention but not from the study, remaining study procedures will be 
completed as indicated by the study protocol (i.e, Post-treatment assessment within 2 weeks after last 
treatment session, and Follow-up assessment 3 months after that). The reason(s) for discontinuing the 
participant from the intervention will be documented on the Participant Tracking sheet. 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Participants may withdraw voluntarily from the study or the study intervention at any time, but 
investigators will seek to minimize participant discontinuation/withdrawal from the study except for 
safety reasons. An investigator may discontinue a participant from the study for the following reasons: 
• 
Lost-to-follow up; unable to contact subject (see Section 7.3, Lost to Follow-Up) 
• 
Any event or medical condition or situation occurs such that continued collection of study data 
would not be in the best interest of the participant or might require an additional treatment that 
would confound the interpretation of the study. 
• 
The participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation. 
The reason for participant discontinuation or withdrawal from the study will be documented on the 
Master File. Because an aim of this study is to track retention and determine attrition rates to power a 
future full-scale trial, participants who discontinue/withdraw from the study will not be replaced. 
7.3 
LOST TO FOLLOW-UP 
A participant will be considered lost to follow-up if they complete at least one study visit and subsequently 
miss two consecutive study visits and are unresponsive to study contact (after at least 3 attempts).  
If a participant misses a scheduled study visit: 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
16 
• 
The OT or study coordinator will attempt to contact the participant, reschedule the missed visit, 
counsel the participant on the importance of maintaining the assigned visit schedule and ascertain 
if the participant wishes to and/or should continue in the study. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee will make every 
effort to regain contact with the participant. These contact attempts will be documented in the 
Master File.  
• 
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
8 
STUDY ASSESSMENTS AND PROCEDURES 
 
8.1 
ENDPOINT AND OTHER NON-SAFETY ASSESSMENTS 
 
A trained tester blind to treatment group will conduct Pre and Post testing while participants are on their 
regular medication (to prevent motor interference63 and best represent their function in daily life). Testing 
will occur at the same time of day to control for potential effects of dosage timing or wearing off. Follow-
up assessment will occur via web-based or mailed survey. 
Primary outcomes: 
Aim 2 
• 
Therapist fidelity: Trained raters who are blind to study purpose and treatment group will use the 
MC Fidelity Tool to perform the following ratings. Adherence: Proportion of protocol steps that 
occurred within the session will be rated as present or absent. Proficiency: Quality of delivery of 
each of MC’s critical treatment components will be rated on a 4-point scale (0=Did not occur, 
1=Little Evidence/Inadequate, 2=Emerging/Adequate, 3=Proficient; averaged for a competence 
score) with detailed guidelines for each component and anchor. The raters will rate a random 
sample (30%, n = 180) of MC and Control session audiofiles (evenly distributed across condition, 
OT, treatment session number, and study month). 
• 
Acceptance: We will administer the Client Satisfaction Questionnaire (CSQ-8)76,77 at post-
treatment via mailed or web-based survey. Items have 4-point response scales (3-4: positive, 2: 
neutral, 1: negative) and are summed for a total score; higher scores indicate higher acceptance.  
• 
Receipt: The raters will rate participants’ engagement in treatment sessions with the Pittsburgh 
Rehabilitation Participation Scale (PRPS)78 from the audiofiles (3 sessions per participant). The 
PRPS is a 6-point scale (1=None, 6=Excellent) with full descriptions of each anchor. Session scores 
are averaged for a single score, which is reliable and predictive of rehabilitation outcomes78,79.  
• 
Enactment (i.e, Adherence): The raters will code homework completion for each session (0=Did 
not do, 0.5=Partial, 1=Complete). We will sum these scores and divide by the total number of 
homework assignments (10) to yield a homework completion rate for each participant. 
Aim 3  

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
17 
• 
Functional cognition: The Bangor Goal-Setting Interview (BGSI)80,81 offers a standardized means 
of eliciting individual goals and rating goal attainment over time and has been successfully used 
in cognitive rehabilitation RCTs with older adults, including those with mild to moderate 
dementia81-83. During the first intervention session, the OT will conduct a semi-structured 
interview to gain an understanding the participant’s functional cognitive performance and 
potential problem areas and goals. Part of the participant’s first homework assignment will be to 
think further about problem areas and functional cognitive goals, and they will be provided with 
a handout and Activity Checklist to guide and document the process. At the second session, the 
OT and participant will review what was discussed in the first session and anything the participant 
wishes to add or modify. Then they will identify and set goals for 3-5 real-life functional cognitive 
problems. They and their informants will rate each of their goals for Attainment, Importance, and 
Readiness to Change on 10-point scales (e.g., Attainment: 1=Cannot do or am not doing 
successfully, 10=Can do and am doing very successfully) in the second session (Pre) and then again 
at Post and Follow-up. Goal attainment ratings are averaged to yield mean attainment scores81.   
Additional Measures:  
In addition to the primary measures above, we will collect other data to characterize participants, as 
covariates, or as exploratory/secondary outcome measures of treatment effect (see Table below). Some 
objective and informant-report measures of functional cognition will be administered as exploratory 
outcomes in this trial to assess their potential to be co-primary outcomes for the future RCT, thus 
mitigating potential limitations associated with self-report. The rater will retrieve clinical characteristics 
from electronic medical records and confirm with the participant in the Pre assessment.  
Purpose/Domain 
Measure/Description 
Baseline characteristics: 
Demographics 
e.g., age, sex, education, ethnicity/race, living/work status, comorbidities 
Clinical characteristics 
e.g., disease duration, side/type of onset, medications, Hoehn & Yahr stage 
Motor dysfunction 
Unified Parkinson Disease Rating Scale (UPDRS) Parts II & III 
Non-motor dysfunction 
Beck Depression Inventory-II; Parkinson Anxiety Scale; Apathy Scale; Fatigue 
Severity Scale 
Cognition 
Montreal Cognitive Assessment (MoCA), NIH Toolbox Cognitive Battery 
Exploratory/secondary outcomes: 
Functional cognition 
(proximal) 
Objective performance: Weekly Calendar Planning Activity84 
Functional cognition 
(proximal) 
Patient-reported: NeuroQOL Cognitive Function; PD-Cognitive Functional Rating 
Scale (PD-CFRS)85 (self & informant); Global Rating of Change86; SRSI 
Self-efficacy (proximal) 
Patient-reported: Cognitive Self-efficacy Scale; General Self-efficacy Scale87 
Participation (distal) 
Patient-reported: NeuroQOL Ability to Participate in Social 
Process measure: 
Credibility and Expectancy Questionnaire88  
 
See also Sections 1.3, 3 
8.2 
SAFETY ASSESSMENTS 
See the Data & Safety Monitoring Plan. 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
18 
8.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
See the Data & Safety Monitoring Plan.  
8.4 
UNANTICIPATED PROBLEMS 
See the Data & Safety Monitoring Plan. 
9 
STATISTICAL CONSIDERATIONS  
9.1 
STATISTICAL HYPOTHESES 
Aim 1: Examine the feasibility of the MC approach within an RCT.  
• 
H1: Study recruitment will be 4 participants/month, retention in both treatment groups will be ≥ 
85%, and ≥ 85% of participants in both groups will complete the intervention in 12 weeks. 
Aim 2: Demonstrate adequate treatment fidelity to the MC approach.  
• 
H2a: Therapists will deliver MC with good adherence (≥ 80%) and proficiency (scores ≥ 2/3, 
indicating Adequate). 
• 
H2b: MC participants will have good acceptance (CSQ-8 ≥ 24/32, indicating all positive responses), 
receipt (PRPS ≥ 4/6, indicating at least “Good”) and enactment (homework completion ≥ 80%). 
Aim 3: Obtain preliminary estimates of the MC approach’s effect on patient-reported functional 
cognition.  
• 
H3 (exploratory): MC participants will report greater improvement in functional cognition than 
Control participants immediately and 3 months after treatment. 
9.2 
SAMPLE SIZE DETERMINATION 
We will enroll 30 participants per group (N = 60). Although not required for an R21 proposal, we provide 
power analyses for our feasibility and fidelity hypotheses (Aims 1 & 2) assuming 15% attrition (see Table). 
We also estimate power for our (exploratory) pre-post comparisons of treatment effect (Aim 3). Based on 
our preliminary data (Goal Attainment Δ M = 2.4, SD = 0.97), with n = 30 per group we will be able to 
detect mean differences in change of 0.85 in Attainment (2-tailed, α = 0.05, 90% power). However, we 
want to reiterate that our reason for measuring treatment effect in this study is not to demonstrate 
efficacy but to obtain effect size estimates to power an efficacy trial. Our proposed sample size will provide 
enough information to achieve our aims and is feasible to accomplish in the timeframe of an R21. 
Confidence bounds around target thresholds assuming 15% attrition 
(for Aim 2) and 95% confidence level. 
Aim 
Outcome 
(with preliminary data source 
reference) 
Target (Lower, upper) 
1 
Recruitment and retention 
85% (73 – 93) 
2a 
Adherence (n=153 observations)61 
80% (78 - 82) 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
19 
2a 
Proficiency (n=153 observations)61 
3 (2.9 – 3.1) 
2b 
Acceptance: CSQ53 
24 (23.8 – 24.2) 
2b 
Receipt: PRPS78 
4 (3.8 – 4.2) 
2b 
Enactment: Homework completion53 
80% (75 – 85) 
9.3 
POPULATIONS FOR ANALYSES 
Our primary population for analysis of treatment effect (Aim 3) will be the Intention-to-Treat (ITT) Analysis 
Population (i.e., all randomized participants). We will also conduct Per-Protocol analyses on the subset 
considered to have completed the intervention (at least 4 treatment sessions). 
9.4 
STATISTICAL ANALYSES 
Aim 1: Examine the feasibility of the MC approach within an RCT.  
• 
H1: Study recruitment will be 4 participants/month, retention in both treatment groups will be ≥ 
85%, and ≥ 85% of participants in both groups will complete the intervention in 12 weeks. 
We will track and report recruitment, retention, intervention duration, and reasons for non-enrollment 
or attrition throughout the study period. Based on our preliminary study, we anticipate no problems in 
meeting our hypothesized thresholds. We enrolled 3 participants/month (with only 1 treating therapist 
and without an existing cohort from which to recruit), had 87.5% retention, and 85.7% of participants 
completed the intervention in the allotted timeframe53. With N=60, if we meet our retention and 
completion goals (85%), we can be 95% certain of true rates of at least 73% (see Table in Section 9.2). 
Aim 2: Demonstrate adequate treatment fidelity to the MC approach.  
• 
H2a: Therapists will deliver MC with good adherence (≥ 80%) and proficiency (scores ≥ 2/3). 
Blinded raters will rate therapist adherence and proficiency for a random sample (30%, n=180) of MC and 
Control treatment sessions. We will calculate adherence and proficiency (to MC) for each therapist; 
adherence ≥ 80% and proficiency ≥ 2 (out of 3, indicating at least “Adequate”) will be benchmarks for 
good treatment integrity. 
• 
H2b: MC participants will have good acceptance (CSQ-8 ≥ 24/32, indicating all positive responses), 
receipt (PRPS ≥ 4/6, indicating at least “Good”) and enactment (homework completion ≥ 80%). 
MC participants will complete the Client Satisfaction Questionnaire (CSQ-8) at post-treatment, and 
blinded raters will rate participants’ session participation (Pittsburgh Rehabilitation Participation Scale; 
PRPS) and homework completion. CSQ-8 scores ≥ 24, PRPS scores ≥ 4, and homework completion rates ≥ 
80% will be benchmarks for good acceptance, receipt, and enactment, respectively. 
For the Aim 2 outcomes, we will calculate mean scores ± 95% confidence bounds (CBs) and compare them 
to our stated thresholds. To assess treatment differentiation, we will compare Proficiency scores for the 
MC and Control sessions using t-tests. We can also categorize participants using cutoffs (e.g., homework: 
<50%=Poor, 50-79%=Fair, ≥80%= Good) for descriptive purposes and compare the MC and Control groups’ 
scores on outcomes using appropriate non-parametric tests. 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
20 
Aim 3: Obtain preliminary estimates of the MC approach’s effect on patient-reported functional 
cognition.  
• 
H3 (exploratory): MC participants will report greater improvement in functional cognition than 
Control participants immediately and 3 months after treatment. 
We will compare treatment effects (Goal Attainment) using mixed model repeated measures ANOVA (2: 
group X 3: time point). We chose this model because we want to use statistical contrasts to compare pre-
post and pre-follow up changes across group. We will evaluate the pattern of correlations within subjects 
and test various correlation structures as appropriate using Akaike’s information criteria and the Schwarz 
Bayesian criteria. However, our purpose is not to demonstrate efficacy, but rather to obtain effect size 
data to inform sample size calculations for a definitive RCT. To this end, we will generate mean change 
between the time points with 95% CBs. We will compare these data to the suggested minimally clinically 
important difference (≥ 2 points improvement)89 to help determine the appropriate sample size to test 
the hypothesis that, in addition to being superior to the Control treatment, MC produces a clinically 
significant effect90. We will also create a sample size table for various effect size values due to uncertainty 
of pilot estimates91. 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
10.1.1 INFORMED CONSENT PROCESS 
 
10.1.1.1 CONSENT/ASSENT 
AND 
OTHER 
INFORMATIONAL 
DOCUMENTS 
PROVIDED 
TO 
PARTICIPANTS 
See Informed Consent document 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
See the Data & Safety Monitoring Plan  
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. If the study is prematurely terminated or suspended, the Principal Investigator (PI) will promptly 
inform study participants, the Institutional Review Board (IRB), and sponsor/funding agency and will 
provide the reason(s) for the termination or suspension. Study participants will be contacted, as 
applicable, and be informed of changes to study visit schedule. 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
21 
Circumstances that may warrant termination or suspension of the study include, but are not limited to 
determination of unexpected, significant, or unacceptable risk to participants, significant protocol 
violations, or determination of futility. 
The study may resume once concerns about safety, protocol compliance, and data quality are addressed, 
and satisfy the funding agency, sponsor, IRB, Food and Drug Administration (FDA), or other relevant 
regulatory or oversight bodies (OHRP, DSMB).] 
10.1.3 CONFIDENTIALITY AND PRIVACY  
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their staff, 
the safety monitor, and funding agency and will be maintained in accordance with applicable state and 
federal laws. This confidentiality is extended to the data being collected as part of this study. Data that 
could be used to identify a specific study participant will be held in strict confidence within the research 
team. No personally-identifiable information from the study will be released to any unauthorized third 
party without prior written approval of the IRB.  
All research activities will be conducted in as private a setting as possible. The study participants’ contact 
information will be securely stored for internal use during the study. At the end of the study, all records 
will continue to be kept in a secure location for as long a period as dictated by the reviewing IRB, 
institutional policies, or sponsor/funding agency requirements. 
Participant data will be coded numerically to protect individual identity. No identifiers will be used in 
presentations or publications. All data will be stored in locked cabinets or on computers within a private 
security network protected by a Cisco PIX firewall with remote access only permitted through VPN 
connections, as per HIPAA guidelines. All key personnel involved in the design or conduct of research 
involving the human subjects will receive the required education on the protection of human research 
participants. 
Participants are asked the following question at Follow-up assessment to monitor for perceived 
confidentiality breach: 
“Do you feel that the study team has protected your privacy over the course of the study?
 
Yes/No” 
 
See also the Data Sharing Plan 
10.1.4 SAFETY OVERSIGHT 
See the Data & Safety Monitoring Plan 
10.1.5 DATA HANDLING AND RECORD KEEPING  
10.1.5.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
22 
Appropriate records will be maintained for this trial, in compliance with ICH GCP and regulatory and 
institutional requirements for the protection of confidentiality of participants. As part of participating in 
a NIH-sponsored study, the site will permit authorized representatives of the NIH, sponsor, and regulatory 
agencies to examine (and when permitted by applicable law, to copy) research records for the purposes 
of quality assurance reviews, audits, and evaluation of the study safety, progress, and data validity. 
Both paper and electronic data capture will be used for this study, and all quantitative data will ultimately 
be entered into the study’s REDCap database. Data not collected directly by REDCap (e.g., those 
administered via REDCap Survey Mode) or imported from another electronic source directly into REDCap 
(e.g., NIH Toolbox Cognitive Battery and NeuroQOL data) will be entered by trained research personnel  
using a double scoring/entry and automated discrepancy flagging protocol to minimize errors. 
Paper sources of data include some of the Pre and Post assessments, questionnaires for participants who 
opt for hard copy completion, all of the record forms and worksheets completed during the treatment 
sessions, and the treatment fidelity assessments. Electronic sources of data include electronic medical 
records (e.g., PD-related clinical characteristics), NIH Toolbox Cognitive Battery, NeuroQOL 
questionnaires, REDCap Survey Mode (web-based questionnaire delivery), and audio recordings of 
treatment sessions. 
Data collection will be the responsibility of the testers and therapists under supervision of the study 
coordinator and PI. The coordinator and PI will be responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported as well as storage and management of source data. 
Hardcopies of the study visit worksheets will be maintained for future reference but will also be scanned 
and stored in a secure, web-based location for access by research personnel. 
10.1.5.2 STUDY RECORDS RETENTION  
Data collected under this protocol will be kept for a minimum of 7 years after the study is complete, as 
per IRB policy. 
10.1.6 PUBLICATION AND DATA SHARING POLICY  
See Data Sharing Plan and Dissemination Plan 
10.1.7 CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence is critical. Therefore, any actual 
conflict of interest of persons who have a role in the design, conduct, analysis, publication, or any aspect 
of this trial will be disclosed and managed. Furthermore, persons who have a perceived conflict of interest 
will be required to have such conflicts managed in a way that is appropriate to their participation in the 
design and conduct of this trial. The university has established policies and procedures for disclosing all 
conflicts of interest and established mechanisms for the management of all reported dualities of interest.  
 
 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
23 
10.2 PROTOCOL AMENDMENT HISTORY 
The table below is intended to capture changes of versions of the protocol, including a description of the 
change and rationale. A Summary of Changes table for the current amendment is located in the Protocol 
Title Page.  
 
Version 
Date 
Description of Change  
Brief Rationale 
2 
May 2020 
Changed randomization process and 
related communication among team 
members 
To remove PI from 
randomization process and 
blind her to study group; 
minimize bias 
2 
May 2020 
All participants will undergo 10 
treatment sessions 
To ensure treatment groups are 
balanced on dose of 
intervention 
2 
May 2020 
Changed definition of screen failure 
from what was initially provided by 
this template 
Study monitor request 
2 
May 2020 
Added criteria used to declare failure 
for each aim to Objectives and 
Endpoints section 
To enhance rigor and inform 
decision-making for next steps 
2 
May 2020 
Specified target interval limits for 
timing of assessment and treatment 
sessions (see Schema) 
To enhance rigor 
2 
May 2020 
Added question to AE report form to 
monitor for psychological risks 
A stated risk of the study, 
needed to capture it 
2 
May 2020 
Added a question to the Follow-up 
assessment to monitor for perceived 
confidentiality breach 
A stated risk of the study, 
needed to capture it 
3 
Nov 2020 
Fixed Schedule of Activities table to 
indicate that inclusion/exclusion 
criteria are assessed in Visit 1 (via 
MoCA); consent form will also be 
modified to include this information 
To fix a prior inconsistency 
pointed out by study monitor 
4 
Dec 2020 
Added phone/blind MoCA to 
screening phone call 
To reduce risk of enrolling 
people who do not meet 
cognitive criteria for entry 
4 
Dec 2020 
Specified randomization ratio 
changes over course of study 
To enhance transparency 
5 
May 2021 
Added note that participants 
excluded post-randomization count 
as failures in retention endpoints 
To enhance rigor and 
transparency 
 
 
 
 
 
 
 
 
 
 
 
 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
24 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
25 
11 REFERENCES  
 
References 
 
1. 
Noyes K, Liu H, Li Y, Holloway R, Dick AW. Economic burden associated with Parkinson's disease on elderly 
Medicare beneficiaries. Mov Disord. 2006;21(3):362-372. 
2. 
Foster ER, Hershey T. Everyday executive function is associated with activity participation in Parkinson 
disease without dementia. OTJR: Occupation, Participation and Health. 2011;31(1):16-22. 
3. 
Klepac N, Trkulja V, Relja M, Babic T. Is quality of life in non-demented Parkinson's disease patients 
related to cognitive performance? A clinic-based cross-sectional study. Eur J Neurol. 2008;15(2):128-133. 
4. 
Rosenthal E, Brennan L, Xie S, et al. Association between cognition and function in patients with Parkinson 
disease with and without dementia. Mov Disord. 2010;25(9):1170-1176. 
5. 
Cools R. Dopaminergic modulation of cognitive function-implications for L-DOPA treatment in Parkinson's 
disease. Neurosci Biobehav Rev. 2006;30(1):1-23. 
6. 
Xie Y, Meng X, Xiao J, Zhang J, Zhang J. Cognitive Changes following Bilateral Deep Brain Stimulation of 
Subthalamic Nucleus in Parkinson's Disease: A Meta-Analysis. Biomed Res Int. 2016;2016:3596415. 
7. 
Leroi I, Collins D, Marsh L. Non-dopaminergic treatment of cognitive impairment and dementia in 
Parkinson's disease: a review. J Neurol Sci. 2006;248(1-2):104-114. 
8. 
Burn D, Weintraub D, Ravina B, Litvan I. Cognition in movement disorders: where can we hope to be in 
ten years? Mov Disord. 2014;29(5):704-711. 
9. 
Deane KH, Flaherty H, Daley DJ, et al. Priority setting partnership to identify the top 10 research priorities 
for the management of Parkinson's disease. BMJ Open. 2014;4(12):e006434. 
10. 
Leung IH, Walton CC, Hallock H, Lewis SJ, Valenzuela M, Lampit A. Cognitive training in Parkinson disease: 
A systematic review and meta-analysis. Neurology. 2015;85(21):1843-1851. 
11. 
Calleo J, Burrows C, Levin H, Marsh L, Lai E, York MK. Cognitive rehabilitation for executive dysfunction in 
Parkinson's disease: application and current directions. Parkinsons Dis. 2012;2012:512892. 
12. 
Hindle JV, Petrelli A, Clare L, Kalbe E. Nonpharmacological enhancement of cognitive function in 
Parkinson's disease: a systematic review. Mov Disord. 2013;28(8):1034-1049. 
13. 
Walton CC, Naismith SL, Lampit A, Mowszowski L, Lewis SJ. Cognitive Training in Parkinson's Disease. 
Neurorehabil Neural Repair. 2017;31(3):207-216. 
14. 
Cicerone KD, Langenbahn DM, Braden C, et al. Evidence-based cognitive rehabilitation: updated review of 
the literature from 2003 through 2008. Arch Phys Med Rehabil. 2011;92(4):519-530. 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
26 
15. 
Haskins EC, Cicerone K, Dams-O'Connor K, Eberle R, Langenbahn DM, Shapiro-Rosenbaum A. Cognitive 
Rehabilitation Manual: Translating Evidence-Based Recommendations into Practice. 1 ed. Reston, VA: 
ACRM Publishing; 2012. 
16. 
Skidmore ER, Dawson DR, Butters MA, et al. Strategy Training Shows Promise for Addressing Disability in 
the First 6 Months After Stroke. Neurorehabil Neural Repair. 2015;29(7):668-676. 
17. 
Foltynie T, Brayne CE, Robbins TW, Barker RA. The cognitive ability of an incident cohort of Parkinson's 
patients in the UK. The CamPaIGN study. Brain. 2004;127(Pt 3):550-560. 
18. 
Muslimovic D, Post B, Speelman JD, Schmand B. Cognitive profile of patients with newly diagnosed 
Parkinson disease. Neurology. 2005;65(8):1239-1245. 
19. 
Cahn DA, Sullivan EV, Shear PK, Pfefferbaum A, Heit G, Silverberg G. Differential contributions of cognitive 
and motor component processes to physical and instrumental activities of daily living in Parkinson's 
disease. ArchClinNeuropsychol. 1998;13(7):575-583. 
20. 
Foster ER. Instrumental activities of daily living performance among people with Parkinson's disease 
without dementia. Am J Occup Ther. 2014;68(3):353-362. 
21. 
Disbrow EA, Russo KA, Higginson CI, et al. Efficacy of tailored computer-based neurorehabilitation for 
improvement of movement initiation in Parkinson's disease. Brain Res. 2012;1452:151-164. 
22. 
Mohlman J, Chazin D, Georgescu B. Feasibility and acceptance of a nonpharmacological cognitive 
remediation intervention for patients with Parkinson disease. J Geriatr Psychiatry Neurol. 2011;24(2):91-
97. 
23. 
Sammer G, Reuter I, Hullmann K, Kaps M, Vaitl D. Training of executive functions in Parkinson's disease. 
JNeurolSci. 2006;248(1-2):115-119. 
24. 
Sinforiani E, Banchieri L, Zucchella C, Pacchetti C, Sandrini G. Cognitive rehabilitation in Parkinson's 
disease. Arch Gerontol Geriatr Suppl. 2004(9):387-391. 
25. 
Naismith SL, Mowszowski L, Diamond K, Lewis SJ. Improving memory in Parkinson's disease: a healthy 
brain ageing cognitive training program. Mov Disord. 2013;28(8):1097-1103. 
26. 
Mateer CA. Fundamentals of cognitive rehabilitation. In: Halligan PW, Wade DT, eds. The Effectiveness of 
Rehabilitation for Cognitive Deficits. Oxford: Oxford University Press; 2007:21-29. 
27. 
Mowszowski L, Lampit A, Walton CC, Naismith SL. Strategy-Based Cognitive Training for Improving 
Executive Functions in Older Adults: a Systematic Review. Neuropsychol Rev. 2016;26(3):252-270. 
28. 
Clare L, Bayer A, Burns A, et al. Goal-oriented cognitive rehabilitation in early-stage dementia: study 
protocol for a multi-centre single-blind randomised controlled trial (GREAT). Trials. 2013;14:152. 
29. 
Chandler MJ, Parks AC, Marsiske M, Rotblatt LJ, Smith GE. Everyday Impact of Cognitive Interventions in 
Mild Cognitive Impairment: a Systematic Review and Meta-Analysis. Neuropsychol Rev. 2016;26(3):225-
251. 
30. 
Rodakowski J, Reynolds CF, 3rd, Lopez OL, Butters MA, Dew MA, Skidmore ER. Developing a Non-
Pharmacological Intervention for Individuals With Mild Cognitive Impairment. J Appl Gerontol. 2016. 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
27 
31. 
Wolf TJ, Doherty M, Kallogjeri D, et al. The Feasibility of Using Metacognitive Strategy Training to Improve 
Cognitive Performance and Neural Connectivity in Women with Chemotherapy-Induced Cognitive 
Impairment. Oncology. 2016;91(3):143-152. 
32. 
Steffener J, Stern Y. Exploring the neural basis of cognitive reserve in aging. Biochim Biophys Acta. 
2012;1822(3):467-473. 
33. 
Rodakowski J, Saghafi E, Butters MA, Skidmore ER. Non-pharmacological interventions for adults with mild 
cognitive impairment and early stage dementia: An updated scoping review. Mol Aspects Med. 2015;43-
44:38-53. 
34. 
Hindle JV, Watermeyer TJ, Roberts J, et al. Cognitive rehabiliation for Parkinson's disease dementia: a 
study protocol for a pilot randomised controlled trial. Trials. 2016;17(1):152. 
35. 
Vlagsma TT, Koerts J, Fasotti L, et al. Parkinson's patients' executive profile and goals they set for 
improvement: Why is cognitive rehabilitation not common practice? Neuropsychol Rehabil. 2015:1-20. 
36. 
Foster ER, McDaniel MA, Rendell PG. Improving Prospective Memory in Persons With Parkinson Disease: 
A Randomized Controlled Trial. Neurorehabil Neural Repair. 2017;31(5):451-461. 
37. 
Goedeken S, Potempa C, Prager EM, Foster ER. Encoding strategy training and self-reported everyday 
prospective memory in people with Parkinson disease: a randomized-controlled trial. Clin Neuropsychol. 
2017:1-21. 
38. 
McDaniel MA, Bugg JM. Memory Training Interventions: What has been forgotten? J Appl Res Mem Cogn. 
2012;1(1):58-60. 
39. 
Geusgens CA, Winkens I, van Heugten CM, Jolles J, van den Heuvel WJ. Occurrence and measurement of 
transfer in cognitive rehabilitation: A critical review. J Rehabil Med. 2007;39(6):425-439. 
40. 
Salomon G, Perkins DN. Rocky roads to transfer: rethinking mechanisms of a neglected phenomenon. 
Educational Psychology. 1989;24:113-142. 
41. 
Butterfield EC, Nelson GD. Theory and practice of teaching for transfer. Educational Technology, Research 
and Development. 1989;37(3):5-38. 
42. 
Cavallini E, Dunlosky J, Bottiroli S, Hertzog C, Vecchi T. Promoting transfer in memory training for older 
adults. Aging Clin Exp Res. 2010;22(4):314-323. 
43. 
Lebeer J. Significance of the Feuerstein approach in neurocognitive rehabilitation. NeuroRehabilitation. 
2016;39(1):19-35. 
44. 
Wood D, Bruner JS, Ross G. Role of Tutoring in Problem-Solving. J Child Psychol Psychiatry. 1976;17(2):89-
100. 
45. 
Missiuna C, Malloy-Miller T, Mandich A. Mediational techniques: Origins and applications to occupational 
therapy in pediatrics. Canadian Journal of Occupational Therapy. 1998;65(4):202-209. 
46. 
Harris KR, Alexander P, Graham S. Michael Pressley's contributions to the history and future of strategies 
research. Educ Psychol. 2008;43(2):86-96. 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
28 
47. 
Dawson D, Richardson J, Troyer A, et al. An occupation-based strategy training approach to managing age-
related executive changes: a pilot randomized controlled trial. Clin Rehabil. 2014;28(2):118-127. 
48. 
Bottiroli S, Cavallini E, Dunlosky J, Vecchi T, Hertzog C. The Importance of Training Strategy Adaptation: A 
Learner-Oriented Approach for Improving Older Adults' Memory and Transfer. Journal of Experimental 
Psychology-Applied. 2013;19(3):205-218. 
49. 
Toglia J, Johnston MV, Goverover Y, Dain B. A multicontext approach to promoting transfer of strategy use 
and self regulation after brain injury: An exploratory study. Brain Inj. 2010;24(4):664-677. 
50. 
Skidmore ER, Butters M, Whyte E, Grattan E, Shen J, Terhorst L. Guided Training Relative to Direct Skill 
Training for Individuals With Cognitive Impairments After Stroke: A Pilot Randomized Trial. Arch Phys Med 
Rehabil. 2017;98(4):673-680. 
51. 
Lorig K, Laurent DD, Plant K, Krishnan E, Ritter PL. The components of action planning and their 
associations with behavior and health outcomes. Chronic Illn. 2014;10(1):50-59. 
52. 
Schwarzer R, Lippke S, Luszczynska A. Mechanisms of Health Behavior Change in Persons With Chronic 
Illness or Disability: The Health Action Process Approach (HAPA). Rehabil Psychol. 2011;56(3):161-170. 
53. 
Foster ER, Spence D, Toglia J. Feasibility of a cognitive strategy training intervention for people with 
Parkinson's disease. Disabil Rehabil. 2018;40(10):1127-1134. 
54. 
Bellg AJ, Borrelli B, Resnick B, et al. Enhancing treatment fidelity in health behavior change studies: best 
practices and recommendations from the NIH Behavior Change Consortium. Health Psychol. 
2004;23(5):443-451. 
55. 
Carroll C, Patterson M, Wood S, Booth A, Rick J, Balain S. A conceptual framework for implementation 
fidelity. Implement Sci. 2007;2:40. 
56. 
Borrelli B. The assessment, monitoring, and enhancement of treatment fidelity in public health clinical 
trials. J Public Health Dent. 2011;71 Suppl 1:S52-63. 
57. 
Borrelli B, Sepinwall D, Ernst D, et al. A new tool to assess treatment fidelity and evaluation of treatment 
fidelity across 10 years of health behavior research. J Consult Clin Psychol. 2005;73(5):852-860. 
58. 
Craig P, Dieppe P, Macintyre S, et al. Developing and evaluating complex interventions: the new Medical 
Research Council guidance. BMJ. 2008;337:a1655. 
59. 
Whyte J, Gordon W, Rothi LJ. A phased developmental approach to neurorehabilitation research: the 
science of knowledge building. Arch Phys Med Rehabil. 2009;90(11 Suppl):S3-10. 
60. 
Gitlin LN. Introducing a new intervention: an overview of research phases and common challenges. Am J 
Occup Ther. 2013;67(2):177-184. 
61. 
Hildebrand MW, Host HH, Binder EF, et al. Measuring treatment fidelity in a rehabilitation intervention 
study. Am J Phys Med Rehabil. 2012;91(8):715-724. 
62. 
Eberling J, Vincent L, Goldman JG, et al. Therapeutic Development Paths for Cognitive Impairment in 
Parkinson's Disease: Report of a Regulatory Roundtable. J Parkinsons Dis. 2014. 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
29 
63. 
Marras C, Troster AI, Kulisevsky J, Stebbins GT. The tools of the trade: a state of the art "How to Assess 
Cognition" in the patient with Parkinson's disease. Mov Disord. 2014;29(5):584-596. 
64. 
Wiklund I. Assessment of patient-reported outcomes in clinical trials: the example of health-related 
quality of life. Fundam Clin Pharmacol. 2004;18(3):351-363. 
65. 
Dalrymple-Alford JC, MacAskill MR, Nakas CT, et al. The MoCA: well-suited screen for cognitive 
impairment in Parkinson disease. Neurology. 2010;75(19):1717-1725. 
66. 
Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a 
clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992;55(3):181-184. 
67. 
Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology. 1967;17(5):427-442. 
68. 
Jessen F, Amariglio RE, van Boxtel M, et al. A conceptual framework for research on subjective cognitive 
decline in preclinical Alzheimer's disease. Alzheimers Dement. 2014;10(6):844-852. 
69. 
Mendonca MD, Alves L, Bugalho P. From Subjective Cognitive Complaints to Dementia: Who is at Risk?: A 
Systematic Review. Am J Alzheimers Dis Other Demen. 2016;31(2):105-114. 
70. 
Erro R, Santangelo G, Barone P, et al. Do subjective memory complaints herald the onset of mild cognitive 
impairment in Parkinson disease? J Geriatr Psychiatry Neurol. 2014;27(4):276-281. 
71. 
Hong JY, Sunwoo MK, Chung SJ, et al. Subjective cognitive decline predicts future deterioration in 
cognitively normal patients with Parkinson's disease. Neurobiol Aging. 2014;35(7):1739-1743. 
72. 
Emre M, Aarsland D, Brown R, et al. Clinical diagnostic criteria for dementia associated with Parkinson's 
disease. Mov Disord. 2007;22(12):1689-1707; quiz 1837. 
73. 
Toglia J. Schedule Activity Module. NY: MC CogRehab Resources LLC; 2017. 
74. 
Toglia J. The Dynamic Interactional Model of Cognition in Cognitive Rehabilitation. In: Katz N, ed. 
Cognition, Occupation, and Participation Across the Life Span: Neuroscience, Neurorehabilitation, and 
Models of Intervention in Occupational Therapy. 3 ed. Bethesda, MD: AOTA Press; 2011:161-201. 
75. 
Toglia J, Goverover Y, Johnston M, Dain B. Application of the Multicontextual Approach in promoting 
learning and transfer of strategy use in an individual with TBI and executive dysfunction. OTJR: 
Occupation, Participation and Health. 2011;31(1):S53-60. 
76. 
Attkisson CC, Zwick R. The client satisfaction questionnaire. Psychometric properties and correlations with 
service utilization and psychotherapy outcome. Eval Program Plann. 1982;5(3):233-237. 
77. 
Larsen DL, Attkisson CC, Hargreaves WA, Nguyen TD. Assessment of client/patient satisfaction: 
development of a general scale. Eval Program Plann. 1979;2(3):197-207. 
78. 
Lenze EJ, Munin MC, Quear T, et al. The Pittsburgh Rehabilitation Participation Scale: reliability and 
validity of a clinician-rated measure of participation in acute rehabilitation. Arch Phys Med Rehabil. 
2004;85(3):380-384. 
79. 
Lenze EJ, Munin MC, Quear T, et al. Significance of poor patient participation in physical and occupational 
therapy for functional outcome and length of stay. Arch Phys Med Rehabil. 2004;85(10):1599-1601. 

MC4PD Pilot 
 
Version 5  
Protocol 201906062 
 
2021.05.18 
 
NIH Protocol Template for Behavioral and Social Sciences 
Research 
 
30 
80. 
Clare L, Hindle JV, Jones IR, et al. The AgeWell study of behavior change to promote health and wellbeing 
in later life: study protocol for a randomized controlled trial. Trials. 2012;13:115. 
81. 
Clare L, Nelis SM, Kudlicka A. Bangor Goal-Setting Interview Version 2 Manual. University of Exeter2016. 
82. 
Clare L, Linden DE, Woods RT, et al. Goal-oriented cognitive rehabilitation for people with early-stage 
Alzheimer disease: a single-blind randomized controlled trial of clinical efficacy. Am J Geriatr Psychiatry. 
2010;18(10):928-939. 
83. 
Clare L, Nelis SM, Jones IR, et al. The Agewell trial: a pilot randomised controlled trial of a behaviour 
change intervention to promote healthy ageing and reduce risk of dementia in later life. BMC Psychiatry. 
2015;15:25. 
84. 
Toglia J. The Weekly Calendar Planning Activity (WCPA): A performance test of executive function. 
Bethesda, MD: AOTA Press; 2015. 
85. 
Kulisevsky J, Fernandez de Bobadilla R, Pagonabarraga J, et al. Measuring functional impact of cognitive 
impairment: validation of the Parkinson's disease cognitive functional rating scale. Parkinsonism Relat 
Disord. 2013;19(9):812-817. 
86. 
Jaeschke R, Singer J, Guyatt GH. Measurement of health status. Ascertaining the minimal clinically 
important difference. Control Clin Trials. 1989;10(4):407-415. 
87. 
Bosscher RJ, Smit JH. Confirmatory factor analysis of the General Self-Efficacy Scale. Behav Res Ther. 
1998;36(3):339-343. 
88. 
Devilly GJ, Borkovec TD. Psychometric properties of the credibility/expectancy questionnaire. J Behav Ther 
Exp Psychiatry. 2000;31(2):73-86. 
89. 
Law M, Baptiste S, Carswell A, McColl MA, Polatajko HJ, Pollack N. Canadian Occupational Performance 
Measure. 5 ed. Ottawa, ON: CAOT Publications ACE; 2014. 
90. 
Kieser M, Hauschke D. Assessment of clinical relevance by considering point estimates and associated 
confidence intervals. Pharm Stat. 2005;4(2):101-107. 
91. 
Thabane L, Ma J, Chu R, et al. A tutorial on pilot studies: the what, why and how. BMC Med Res Methodol. 
2010;10:1.