In Their Own Words: Fears Expressed by People with Parkinson's Disease in an Online Symptom Database.

Parkinson's disease (PD) carries substantial psychosocial burden. Using a database of responses by people with PD reporting up to five "most bothersome problems," we identified 225 fear-based verbatims, which were organized using the framework method into 26 categories. Commonly-reported fears included uncertainty of progression (n = 60, 26.7%), fear of future cognitive impairment (n = 24, 10.7%) and fear of becoming a burden on others (n = 23, 10.2%). Fears in PD are wide-ranging and can constitute the most bothersome aspect of the condition. These data can be used to design interventions to lessen the psychosocial burden of PD.

Perspectives of People At-Risk on Parkinson's Prevention Research.

 The movement toward prevention trials in people at-risk for Parkinson's disease (PD) is rapidly becoming a reality. The authors of this article include a genetically at-risk advocate with the LRRK2 G2019 S variant and two patients with rapid eye movement sleep behavior disorder (RBD), one of whom has now been diagnosed with PD. These authors participated as speakers, panelists, and moderators in the "Planning for Prevention of Parkinson's: A Trial Design Forum" hosted by Massachusetts General Hospital in 2021 and 2022. Other authors include a young onset person with Parkinson's (PwP) and retired family physician, an expert in patient engagement in Parkinson's, and early career and veteran movement disorders clinician researchers. Several themes emerged from the at-risk participant voice concerning the importance of early intervention, the legitimacy of their input in decision-making, and the desire for transparent communication and feedback throughout the entire research study process. Challenges and opportunities in the current environment include lack of awareness among primary care physicians and general neurologists about PD risk, legal and psychological implications of risk disclosure, limited return of individual research study results, and undefined engagement and integration of individuals at-risk into the broader Parkinson's community. Incorporating the perspectives of individuals at-risk as well as those living with PD at this early stage of prevention trial development is crucial to success.

Association between Subjective Cognitive Complaints and Incident Functional Impairment in Parkinson's Disease.

BACKGROUND: Early identification of subjective cognitive complaints (SCC) in Parkinson's disease (PD) may improve patient care if it predicts cognition-related functional impairment (CFI). OBJECTIVES: The aim was to determine the cross-sectional and longitudinal association between SCC and CFI in PD. METHODS: Data were obtained from Fox Insight, an online longitudinal study that collects PD patient-reported outcomes. Participants completed a PD Patient Report of Problems that asked participants for their five most bothersome disease problems. SCCs were placed into eight categories through human-in-the-loop curation and classification. CFI had a Penn Parkinson's Daily Activities Questionnaire (PDAQ-15) score ≤49. Cox proportional hazards models and Kaplan-Meier survival analyses determined if baseline SCC was associated with incident CFI. RESULTS: The PD-PROP cohort (N = 21,160) was 55.8% male, mean age was 65.9 years, and PD duration was 4.8 years. At baseline, 31.9% (N = 6750) of participants reported one or more SCCs among their five most bothersome problems, including memory (13.2%), language/word finding (12.5%), and concentration/attention (9.6%). CFI occurred in 34.7% (N = 7332) of participants. At baseline, SCC was associated with CFI (P-value <0.001). SCC at baseline was associated with incident CFI (hazard ratio [HR] = 1.58 [95% confidence interval: 1.45, 1.72], P-value <0.001), as did cognitive impairment not otherwise specified (HR = 2.31), executive abilities (HR = 1.97), memory (HR = 1.85), and cognitive slowing (HR = 1.77) (P-values <0.001). Kaplan-Meier curves showed that by year 3 an estimated 45% of participants with any SCC at baseline developed new-onset CFI. CONCLUSIONS: Self-reported bothersome cognitive complaints are associated with new-onset CFI in PD. Remote electronic assessment can facilitate widespread use of patient self-report at population scale. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Internal tremor in people with Parkinson's Disease: Demographic characteristics and comorbid symptoms.

Introduction: Internal tremor (IT) occurs in > 30 % of people with Parkinson's Disease (PwPD), but remains largely uninvestigated. Our objective was to describe demographic characteristics and associated symptoms in PwPD who reported IT. Methods: This was a matched case-control survey study. Data were from PwPD in the Fox Insight study who answered the Patient Report of Problems (PD-PROP) assessment, a series of open-ended questions that asks people to report in their own words their most bothersome PD-related problems. Cases were those who reported IT ≥ 1 times compared with PwPD controls who did not report IT and were matched 1:3 by age and disease duration. Results: 243 PwPD reported IT as a bothersome problem. Mean (SD) age of cases was 64.9 (9.4) years and disease duration was 3.8 (4.0) years. The proportion of women was greater among cases compared to controls (74 % vs 47 %, p < 0.0001). External tremor as a PD-PROP symptom was reported by 98 % cases and 48 % controls (p < 0.0001). Several non-motor symptoms were more common among cases than controls, including anxiety (35 % vs 20 %), fatigue (41 % vs 31 %), and pain (57 % vs 37 %). The odds of IT was significantly higher in women when adjusting for anxiety and motor experiences of daily living score (OR 3.07, 95 %CI 2.14-4.41, p < 0.0001). Conclusion: PwPD with IT report a range of associated symptoms, including external tremor, anxiety, and pain. Sex differences in the experience of IT may exist. Studies of IT are needed to understand its etiology and inform clinical care.

Staying hidden: The burden of stigma in PD.

BACKGROUND: Despite the myriad motor and non-motor challenges associated with Parkinson's disease (PD) diagnosis, the hidden issue of stigma may be among the most influential factors negatively affecting quality of life. A number of qualitative studies have been published assessing various aspects of stigma in PD, and quantitative studies assert that most people with PD experience stigma during the course of their disease. Stigma is associated with poorer mental and physical health, poorer quality of life, decreased levels of hope, self-esteem and self-efficacy. The resulting stigma can lead to social anxiety and isolation, reluctance to seek medical care, loneliness, depression and anxiety. Therefore, understanding what stigma is, where it comes from, and how it affects people living with PD may offer clinicians and care partners tools to help mitigate the negative effects. FOCUS: Over the past few decades, we have seen a move away from simply focusing on the effects of a disease (medical model) toward a holistic biopsychosocial approach that considers the role of environmental factors (stigma) when assessing overall well-being. We review some proactive practical suggestions to help people living with PD effectively combat the negative effects of stigma. CONCLUSION: The additional hidden burden of stigma from PD affects quality of life. Having a better understanding of the role of stigma and its impact may allow clinicians to provide proactive care and greater empathy for those living with the challenges of this disease.

What Patients Say: Large-Scale Analyses of Replies to the Parkinson's Disease Patient Report of Problems (PD-PROP).

BACKGROUND: Free-text, verbatim replies in the words of people with Parkinson's disease (PD) have the potential to provide unvarnished information about their feelings and experiences. Challenges of processing such data on a large scale are a barrier to analyzing verbatim data collection in large cohorts. OBJECTIVE: To develop a method for curating responses from the Parkinson's Disease Patient Report of Problems (PD-PROP), open-ended questions that asks people with PD to report their most bothersome problems and associated functional consequences. METHODS: Human curation, natural language processing, and machine learning were used to develop an algorithm to convert verbatim responses to classified symptoms. Nine curators including clinicians, people with PD, and a non-clinician PD expert classified a sample of responses as reporting each symptom or not. Responses to the PD-PROP were collected within the Fox Insight cohort study. RESULTS: Approximately 3,500 PD-PROP responses were curated by a human team. Subsequently, approximately 1,500 responses were used in the validation phase; median age of respondents was 67 years, 55% were men and median years since PD diagnosis was 3 years. 168,260 verbatim responses were classified by machine. Accuracy of machine classification was 95% on a held-out test set. 65 symptoms were grouped into 14 domains. The most frequently reported symptoms at first report were tremor (by 46% of respondents), gait and balance problems (>39%), and pain/discomfort (33%). CONCLUSION: A human-in-the-loop method of curation provides both accuracy and efficiency, permitting a clinically useful analysis of large datasets of verbatim reports about the problems that bother PD patients.

Self-Image in Women with Parkinson's Disease.

There is a fundamental gap in knowledge in how Parkinson's disease manifests and affects women throughout their hormonal life cycle, resulting in unmet needs and adversely impacting women's quality of life. A set of questionnaires was developed and deployed through Fox Insight (open access) to address these issues by gathering data. This is the data from the first survey. The data from the questions regarding self-image were striking. 61% of women report that their Parkinson's disease negatively impacts their self-image. Here we explore the negative impact of Parkinson's disease on women to begin to fill the gaps in knowledge.

More than a participant in trials of cell and gene therapy: Hearing the voices of people living with neurodegenerative diseases.

With the advent of novel advanced therapy medicinal products (ATMPs) for neurodegenerative diseases, their pathway to clinical trials and the therapeutic landscape has highlighted some new challenges, many of which are outlined in other chapters of this volume. The practical considerations of all these aspects from basic research and animal models through to clinical trials and eventual clinical implementation are significant. By and large, the major voices surrounding these challenges are the scientists and clinical teams who both develop the interventions and design and deliver the clinical trials to test these novel ATMPs. Their expertise is of course essential, but there is a key voice that can add considerable benefit to the pipeline, that of the lived experience of the disease being treated and the new intervention being considered. While still in their relative infancy in neurodegenerative disease, some ATMPs are already in clinical application in other disease areas, mainly cancer and inherited disorders. This more advanced status has raised some interesting questions about the role of the patient voice across all aspects of the therapeutic research and clinical delivery pipeline. This chapter highlights what has been learnt from the patient voice in their understanding and perspectives of ATMPs and in their experiences of clinical trials in neurodegenerative diseases to date. We discuss when, and how, including people living with neurodegenerative disease is of value in the development and implementation of ATMPs and the questions this collaborative effort can allow us to answer.

Multiple N-of-1 trials to investigate hypoxia therapy in Parkinson's disease: study rationale and protocol.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease, for which no disease-modifying therapies exist. Preclinical and clinical evidence suggest that hypoxia-based therapy might have short- and long-term benefits in PD. We present the contours of the first study to assess the safety, feasibility and physiological and symptomatic impact of hypoxia-based therapy in individuals with PD. METHODS/DESIGN: In 20 individuals with PD, we will investigate the safety, tolerability and short-term symptomatic efficacy of continuous and intermittent hypoxia using individual, double-blind, randomized placebo-controlled N-of-1 trials. This design allows for dose finding and for including more individualized outcomes, as each individual serves as its own control. A wide range of exploratory outcomes is deployed, including the Movement Disorders Society Unified Parkinson's Disease Rating scale (MDS-UPDRS) part III, Timed Up & Go Test, Mini Balance Evaluation Systems (MiniBES) test and wrist accelerometry. Also, self-reported impression of overall symptoms, motor and non-motor symptoms and urge to take dopaminergic medication will be assessed on a 10-point Likert scale. As part of a hypothesis-generating part of the study, we also deploy several exploratory outcomes to probe possible underlying mechanisms of action, including cortisol, erythropoietin and platelet-derived growth factor ß. Efficacy will be assessed primarily by a Bayesian analysis. DISCUSSION: This evaluation of hypoxia therapy could provide insight in novel pathways that may be pursued for PD treatment. This trial also serves as a proof of concept for deploying an N-of-1 design and for including individualized outcomes in PD research, as a basis for personalized treatment approaches. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05214287 (registered January 28, 2022).

Unmet Needs of Women Living with Parkinson's Disease: Gaps and Controversies.

Personalized medicine considering sex, gender, and cultural context has become the vanguard of delivery of care. However, women's issues in Parkinson disease (PD), especially from a psychosocial standpoint, have been an overlooked field. The key research areas include women-inclusive drug and device studies and genetic and hormonal considerations. Moreover, women with PD need to be educated and empowered on how to communicate their symptoms and needs, get engaged in research, get organized as a community, and support one another. Women with PD need tools to help track and convey their unique motor and nonmotor symptoms and psychological and social support needs. The management of PD needs to be customized to include the unique stages of women's lives, including menstrual cycles, pregnancy, perimenopause, menopause, and postmenopause. Specific guidelines for the use of hormonal treatments and customized dopamine replacement dosing need to be developed. Women need guidance on culturally sensitive wellness and self-care strategies that are customized for them. Basic core competencies in knowledge for all clinicians treating women with PD need to be established, including how to accurately diagnose, proactively identify, and treat the symptoms of PD in women and to ensure timely referral for specialty care, advanced therapies, and research studies. Caregivers and families need guidance on holistically supporting women with PD. The voices of women living with PD must be amplified to catalyze real change in this neglected field. This paper provides an overview of the current knowledge, gaps, and possible strategies to deal with the unmet needs of women living with PD with a focus on the clinical and psychosocial aspects. © 2022 International Parkinson and Movement Disorder Society.

Bringing Advanced Therapies for Parkinson's Disease to the Clinic: The Patient's Perspective.

There is an urgent unmet need in the Parkinson's disease community-advanced therapies to modify the inevitable decline that occurs in those affected by this progressive neurodegenerative disease for which there is no cure. This will require collaboration from all stakeholders and central to those partnerships are patients themselves. But participation in clinical trials and clinical use of advanced therapies have their own risk profile above and beyond standard therapeutics as evidenced by past invasive procedures. Therefore, it is of utmost importance that clear, evidence-based information about these potential treatments be clearly communicated by those exploring their use to ensure safe and informed participation from the patient community. Likewise, patients must weigh the benefits of these treatments their limitations and risks in order to truly give informed consent to participate in bringing these treatments to the clinic. Here we explore these issues from the patient perspective.

Digital Progression Biomarkers as Novel Endpoints in Clinical Trials: A Multistakeholder Perspective.

The burden of Parkinson's disease (PD) continues to grow at an unsustainable pace particularly given that it now represents the fastest growing brain disease. Despite seminal discoveries in genetics and pathogenesis, people living with PD oftentimes wait years to obtain an accurate diagnosis and have no way to know their own prognostic fate once they do learn they have the disease. Currently, there is no objective biomarker to measure the onset, progression, and severity of PD along the disease continuum. Without such tools, the effectiveness of any given treatment, experimental or conventional cannot be measured. Such tools are urgently needed now more than ever given the rich number of new candidate therapies in the pipeline. Over the last decade, millions of dollars have been directed to identify biomarkers to inform progression of PD typically using molecular, fluid or imaging modalities. These efforts have produced novel insights in our understanding of PD including mechanistic targets, disease subtypes and imaging biomarkers. While we have learned a lot along the way, implementation of robust disease progression biomarkers as tools for quantifying changes in disease status or severity remains elusive. Biomarkers have improved health outcomes and led to accelerated drug approvals in key areas of unmet need such as oncology. Quantitative biomarker measures such as HbA1c a standard test for the monitoring of diabetes has impacted patient care and management, both for the healthcare professionals and the patient community. Such advances accelerate opportunities for early intervention including prevention of disease in high-risk individuals. In PD, progression markers are needed at all stages of the disease in order to catalyze drug development-this allows interventions aimed to halt or slow disease progression (very early) but also facilitates symptomatic treatments at moderate stages of the disease. Recently, attention has turned to the role of digital health technologies to complement the traditional modalities as they are relatively low cost, objective and scalable. Success in this endeavor would be transformative for clinical research and therapeutic development. Consequently, significant investment has led to a number of collaborative efforts to identify and validate suitable digital biomarkers of disease progression.

What People with Parkinson's Disease Want.

Parkinson's disease is an incurable, progressive neurodegenerative disease. This condition is complicated by the varying symptoms in individuals who differ in age of onset, symptoms, progression of disease, response to treatment and prognosis. In this paper, we focus on quality of life achieved through a combination of comprehensive health care, continuous support, and self care. Determining what people with Parkinson's disease want is like assembling multiple puzzles simultaneously. While we surmise that patient centered care, support programs, access to comprehensive health care, and relevant symptom control are pieces of this puzzle, more longitudinal studies- which are observational in nature and correlate the impact of symptoms with patients' reported needs- are necessary.

Challenges of Improving Patient-Centred Care in Parkinson's Disease.

BACKGROUND: Parkinson's disease is a neurodegenerative condition with a complex pattern of motor and non-motor symptoms. Of several clinical scales used to measure patient experience few are delivered by patients themselves. OBJECTIVE: The present study reports the results of an online survey to establish (a) factors that most influence QoL (quality of life) for people with Parkinson's and (b) areas where self-monitoring may help. METHODS: A 27 question online survey (using Survey Monkey) was developed by The Cure Parkinson's Trust, comprising four main sections (demographics, monitoring, symptoms and communication). RESULTS: 492 patients participated. 97% felt it 'very' or 'moderately' important to understand their own Parkinson's symptoms and recognise patterns in their condition (n = 420). Although, 87% (n = 467) were interested in recording information about their Parkinson's to monitor their well-being, only 49% of respondents were actually doing so. Slowness of movement (82% n = 432) and lack of energy (61% n = 432) were the most reported motor and non-motor symptoms, respectively. These symptoms were also commonly reported to impact QoL (n = 407). In monitoring these symptoms 75% (n = 409) thought it would help improve their understanding of their condition, 64% thought it would improve their wellbeing and ability to cope, 61% thought it would improve their treatment and 59% thought it would improve communication with their healthcare team. CONCLUSION: Collectively, the data suggest that a measurement tool supporting a patient-centred care model would be a combination of objective and accurate measurement of the most bothersome symptoms for patients towards the end goal of improving patients' QoL.

Rising to the Challenges of Clinical Trial Improvement in Parkinson's Disease.

BACKGROUND: Despite an urgent need for new medications, clinical trials in Parkinson's have a relatively low rate of success. Although many reasons have been proposed for this, the opinions of patients and scientists, the two principal stakeholders, have not been widely canvassed. OBJECTIVE: The objective of the present study was to establish the main barriers to clinical trials success in Parkinson's, as perceived by people with Parkinson's and those engaged in conducting clinical trials in Parkinson's. METHOD: Three hundred and three people (303) with a connection to Parkinson's completed an online four-item questionnaire, directed towards discovering the barriers that interfere with the establishment of effective clinical trials. RESULTS: 87% of respondents were patients and their care partners and 11% were medical professionals involved with clinical research. In the survey, those involved in conducting research cited insufficient financial and administrative support as the biggest obstacles to carrying out effective clinical trials. For responders with Parkinson's, the principal barrier to their participation in medical research was fear of potential adverse consequences and misconceptions regarding the clinical trial system as a whole, issues rooted in a perceived lack of communication of relevant information between the research and patient communities. CONCLUSIONS: Areas for future improvement as highlighted by this survey and debated at the Rallying to the Challenge meeting of people with Parkinson's (PwP) at the Van Andel Research Institute that followed included recommendations in the areas of communication, education, funding, recruitment and compliance.