Catherine Kopil

Cognitive dysfunction is a prevalent and impactful feature of Parkinson's disease (PD), with substantial heterogeneity in onset, severity, and progression, and a high lifetime risk of dementia. Despite its clinical importance, effective treatments and fit-for-purpose outcome measures remain limited. This article reports outcomes from a multi-stakeholder roundtable convened by The Michael J. Fox Foundation for Parkinson's Research, outlining priorities to advance patient-focused endpoints and improve clinical trial design to accelerate therapeutic development for cognitive dysfunction. In the context of the current understanding of cognitive impairment across the PD/dementia with Lewy bodies (DLB) spectrum and existing neuropsychological assessment approaches, recommendations are made regarding necessary literature reviews, including qualitative data and related conceptual models, disease models including pathophysiology and neuropsychological profile, and clinical outcome assessment (COA) reviews, including content validity, psychometrics, and fitness-for-purpose. Additionally, novel conceptual models of cognitive impairment across the normal, mild cognitive impairment (MCI) and dementia spectrum are needed and may require further qualitative evidence.

Background: The patient experience of Parkinson's disease (PD) is heterogeneous, with limited prognostic tools to predict individual outcomes, leading to significant uncertainty for people with PD. Under-recognition of both psychosocial and biological drivers of fear and uncertainty in Parkinson's disease (PD) by clinicians may further contribute to patient distress. Objective: The objective of the present study is to investigate fear and uncertainty in people with PD. Methods: In-depth interviews were conducted with twenty people with PD (11 semi-structured, 9 guided/prompted). Thematic analysis organized the fears/uncertainties by topic as well as by contextual factors such as the timing of the fear (e.g., active or anticipatory; at the time of diagnosis or developed subsequent to diagnosis) and the lexicon used to describe it. Results: Participants expressed a wide range of fears and uncertainties about their future and quality of life with PD, which shifted with disease progression. Most fears were anticipatory rather than in response to current concerns. Participants reported substantial psychosocial influence from media personalities or family/friends with PD. Most participants reported that they had not disclosed their fears to their healthcare providers. Conclusions: Clinicians caring for people with PD should be aware of a range of often-unspoken fears and uncertainties, which may carry a substantial psychosocial burden. Open acknowledgement and normalization by clinicians may help patients feel less isolated in their disease.

Background: Research over the past twenty years has shown that gait outcomes have a high sensitivity for diagnosing Parkinson's disease (PD), for detecting the effects of interventions, and for monitoring disease progression, even in early disease. However, the lack of standardization in protocols and reported gait measures is impeding data aggregation across study sites and contributes to heterogeneity in the results, thus limiting the adoption of gait outcomes in clinical trials. Objective: To provide recommendations for a minimum set of gait measures to be adopted in projects evaluating people with PD to enhance standardization across the field. Methods: The Gait Advisors Leading Outcomes for Parkinson's (GALOP) committee is an advisory committee for the MJFF. Based on a five-step approach, GALOP generated recommendations for standardizing protocols that assess quantitative gait measures, following expert consensus on best practices. Results: Built on the literature and consensus amongst experts, we recommend a minimum set of meta-data to accompany gait protocols and a minimum gait assessment protocol to be performed at a comfortable speed. Suggestions on challenging testing are provided. Conclusions: To support and empower the scientific community, we have generated recommendations to collect and share gait data gathered from people with PD using an open data repository. Standardizing gait protocols and outcomes in PD has the potential of accelerating research and clinical trials, harmonizing protocols across study sites, fostering collaborations, and in the long run, improving patient care and quality of life.

The Neuronal alpha-Synuclein Disease (NSD) biological definition and Integrated Staging System (NSD-ISS) provide a research framework to identify individuals with Lewy body pathology and stage them based on underlying biology and increasing degree of functional impairment. Utilizing data from the PPMI, PASADENA and SPARK studies, we developed and applied biologic and clinical data-informed definitions for the NSD-ISS across the disease continuum. Individuals enrolled as Parkinson’s disease, Prodromal, or Healthy Controls were defined and staged based on biological, clinical, and functional anchors at baseline. Across the three studies 1,741 participants had SAA data and of these 1,030 (59%) were S+ consistent with NSD. Among sporadic PD, 683/736 (93%) were NSD, and the distribution for Stages 2B, 3, and 4 was 25%, 63%, and 9%, respectively. Median (95% CI) time to developing a clinically meaningful outcome was 8.3 (6.2, 10.1), 5.9 (4.1, 6.0), and 2.4 (1.0, 4.0) years for baseline stage 2B, 3, and 4, respectively. We propose pilot biologic and clinical anchors for NSD-ISS. Our results highlight the baseline heterogeneity of individuals currently defined as early PD. Baseline stage predicts time to progression to clinically meaningful milestones. Further research on validation of the anchors in longitudinal cohorts is necessary.

The recent advent of an “ecosystem” of shared biosample biorepositories and data sets will aid efforts to define biomarkers for Parkinson’s disease.