Genetic and phenotypic characterization of Parkinson's disease at the clinic-wide level.

Observational studies in Parkinson's disease (PD) deeply characterize relatively small numbers of participants. The Molecular Integration in Neurological Diagnosis Initiative seeks to characterize molecular and clinical features of every PD patient at the University of Pennsylvania (UPenn). The objectives of this study are to determine the feasibility of genetic characterization in PD and assess clinical features by sex and GBA1/LRRK2 status on a clinic-wide scale. All PD patients with clinical visits at the UPenn PD Center between 9/2018 and 12/2022 were eligible. Blood or saliva were collected, and a clinical questionnaire administered. Genotyping at 14 GBA1 and 8 LRRK2 variants was performed. PD symptoms were compared by sex and gene groups. 2063 patients were approached and 1,689 (82%) were enrolled, with 374 (18%) declining to participate. 608 (36%) females were enrolled, 159 (9%) carried a GBA1 variant, and 44 (3%) carried a LRRK2 variant. Compared with males, females across gene groups more frequently reported dystonia (53% vs 46%, p = 0.01) and anxiety (64% vs 55%, p < 0.01), but less frequently reported cognitive impairment (10% vs 49%, p < 0.01) and vivid dreaming (53% vs 60%, p = 0.01). GBA1 variant carriers more frequently reported anxiety (67% vs 57%, p = 0.04) and depression (62% vs 46%, p < 0.01) than non-carriers; LRRK2 variant carriers did not differ from non-carriers. We report feasibility for near-clinic-wide enrollment and characterization of individuals with PD during clinical visits at a high-volume academic center. Clinical symptoms differ by sex and GBA1, but not LRRK2, status.

Novel computerized measure of apathy associates with care partner burden and instrumental activities of daily living in Parkinson's disease.

BACKGROUND: Impairment in goal-directed behavior (GDB) contributes to apathy, a prevalent syndrome in Parkinson's disease (PD). The Philadelphia Apathy Computerized Task (PACT) is a performance-based measure of GDB that may be less confounded by reduced patient insight, cognitive impairment, and care partner burnout. OBJECTIVE: To examine how the PACT is related to patient function and care partner burden. METHODS: PD patients with normal cognition (n = 19) or mild cognitive impairment (n = 14) and their care partners were recruited. Participants completed the PACT, a computerized paradigm consisting of subtasks specific to each component of GDB: initiation, motivation, and planning. Care partners completed the Zarit Burden Interview (ZBI) and the Penn Parkinson's Daily Activities Questionnaire (PDAQ-15). The associations between mean latency on each PACT subtask and ZBI and PDAQ-15 scores, respectively, were tested using Spearman's rank correlation coefficients. Significant associations were further delineated using multivariate regression with the following covariates: age, years of education, MoCA score, daily levodopa equivalency dose, UPDRS Part III score, and GDS-15 score. RESULTS: Worse performance on the planning subtask of the PACT related to higher ZBI scores and lower PDAQ-15 scores when adjusting for covariates. Decreased initiation was associated with higher ZBI and decreased motivation with lower PDAQ-15. CONCLUSIONS: Specific components of the PACT are related to patient and care partner outcomes in PD. The main advantage of this measure is to minimize the confounds of poor insight and care partner distress. We propose future research directions to refine the PACT for potential use in research and clinical practice.

Ethnoracial differences for caregiving burden in Parkinson's disease.

INTRODUCTION: Caregivers play an important role in Parkinson's disease (PD) treatment, especially as the disease progresses. As the symptom profile and needs of people with PD (PwP) differ across ethnoracial groups, whether caregiving needs also differ for different ethnoracial groups should be investigated. METHODS: Data were obtained from the Parkinson's Foundation funded Parkinson's Outcomes Project for PwP identifying as Hispanic (n = 495), non-Hispanic Asian (n = 170), non-Hispanic Black (n = 162), or non-Hispanic White (n = 7687). Cross-sectional and longitudinal total Multidimensional Caregiver Strain Index (MCSI) and domain-specific scores for caregiving burden were compared across the ethnoracial groups. Effect of demographics and clinical variables, interaction of these variables with ethnoracial groups for caregiver burden was assessed. RESULTS: Care partners of PwP identifying as non-Hispanic Asian experienced the most burden. PwP identifying as non-Hispanic White were oldest, yet their care partners experienced the least burden. Care partners of PwP identifying as non-Hispanic Asian experienced more burden in physical and social domains, care partners of PwP identifying as Hispanic experienced more burden in financial and elder demanding/manipulative domains. Over time, burden increased similarly across the ethnoracial groups. Effect of frequency of falls, hospital admission, neuropsychiatric disorder and social support on burden over time differed across the groups. CONCLUSION: PwP from different ethnoracial groups can experience different levels of caregiving burden. Predictors for caregiving burden, such as social support and falls can have different impacts based on ethnicity and race. Caregiver needs should also be assessed and culturally competent support should be provided to benefit all affected by PD.

Unique characteristics of end-of-life hospitalizations in Parkinson disease.

Introduction: Persons with Parkinson disease (PD) are hospitalized at higher rates, have longer lengths of stay, and are more likely to die in the hospital than age-matched peers. Although prior studies have compared inpatient outcomes between persons with and without PD, little is known about inpatient outcomes across the PD trajectory, or whether hospitalizations occurring in the last 6 months of life differ from earlier hospitalizations. Methods: This cross-sectional study compared Medicare Part A and B beneficiaries aged 65 and older with a qualifying PD diagnosis who were hospitalized in 2017: decedents who died between 7/1/2017 and 12/31/2017 from all causes and were hospitalized at least once in their last 6 months of life, and non-decedents who were hospitalized between 1/1/2017 and 6/30/2017 and lived 6 or more months after discharge. End-of-life (EoL) hospitalizations were defined as those occurring in the last 6 months of life. Descriptive analyses compared patient-level variables (e.g., demographics, comorbidities, treatment intensity) and encounter-level variables (e.g., length of stay, total charges) between groups. Multivariable logistic regression models also compared rates of intensive care unit (ICU) admission and 30-day readmission between hospitalized decedents and hospitalized non-decedents, adjusting for age, sex, race/ethnicity, rural residence, and Charlson Comorbidity Index Score. Results: Of 26,492 Medicare decedents with PD, 16,187 (61.1%) were hospitalized in their last 6 months of life. Of 347,512 non-decedents with PD, 62,851 (18.1%) were hospitalized in a 6-month period. Hospitalized decedents were slightly older than hospitalized non-decedents (82.3 [SD 7.40] vs. 79.5 [SD 7.54] years) and had significantly more comorbidities. Compared to non-EoL hospitalizations, EoL hospitalizations were slightly longer (5 [IQR 3-9] vs. 4 [IQR 3-7] days) and more expensive based on total charges per admission ($36,323 [IQR 20,091-69,048] vs. $32,309 [IQR 18,789-57,756]). In covariate-adjusted regression models using hospitalized non-decedents as the reference group, hospitalized decedents were more likely to experience an ICU admission (AOR 2.36; CI 2.28-2.45) and 30-day readmission (AOR 2.43; CI 2.34-2.54). Discussion: Hospitalizations occurring in the last 6 months of life among persons with PD in the United States are longer, more costly, and more resource intensive than earlier hospitalizations and may stem from medical comorbidities. Once hospitalized, ICU admission and 30-day readmission may aid in prognostication and serve as markers of transition to the EoL period.

Parkinson's Pals: A Student-Led Program to Facilitate Intergenerational Connections and Promote Psychosocial Well-Being Among Persons with Parkinson's Disease.

Parkinson's disease (PD) causes unique motor and non-motor symptoms. Despite symptomatic treatment with pharmacotherapies, many persons with PD report feelings of loneliness and demoralization as their disease progresses. These symptoms greatly interfere with quality of life, necessitating novel treatment strategies. In this report, we introduce a new student-led program to improve psychosocial well-being among persons with PD by pairing them with college students. Through weekly one-on-one meetings, students gain a deeper understanding of PD, while patients gain a new social outlet and purpose. Based on the program's initial successes, we advocate for the adoption of similar programs at universities worldwide.

Association of Caregiver Depression Risk With Patient Outcomes in Parkinson Disease.

Importance: Caregivers are integral to Parkinson disease (PD) care, but little information exists regarding how caregivers impact patient outcomes. Objective: To assess the association between caregivers reporting depression symptoms and patient quality of life (QOL), emergency department (ED) visits, and hospitalizations. Design, Setting, and Participants: This retrospective cohort study was conducted at 15 Parkinson's Foundation Centers of Excellence within the US. The Parkinson's Foundation Parkinson Outcomes Project registry was used to collect baseline data from January 1, 2016, to December 31, 2018, with subsequent annual study visits through July 31, 2020. Data were analyzed from August 5, 2020, to June 9, 2023. A convenience sample of 454 patients with PD and their caregivers was recruited during routine clinical visits with movement disorder specialists. Patients with a physician diagnosis of idiopathic PD who lived at home and had 1 or more follow-up study visits were included. Exposure: Caregiver depression symptoms using the Center for Epidemiologic Studies Depression Scale. Main Outcomes and Measures: Patient health-related QOL (measured by the 39-item Parkinson Disease Questionnaire), number of annual ED visits, and number of annual hospitalizations were measured. The independent association between caregivers reporting depression symptoms and patient outcomes was assessed using linear mixed-effects and Poisson regression models. The a priori hypotheses were that a greater number of depression symptoms reported via the Center for Epidemiologic Studies Depression Scale would be associated with worse patient QOL and a greater number of ED visits and hospitalizations. Results: Among 454 patient-caregiver dyads (patients: mean [SD] age, 67.3 [8.4] years; 320 men [70.5%]; caregivers: mean [SD] age, 65.9 [8.7] years; 326 women [71.8%]), the mean (SD) follow-up was 2.0 (1.4) study visits. Greater depression symptoms among caregivers were associated with worse patient QOL as measured by the Parkinson Disease Questionnaire (mean [SD] score, 33.78 [17.71], on a scale of 0-100, with higher scores indicating worse QOL, among patients with caregivers who had depression symptoms vs 24.50 [14.19] among patients with caregivers who did not have depression symptoms; ß = 0.43; 95% CI, 0.28-0.58; P < .001) and more annual ED visits (ß = 0.02; 95% CI, 0 to 0.04; P = .03) but not more hospitalizations (ß = 0.02; 95% CI, -0.01 to 0.03; P = .10). Conclusions and Relevance: In this cohort study, patients with PD who had caregivers at higher risk of depression were more likely to have worse QOL and higher ED use than patients who had caregivers not at higher risk of depression. Additional caregiving resources and interventions to reduce caregiver depression symptoms could potentially improve patient outcomes.

Validation of the Rainbow Model of Integrated Care Measurement Tool in Parkinson's Disease.

BACKGROUND: Integrated care is essential for improving the management and health outcomes for people with Parkinson's disease (PD); reliable and objective measures of care integration are few. OBJECTIVE: The aim of this study was to test the psychometric properties of the Rainbow Model of Integrated Care Measurement Tool (RMIC-MT, provider version) for healthcare professionals involved in PD care. METHODS: A cross-sectional survey was administered online to an international network representing 95 neurology centers across 41 countries and 588 healthcare providers. Exploratory factor analysis with principal axis extraction method was used to assess construct validity. Confirmatory factor analysis was used to evaluate model fit of the RMIC-MT provider version. Cronbach's alpha was used to assess the internal consistency reliability. RESULTS: Overall, 371 care providers (62% response rate) participated in this study. No item had psychometric sensitivity problems. Nine factors (professional coordination, cultural competence, triple aims outcome, system coordination, clinical coordination, technical competence, community-centeredness, person-centeredness, and organizational coordination) with 42 items were determined by exploratory factor analysis. Cronbach's alpha ranged from 0.76 (clinical coordination) to 0.94 (system coordination) and showed significant correlation among all items in the scale (>0.4), indicating good internal consistency reliability. The confirmatory factor analysis model passed most goodness-of-fit tests, thereby confirming the factor structure of nine categories with a total of 40 items. CONCLUSIONS: The results provide evidence for the construct validity and other psychometric properties of the provider version of the RMIC-MT to measure integrated care in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Racial and Ethnic Disparities in Parkinson Disease: A Call to Action.

Health disparities are pervasive in the United States. In the field of Parkinson disease (PD), profound racial and ethnic disparities exist in diagnosis, treatment, and research participation, leading to differential health outcomes and lack of generalizable research data. Racial and ethnic disparities not only limit our understanding of this complex heterogeneous disorder but also hamper our ability to provide new evidence-based care for America's most vulnerable populations. In this report, we summarize findings from our comprehensive white paper for the Michael J. Fox Foundation that reviews the current state of knowledge on racial and ethnic disparities in PD care in the following areas: epidemiology, etiology, phenotype and diagnosis, treatment, and research. We also identify knowledge gaps and necessary policy changes to ensure equitable, high-value care for all persons with PD. These strategies are designed to help identify and reduce health disparities among persons with PD and may serve as a model for other neurologic diseases.

Racial and Ethnic Differences in Health-Related Quality of Life for Individuals With Parkinson Disease Across Centers of Excellence.

BACKGROUND AND OBJECTIVES: Racial and ethnic minorities have been underrepresented in Parkinson disease (PD) research, limiting our understanding of treatments and outcomes across all non-White groups. The goal of this research is to investigate variability in health-related quality of life (HRQoL) and other outcomes in patients with PD across different races and ethnicities. METHODS: This was a retrospective, cross-sectional and longitudinal, cohort study of individuals evaluated at PD Centers of Excellence. A multivariable regression analysis adjusted for sex, age, disease duration, Hoehn and Yahr (H&Y) stage, comorbidities, and cognitive score was used to investigate differences between racial and ethnic groups. A multivariable regression with skewed-t errors was performed to assess the individual contribution of each variable to the association of 39-item PD Questionnaire (PDQ-39) with race and ethnicity. RESULTS: A total of 8,514 participants had at least 1 recorded visit. Most of them (90.2%) self-identified as White (n = 7,687), followed by 5.81% Hispanic (n = 495), 2% Asians (n = 170), and 1.9% African American (n = 162). After adjustment, total PDQ-39 scores were significantly higher (worse) in African Americans (28.56), Hispanics (26.62), and Asians (25.43) when compared with those in White patients (22.73, p < 0.001). This difference was also significant in most PDQ-39 subscales. In the longitudinal analysis, the inclusion of cognitive scores significantly decreased the strength of association of the PDQ-39 and race/ethnicity for minority groups. A mediation analysis demonstrated that cognition partially mediated the association between race/ethnicity and PDQ-39 scores (proportion mediated 0.251, p < 0.001). DISCUSSION: There were differences in PD outcomes across racial and ethnic groups, even after adjustment for sex, disease duration, HY stage, age, and some comorbid conditions. Most notably, there was worse HRQoL among non-White patients when compared with White patients, which was partially explained by cognitive scores. The underlying reason for these differences needs to be a focus of future research.

The Impact of the COVID-19 Pandemic on Care Partners of People with Parkinson's Disease.

Background: Since the onset of the coronavirus disease 2019 pandemic, the caregiving routine for care partners of people with Parkinson's disease (PwPD) changed substantially. Objectives: To understand the nature and severity of burden in care partners of PwPD during the ongoing pandemic. We also sought to describe care partners' perceived change in burden and factors associated with increased burden. Methods: Cross-sectional online questionnaire-based study among care partners of PwPD, registered in the Fox Insight study. The questionnaire consisted of the Modified Caregiver Strain Index, whether an aspect of strain had changed over the course of the pandemic and additional pandemic-specific infection and lifestyle-related items. Results: Two hundred seventy-three non-paid primary care partners responded to the questionnaire, 73% female with a median age at enrollment of 64 years, 56% reporting a household income greater than 75,000 USD per year, and 61% retired. An increase in burden compared to before the pandemic was prevalent, ranging from 33% to 63% for individual items. Emotional strain increased most frequently (63%). Decreases in burden were uncommon; work adjustments (7%) and time demands (6%) decreased most frequently. PD-related factors and care partner roles in personal care of the PwPD were the factors that were associated with strain in multivariable analysis, whereas social and pandemic-related factors were not. Conclusion: In this affluent and mostly retired cohort, increases in emotional strain during the pandemic were prevalent. Despite this, caregiving roles in personal care and severity of symptoms in the PwPD were more strongly associated with strain than social and pandemic-related factors.

Adverse Childhood Experiences in Patients With Neurologic Disease.

Background and Objectives: To describe the prevalence of high adverse childhood experiences (ACEs) among neurology outpatients and determine their association with health care utilization rates and comorbid medical and psychiatric disease. Methods: This was a cross-sectional study of adults seen for outpatient neurology follow-up at the University of Pennsylvania. Participants completed the ACE questionnaire and depression/anxiety screenings. Health care utilization metrics (emergency department [ED] visits, hospitalizations, and outpatient calls) were obtained for all participants. High ACE scores were defined as a score of ≥4. The prevalence of high ACE scores in our cohort was compared with US historical controls. Statistical associations were adjusted for age, sex, and race/ethnicity. Results: One hundred ninety-eight patients were enrolled in the study. Neurology patients were more likely to have elevated ACE scores compared with US population estimates (23.7% vs 12.6%, p < 0.01). High ACE scores were associated with increased ED utilization (odds ratio [OR] = 21, 95% CI [5.8-76.0], p < 0.01), hospitalizations (OR = 5.2, 95% CI [1.7-15.0], p < 0.01), and telephone encounters (OR 3, 95% CI [1.1-8.2], p < 0.05). High ACEs were also associated with medical and psychiatric comorbidities (OR 5.8, 95% CI [2.0-17.0], p < 0.01 and OR 4.5, 95% CI [2.1-9.6], p < 0.01) and high depression and anxiety scores (OR = 6.9, 95% CI [2.8-17.0], p < 0.01, and OR = 4.3, [95% CI 1.7-11.0], p < 0.01). Discussion: Patients with neurologic conditions are more likely to have high ACEs than the US population, which was associated with higher rates of health care utilization, increased number of medical and psychiatric comorbidities, and higher anxiety and depression scores. Addressing ACEs may be a way to improve the health outcomes of patients with neurologic conditions.

Non-tremor motor dysfunction in Lewy body dementias is associated with AD biomarkers.

Motor features of Parkinson's disease (PD) are heterogeneous and well-studied; non-tremor features of postural instability and gait dysfunction (PIGD) have been linked to worse outcomes and Alzheimer's disease (AD) co-pathology. However, these features are understudied in Lewy body dementias (LBD). Here we perform retrospective analysis of a unique cohort of LBD (n = 30) with Unified Parkinson's Disease Rating Scale (UPDRS) data collected at baseline in proximity to cerebrospinal fluid collection to test the hypothesis that LBD patients with a positive AD biomarker profile (LBD + AD = 13) would have higher PIGD burden compared with LBD patients without AD biomarker positivity (LBD-AD = 17). We find novel evidence for selective impairment of PIGD burden in LBD + AD vs LBD-AD (OR = 1.95, 95%CI = 1.02-3.70, p = 0.04) and a direct association of increasing CSF tau/Aß1-42 ratio with increasing PIGD disability in the total cohort (ß = 0.23, SE = 0.08, p = 0.01). This unique biomarker stratification approach suggests AD co-pathology may contribute to PIGD motor signs in LBD.

Sex-Related Longitudinal Change of Motor, Non-Motor, and Biological Features in Early Parkinson's Disease.

BACKGROUND: Investigation of sex-related motor and non-motor differences and biological markers in Parkinson's disease (PD) may improve precision medicine approach. OBJECTIVE: To examine sex-related longitudinal changes in motor and non-motor features and biologic biomarkers in early PD. METHODS: We compared 5-year longitudinal changes in de novo, untreated PD men and women (at baseline N = 423; 65.5%male) of the Parkinson's Progression Markers Initiative (PPMI), assessing motor and non-motor manifestations of disease; and biologic measures in cerebrospinal fluid (CSF) and dopamine transporter deficit on DaTscanTM uptake. RESULTS: Men experienced greater longitudinal decline in self-reported motor (p < 0.001) and non-motor (p = 0.009) aspects of experiences of daily living, such that men had a yearly increase in MDS-UPDRS part II by a multiplicative factor of 1.27 compared to women at 0.7, while men had a yearly increase in MDS-UPDRS part I by a multiplicative factor of 0.98, compared to women at 0.67. Compared to women, men had more longitudinal progression in clinician-assessed motor features in the ON medication state (p = 0.010) and required higher dopaminergic medication dosages over time (p = 0.014). Time to reach specific disease milestones and longitudinal changes in CSF biomarkers and DaTscanTM uptake were not different by sex. CONCLUSION: Men showed higher self-assessed motor and non-motor burden of disease, with possible contributions from suboptimal dopaminergic therapeutic response in men. However, motor features of disease evaluated with clinician-based scales in the OFF medication state, as well as biological biomarkers do not show specific sex-related progression patterns.

Current Knowledge on the Evolution of Care Partner Burden, Needs, and Coping in Parkinson's Disease.

BACKGROUND: Care partners support people with Parkinson's disease through a long journey ranging from independence to dependence for many daily tasks. Longitudinal studies are important to understand the evolution of this process and predictors of future needs of care partners. METHODS: A scoping review was conducted, searching PubMed for longitudinal studies examining care partner burden, needs or coping in Parkinson's disease published through May 2020. RESULTS: Eight observational studies and 19 interventional studies met the eligibility criteria. Longitudinal observation ranged from 7 weeks to 10 years, involving between six and 8515 care partners. All studies addressed care partner burden, while two and three studies respectively addressed needs and coping. Only one study related burden to specific stages or duration of disease. Results from identified studies show that care partners in Parkinson's disease are at risk for increasing burden over time. Multiple predictors of future burden have been identified related to the person with Parkinson's disease, the care partner, or an intervention. No studies examined the evolution of needs and coping in caregiving in Parkinson's disease. CONCLUSION: The scarcity of longer term, observational research on the temporal evolution of burden and particularly needs and coping in caregiving for someone with PD is a main identified gap. Even within these observational studies, the impact of caregiving is not often reported. Longitudinal studies on these topics are needed to help understand their change over time and relation to each other, which can inform support planning for care partners.

Cognitive Profile and Markers of Alzheimer Disease-Type Pathology in Patients With Lewy Body Dementias.

OBJECTIVE: To determine whether patients with Lewy body dementia (LBD) with likely Alzheimer disease (AD)-type copathology are more impaired on confrontation naming than those without likely AD-type copathology. METHODS: We selected 57 patients with LBD (dementia with Lewy bodies [DLB], n = 38; Parkinson disease dementia [PDD], n = 19) with available AD CSF biomarkers and neuropsychological data. CSF ß-amyloid1-42 (Aß42), phosphorylated-tau (p-tau), and total-tau (t-tau) concentrations were measured. We used an autopsy-validated CSF cut point (t-tau:Aß42 ratio > 0.3, n = 43), or autopsy data when available (n = 14), to categorize patients as having LBD with (LBD + AD, n = 26) and without (LBD - AD, n = 31) likely AD-type copathology. Analysis of covariance tested between-group comparisons across biologically defined groups (LBD + AD, LBD - AD) and clinical phenotypes (DLB, PDD) on confrontation naming (30-item Boston Naming Test [BNT]), executive abilities (letter fluency [LF], reverse digit span [RDS]), and global cognition (Mini-Mental State Examination [MMSE]), with adjustment for age at dementia onset, time from dementia onset to test date, and time from CSF to test date. Spearman correlation related cognitive performance to CSF analytes. RESULTS: Patients with LBD + AD performed worse on BNT than patients with LBD - AD (F = 4.80, p = 0.03); both groups performed similarly on LF, RDS, and MMSE (all p > 0.1). Clinically defined PDD and DLB groups did not differ in performance on any of these measures (all p > 0.05). A correlation across all patients showed that BNT score was negatively associated with CSF t-tau (ρ = -0.28, p < 0.05) and p-tau (ρ = -0.26, p = 0.05) but not Aß42 (p > 0.1). CONCLUSION: Markers of AD-type copathology are implicated in impaired language performance in LBD. Biologically based classification of LBD may be advantageous over clinically defined syndromes to elucidate clinical heterogeneity.

Low Sustainment of High-Dose Oral Medication Regimens for Advanced Parkinson's Disease in Medicare Beneficiaries.

BACKGROUND: Increasing doses of oral antiparkinson medications are indicated in advanced Parkinson's disease (PD), but little is known about sustainment of high-dose regimens. OBJECTIVE: To investigate sustainment of high-dose oral medication regimens in Medicare beneficiaries with incident advanced PD. METHODS: This retrospective cohort study utilized 100%fee-for-service Medicare claims from 2011-2013. We identified advanced PD using a pharmacy claims-based proxy and selected patients who initiated a new high-dose oral medication regimen (daily levodopa equivalent dose [LED] >1000 mg/day for ≥30 days) in 2012. In the following 12 months, we examined: 1) annual proportion of days covered (PDC)≥0.80 and 2) presence of a ≥ 90 day continuous gap at varying dosage thresholds: the initial >1000 mg/day, >800 mg/day, >500 mg/day, or >0 mg/day. RESULTS: We identified 9,405 patients with advanced PD (mean age 77.4 [SD 6.8] years; 53%men). Only 5%maintained a regimen of >1000 mg/day at PDC ≥0.80; 75% had a ≥ 90-day gap in that dosage level. At a dosage threshold of >800 mg/day, 20% had a PDC ≥0.80 and 53% had a ≥ 90-day gap; at >500 mg/day, 56% had a PDC ≥0.80 and 19%had a ≥ 90-day gap; and at >0 mg/day (any dose), 76% had a PDC ≥0.80 and only 10%had a≥90-day gap. CONCLUSION: Few patients with advanced PD sustained a high-dose oral medication regimen in the year following initiation, but most sustained a substantially lower-dose regimen. Strategies to improve advanced PD treatment are needed.

Psychometric Properties of the Clinical Dementia Rating Scale Sum of Boxes in Parkinson's Disease.

BACKGROUND: A composite measure that assesses both cognitive and functional abilities in Parkinson's disease (PD) would be useful for diagnosing mild cognitive impairment (MCI) and PD dementia (PDD) and as an outcome measure in randomized controlled trials. The Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) was designed to assess both cognition and basic-instrumental activities of daily living in Alzheimer's disease but has not yet been validated in PD. OBJECTIVE: To validate the CDR-SOB as a composite cognitive-functional measure for PD patients, as well as to assess its sensitivity to change. METHODS: The CDR-SOB and a comprehensive cognitive and functional battery was administered to 101 PD patients at baseline (39 normal cognition [NC], 41 MCI and 21 PDD by expert consensus panel), and re-administered to 64 patients after 1-2 years follow-up (32 NC and 32 cognitive impairment [CI] at baseline). RESULTS: Cross-sectionally, CDR-SOB and domain scores were correlated with corresponding neuropsychological or functional measures and were significantly different between cognitive subgroups both at baseline and at follow-up. In addition, CDR-SOB ROC curves distinguished between normal cognition and dementia with high sensitivity, but did not distinguish well between NC and MCI. Longitudinal changes in the CDR-SOB and domain scores were not significant and were inconsistent in predicting change in commonly-used cognitive and functional tests. CONCLUSION: The CDR-SOB detects dementia-level cognitive impairment in PD but may not be appropriate for predicting longitudinal combined cognitive-functional changes in patients without significant cognitive impairment at baseline.

Whole Clinic Research Enrollment in Parkinson's Disease: The Molecular Integration in Neurological Diagnosis (MIND) Study.

BACKGROUND: Observational studies in Parkinson's disease (PD) have focused on relatively small numbers of research participants who are studied extensively. The Molecular Integration in Neurological Diagnosis Initiative at the University of Pennsylvania aims to characterize molecular and clinical features of PD in every patient in a large academic center. OBJECTIVE: To determine the feasibility and interest in a global-capture biomarker research protocol. Additionally, to describe the clinical characteristics and GBA and LRRK2 variant carrier status among participants. METHODS: All patients at UPenn with a clinical diagnosis of PD were eligible. Informed consent included options for access to the medical record, future recontact, and use of biosamples for additional studies. A blood sample and a completed questionnaire were obtained from participants. Targeted genotyping for four GBA and eight LRRK2 variants was performed, with plasma and DNA banked for future research. RESULTS: Between September 2018 and December 2019, 704 PD patients were approached for enrollment; 652 (92.6%) enrolled, 28 (3.97%) declined, and 24 (3.41%) did not meet eligibility criteria. Median age was 69 (IQR 63_75) years, disease duration was 5.41 (IQR 2.49_9.95) years, and 11.10%of the cohort was non-white. Disease risk-associated variants in GBA were identified in 39 participants (5.98%) and in LRRK2 in 16 participants (2.45%). CONCLUSIONS: We report the clinical and genetic characteristics of PD patients in an all-comers, global capture protocol from an academic center. Patient interest in participation and yield for identification of GBA and LRRK2 mutation carriers is high, demonstrating feasibility of PD clinic-wide molecular characterization.

Burden of Parkinson's Disease by Severity: Health Care Costs in the U.S. Medicare Population.

BACKGROUND: Current understanding of the health care costs of Parkinson's disease (PD) and the incremental burden of advanced disease is incomplete. OBJECTIVES: The aim of this study was to assess the direct economic burden associated with advanced versus mild/moderate PD in a prevalent national sample of elderly U.S. Medicare beneficiaries with a PD diagnosis. METHODS: Analyzing 100% fee-for-service Medicare claims from 2013, we defined advanced PD with a medication-based algorithm and calculated all-cause and PD-related costs for the overall sample and by disease severity. We measured primary PD-related costs (based on claims with a primary diagnosis of PD) and any PD-related costs (based on claims with PD in any diagnostic field). Generalized linear models were used to estimate risk-adjusted mean cost differences between the advanced and mild/moderate PD groups for the calendar year. RESULTS: The final sample (N = 144,703) had mean observed all-cause, primary PD-related, and any PD-related costs of $23,041 (SD, $34,045), $3429 (SD, $7431), and $9924 (SD, $22,140), respectively. Twenty percent of patients were classified as advanced PD. Costs varied substantially; any PD-related mean costs were $483 for the lowest patient decile (which included 1% of the advanced group) and $48,145 for the highest decile (which included 15% of the advanced group). Incremental risk-adjusted costs of advanced PD were $5818 (95% confidence interval [CI]: $5411-$6225) for all-cause costs, $3644 (95% CI: $3484-$3806) for primary PD-related costs, and $6088 (95% CI: $5779-$6398) for any PD-related costs. CONCLUSIONS: Elderly Medicare beneficiaries with PD had substantial variation in PD-related costs. Advanced PD was associated with a larger economic burden than mild/moderate PD. © 2020 International Parkinson and Movement Disorder Society.

Overcoming Barriers to Parkinson Disease Trial Participation: Increasing Diversity and Novel Designs for Recruitment and Retention.

Parkinson disease (PD) is highly prevalent among neurodegenerative diseases, affecting a diverse patient population. Despite a general willingness of patients to participate in clinical trials, only a subset of patients enroll in them. Understanding the barriers to trial participation will help to alleviate this discrepancy and improve trial participation. Underrepresented minorities, older patients, and patients with more medical comorbidities in particular are underrepresented in research. In clinical trials, this has the effect of delaying trial completion, exacerbating disparities, and limiting our ability to generalize study results. Efforts to improve trial design and recruitment are necessary to ensure study enrollment reflects the diversity of patients with PD. At the trial design level, broadening inclusion criteria, attending to participant burden, and focusing on trial efficiency may help. At the recruitment stage, increasing awareness, with traditional outreach or digital approaches; improving engagement, particularly with community physicians; and developing targeted recruitment efforts can also help improve enrollment of underrepresented patient groups. The use of technology, for virtual visits, technology-based objective measures, and community engagement, can also reduce participant burden and increase recruitment. By designing trials to consider these barriers to trial participation, we can improve not only the access to research for all our patients but also the quality and generalizability of clinical research in PD.