The Parkinson's disease (PD) research field has seen the advent of several promising biomarkers and a deeper understanding of the clinical features of the disease from the earliest stages of ...pathology to manifest disease. Despite progress, a biologically based PD staging system does not exist. Such staging would be a useful framework within which to model the disease, develop and validate biomarkers, guide therapeutic development, and inform clinical trials design. We propose that the presence of aggregated neuronal α-synuclein, dopaminergic neuron dysfunction/degeneration, and clinical signs and symptoms identifies a group of individuals that have Lewy body pathology, which in early stages manifests with what is now referred to as prodromal non-motor features and later stages with the manifestations of PD and related Lewy body diseases as defined by clinical diagnostic criteria. Based on the state of the field, we herein propose a definition and staging of PD based on biology. We present the biologic basis for such a staging system and review key assumptions and evidence that support the proposed approach. We identify gaps in knowledge and delineate crucial research priorities that will inform the ultimate integrated biologic staging system for PD.
Parkinson's disease psychosis (PDP) has a major impact on quality of life and care partner burden; however, little is known about the lived experiences of care partners in managing PDP.
To understand ...how care partners of individuals with PDP experience their role and articulate their needs related to psychosis.
This was a qualitative study of semi-structured telephone interviews. Recruitment was conducted online via the clinical study matching tool, Fox Trial Finder; study activities took place remotely via telephone interviews. Transcripts of the phone interviews were analyzed by grounded theory methods, and a codebook of key themes that emerged from the analysis was developed.
Nine care partners (all female) were interviewed. Discussion topics in the codebook included (1) care partner burden and guilt; (2) communication with medical professionals; (3) coping strategies; (4) emotional reactions of the care partner to psychosis; (5) sources of knowledge about PD psychosis; (6) attitudes towards medications for PDP; (7) strategies to care for loved ones with psychosis; (8) psychosis triggers.
This qualitative analysis uncovers important aspects of the care partner experience, including challenges in navigating the medical system and communicating with professionals. Providers treating patients with PDP should be aware of these constraints and provide added support for strained care partners.
Objective
We analyzed the longitudinal profile of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers in early Parkinson's disease (PD) compared with healthy controls (HCs) and tested ...baseline CSF biomarkers for prediction of clinical decline in PD.
Methods
Amyloid‐β 1 to 42 (Aβ42), total tau (t‐tau) and phosphorylated tau (p‐tau) at the threonine 181 position were measured using the high‐precision Roche Elecsys electrochemiluminescence immunoassay in all available CSF samples from longitudinally studied patients with PD (n = 416) and HCs (n = 192) followed for up to 3 years in the Parkinson's Progression Markers Initiative (PPMI). Longitudinal CSF and clinical data were analyzed with linear‐mixed effects models.
Results
We found patients with PD had lower CSF t‐tau (median = 157.7 pg/mL; range = 80.9–467.0); p‐tau (median = 13.4 pg/mL; range = 8.0–40.1), and Aβ42 (median = 846.2 pg/mL; range = 238.8–3,707.0) than HCs at baseline (CSF t‐tau median = 173.5 pg/mL; range = 82.0–580.8; p‐tau median = 15.4 pg/mL; range = 8.1–73.6; and Aβ42 median = 926.5 pg/mL; range = 239.1–3,297.0; p < 0.05–0.001) and a moderate‐to‐strong correlation among these biomarkers in both patients with PD and HCs (Rho = 0.50–0.97; p < 0.001). Of the patients with PD, 31.5% had pathologically low levels of CSF Aβ42 at baseline and these patients with PD had lower p‐tau levels (median = 10.8 pg/mL; range = 8.0–32.8) compared with 27.7% of HCs with pathologically low CSF Aβ42 (CSF p‐tau median = 12.8 pg/mL; range 8.2–73.6; p < 0.03). In longitudinal CSF analysis, we found patients with PD had greater decline in CSF Aβ42 (mean difference = −41.83 pg/mL; p = 0.03) and CSF p‐tau (mean difference = −0.38 pg/mL; p = 0.03) at year 3 compared with HCs. Baseline CSF Aβ42 values predicted small but measurable decline on cognitive, autonomic, and motor function in early PD.
Interpretation
Our data suggest baseline CSF AD biomarkers may have prognostic value in early PD and that the dynamic change of these markers, although modest over a 3‐year period, suggest biomarker profiles in PD may deviate from healthy aging. ANN NEUROL 2020;88:574–587
The effect of the COVID-19 pandemic on people with Parkinson's disease (PD) is poorly understood.
To rapidly identify areas of need and improve care in people with PD during the COVID-19 pandemic, we ...deployed a survey to assess COVID-19 symptoms and the pandemic's effect among those with and without COVID-19.
People with and without PD participating in the online study Fox Insight (FI) were invited to complete a survey between April 23 and May 23, 2020. Among people reporting COVID-19 diagnoses, we compared symptoms and outcomes in people with and without PD. Among people not reporting COVID-19, we assessed access to healthcare and services and PD symptoms.
7,209/9,762 active FI users responded (approximately 74% response rate), 5,429 people with PD and 1,452 without PD. COVID-19 diagnoses were reported by 51 people with and 26 without PD. Complications were more frequent in people with longer PD duration. People with PD and COVID-19 experienced new or worsening motor (63%) and nonmotor (75%) symptoms. People with PD not diagnosed with COVID-19 reported disrupted medical care (64%), exercise (21%), and social activities (57%), and worsened motor (43%) and non-motor (52%) symptoms. Disruptions were more common for those living alone, with lower income and non-White race.
The COVID-19 pandemic is associated with wide-ranging effects on people with PD, and certain groups may be at particular risk. FI provides a rapid, patient-centered means to assess these effects and identify needs that can be used to improve the health of people with PD.
Parkinson's disease (PD) has variable progression; identifying determinants of functional decline in PD is needed for accurate prognostication. Autonomic symptoms can result from dopaminergic therapy ...but may also independently predict functional decline.
The sample included individuals with newly diagnosed PD in Parkinson's Progression Markers Initiative. Autonomic symptoms were measured with the Scales-for-Outcomes-in-Parkinson's-Disease-Autonomic (SCOPA-AUT). Presence/absence of autonomic symptoms for SCOPA-AUT total scale and seven subscales was defined, and baseline demographic/clinical data were compared between groups with and without autonomic symptoms. Time-to-functional-dependence, or Schwab-and-England Activities-of-Daily-Living (SE-ADL) ≤70, was compared between groups using hazard models, adjusting for covariates including time-varying levodopa-equivalent daily dosage. If a subscale was associated with a significant subhazard ratio (SHR), hazard models for items in that subscale were generated and gender was evaluated as an effect modifier.
399 participants were included. Over a median of 72 months (range 6-84), 91 (22.81%) reached SE-ADL ≤70. SCOPA-AUT total/gastrointestinal/urinary/pupillomotor scales were associated with SE-ADL ≤70; respective multivariable SHRs (95% CI, p value) were 1.98 (1.06-3.70, 0.03), 1.71 (1.04-2.81, 0.03), 1.94 (1.25-3.01, <0.01), 2.56 (1.24-5.31, 0.01). Individual items in the gastrointestinal and urinary scales drove associations. Urinary scale associations were seen in males only.
Symptoms of gastrointestinal, urinary, pupillomotor dysfunction are associated with functional decline risk in PD, independent of dopaminergic therapy. Detailed assessments of autonomic symptomatology should be utilized in studies attempting to refine predictive models of PD progression.
Abstract
Background
Mild parkinsonian signs (MPS), highly prevalent in older adults, predict disability. It is unknown whether energy decline, a predictor of mobility disability, is also associated ...with MPS. We hypothesized that those with MPS had greater decline in self-reported energy level (SEL) than those without MPS, and that SEL decline and MPS share neural substrates.
Method
Using data from the Health, Aging and Body Composition Study, we analyzed 293 Parkinson’s disease-free participants (83 ± 3 years old, 39% Black, 58% women) with neuroimaging data, MPS evaluation by Unified Parkinson Disease Rating Scale in 2006–2008, and ≥3 measures of SEL since 1999–2000. Individual SEL slopes were computed via linear mixed models. Associations of SEL slopes with MPS were tested using logistic regression models. Associations of SEL slope with volume of striatum, sensorimotor, and cognitive regions were examined using linear regression models adjusted for normalized total gray matter volume. Models were adjusted for baseline SEL, mobility, demographics, and comorbidities.
Results
Compared to those without MPS (n = 165), those with MPS (n = 128) had 37% greater SEL decline in the prior 8 years (p = .001). Greater SEL decline was associated with smaller right striatal volume (adjusted standardized β = 0.126, p = .029). SEL decline was not associated with volumes in other regions. The association of SEL decline with MPS remained similar after adjustment for right striatal volume (adjusted odds ratio = 2.03, 95% CI: 1.16–3.54).
Conclusion
SEL decline may be faster in those with MPS. Striatal atrophy may be important for declining energy but does not explain the association with MPS.
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