ABSTRACT
Introduction
The off periods in Parkinson's disease have a significantly negative impact on quality of life. What the most bothersome aspects of off periods are from the patient's ...perspective are not well studied, nor is the degree to which screening tools for wearing off such as the Wearing Off Questionnaires (WOQs) capture what bothers patients most.
Methods
A questionnaire was deployed to eligible participants of Fox Insight, an online study of individuals with self‐reported Parkinson's disease. Inclusion criteria were the use of ≥1 dopaminergic medications and an affirmative response to a question on experiencing off periods. Participants provided free‐text responses regarding the top 3 most bothersome symptoms they experience when off. A determination was made regarding whether each response would have been captured by the 32‐item, 19‐item, and 9‐item WOQs.
Results
The final sample had 2106 participants, a mean age of 66.6 years, 52.3% were men, and had a disease duration of 4.9 years. The WOQ‐32 items covered all of the most bothersome symptoms for 53.2% of respondents. Among bothersome aspects of off not captured by the WOQs, 597 (66.2%) were specific symptoms, with freezing of gait, apathy, and memory problems being the most common. The functional consequences of off periods were most bothersome to 232 (25.7%), with walking problems being the most common. The emotional response to off periods was the most bothersome aspect to 169 respondents (18.7%).
Discussion
This study emphasizes the value of narrative data in understanding patient experiences, and what bothers patients most about off periods. The WOQs, although of established utility in the screening for wearing off, may not capture those symptoms most bothersome to patients.
Background
Fatigue has a major impact on health‐related quality of life (HR‐QOL) in Parkinson's disease (PD).
Objectives
To determine whether demographic characteristics modify the relationship ...between fatigue and HR‐QOL.
Methods
Patients with PD in the Fox Insight study completed the Parkinson Fatigue Scale (PFS‐16) and Geriatric Depression Scale (GDS‐15). Linear regression examined the relationship between the PFS‐16 and Parkinson Disease Quality of Life, as modified by age, sex, and GDS‐15.
Results
A total of 1029 participants (44% female, mean age 67.4 years, and mean disease duration 4.6 years) were included in this analysis. Multivariable regression modeling demonstrated a negative effect modification for age (β = −0.07, P < 0.001) and a positive effect modification for the GDS‐15 (β = 0.057, P = 0.002), but not for sex (β = −0.021, P = 0.231).
Conclusion
The association between fatigue and worse HR‐QOL is greater at younger ages and in individuals with more depressive symptoms. Targeted therapeutics for these individuals may provide the greatest impact on fatigue in PD.
Background
Objective measures of Parkinson's disease (PD) are needed for purposes of diagnosis and prognostication, as well as identification of those at risk of PD. In this qualitative review, we ...provide an overview of the current state of the field of PD biomarker development, delineate challenges, and discuss how the field is evolving.
Methods
A search of PubMed was conducted for articles pertaining to objective biomarkers for PD. Articles were selected based on relevance and methodology; where available, meta‐analyses, systematic reviews, and comprehensive qualitative review articles were preferentially referenced.
Results
There are several potential sources of objective PD biomarkers including biofluids, peripheral tissue, imaging, genetics, and technology based objective motor testing. Approaches to biomarker identification include the candidate biomarker approach and unbiased discovery methods, each of which has advantages and disadvantages. Several emerging techniques hold promise in each of these areas. Advances in technology and bioinformatics, and the increasing availability of biobanks, are expected to facilitate future PD biomarker development.
Conclusions
The field of objective biomarkers for PD has made great progress but much remains to be done in translating putative biomarkers into tools useful in the clinic and for research. Multimodal biomarker platforms have the potential to capitalize on the utility and strengths of individual biomarkers. Rigorous methodology and standards for replication of findings will be key to meaningful progress in the field.
Introduction
Individuals with idiopathic rapid eye movement sleep behavior disorder (iRBD) are at high risk for a clinical diagnosis of an α‐synucleinopathy (aSN). They could serve as a key ...population for disease‐modifying trials. Abnormal dopamine transporter (DAT) imaging is a strong candidate biomarker for risk of aSN diagnosis in iRBD. Our primary objective was to identify a quantitative measure of DAT imaging that predicts diagnosis of clinically‐defined aSN in iRBD.
Methods
The sample included individuals with iRBD, early Parkinson’s Disease (PD), and healthy controls (HC) enrolled in the Parkinson Progression Marker Initiative, a longitudinal, observational, international, multicenter study. The iRBD cohort was enriched with individuals with abnormal DAT binding at baseline. Motor and nonmotor measures were compared across groups. DAT specific binding ratios (SBR) were used to calculate the percent of expected DAT binding for age and sex using normative data from HCs. Receiver operative characteristic analyses identified a baseline DAT binding cutoff that distinguishes iRBD participants diagnosed with an aSN in follow‐up versus those not diagnosed.
Results
The sample included 38 with iRBD, 205 with PD, and 92 HC who underwent DAT‐SPECT at baseline. Over 4.7 years of mean follow‐up, 14 (36.84%) with iRBD were clinically diagnosed with aSN. Risk of aSN diagnosis was significantly elevated among those with baseline putamen SBR ≤ 48% of that expected for age and sex, relative to those above this cutoff (hazard ratio = 17.8 95%CI: 3.79–83.3, P = 0.0003).
Conclusion
We demonstrate the utility of DAT SBR to identify individuals with iRBD with increased short‐term risk of an aSN diagnosis.
Online tools for data collection could be of value in patient-oriented research. The Fox Insight (FI) study collects data online from individuals with self-reported Parkinson's disease (PD). ...Comparing the FI cohort to other cohorts assessed through more traditional (in-person) observational research studies would inform the representativeness and utility of FI data.
To compare self-reported demographic characteristics, symptoms, medical history, and PD medication use of the FI PD cohort to other recent observational research study cohorts assessed with in-person visits.
The FI PD cohort (n = 12,654) was compared to 3 other cohorts, selected based on data accessibility and breadth of assessments: Parkinson's Progression Markers Initiative (PPMI; PD n = 422), Parkinson's Disease Biomarker Program (PDBP; n = 700), and PD participants in the LRRK2 consortium without LRRK2 mutations (n = 508). Demographics, motor and non-motor assessments, and medications were compared across cohorts. Where available, identical items on surveys and assessments were compared; otherwise, expert opinion was used to determine comparable definitions for a given variable.
The proportion of females was significantly higher in FI (45.56%) compared to PPMI (34.36%) and PDBP (35.71%). The FI cohort had greater educational attainment as compared to all other cohorts. Overall, prevalence of difficulties with motor experiences of daily living and non-motor symptoms in the FI cohort was similar to other cohorts, with only a few significant differences that were generally small in magnitude. Missing data were rare for the FI cohort, except on a few variables.
Patterns of responses to patient-reported assessments obtained online on the PD cohort of the FI study were similar to PD cohorts assessed in-person.
Background
The effect of surgery on impulse control disorders (ICDs) remains unclear in Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS).
Objective
To examine changes in ICD ...symptoms in PD patients undergoing DBS compared to a medication‐only control group.
Methods
The study was a 2‐center, 12‐month, prospective, observational investigation of PD patients undergoing DBS and a control group matched on age, sex, dopamine agonist use, and baseline presence of ICDs. Questionnaire for Impulsive‐Compulsive Disorders in Parkinson's Disease‐Rating Scale (QUIP‐RS) and total levodopa equivalent daily dose (LEDD) were collected at baseline, 3, 6, and 12 months. Linear mixed‐effects models assessed changes in mean QUIP‐RS score (sum of buying, eating, gambling, and hypersexuality items).
Results
The cohort included 54 participants (DBS = 26, controls = 28), mean (SD) age 64.3 (8.1) and PD duration 8.0 (5.2) years. Mean baseline QUIP‐RS was higher in the DBS group at baseline (8.6 (10.7) vs. 5.3 (6.9), P = 0.18). However, scores at 12 months follow‐up were nearly identical (6.6 (7.3) vs. 6.0 (6.9) P = 0.79). Predictors of change in QUIP‐RS score were baseline QUIP‐RS score (β = 0.483, P < 0.001) and time‐varying LEDD (β = 0.003, P = 0.02). Eight patients (four in each group) developed de novo ICD symptoms during follow‐up, although none met diagnostic criteria for an impulse control disorder.
Conclusions
ICD symptoms (including de novo symptoms) at 12 months follow‐up were similar between PD patients undergoing DBS and patients treated with pharmacological therapy only. Monitoring for emergence of ICD symptoms is important in both surgically‐ and medication‐only‐treated PD patients.
Background
Little is known about the impact of the dopamine system on development of cognitive impairment (CI) in Parkinson disease (PD).
Objectives
We used data from a multi‐site, international, ...prospective cohort study to explore the impact of dopamine system‐related biomarkers on CI in PD.
Methods
PD participants were assessed annually from disease onset out to 7 years, and CI determined by applying cut‐offs to four measures: (1) Montreal Cognitive Assessment; (2) detailed neuropsychological test battery; (3) Movement Disorder Society‐Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) cognition score; and (4) site investigator diagnosis of CI (mild cognitive impairment or dementia). The dopamine system was assessed by serial Iodine‐123 Ioflupane dopamine transporter (DAT) imaging, genotyping, and levodopa equivalent daily dose (LEDD) recorded at each assessment. Multivariate longitudinal analyses, with adjustment for multiple comparisons, determined the association between dopamine system‐related biomarkers and CI, including persistent impairment.
Results
Demographic and clinical variables associated with CI were higher age, male sex, lower education, non‐White race, higher depression and anxiety scores and higher MDS‐UPDRS motor score. For the dopamine system, lower baseline mean striatum dopamine transporter values (P range 0.003–0.005) and higher LEDD over time (P range <0.001–0.01) were significantly associated with increased risk for CI.
Conclusions
Our results provide preliminary evidence that alterations in the dopamine system predict development of clinically‐relevant, cognitive impairment in Parkinson's disease. If replicated and determined to be causative, they demonstrate that the dopamine system is instrumental to cognitive health status throughout the disease course.
TRIAL REGISTRATION
Parkinson's Progression Markers Initiative is registered with ClinicalTrials.gov (NCT01141023).
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