The intrinsically restructured fovea is correlated with contrast sensitivity loss in Parkinson's disease.

Foveal structure that is specified by the thickness, depth and the overall shape of the fovea is a promising tool to qualify and quantify retinal pathology in Parkinson's disease. To determine the model variable that is best suited for discriminating Parkinson's disease eyes from those of healthy controls and to assess correlations between impaired contrast sensitivity and foveal shape we characterized the fovea in 48 Parkinson's disease patients and 45 control subjects by optical coherence tomography (OCT). The model quantifies structural changes in the fovea of Parkinson's disease patients that are correlated with a decline in contrast sensitivity. Retinal foveal remodeling may serve as a parameter for vision deficits in Parkinson's disease. Whether foveal remodeling reflects dopaminergic driven pathology or rather both dopaminergic and non-dopaminergic pathology has to be investigated in longitudinal studies.

α-synuclein in the inner retina in parkinson disease.

Behavioral, electrophysiological, and imaging data reveal impaired visual processing and altered retinal morphology in Parkinson disease. Are visual changes epiphenomena? We report the presence of misfolded α-synuclein in the retina, not hitherto shown, in discrete retinal neurons within the inner retina. They demonstrate the histopathology that may underlie impaired vision and retinal remodeling in Parkinson disease. Furthermore, the histological localization of α-synuclein gives clues to the nonsynaptic mode of α-synuclein propagation.

A novel retinal biomarker for Parkinson's disease: Quantifying the foveal pit with optical coherence tomography.

BACKGROUND: Optical coherence tomography offers a potential biomarker tool in Parkinson's disease (PD). A mathematical model quantifying symmetry, breadth, and depth of the fovea was applied. METHODS: Nintey-six subjects (72 PD and 24 healthy controls) were included in the study. Macular scans of each eye were obtained on two different optical coherence tomography devices: Cirrus and RTVue. RESULTS: The variables corresponding to the cardinal gradients of the fovea were the most sensitive indicators of PD for both devices. Principal component analysis distinguished 65% of PD patients from controls on Cirrus, 57% on RTVue. CONCLUSION: Parkinson's disease shallows the superior/inferior and to a lesser degree nasal-temporal foveal slope. The symmetry, breadth, and depth model fits optical coherence tomography data derived from two different devices, and it is proposed as a diagnostic tool in PD.

Dance for PD: a preliminary investigation of effects on motor function and quality of life among persons with Parkinson's disease (PD).

In 2001, Dance for Parkinson's disease (DfPD(®)) classes for persons with Parkinson's disease and care partners were developed by Brooklyn Parkinson Group and Mark Morris Dance Group. A previous assessment suggested that individuals experience positive benefits from DfPD(®). The current preliminary uncontrolled study investigated the effects of a dance intervention on several motor and quality of life aspects of PD following 16 sessions (8 weeks; 20 h) taught by professional dancers/teachers. A mixed methods design was used to determine the effects of the class. Assessment instruments administered at baseline and post-intervention included the Hoehn and Yahr, UPDRS (part III), Berg Balance Scale, Beck Depression Inventory, and PDQ-39 and individual interviews after the last class. Hoehn and Yahr scores ranged from 1 to 4. UPDRS III total scores and sub scores of gait and tremor improved following the intervention (P < 0.05). During interviews participants reported physical, emotional, and social benefits. Despite the diversity of baseline measures post-class interview results were consistently positive across the sample. Twelve of 14 subjects (mean age 66.2) with idiopathic PD completed the sessions. After 4 years, four participants regularly attended DfPD(®) classes. The low attrition rate and continued attendance suggest notable adherence to the DfPD(®) class. The importance of the results is both clinical and conceptual, highlighting the value of using both quantitative and qualitative data to evaluate the benefits of dance with PD.

Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial.

IMPORTANCE: There are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies. OBJECTIVE: To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease. DESIGN, SETTING, AND PATIENTS: The Long-term Study 1, a multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1741 men and women with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) Parkinson disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013. INTERVENTIONS: Participants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years). MAIN OUTCOMES AND MEASURES: The primary outcome measure was a difference in clinical decline from baseline to 5-year follow-up, compared between the 2 treatment groups using a global statistical test. Clinical status was defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity. All outcomes were coded such that higher scores indicated worse outcomes and were analyzed by a global statistical test. Higher summed ranks (range, 5-4775) indicate worse outcomes. RESULTS: The trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2360 (95% CI, 2249-2470) and for creatine was 2414 (95% CI, 2304-2524). The global statistical test yielded t1865.8 = -0.75 (2-sided P = .45). There were no detectable differences (P < .01 to partially adjust for multiple comparisons) in adverse and serious adverse events by body system. CONCLUSIONS AND RELEVANCE: Among patients with early and treated Parkinson disease, treatment with creatine monohydrate for at least 5 years, compared with placebo did not improve clinical outcomes. These findings do not support the use of creatine monohydrate in patients with Parkinson disease. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00449865.

Venturing into the no-man's land of the retina in Parkinson's disease.

The development of optical coherence tomography (OCT) has led to increasing interest in the retina in Parkinson's disease (PD). The retina is a multilayered tissue: looking into the eye from the outside, these layers comprise the nerve fiber layer (NFL); the ganglion cell layer (GCL); the inner plexiform layer (IPL), which contains the interconnecting plexus, including tyrosine hydroxylase-positive (dopaminergic) fibers of amacrine cells; the inner nuclear layer; and several outer retinal layers. Commercial spectral-domain OCT has a specific program for detecting peripapillary NFL defects and a different macular program for diabetic retinopathy. Specific programs for PD are not commercially available. Taking all studies together, it seems that macular programs have a higher diagnostic yield than NFL programs, but the numbers of studies and examined patients are relatively small. It is not certain that all retinal thinning in PD is due to dopaminergic neuronal loss. When applying OCT, the where (region of interest) and the what of the focus of automated programs must be considered. With these caveats, one could take advantage of the power of OCT for looking in-depth into the terra incognita of individual retinal layers at the fovea and perhaps at other appropriate retinal locations.

Application of an OCT data-based mathematical model of the foveal pit in Parkinson disease.

Spectral-domain Optical coherence tomography (OCT) has shown remarkable utility in the study of retinal disease and has helped to characterize the fovea in Parkinson disease (PD) patients. We developed a detailed mathematical model based on raw OCT data to allow differentiation of foveae of PD patients from healthy controls. Of the various models we tested, a difference of a Gaussian and a polynomial was found to have "the best fit". Decision was based on mathematical evaluation of the fit of the model to the data of 45 control eyes versus 50 PD eyes. We compared the model parameters in the two groups using receiver-operating characteristics (ROC). A single parameter discriminated 70 % of PD eyes from controls, while using seven of the eight parameters of the model allowed 76 % to be discriminated. The future clinical utility of mathematical modeling in study of diffuse neurodegenerative conditions that also affect the fovea is discussed.

Correlation of inner retinal thickness evaluated by spectral-domain optical coherence tomography and contrast sensitivity in Parkinson disease.

BACKGROUND: To compare inner retinal layer (IRL) thickness measured by spectral-domain optical coherence tomography (SD-OCT) and contrast sensitivity (CS) in patients with Parkinson disease (PD) and in healthy control (HC) subjects. METHODS: Consecutive patients with and without PD were prospectively analyzed using SD-OCT and Pelli-Robson CS testing. SD-OCT IRL (ganglion-cell complex) thickness, consisting of the nerve fiber layer, ganglion cell layer, and inner plexiform layer, was segmented using an RTVue Model-RT100 with an EMM5 scan parameter covering a 5.0 × 5.0 mm cube centered on the fovea. Thickness voxel measurements at 0.25-mm intervals at sequential radial distances from the foveola were acquired horizontally and vertically. SD-OCT thickness raw data files were imported and analyzed within MATLAB (version 7.10.0). A database of CS scores and IRL thickness values by foveal location was constructed and statistically evaluated using JMP 10 (SAS Institute, Inc, Cary, NC). RESULTS: The results were compared between 28 eyes of 14 patients with PD and 28 eyes of 14 HC subjects. Controlling for age, mean CS scores of monocular right and randomized eyes were statistically lower in PD eyes (P < 0.05). IRL was significantly thinner in PD eyes than in HC eyes at several distances from the foveola (P < 0.05). The most numerous and significant thickness differences by diagnosis were located in the superior quadrant at a distance of 1.00-1.75 mm from the foveal center (17 µm; P < 0.01, maximum significant thickness difference and P value). Correlation was demonstrated between monocular CS and IRL thickness by diagnosis at multiple foveal locations for HC eyes as follows: nasal quadrant, 0.75-1.00 mm (P < 0.02); temporal quadrant, 0.50-1.00 mm (P < 0.05); superior quadrant, 1.00 mm (P < 0.05); and inferior quadrant, 1.00 mm (P < 0.03). No significant correlation was found between monocular CS and IRL thickness within PD subjects (P > 0.05 for each foveal location measured). CONCLUSION: CS and foveal IRL thickness are decreased in patients with PD. CS and IRL thickness correlated in HC subjects; however, no such correlation was demonstrated in PD. The functional deficit of dopaminergic interneurons, including amacrine cells, may outstrip the anatomic structural changes in the inner retina of PD patients. Inner retinal atrophic changes may underlie the pathogenesis of CS deficit and IRL thinning in PD.

Retinopathy in Parkinson Disease.

One of the non-motor manifestations of PD is visual system involvement. Foveal vision is a main contributor to both visual recognition and discrimination and to both overt and covert visual attention. Experimental evidence from humans and monkeys shows that D1 and D2 receptors are essential for retinal ganglion cell receptive field organization. The evidence linking retinopathy and foveal visual impairment in PD is discussed. A model of retinal preganglionic dopaminergic circuitry is presented. Experimental evidence in humans, using Optical Coherence Tomography shows morphological changes of retinal neurons, including ganglion cells in PD. The diagnosis of pre-cardinal stage of PD (PCPD) may take advantage of the wide availability of optical coherence tomography as a potential biomarker. Fourier-domain OCT and visual testing may contribute a quantitative approach to the early diagnosis, the effects of treatment and follow-up of progression of PD.

Different spatial organizations of saccade related BOLD-activation in parietal and striate cortex.

Voluntary saccades performed in total darkness provide the opportunity to investigate the brain system active during saccades without confounding effects caused by the saccade induced shifts of the retinal image. Using this approach saccade related activation has been demonstrated not only in parietal but also in striate cortex. Currently no information is available about the reference frame in which this activation is represented in parietal and in striate cortex. However, knowledge about how the brain codes spatial information about saccades in the absence of visual input is potentially relevant to our understanding of visually guided behaviour. The present study combines functional magnetic resonance imaging (fMRI) with simultaneous electrooculogram-recordings to provide evidence that volitional saccades executed in total darkness are represented in a retinotopic reference frame in a parietal brain area, the putative homologue of human LIP, and in a head/body centred egocentric reference frame in human V1. The potential co-existence of retinotopic and egocentric space representations in the primary visual cortex indicates that V1 may be involved in visuo-motor integration.

Autonomic and electrocardiographic findings in Parkinson's disease.

Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms and signs. Many reports suggest that diminished heart rate variability occurs early, even prior to the cardinal signs of PD. In a longitudinal study of PD, we evaluated whether heart rate variability (HRV) obtained using a 10-second ECG tracing, and the electrocardiographic QT-interval would be associated with PD severity and progression. Subjects were derived from a longitudinal study of 1741 individuals with early, stable PD. The severity of PD was measured using the global statistical test (GST). In a subset, the heart rate corrected QT-interval (QTcB) was calculated for each electrocardiogram (ECG). The HRV was measured for each ECG and then transformed to fit a normal distribution. The baseline analysis included 653 subjects, with 256 completing the 5-year follow up study. There was an association (P<0.05) between QTcB and PD severity in individuals that were taking QT-interval affecting drugs. A longer QT-interval at baseline was associated with more advanced PD at 5years (P<0.05), and greater disease progression over 5years (P<0.05). There was an association between diminished HRV and an orthostatic decrease in standing blood pressure at baseline in individuals with PD (P<0.05). HRV was not associated with PD severity or progression. In conclusion, we were able to detect measurable associations between the QTcB interval and PD severity, PD severity 5years later, and the change in disease over time. However, routine ECG tracings appear inadequate for the evaluation of autonomic function in PD.

Longer Duration of MAO-B Inhibitor Exposure is Associated with Less Clinical Decline in Parkinson's Disease: An Analysis of NET-PD LS1.

BACKGROUND: Monoamine oxidase type B (MAO-B) inhibitors exhibit neuroprotective effects in preclinical models of PD but clinical trials have failed to convincingly demonstrate disease modifying benefits in PD patients. OBJECTIVE: To perform a secondary analysis of NET-PD LS1 to determine if longer duration of MAO-B inhibitor exposure was associated with less clinical decline. METHODS: The primary outcome measure was the Global Outcome (GO), comprised of 5 measures: change from baseline in the Schwab and England (ADL) scale, the 39-item Parkinson's Disease Questionnaire (PDQ-39), the UPDRS Ambulatory Capacity Scale, the Symbol Digit Modalities Test, and the most recent Modified Rankin Scale. A linear mixed model was used to explore the association between the cumulative duration of MAO-B inhibitor exposure and the GO, adjusting for necessary factors and confounders. Associations between MAO-B inhibitor exposure and each of the five GO components were then studied individually. RESULTS: 1616 participants comprised the analytic sample. Mean observation was 4.1 (SD = 1.4) years, and 784 (48.5%) participants received an MAO-B inhibitor. The regression coefficient of cumulative duration of MAO-B inhibitor exposure (in years) on the GO was - 0.0064 (SE = 0.002, p = 0.001). Significant associations between duration of MAO-B inhibitor exposure and less progression were observed for ADL (p < 0.001), Ambulatory Capacity (p < 0.001), and the Rankin (p = 0.002). CONCLUSIONS: Our analysis identified a significant association between longer duration of MAO-B inhibitor exposure and less clinical decline. These findings support the possibility that MAO-B inhibitors slow clinical disease progression and suggest that a definitive prospective trial should be considered.

Factors associated with falling in early, treated Parkinson's disease: The NET-PD LS1 cohort.

BACKGROUND: Recognizing the factors associated with falling in Parkinson's disease (PD) would improve identification of at-risk individuals. OBJECTIVE: To examine frequency of falling and baseline characteristics associated with falling in PD using the National Institute of Neurological Disorders and Stroke (NINDS) Exploratory Trials in PD Long-term Study-1 (NET-PD LS-1) dataset. METHODS: The LS-1 database included 1741 early treated PD subjects (median 4year follow-up). Baseline characteristics were tested for a univariate association with post-baseline falling during the trial. Significant variables were included in a multivariable logistic regression model. A separate analysis using a negative binomial model investigated baseline factors on fall rate. RESULTS: 728 subjects (42%) fell during the trial, including at baseline. A baseline history of falls was the factor most associated with post-baseline falling. Men had lower odds of post-baseline falling compared to women, but for men, the probability of a post-baseline fall increased with age such that after age 70, men and women had similar odds of falling. Other baseline factors associated with a post-baseline fall and increased fall rate included the Unified PD Rating Scale (UPDRS) Activities of Daily Living (ADL) score, total functional capacity (TFC), baseline ambulatory capacity score and dopamine agonist monotherapy. CONCLUSION: Falls are common in early treated PD. The biggest risk factor for falls in PD remains a history of falling. Measures of functional ability (UPDRS ADL, TFC) and ambulatory capacity are novel clinical risk factors needing further study. A significant age by sex interaction may help to explain why age has been an inconsistent risk factor for falls in PD.

Conjugate eye movements and gamma power modulation of the EEG in persistent vegetative state.

BACKGROUND: Power in the gamma band EEG increases during saccades in normal subjects. OBJECTIVE: To develop a potential method to quantify signs of cortical responsiveness in persistent vegetative state (PVS) we quantified gamma range EEG in association with conjugate slow ballistic eye movements (SBEM). METHODS: The EEG and the simultaneous electro-oculogram were recorded in 14 (8F/6M) PVS patients. Clinical scoring was based on the Glasgow Coma Scale (GCS) and Coma Rating Scale (CRS). The Wavelet Transform, followed by Hilbert transform was applied to the EEG and gamma power distribution was quantified relative to the timing of an eye movement. We correlated the clinical and the neurophysiological measures. RESULTS: Gamma activity was present in all PVS patients. Its power was modulated in association with eye movements only in less severely affected patients, with minimum power prior to, and maximum power during the eye movement. In severely affected patients there was no evidence of a temporal relationship between gamma power and the phase of the eye movement. CONCLUSIONS: Detecting changes in the time course of gamma power in relation to conjugate ballistic eye movements provides a quantitative neurophysiological method for prospective longitudinal studies to explore if the preservation of this CNS function relates to the potential for recovery in PVS patients.

A combination of retinal morphology and visual electrophysiology testing increases diagnostic yield in Parkinson's disease.

BACKGROUND: Impaired vision and remodeled foveal pit have been demonstrated in Parkinson's disease (PD) patients using different techniques. METHODS: Ten PD (20 eyes) and eight healthy controls (HC) subjects (16 eyes) were enrolled. Subjects were evaluated for N70 and P100 latencies using two-channel VEP with pattern reversal and on/off pattern; Contrast sensitivity (CS) using Pelli-Robson chart; macular thickness measured using Zeiss-HD optical coherence tomography (OCT). RESULTS: PD patients had a significantly delayed N70 (reversal pattern) and P100 (on/off pattern), lower CS score, and decreased retinal thickness at temporal 1.5-2.5 mm from the foveola. N70 latency was negatively correlated with CS (R = -0.419, P = 0.01) and average GCL-IPL thickness (R = -0.529, P = 0.001). CS was positively correlated with parafoveal thickness (R = 0.490, P = 0.002). A combination of parafoveal thickness and CS score yielded an AUC of 0.784 for PD discrimination which increased to 0.844 when combined with N70 and P100 measures. CONCLUSION: A combination of pattern reversal VEP latency, CS score, and inner retinal foveal thickness measures has a high diagnostic yield for PD.

Gamma-Band Modulation and Coherence in the EEG by Involuntary Eye Movements in Patients in Unresponsive Wakefulness Syndrome.

Gamma power and coherence in the electroencephalogram increase in healthy individuals in association with voluntary eye movements, saccades. Patients with unresponsive wakefulness syndrome show repetitive involuntary eye movements that are similar to saccades but progress at a much lower speed. In the present study, we explored the changes in gamma power and coherence related to these eye movements and investigated whether any relationship to the patients' clinical status could be found that would indicate first neurophysiological signs of recovery. To this end, we assessed the clinical status and registered classical scalp electroencephalography with 19 surface electrodes and electro-oculogram of 45 consecutive patients at admission and at 4 weekly intervals. Slow gamma activity (in the frequency range of 37-40 Hz) was analyzed before, during, and after eye movements (pre, -intra and post-eye movement) by means of "continuous wavelet transform." We graded recovery using clinical behavioral scales, taking into account the variables, age, gender, recovery (yes or no), as well as the patients diagnoses (traumatic brain injury, hypoxia, hemorrhage, infection). Statistical evaluation was performed using DataLab, R, and Kruskal-Wallis methods. Based on the clinical status, we distinguished between recovering and chronic groups of patients. In comparison with the chronic group, the recovering group showed significantly higher gamma power over the posterior electrodes and significant higher values of coherence in the gamma-band activity during the presaccadic period of eye movements. We suggest that our findings on the onset of involuntary eye movements in the recovering group of patients with unresponsive wakefulness syndrome indicates a first neurophysiological sign of favorable prognosis.

Cognitive function in 1736 participants in NINDS Exploratory Trials in PD Long-term Study-1.

INTRODUCTION: Clinical cohort studies suggest that mild cognitive impairment (MCI) is common in early Parkinson's disease (PD). The objectives of this paper were to describe cognitive function in a large clinical trial of early treated PD patients at baseline and over time using two brief cognitive screening tests. METHODS: In total 1741 participants were enrolled in the NINDS Exploratory Trials in Parkinson's disease (NET-PD) Long-term Study-1 (LS-1). The Symbol Digit Modalities Test (SDMT) was collected annually. The SCales for Outcomes in PArkinson's disease-COGnition (SCOPA-COG) was collected at baseline and at year 5. The trial was stopped early based on a planned interim analysis after half the cohort completed 5 years of follow-up. The median length of follow-up was 4 years (range 3-6 years). Predictors of cognitive change were examined using cross sectional (baseline) and longitudinal multivariable linear regression. RESULTS: The mean (SD) change from baseline to 5 years was -1.9 (5.1) for the SCOPA-COG and -2.1 (11.1) for the SDMT. Age and baseline UPDRS motor scores were associated with a more rapid decline in SDMT scores and 5 year SCOPA-COG scores. Male gender was associated with more rapid decline in SDMT. Self-reported income was a novel predictor of baseline cognitive function, even adjusted for educational status, although not significantly associated with change over time. CONCLUSION: This large prospective cohort study demonstrated mild cognitive decline in early treated Parkinson's disease. The study identified income level as a novel predictor of cognitive function.

Activity engagement and health quality of life in people with Parkinson's disease.

PURPOSE: This descriptive study examined differences in health quality of life (HQoL) and activity engagement in two groups of people with Parkinson's disease (PD): those who regularly participated in classes offered by the community-based program, Brooklyn Parkinson's Group (BPg), and a comparison group. Individuals in the comparison group did not participate in any community-based programs for people with PD, and were recruited from a clinic for PD and related disorders (PDRD) in an urban medical center. METHOD: We enrolled 26 participants; 13 participants were recruited from BPg and 13 from PDRD Clinic. Activity engagement was measured using the Activity Card Sort (ACS) and HQoL was measured using the PD Questionnaire (PDQ-39). Additionally, each participant completed a brief, interview-based questionnaire. RESULTS: A statistically significant difference was found in ACS scores between the BPg and comparison groups. BPg participants showed higher activity retention scores in all domains measured by the ACS. There was no statistically significant difference in PDQ-39 scores. CONCLUSION: This study provides preliminary evidence that regular participation in community programs like BPg may increase retention rates of activity engagement in people with PD. Participation in BPg programs, though, was not shown to improve HQoL as measured by the PDQ-39. Implications for Rehabilitation Continued participation in a wide repertoire of activities is a valuable rehabilitation goal for clients with Parkinson's disease (PD). People with PD who participate in specially designed community-based programs are more likely to retain a wide repertoire of activity and role engagement, as compared to people with PD who do not have acess to these programs.

The avascular zone and neuronal remodeling of the fovea in Parkinson disease.

Inner foveal thinning and intracellular alpha-synuclein were demonstrated in the retina in Parkinson disease. While pathognomonic alpha-synuclein is associated with embryonic dopaminergic (DA) neurons, postmortem studies in the nervous system and retina show prominent effect also in non-DA neurons. We evaluated foveal capillaries and foveal thickness in 23 Parkinson disease subjects and 13 healthy controls using retinal fluorescein angiography and optical coherence tomography. The size of the foveal avascular zone inversely correlates with foveal thinning. Foveal thinning highly correlates with motor impairment and also disease duration. Quantifying capillary and neuronal remodeling could serve as biological markers.

Parkinson's disease severity and use of dopaminergic medications.

BACKGROUND: The effects of dopaminergic therapy in parkinson's disease (PD) can vary depending on the class of medication selected. OBJECTIVE: The aim of this post hoc study was to determine if the class of dopaminergic therapy correlated with disease severity in persons with early, treated PD. METHODS: A non-parametric global statistical test (GST) was used to assess the status of participants treated with dopamine agonist (DA) monotherapy, levodopa (LD) monotherapy or combined LD and DA therapy on multiple PD outcomes encompassing motor, cognitive, psychiatric and autonomic function, as well as disability and quality of life. RESULTS: The outcomes measured at the beginning of the study showed lower disease burden for participants on initial DA monotherapy compared to those taking combined LD and DA therapy after controlling for age, education, taking cog-meds and amantadine. CONCLUSION: This observation suggests that clinicians treating early PD patients favor combined LD and DA therapy in patients with more disabling features over DA monotherapy. As such, studies of PD progression in treated PD patients may be affected by the class of symptomatic dopaminergic therapy.