Gene delivery of neurturin to putamen and substantia nigra in Parkinson disease: A double-blind, randomized, controlled trial.

OBJECTIVE: A 12-month double-blind sham-surgery-controlled trial assessing adeno-associated virus type 2 (AAV2)-neurturin injected into the putamen bilaterally failed to meet its primary endpoint, but showed positive results for the primary endpoint in the subgroup of subjects followed for 18 months and for several secondary endpoints. Analysis of postmortem tissue suggested impaired axonal transport of neurturin from putamen to substantia nigra. In the present study, we tested the safety and efficacy of AAV2-neurturin delivered to putamen and substantia nigra. METHODS: We performed a 15- to 24-month, multicenter, double-blind trial in patients with advanced Parkinson disease (PD) who were randomly assigned to receive bilateral AAV2-neurturin injected bilaterally into the substantia nigra (2.0 × 10(11) vector genomes) and putamen (1.0 × 10(12) vector genomes) or sham surgery. The primary endpoint was change from baseline to final visit performed at the time the last enrolled subject completed the 15-month evaluation in the motor subscore of the Unified Parkinson's Disease Rating Scale in the practically defined off state. RESULTS: Fifty-one patients were enrolled in the trial. There was no significant difference between groups in the primary endpoint (change from baseline: AAV2-neurturin, -7.0 ± 9.92; sham, -5.2 ± 10.01; p = 0.515) or in most secondary endpoints. Two subjects had cerebral hemorrhages with transient symptoms. No clinically meaningful adverse events were attributed to AAV2-neurturin. INTERPRETATION: AAV2-neurturin delivery to the putamen and substantia nigra bilaterally in PD was not superior to sham surgery. The procedure was well tolerated, and there were no clinically significant adverse events related to AAV2-neurturin.

Effects of deep brain stimulation frequency on bradykinesia of Parkinson's disease.

Deep brain stimulation (DBS) in Parkinson's disease (PD) is frequency-dependent. Past studies of the effect of DBS frequency, however, involved scrutiny of too few frequencies to eliminate risk of undersampling. Also, these studies presented averaged measures across subjects; high intersubject variability makes these measures problematic. In this study, 6 subjects with PD were tested in a drug-minimal state. Following 10 minutes of stimulation at the new frequency, all available frequencies were tested. Hand-opening and hand-closing amplitude and frequency were measured in 3 epochs of 15 seconds each. Multiple frequencies (low and high) resulted in peaks of increased movement amplitudes. Peaks were specific and varied among individuals. No clear relationship between stimulation frequency and movement frequency was discovered. In light of the findings, a wider range of stimulation frequencies should be examined, particularly lower frequencies. Most current theories of PD pathophysiology and DBS mechanisms of action fail to explain results of the kind demonstrated herein.

Short latency activation of cortex by clinically effective thalamic brain stimulation for tremor.

Deep brain stimulation (DBS) relieves disabling symptoms of neurologic and psychiatric diseases when medical treatments fail, yet its therapeutic mechanism is unknown. We hypothesized that ventral intermediate (VIM) nucleus stimulation for essential tremor activates the cortex at short latencies, and that this potential is related to the suppression of tremor in the contralateral arm. We measured cortical activity with electroencephalography in 5 subjects (seven brain hemispheres) across a range of stimulator settings, and reversal of the anode and cathode electrode contacts minimized the stimulus artifact, allowing visualization of brain activity. Regression quantified the relationship between stimulation parameters and both the peak of the short latency potential and tremor suppression. Stimulation generated a polyphasic event-related potential in the ipsilateral sensorimotor cortex, with peaks at discrete latencies beginning less than 1 ms after stimulus onset (mean latencies 0.9 ± 0.2, 5.6 ± 0.7, and 13.9 ± 1.4 ms, denoted R1, R2, and R3, respectively). R1 showed more fixed timing than the subsequent peaks in the response (P < 0.0001, Levene's test), and R1 amplitude and frequency were both closely associated with tremor suppression (P < 0.0001, respectively). These findings demonstrate that effective VIM thalamic stimulation for essential tremor activates the cerebral cortex at approximately 1 ms after the stimulus pulse. The association between this short latency potential and tremor suppression suggests that DBS may improve tremor by synchronizing the precise timing of discharges in nearby axons and, by extension, the distributed motor network to the stimulation frequency or one of its subharmonics.

Short latency activation of cortex during clinically effective subthalamic deep brain stimulation for Parkinson's disease.

Subthalamic deep brain stimulation (DBS) is superior to medical therapy for the motor symptoms of advanced Parkinson's disease (PD), and additional evidence suggests that it improves refractory symptoms of essential tremor, primary generalized dystonia, and obsessive-compulsive disorder. Despite this, its therapeutic mechanism is unknown. We hypothesized that subthalamic stimulation activates the cerebral cortex at short latencies after stimulus onset during clinically effective stimulation for PD. In 5 subjects (six hemispheres), EEG measured the response of cortex to subthalamic stimulation across a range of stimulation voltages and frequencies. Novel analytical techniques reversed the anode and cathode electrode contacts and summed the resulting pair of event-related potentials to suppress the stimulation artifact. We found that subthalamic brain stimulation at 20 Hz activates the somatosensory cortex at discrete latencies (mean latencies: 1.0 ± 0.4, 5.7 ± 1.1, and 22.2 ± 1.8 ms, denoted as R1, R2, and R3, respectively). The amplitude of the short latency peak (R1) during clinically effective high-frequency stimulation is nonlinearly dependent on stimulation voltage (P < 0.001; repeated-measures analysis of variance), and its latency is less variable than that of R3 (1.02 versus 19.46 ms; P < 0.001, Levene's test). We conclude that clinically effective subthalamic brain stimulation in humans with PD activates the cerebral cortex at 1 ms after stimulus onset, most likely by antidromic activation. These findings suggest that alteration of the precise timing of action potentials in cortical neurons with axonal projections to the subthalamic region may be an important component of the therapeutic mechanism of subthalamic brain stimulation.

Reliability of a new scale for essential tremor.

BACKGROUND: The objective of this study was to determine the reliability of a new scale for the clinical assessment of essential tremor. The Essential Tremor Rating Assessment Scale contains 9 performance items that rate action tremor in the head, face, voice, limbs, and trunk from 0 to 4 in half-point intervals. Head and limb tremor ratings are defined by specific amplitude ranges in centimeters. METHODS: Videos of 44 patients and 6 controls were rated by 10 specialists on 2 occasions 1-2 months apart. Inter- and intrarater reliability was assessed with a 2-way random-effects intraclass correlation, using an absolute agreement definition. RESULTS: Inter- and intrarater intraclass correlations for head and upper-limb tremor ranged from 0.86 to 0.96, and intraclass correlations for total score were 0.94 and 0.96. The intraclass correlations for voice, face, trunk, and leg were less robust. CONCLUSIONS: This scale is an exceptionally reliable tool for the clinical assessment of essential tremor.

Striatal overexpression of DeltaFosB reproduces chronic levodopa-induced involuntary movements.

Long-term dopamine replacement therapy in Parkinson's disease leads to the development of disabling involuntary movements named dyskinesias that are related to adaptive changes in striatal signaling pathways. The chronic transcription factor DeltaFosB, which is overexpressed in striatal neurons after chronic dopaminergic drug exposure, is suspected to mediate these adaptive changes. Here, we sought to demonstrate the ability of DeltaFosB to lead directly to the abnormal motor responses associated with chronic dopaminergic therapy. Using rAAV (recombinant adenoassociated virus) viral vectors, high levels of DeltaFosB expression were induced in the striatum of dopamine-denervated rats naive of chronic drug administration. Transgenic DeltaFosB overexpression reproduced the entire spectrum of altered motor behaviors in response to acute levodopa tests, including different types of abnormal involuntary movements and hypersensitivity of rotational responses that are typically associated with chronic levodopa treatment. JunD, the usual protein partner of DeltaFosB binding to AP-1 (activator protein-1) sites of genes, remained unchanged in rats with high DeltaFosB expression induced by viral vectors. These findings demonstrate that the increase of striatal DeltaFosB in the evolution of chronically treated Parkinson's disease may be a trigger for the development of abnormal responsiveness to dopamine and the emergence of involuntary movements.

Activation of subthalamic neurons by contralateral subthalamic deep brain stimulation in Parkinson disease.

Multiple studies have shown bilateral improvement in motor symptoms in Parkinson disease (PD) following unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) and internal segment of the globus pallidus, yet the mechanism(s) underlying this phenomenon are poorly understood. We hypothesized that STN neuronal activity is altered by contralateral STN DBS. This hypothesis was tested intraoperatively in humans with advanced PD using microelectrode recordings of the STN during contralateral STN DBS. We demonstrate alterations in the discharge pattern of STN neurons in response to contralateral STN DBS including short latency, temporally precise, stimulation frequency-independent responses consistent with antidromic activation. Furthermore, the total discharge frequency during contralateral high frequency stimulation (160 Hz) was greater than during low frequency stimulation (30 Hz) and the resting state. These findings demonstrate complex responses to DBS and imply that output activation throughout the basal ganglia-thalamic-cortical network rather than local inhibition is a therapeutic mechanism of DBS.

High-frequency deep brain stimulation of the putamen improves bradykinesia in Parkinson's disease.

Deep brain stimulation is effective for a wide range of neurological disorders; however, its mechanisms of action remain unclear. With respect to Parkinson's disease, the existence of multiple effective targets suggests that putamen stimulation also may be effective and raises questions as to the mechanisms of action. Are there as many mechanisms of action as there are effective targets or some single or small set of mechanisms common to all effective targets? During the course of routine surgery of the globus pallidus interna in patients with Parkinson's disease, the deep brain stimulation lead was placed in the putamen en route to the globus pallidus interna. Recordings of hand opening and closing during high-frequency and no stimulation were made. Speed of the movements, based on the amplitude and frequency of the repetitive hand movements as well as the decay in amplitude, were studied. Hand speed in 6 subjects was statistically significantly faster during active deep brain stimulation than the no-stimulation condition. There were no statistically significant differences in decay in the amplitude of hand movements. High-frequency deep brain stimulation of the putamen improves bradykinesia in a hand-opening and -closing task in patients with Parkinson's disease. Consequently, high-frequency deep brain stimulation of virtually every structure in the basal ganglia-thalamic-cortical system improves bradykinesia. These observations, together with microelectrode recordings reported in the literature, argue that deep brain stimulation effects may be system specific and not structure specific.

Returning to Growth: One Academic Medical Center's Successful Five-Step Approach to Change Management.

The University of Alabama at Birmingham academic medical center (UAB AMC) had achieved great success and growth during the 50 years since its founding. However, the challenging and more competitive environment of the 2000s left the UAB AMC on a downward trajectory. The UAB AMC had to overcome difficult internal cultural and structural barriers that stood in the way of the transformational change needed to remain competitive. Competition rather than collaborative and strategic financial investment were the primary cultural barriers for the UAB AMC, while people were the primary structural barrier. Leadership identified 5 steps that were critical for the transformation that occurred between 2013 and 2018: alignment of leadership; creating a compelling and credible shared vision; identifying cultural and structural barriers; creating a thoughtful, data-driven intervention; and improved communication and accountability. Following these steps enabled the UAB AMC to transform its institutional structure and culture. As a result, the UAB AMC thrived, returning to substantial growth in research and clinical care. UAB AMC School of Medicine grew by $100 million in National Institutes of Health funding and moved up 10 spots in ranking. In 2018, UAB Hospital had 10 specialties ranked by U.S. News & World Report, 7 more than in 2013. This article outlines the approach taken and provides a conceptual framework for other AMCs eager to transform their structure and culture and position themselves for growth.

Onset of dyskinesia with adjunct ropinirole prolonged-release or additional levodopa in early Parkinson's disease.

Levodopa-induced dyskinesia can result in significant functional disability and reduced quality of life in patients with Parkinson's disease (PD). The goal of this study was to determine if the addition of once-daily ropinirole 24-hour prolonged-release (n = 104) in PD patients not optimally controlled with levodopa after up to 3 years of therapy with less than 600 mg/d delays the onset of dyskinesia compared with increasing doses of levodopa (n = 104). During the study, 3% of the ropinirole prolonged-release group (mean dose 10 mg/d) and 17% of the levodopa group (mean additional dose 284 mg/d) developed dyskinesia (P < 0.001). There were no significant differences in change in Unified Parkinson's Disease Rating Scale activities of daily living or motor scores, suggesting comparable efficacy between the two treatments. Adverse events were comparable in the two groups with nausea, dizziness, insomnia, back pain, arthralgia, somnolence, fatigue, and pain most commonly reported. Ropinirole prolonged-release delayed the onset of dyskinesia with comparable efficacy to increased doses of levodopa in early PD patients not optimally controlled with levodopa.

Quality of life in Parkinson's disease patients following adjunctive tolcapone therapy: results of an open-label, multicenter, community-based trial.

OBJECTIVE: To examine changes in quality of life (QOL) and global clinical status after 30 days of adjunctive treatment with tolcapone, a revers-ible inhibitor of catechol-O-methyltransferase, in patients with fluctuating Parkinson's disease. METHODS: This 30-day, multicenter, open-label, community-based study enrolled fluctuating Parkinson's disease patients to receive tolcapone 100 mg TID as an adjunct to levodopa/carbidopa. The primary end point was QOL change assessed using the Parkinson's Disease Questionnaire (PDQ)-8. Clinical change was assessed using the investigator-rated Clinical Global Impression of Improvement Scale (CGI-I). RESULTS: Fifty-six physicians enrolled 202 patients; 138 (68%) were > or = 65 years of age and 116 (57%) had Parkinson's disease for > or = 5 years. The mean PDQ-8 total score improved from 42.1 to 34.8 after 30 days of tolcapone (P<.0001). Sixty-nine percent of patients improved on the CGI-I. Physicians planned to continue tolcapone beyond the 30 days in 72%, most commonly because of positive changes in motor function and overall general improvement. No patient discontinued because of liver adverse events. CONCLUSIONS: Adjunctive tolcapone treatment was associated with statistically significant improvement in QOL in fluctuating Parkinson's disease patients. A majority of patients experienced clinical benefits and continued treatment beyond the end of this study. No liver-related adverse events were reported.

Construction of relational topographies from the quantitative measurements of functional deep brain stimulation using a 'roving window' interpolation algorithm.

The delivery of stimulus by a deep brain stimulation (DBS) contact electrode at a particular location may lead to a quantifiable physiologic effect, both intraoperatively and postoperatively. Consequently, measured data values can be attributed to discrete scattered points in neuroanatomic space, allowing for interpolative techniques to generate a topographic map of spatial patterns. Ultimately, by relating the topographies of various intraoperative measurements to the postoperative counterparts and neuroanatomic atlases, outcome-guided adjustments to electrode position can be pursued intraoperatively. In this study, 52 Parkinson's disease patients were tested with a postoperative trial of stimulation and thresholds were recorded for motor adverse effects. A 'roving window' interpolation algorithm was adapted to generate a topographic map of voltage threshold along selected axial, coronal and sagittal planes. By developing these relational topographies for a variety of intraoperative and postoperative effects, a multivariable approach towards DBS optimization emerges.

Replication of association between ELAVL4 and Parkinson disease: the GenePD study.

Genetic variants in embryonic lethal, abnormal vision, Drosophila-like 4 (ELAVL4) have been reported to be associated with onset age of Parkinson disease (PD) or risk for PD affection in Caucasian populations. In the current study we genotyped three single nucleotide polymorphisms in ELAVL4 in a Caucasian study sample consisting of 712 PD patients and 312 unrelated controls from the GenePD study. The minor allele of rs967582 was associated with increased risk of PD (odds ratio = 1.46, nominal P value = 0.011) in the GenePD population. The minor allele of rs967582 was also the risk allele for PD affection or earlier onset age in the previously studied populations. This replication of association with rs967582 in a third cohort further implicates ELAVL4 as a PD susceptibility gene.

The Gly2019Ser mutation in LRRK2 is not fully penetrant in familial Parkinson's disease: the GenePD study.

BACKGROUND: We report age-dependent penetrance estimates for leucine-rich repeat kinase 2 (LRRK2)-related Parkinson's disease (PD) in a large sample of familial PD. The most frequently seen LRRK2 mutation, Gly2019Ser (G2019S), is associated with approximately 5 to 6% of familial PD cases and 1 to 2% of idiopathic cases, making it the most common known genetic cause of PD. Studies of the penetrance of LRRK2 mutations have produced a wide range of estimates, possibly due to differences in study design and recruitment, including in particular differences between samples of familial PD versus sporadic PD. METHODS: A sample, including 903 affected and 58 unaffected members from 509 families ascertained for having two or more PD-affected members, 126 randomly ascertained PD patients and 197 controls, was screened for five different LRRK2 mutations. Penetrance was estimated in families of LRRK2 carriers with consideration of the inherent bias towards increased penetrance in a familial sample. RESULTS: Thirty-one out of 509 families with multiple cases of PD (6.1%) were found to have 58 LRRK2 mutation carriers (6.4%). Twenty-nine of the 31 families had G2019S mutations while two had R1441C mutations. No mutations were identified among controls or unaffected relatives of PD cases. Nine PD-affected relatives of G2019S carriers did not carry the LRRK2 mutation themselves. At the maximum observed age range of 90 to 94 years, the unbiased estimated penetrance was 67% for G2019S families, compared with a baseline PD risk of 17% seen in the non-LRRK2-related PD families. CONCLUSION: Lifetime penetrance of LRRK2 estimated in the unascertained relatives of multiplex PD families is greater than that reported in studies of sporadically ascertained LRRK2 cases, suggesting that inherited susceptibility factors may modify the penetrance of LRRK2 mutations. In addition, the presence of nine PD phenocopies in the LRRK2 families suggests that these susceptibility factors may also increase the risk of non-LRRK2-related PD. No differences in penetrance were found between men and women, suggesting that the factors that influence penetrance for LRRK2 carriers are independent of the factors which increase PD prevalence in men.

Medical decision-making capacity in cognitively impaired Parkinson's disease patients without dementia.

Little is currently known about the higher order functional skills of patients with Parkinson disease and cognitive impairment. Medical decision-making capacity (MDC) was assessed in patients with Parkinson's disease (PD) with cognitive impairment and dementia. Participants were 16 patients with PD and cognitive impairment without dementia (PD-CIND), 16 patients with PD dementia (PDD), and 22 healthy older adults. All participants were administered the Capacity to Consent to Treatment Instrument (CCTI), a standardized capacity instrument assessing MDC under five different consent standards. Parametric and nonparametric statistical analyses were utilized to examine capacity performance on the consent standards. In addition, capacity outcomes (capable, marginally capable, or incapable outcomes) on the standards were identified for the two patient groups. Relative to controls, PD-CIND patients demonstrated significant impairment on the understanding treatment consent standard, clinically the most stringent CCTI standard. Relative to controls and PD-CIND patients, PDD patients were impaired on the three clinical standards of understanding, reasoning, and appreciation. The findings suggest that impairment in decisional capacity is already present in cognitively impaired patients with PD without dementia and increases as these patients develop dementia. Clinicians and researchers should carefully assess decisional capacity in all patients with PD with cognitive impairment.

Huntington CAG repeat size does not modify onset age in familial Parkinson's disease: the GenePD study.

The ATP/ADP ratio reflects mitochondrial function and has been reported to be influenced by the size of the Huntington disease gene (HD) repeat. Impaired mitochondrial function has long been implicated in the pathogenesis of Parkinson's disease (PD), and therefore, we evaluated the relationship of the HD CAG repeat size to PD onset age in a large sample of familial PD cases. PD affected siblings (n = 495), with known onset ages from 248 families, were genotyped for the HD CAG repeat. Genotyping failed in 11 cases leaving 484 for analysis, including 35 LRRK2 carriers. All cases had HD CAG repeats (range, 15-34) below the clinical range for HD, although 5.2% of the sample (n = 25) had repeats in the intermediate range (the intermediate range lower limit = 27; upper limit = 35 repeats), suggesting that the prevalence of intermediate allele carriers in the general population is significant. No relation between the HD CAG repeat size and the age at onset for PD was found in this sample of familial PD.

A founding LRRK2 haplotype shared by Tunisian, US, European and Middle Eastern families with Parkinson's disease.

The Leucine-rich repeat kinase 2 (LRRK2) gene has been identified as a disease susceptibility gene for Parkinson's disease (PD), with G2019 (6055G>A) being the most frequent mutation. This mutation was present in 42% (38/91) of Tunisian families and 2% (1/39) of US families we have studied. A founding haplotype was identified in our data and it is shared by families from Tunisia, US, European and Middle Eastern countries. The most recent common founder of the mutation was dated to 2600 (95% CI: 1950-3850) years ago although additional studies are warranted to ensure an accurate age estimate for this mutation.

Brain metabolism differs in Alzheimer's disease and Parkinson's disease dementia.

BACKGROUND: Few comparative studies exist of metabolic brain changes among neurodegenerative illnesses. We compared brain metabolic abnormalities in Alzheimer's disease (AD) and in Parkinson's disease with dementia (PDD) as measured by proton magnetic resonance spectroscopy (MRS). METHODS: Twelve patients with idiopathic PDD, 22 patients with probable mild AD, and 61 healthy older controls underwent posterior cingulate MRS. RESULTS: Patients with AD exhibited reduced N-acetyl aspartate (NAA)/creatine (Cr) (P < .05) and increased choline (Cho)/Cr (P < .05) and myo-inositol (mI)/Cr (P < .01) compared with controls. Patients with PDD exhibited reduced NAA/Cr (P < .05) and glutamate (Glu)/Cr (P < .01) compared with controls. There was reduced Glu/Cr in PDD compared with AD (P < .01). CONCLUSIONS: Patients with AD and patients with PDD exhibited distinct brain metabolic MRS profiles. Findings suggest that comparison of brain MRS profiles across dementias provides useful direction for future study.

Transdermal rotigotine: double-blind, placebo-controlled trial in Parkinson disease.

OBJECTIVE: To assess the response to the rotigotine transdermal system (Neupro; Schwarz Pharma Ltd, Monheim, Germany), a nonergolinic dopamine agonist, in patients with early Parkinson disease. DESIGN: Randomized, double-blind, multicenter, placebo-controlled study. SETTING: Fifty sites in the United States and Canada. PATIENTS: Two hundred seventy-seven patients with early Parkinson disease. Eligibility was assessed by means of routine clinical and neurological examinations. Patients were randomized 2:1 to receive either rotigotine therapy or placebo. INTERVENTION: Treatment with the rotigotine transdermal system, 2, 4, or 6 mg during 24 hours, for 24 weeks. MAIN OUTCOME MEASURE: Percentage of subjects achieving a 20% response or greater (reduction) as assessed with the Unified Parkinson Disease Rating Scale subtotal (parts II [activities of daily living] and III [motor function]) from baseline to the end of the maintenance phase. RESULTS: Significant differences were observed between the rotigotine-treated and placebo groups for the 20% responder rate (48% for the rotigotine group and 19% for the placebo group; P<.001), least squares mean change in Unified Parkinson Disease Rating Scale subtotal (parts II and III) score (-941 for rotigotine vs -157 for placebo; P<.001), and percentage changes in Unified Parkinson Disease Rating Scale subtotal (parts II and III) score (-15.1% for rotigotine vs 7.3% for placebo; P<.001). Rotigotine treatment significantly increased the patients' Clinical Global Impression Scale scores (57% for rotigotine vs 30% for placebo; P<.001) and had a positive effect on their quality of life. The most common adverse events were application site reactions, nausea, and somnolence. Twenty-five (14%) of 181 patients in the rotigotine group withdrew from the study because of adverse effects. CONCLUSION: The rotigotine transdermal system consistently demonstrated statistically significant and clinically relevant efficacy over placebo in patients with early Parkinson disease and was well tolerated.

The effect of unilateral subthalamic nucleus deep brain stimulation on depression in Parkinson's disease.

BACKGROUND: Depression is common in Parkinson's disease (PD) and adversely affects quality of life. Both unilateral and bilateral subthalamic (STN) deep brain stimulation (DBS) effectively treat the motor symptoms of PD, but questions remain regarding the impact of unilateral STN DBS on non-motor symptoms, such as depression. METHODS: We report changes in depression, as measured by the Hamilton Depression Rating Scale (HAMD-17), in 50 consecutive PD patients who underwent unilateral STN DBS. Participants were also evaluated with UPDRS part III, Parkinson's Disease Questionnaire-39, and Pittsburgh Sleep Quality Index. The primary outcome was change in HAMD-17 at 6 months versus pre-operative baseline, using repeated measures analysis of variance (ANOVA). Secondary outcomes included the change in HAMD-17 at 3, 12, 18, and 24 months post-operatively and correlations amongst outcome variables using Pearson correlation coefficients. As a control, we also evaluated changes in HAMD-17 in 25 advanced PD patients who did not undergo DBS. RESULTS: Participants with unilateral STN DBS experienced significant improvement in depression 6 months post-operatively (4.94 ± 4.02) compared to preoperative baseline (7.90 ± 4.44) (mean ± SD) (p = <0.0001). HAMD-17 scores did not correlate with UPDRS part III at any time-point. Interestingly, the HAMD-17 was significantly correlated with sleep quality and quality of life at baseline, 3 months, and 6 months post-operatively. Participants without DBS experienced no significant change in HAMD-17 over the same interval. CONCLUSION: Unilateral STN DBS improves depression 6 months post-operatively in patients with PD. Improvement in depression is maintained over time and correlates with improvement in sleep quality and quality of life.