Dual dopamine agonist treatment in Parkinson’s disease

We studied the effectiveness of cabergoline as an adjunct in patients with early Parkinson's disease receiving another dopamine agonist (pramipexole or ropinirole), at the maximal permitted dose. The study enrolled 47 patients: 35 had motor fluctuations and were receiving a dopamine agonist with levodopa; and 12, without motor fluctuations, were receiving a dopamine agonist without levodopa. These medications had in all cases failed to achieve adequate symptom control. In the 35 patients with motor fluctuations, when cabergoline was added to therapy, the time spent in the OFF period decreased by 65.6% (from 3.14+/-1.11 to 1.08+/-1.07 hours p<0.0001); and the Unified Parkinson's Disease Rating Scale (UPDRS) motor score decreased by 19.24% (from 41.68+/-12.6 to 33.66+/-10.22; (p<0.0001) during the OFF condition, and by 7.11% (from 17.01+/-6.63 to 15.8+/-7.22; p<0.001) during the ON condition. Nocturnal akinesia improved in all the patients except one. In the 12 patients without motor fluctuations, when cabergoline was added, the UPDRS score improved by 34.4% (from 23.5+/-5.3 to 15.5+/-4.7).This open study shows that dual dopamine agonist therapy can be useful in the symptomatic treatment of patients with early or more advanced Parkinson's disease receiving therapy with or without levodopa.     

Computerized assessment of goal-directed behavior in Parkinson’s disease

Introduction: Apathy is a syndrome characterized by a reduction in goal-directed behavior. Neurodegenerative diseases frequently exhibit apathy. However, we lack an objective measure of apathy. The Philadelphia Apathy Computerized Task (PACT) measures impairments in goal-directed behavior that contribute to apathy, including initiation, planning, and motivation. We sought to examine these mechanisms in Parkinson’s disease (PD) patients. Method: PD patients and healthy controls with a caregiver were recruited for the study. Participants were administered the PACT, a novel computerized assessment of goal-directed behavior based on reaction times, and the Starkstein Apathy Scale (AS). Care partners completed the Neuropsychiatric Inventory (NPI). Baseline demographic characteristics of PD and control participants were compared using t tests and Wilcoxon rank sum tests. Linear regressions were used to compare PD patients to controls on each of the three PACT subtasks (initiation, planning, and motivation) while controlling for motor slowing. We then compared performance on each PACT subtask between PD subjects defined as apathetic using the NPI and Starkstein Apathy Scale and controls. Results: We included 30 PD and 15 control participants in the analysis. When controlling for motor slowing, both all PD and PD apathetic subjects were significantly slower than controls on the planning task and on the initiation task. There were no significant differences between PD patients and controls on the motivation tasks. Conclusions: PD patients showed specific initiation and planning deficits compared to control participants. After using traditional scales to define apathy, PD apathetic patients still exhibited impaired initiation and planning behaviors. These results suggest that the PACT measures aspects of impaired goal-directed behavior that may contribute to apathy in PD.     

Does REM sleep behavior disorder change in the progression of Parkinson’s disease?

Objectives/backgroundRapid eye movement (REM) Sleep Behavior Disorder (RBD) in Parkinson's disease (PD) may be associated with a malignant phenotype. Despite its prognostic value, little is known about the time course of RBD in PD. In this study, we aimed to ascertain whether or not RBD is a stable feature in PD. In this study, we prospectively evaluated clinical and neurophysiological features of RBD, including REM Sleep Without Atonia (RSWA), in PD patients with RBD at baseline and after three years then assessed whether the changes in measures of RSWA parallel the progression of PD.Patients/methodsIn sum, 22 (17M, mean age 64.0 ± 6.9 years) moderate-to-advanced PD patients (mean PD duration at baseline:7.6±4.8 years) with RBD, underwent a video-polysomnography (vPSG) recording and clinical and neuropsychological assessment at baseline and after three years.ResultsAt follow-up, the self-assessed frequency of RBD symptoms increased in six patients, decreased in six and remained stable in 10, while RSWA measures significantly increased in all subjects. At follow-up, patients showed worse H&Y stage (p = 0.02), higher dopaminergic doses (p = 0.05) and they performed significantly worse in phonetic and semantic fluency tests (p = 0.02; p = 0.04). Changes in RSWA correlated significantly with the severity in levodopa-induced dyskinesia (r = 0.61,p = 0.05) and motor fluctuation (r = 0.54,p = 0.03) scores, and with the worsening of executive functions (r = 0.78,p = 0.001) and visuo-spatial perception (r = −0.57,p = 0.04).ConclusionDespite the subjective improvement of RBD symptoms in one-fourth of PD patients, all RSWA measures increased significantly at follow-up, and their changes correlated with the clinical evolution of motor and non-motor symptoms. RBD is a long-lasting feature in PD and RSWA is a marker of the disease's progression.     

Depression and apathy in Parkinson’s disease

This article provides an update on depression and apathy in Parkinson’s disease (PD), both of which are common but often misunderstood. The diagnosis of depression in PD can be challenging and we still do not have solid evidence on which to base our treatment decisions. Apathy is most commonly seen in the setting of dementia or depression but emerging evidence suggests that it may be a core feature of PD. There are conflicting reports about the effects of deep brain stimulation (DBS) on mood and apathy, but studies suggest that at least some patients may develop depression and apathy after the procedure. Although we are making strides toward a better understanding of depression and apathy in PD, it is clear that more research is needed about these non-motor features.     

Does freezing in Parkinson’s disease change limb coordination?

The aim of this study was to analyse the kinematic characteristics of the strides before freezing and compare this with a voluntary stop and ongoing gait. Also, we investigated whether gait profiles were different as a function of the side of the body. Ten patients were included with a mean age of 64.8 years (SD 5.1). Within a Vicon 3D gait laboratory, patients performed several trials of normal walking and voluntary stops or were exposed to circumstances, which provoked freezing in the off-phase of the medication cycle. Spatiotemporal and key kinematic data of the four strides prior to freezing were compared between body sides and walking conditions using multiple regression models for repeated measures. Prior to freezing patients had severely decreased movement ranges in the sagittal plane (ranging between 31% and 61.5%), most notably in the ankle and hip joints. The general shape of movement remained in the pre-freezing profiles with largely intact dissociation of knee and hip movement in stance but reduced dissociation in swing. Also present were reduced push-off movements in the ankle with fixed dorsiflexion, increased flexion in hip and knee and anterior tilt of the pelvis. During both voluntary (stopping) and involuntary deceleration (freezing), the body side with the last complete stride before the freeze, showed significantly smaller joint ranges (p < .01). Body side differences were larger than sequential deterioration of consecutive steps within each side. Freezing is distinct from normal deceleration of gait in that the reduction of propulsive movement is much greater. Despite hastening of steps, timing deficits did not affect overall movement shapes, except for the tendency to have a flexed walking pattern. The side of the body where gait terminated before freezing was in most cases the side of symptom-dominance, but not consistently so.     

Neuroimaging in Parkinson’s disease

In this review, the potential role of positron emission tomography and single photon emission computed tomography as biological markers for diagnosing and following the progression of Parkinson’s disease (PD) is discussed. Their value for assessing the efficacy of putative neuroprotective agents in PD and for revealing the pharmacological changes underlying the symptomatology and complications of this disorder is also considered. It is concluded that in the future functional imaging will provide a valuable adjunct to clinical assessment when judging the efficacy of putative neuroprotective approaches to PD.     

Depression in Parkinson’s disease

Among the recently well appreciated non-motor symptoms in Parkinson’s disease (PD), depression plays a prominent role due to its frequency and impact on quality of life. However, depression may be confounded by motor symptoms, especially akinesia and other non-motor symptoms such as apathy, anxiety and dementia. Data on specific diagnostic tools or treatment for depressive symptoms in PD patients are still sparse. Here we summarize an expert opinion based on available data and clinical experience.

     

Chronic subthalamic nucleus stimulation and striatal D2 dopamine receptors in Parkinson’s disease

Abstract. Context: Subthalamic nucleus (STN) stimulation mechanism of action remains a matter for debate. In animals, an increased striatal dopamine (DA) release due to STN stimulation has been reported. Objective: To determine in Parkinsons disease (PD) patients using positron emission tomography (PET) and [¹¹C]-Raclopride, whether STN stimulation induces a striatal DA release. Methods: Nine PD patients with bilateral STN stimulation were enrolled and underwent two [¹¹C]-Raclopride PET scans. The scans were randomly performed in off and on stimulation conditions. Striatal [¹¹C]-Raclopride binding potential (BP) was calculated using regions of interest and statistical parametric mapping. Results: For PD patients, the mean [¹¹C]-Raclopride BP (± SD) were, in Off stimulation condition: 1.7 ± 0.3 for the right caudate nucleus, 1.8 ± 0.4 for the left caudate nucleus, 2.6 ± 0.5 for the right putamenand 2.6 ± 0.5 for the left putamen. In On stimulation condition: 1.7 ± 0.4 for the right caudate nucleus, 1.9 ± 0.5 for the left caudate nucleus, 2.8 ± 0.7 for the right putamen and 2.7 ± 0.8 for the left putamen. No significant difference of BP related to the stimulation was noted. Conclusion: STN stimulation does not produce significant variations of striatal DA release as assessed by PET and [¹¹C]-Raclopride.     

Depression in Parkinson’s disease

Abstract Objectives The pathophysiology of depression and anxiety in Parkinson's disease remains obscure. We aimed to compare the fractional anisotropy (FA) values of Parkinson's disease (PD) patients with and without depression to investigate the nature of depression in PD. Methods Twenty-eight patients were divided into two groups: those with depression and those without. Diagnosis of depression was made using the DSM-IV criteria. Patients in the two groups were matched for Hoehn Yahr stage. Results There were significant reductions in FA values in the bilateral frontal ROIs possibly representing anterior cingulate bundles. Conclusions The anterior cingulate bundles play an important role in depression in PD, and some aspects of depression in PD have pathological processes in common with de novo depression.     

Cancer in Parkinson’s disease

INTRODUCTIONWe examined the prevalence of cancer in patients with Parkinson’s disease (PD) and controls evaluated at the Mayo Clinic in Jacksonville, Florida, between 2003 and 2014.METHODSWe retrospectively collected information regarding cancer diagnoses and diagnosis of PD from 971 unrelated PD patients and 478 controls, and all were white. For PD patients, we examined cancers diagnosed before and after PD diagnosis separately in addition to considering all cancer diagnoses.RESULTSTwenty different cancers were identified. In PD patients, the most common types of cancer were skin cancer (17.3% overall; 10.6% before PD), followed by nonmelanoma skin cancer (16.0% overall; 9.7% before PD), prostate cancer in men (12.8% overall; 9.2% before PD), breast cancer in women (10.6% overall; 6.3% before PD), and melanoma (2.4% overall; 1.1% before PD). Compared to controls, a significantly lower frequency of nonmelanoma skin cancer (odds ratio [OR]: 0.62, P = 0.0024) and any skin cancer (OR: 0.57, P = 0.0002) was observed in PD patients. These differences were greater when considering only cases with cancers that occurred before PD diagnosis (OR: 0.49, P < 0.0001; OR: 0.45, P < 0.0001, respectively), and there was a lower frequency of melanoma and any cancer preceding PD diagnosis compared to controls (OR: 0.31, P = 0.003; OR: 0.36, P < 0.0001). There was no evidence of a frequency difference for any other cancer.CONCLUSIONSPD patients had a lower frequency of skin cancers or any cancer prior to PD diagnosis compared to controls, suggesting that cancer may have a protective effect on PD risk.     

Depression in Parkinson’s disease

Depression is common in Parkinson’s disease (PD), and its identification and treatment are critically important in disease management. Despite depression’s high prevalence and major impact on patient quality of life, questions remain regarding its epidemiology and preferred treatment. The authors of this paper summarize available information on the epidemiology of depression in PD, review treatment options, and discuss possible interactions between antidepressants and other agents. This information may help guide clinical treatment and define the need for further studies.     

Caregiving and Parkinson’s disease

Abstract. Relatively little has been published in the international literature concerning the caregiving-related problems associated with Parkinsons disease. We therefore undertook two exploratory studies that have allowed us to identify the needs and specific problems perceived by such caregivers in both qualitative and quantitative terms.     

Depression and Parkinson’s disease

Abstract.   Depression occurs in approximately 45% of all patients with Parkinsons disease (PD), reduces quality of life independent of motor symptoms and seems to be underrated and undertreated. Characteristics of symptoms differ from major depression. Because of overlapping clinical symptoms, diagnosis is based on subjectively experienced anhedonia and feeling of emptiness. Available rating scales for major depression may not be adequate to correctly measure severity of depression in PD. Anxiety and depression may manifest as first symptoms of PD many years before motor symptoms. Serotonergic, noradrenergic and dopaminergic mechanisms play key roles in the etiology of depression in PD. Tricyclic and newer, selective antidepressants including serotonin and noradrenaline reuptake inhibitors (SSRI, SNRI) appear to be effective in treating depression in PD. Selective reuptake inhibitors seem to have a favorable side effect profile. Recent controlled studies show antidepressant effects of pramipexole in bipolar II depression. New dopamine agonists pramipexole and ropinirole appear to ameliorate depressive symptoms in PD in addition to effects on motor symptoms. There is a lack of appropriate rating scales and controlled studies regarding depression in PD.     

Rifampicin and Parkinson’s disease

Rifampicin is a macrocyclic antibiotic used extensively for the treatment of Mycobacterium tuberculosis and other mycobacterial infections. Recently, it was discovered that rifampicin exhibits neuroprotective effects. It has been shown to protect PC12 cells against MPP⁺-induced apoptosis and inhibit the expression of α-synuclein multimers. In in vitro studies, rifampicin pretreatment protects PC12 cells against rotenone-induced cell death. Qualitative and quantitative analyses uncover that rifampicin significantly suppresses rotenone-induced apoptosis by ameliorating mitochondrial oxidative stress. It reduces microglial inflammation and improves neuron survival. Our results indicate that rifampicin is cytoprotective under a variety of experimental conditions, and suggest that it may be useful in PD therapeutics. It is the aim of this paper to review the experimental neuroprotection data reported using rifampicin with a focus on the molecular and cellular mechanisms of cytoprotective effect in in vitro models of PD.