Seniors with Parkinson's Disease: Initial Medical Treatment

Parkinson's disease most often presents after age 60, and patients in this age group are best managed with levodopa therapy as the primary treatment modality. Unlike young-onset parkinsonism (onset <age 40), this older age group is much less prone to subsequent development of levodopa responsive instability (dyskinesias, fluctuations). When these problems do occur in seniors, they usually can be managed by medication adjustments. The treatment goal is to keep patients active and engaged; levodopa dosage should be guided by the patients' responses and not arbitrarily limited to low doses, which may compromise patients' lives

Non-motor predictors of 36-month quality of life after subthalamic stimulation in Parkinson disease

Publisher Copyright: © 2021, The Author(s).To identify predictors of 36-month follow-up quality of life (QoL) outcome after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD). In this ongoing, prospective, multicenter international study (Cologne, Manchester, London) including 73 patients undergoing STN-DBS, we assessed the following scales preoperatively and at 6-month and 36-month follow-up: PD Questionnaire-8 (PDQ-8), NMSScale (NMSS), Scales for Outcomes in PD (SCOPA)-motor examination, -activities of daily living, and -complications, and levodopa equivalent daily dose (LEDD). We analyzed factors associated with QoL improvement at 36-month follow-up based on (1) correlations between baseline test scores and QoL improvement, (2) step-wise linear regressions with baseline test scores as independent and QoL improvement as dependent variables, (3) logistic regressions and receiver operating characteristic curves using a dichotomized variable “QoL responders”/“non-responders”. At both follow-ups, NMSS total score, SCOPA-motor examination, and -complications improved and LEDD was reduced significantly. PDQ-8 improved at 6-month follow-up with subsequent decrements in gains at 36-month follow-up when 61.6% of patients were categorized as “QoL non-responders”. Correlations, linear, and logistic regression analyses found greater PDQ-8 improvements in patients with younger age, worse PDQ-8, and worse specific NMS at baseline, such as ‘difficulties experiencing pleasure’ and ‘problems sustaining concentration’. Baseline SCOPA scores were not associated with PDQ-8 changes. Our results provide evidence that 36-month QoL changes depend on baseline neuropsychological and neuropsychiatric non-motor symptoms burden. These findings highlight the need for an assessment of a wide range of non-motor and motor symptoms when advising and selecting individuals for DBS therapy.Peer reviewe

A systematic review of biomarkers for disease progression in Parkinson's disease

Peer reviewedPublisher PD

Clinical Practice Patterns in Tic Disorders Among Movement Disorder Society Members

[Background] Tic disorders belong to the broad spectrum of pediatric and adult movement disorders. The wide variability in clinical presentations, applied assessment tools, and treatments are poorly understood.[Objectives] To map practices and knowledge base of movement disorder clinicians concerning clinical features, pathophysiology, and treatment approaches in tic disorders. [Methods] A 33-item survey was developed by the Tic Disorders and Tourette syndrome Study Group members of the Movement Disorder Society. The survey was distributed to the complete society membership and included responses from 346 members, 314 of whom reported treating tic disorders. [Results] Approximately one third of survey respondents (35%) frequently evaluated patients with tics. The data revealed widespread use of existing guidelines (about 70%) and screening for comorbid disorders (>90%). The most common investigations used to rule out secondary causes of tics were imaging (92%), laboratory tests (66%) and neurophysiology (38%). Functional tics were the second most common tic etiology following primary tics. Only 27% of respondents reported confidence in knowledge about tic pathogenesis. Top rated interventions to treat tics were psychoeducation, cognitive behavioral intervention for tics (CBIT) and treatment for neuropsychiatric comorbidities. Antipsychotics were ranked as the most effective pharmacologic tic intervention. Conclusions: The majority of movement disorders specialists do not frequently encounter tics. There was sparse knowledge about tic pathophysiology. Psychoeducation, CBIT, the treatment of neuropsychiatric comorbidities and use of antipsychotics emerged as the most common interventions to treat tics. These results provide insight into what will be needed to improve the diagnosis and treatment of tic disorders.CG is supported by the Freigeist Fellowship of the VolkswagenStiftung. He has served as ad hoc advisory board to Biomarin and received honoraria from the International Parkinsons Disease and Movement Disorders Society for educational activities

parkin-induced defects in neurophysiology and locomotion are generated by metabolic dysfunction and not oxidative stress

Parkinson's disease (PD) is characterized by movement disorders, including bradykinesia. Analysis of inherited, juvenile PD, identified several genes linked via a common pathway to mitochondrial dysfunction. In this study, we demonstrate that the larva of the Drosophila parkin mutant faithfully models the locomotory and metabolic defects of PD and is an excellent system for investigating their inter-relationship. parkin larvae displayed a marked bradykinesia that was caused by a reduction in both the frequency of peristalsis and speed of muscle contractions. Rescue experiments confirmed that this phenotype was due to a defect in the nervous system and not in the muscle. Furthermore, recordings of motoneuron activity in parkin larvae revealed reduced bursting and a striking reduction in evoked and miniature excitatory junction potentials, suggesting a neuronal deficit. This was supported by our observations in parkin larvae that the resting potential was depolarized, oxygen consumption and ATP concentration were drastically reduced while lactate was increased. These findings suggest that neuronal mitochondrial respiration is severely compromised and there is a compensatory switch to glycolysis for energy production

Presynaptic monoaminergic vesicles in Parkinson's disease and normal aging

We present development and human application of a method for determining the regional cerebral density of the type 2 vesicular monoamine transporter (VMAT2) using positron emission tomography (PET) and [ 11 C]dihydrotetrabenazine (DTBZ). Previous animal studies indicate striatal VMAT2 density is linearly related to the integrity of substantia nigra dopamine neurons and is not subject to drug-or lesion-compensatory regulation. In the present studies, kinetic compartmental modeling was employed to estimate blood-brain [ 11 C]DTBZ transport ( K 1 ,) and VMAT2 binding site density (tissue-to-plasma DTBZ distribution volume, DV )from the cerebral and plasma DTBZ time courses her intravenous tracer injection. In controls, we found reductions of putamen DTBZ DV with advancing age, corresponding to losses of 0.77% per year in specific VMAT2 binding. Parkinson's disease (PD) patients had reduction in specific DTBZ DV in the putamen (−61%) and in the caudate nucleus (−43%). There was no overlap of lowest specific putamen DTBZ DV between individual elderly controls and PD patients. The present results indicate the suitability of [ 11 C]DTBZ PET for objective quantification of nigrostriatal integrity, including evaluation of PD progression and its possible therapeutic modification.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50362/1/410400609_ftp.pd

Drug-Induced Parkinsonism

Drug-induced parkinsonism (DIP) is the second-most-common etiology of parkinsonism in the elderly after Parkinson's disease (PD). Many patients with DIP may be misdiagnosed with PD because the clinical features of these two conditions are indistinguishable. Moreover, neurological deficits in patients with DIP may be severe enough to affect daily activities and may persist for long periods of time after the cessation of drug taking. In addition to typical antipsychotics, DIP may be caused by gastrointestinal prokinetics, calcium channel blockers, atypical antipsychotics, and antiepileptic drugs. The clinical manifestations of DIP are classically described as bilateral and symmetric parkinsonism without tremor at rest. However, about half of DIP patients show asymmetrical parkinsonism and tremor at rest, making it difficult to differentiate DIP from PD. The pathophysiology of DIP is related to drug-induced changes in the basal ganglia motor circuit secondary to dopaminergic receptor blockade. Since these effects are limited to postsynaptic dopaminergic receptors, it is expected that presynaptic dopaminergic neurons in the striatum will be intact. Dopamine transporter (DAT) imaging is useful for diagnosing presynaptic parkinsonism. DAT uptake in the striatum is significantly decreased even in the early stage of PD, and this characteristic may help in differentiating PD from DIP. DIP may have a significant and longstanding effect on patients' daily lives, and so physicians should be cautious when prescribing dopaminergic receptor blockers and should monitor patients' neurological signs, especially for parkinsonism and other movement disorders

Visual hallucinations in the psychosis spectrum and comparative information from neurodegenerative disorders and eye disease

Much of the research on visual hallucinations (VHs) has been conducted in the context of eye disease and neurodegenerative conditions, but little is known about these phenomena in psychiatric and nonclinical populations. The purpose of this article is to bring together current knowledge regarding VHs in the psychosis phenotype and contrast this data with the literature drawn from neurodegenerative disorders and eye disease. The evidence challenges the traditional views that VHs are atypical or uncommon in psychosis. The weighted mean for VHs is 27% in schizophrenia, 15% in affective psychosis, and 7.3% in the general community. VHs are linked to a more severe psychopathological profile and less favorable outcome in psychosis and neurodegenerative conditions. VHs typically co-occur with auditory hallucinations, suggesting a common etiological cause. VHs in psychosis are also remarkably complex, negative in content, and are interpreted to have personal relevance. The cognitive mechanisms of VHs in psychosis have rarely been investigated, but existing studies point to source-monitoring deficits and distortions in top-down mechanisms, although evidence for visual processing deficits, which feature strongly in the organic literature, is lacking. Brain imaging studies point to the activation of visual cortex during hallucinations on a background of structural and connectivity changes within wider brain networks. The relationship between VHs in psychosis, eye disease, and neurodegeneration remains unclear, although the pattern of similarities and differences described in this review suggests that comparative studies may have potentially important clinical and theoretical implications. © 2014 The Author