Determining the impact of specialized care on health outcomes and health care utilization in Parkinsonism.

BACKGROUND: Although care of Parkinsonism (PKM) is assumed to be optimally provided by movement disorder neurologists within an interdisciplinary clinic model, there is a paucity of published data to support this. OBJECTIVES: To investigate the impact of movement disorder neurologist care of individuals with Parkinsonism (PKM). METHODS: A retrospective exposure design was adopted using administrative data. Incident PKM individuals were identified in billing claims. A nine-year exposure period to movement disorder neurologist, general neurologist and non-neurologist care was calculated based on the billing codes. Regression models were used to test the association of provider exposure on time to death and long-term care (LTC) admission. Linear models were used to test varying provider exposure and hospital admissions, hospital days and emergency department visits. RESULTS: 1914 incident individuals were identified. There was no difference in PKM mortality, emergency visits, hospital admissions, or hospital days between providers, however exposure to general neurology and non-neurology care was associated with a significantly higher risk of admission to LTC compared to movement disorder neurologist care (HR 1.43; 95% CI 1.09-1.87 for general neurology (p-value = 0.0089); HR 1.61; 95% CI 1.25-2.05 for non-neurology (p-value = 0.0002), respectively. CONCLUSION: Movement disorder neurologist care is associated with a lower risk of admission to LTC over general neurologist care in individuals with PKM.

Changes in Metabolic Activity and Gait Function by Dual-Task Cognitive Game-Based Treadmill System in Parkinson's Disease: Protocol of a Randomized Controlled Trial.

Balance and gait impairments, and consequently, mobility restrictions and falls are common in Parkinson's disease (PD). Various cognitive deficits are also common in PD and are associated with increased fall risk. These mobility and cognitive deficits are limiting factors in a person's health, ability to perform activities of daily living, and overall quality of life. Community ambulation involves many dual-task (DT) conditions that require processing of several cognitive tasks while managing or reacting to sudden or unexpected balance challenges. DT training programs that can simultaneously target balance, gait, visuomotor, and cognitive functions are important to consider in rehabilitation and promotion of healthy active lives. In the proposed multi-center, randomized controlled trial (RCT), novel behavioral positron emission tomography (PET) brain imaging methods are used to evaluate the molecular basis and neural underpinnings of: (a) the decline of mobility function in PD, specifically, balance, gait, visuomotor, and cognitive function, and (b) the effects of an engaging, game-based DT treadmill walking program on mobility and cognitive functions. Both the interactive cognitive game tasks and treadmill walking require continuous visual attention, and share spatial processing functions, notably to minimize any balance disturbance or gait deviation/stumble. The ability to "walk and talk" normally includes activation of specific regions of the prefrontal cortex (PFC) and the basal ganglia (site of degeneration in PD). The PET imaging analysis and comparison with healthy age-matched controls will allow us to identify areas of abnormal, reduced activity levels, as well as areas of excessive activity (increased attentional resources) during DT-walking. We will then be able to identify areas of brain plasticity associated with improvements in mobility functions (balance, gait, and cognition) after intervention. We expect the gait-cognitive training effect to involve re-organization of PFC activity among other, yet to be identified brain regions. The DT mobility-training platform and behavioral PET brain imaging methods are directly applicable to other diseases that affect gait and cognition, e.g., cognitive vascular impairment, Alzheimer's disease, as well as in aging.

Imaging Cerebral Glucose Metabolism during Dual-Task Walking in Patients with Parkinson's disease.

BACKGROUND AND PURPOSE: Gait impairment is a hallmark of Parkinson's disease (PD). Natural walking involves more cognitive demand than treadmill walking or in-laboratory walking tests because patients have to actively work on navigation and top-down cognitive control which taxes cognitive reserve in the prefrontal cortex. To mimic the prefrontal engagement occurring with natural walking in a controlled and safe environment, dual-task (DT) treadmill walking has been developed. In this study, we tested the feasibility of imaging DT walking-related changes in brain glucose metabolism in patients with PD. METHODS: Fifteen patients with PD were scanned with fluorodeoxyglucose (FDG) positron emission tomography. Five patients performed DT walking, and 10 patients were rested during the FDG uptake period. First, the images were contrasted between the groups. Second, the walking-related brain glucose metabolism was inspected at the individual level. RESULTS: Consistently increased glucose metabolism was identified in DT walking versus rest in the primary visual/sensorimotor areas, thalamus, superior colliculus, and cerebellum. In individual level analysis, patients with less progressed disease (n = 3) showed prefrontal activity during DT walking while patients with more progressed disease (n = 2) did not. CONCLUSION: This study confirms the feasibility of imaging glucose metabolism during DT walking in patients with PD. We also report that during DT walking, there is a lesser degree of prefrontal engagement in the patients with more progressed disease compared to those with less progressed disease, implying increased degrees of frontal dysfunction with PD progression.

Elevated caudate connectivity in cognitively normal Parkinson's disease patients.

Mild cognitive impairment (MCI) is common in Parkinson's disease patients. However, its underlying mechanism is not well understood, which has hindered new treatment discoveries specific to MCI. The aim of this study was to investigate functional connectivity changes of the caudate nucleus in cognitively impaired Parkinson's patients. We recruited 18 Parkinson's disease patients-10 PDNC [normal cognition Parkinson's disease; Montreal Cognitive Assessment (MoCA) ≥ 26], 8 PDLC (low cognition Parkinson's disease; MoCA < 26) -and 10 age-matched healthy controls. All subjects were scanned with resting-state functional magnetic resonance imaging (MRI) and perfusion MRI. We analyzed these data for graph theory metrics and Alzheimer's disease-like pattern score, respectively. A strong positive correlation was found between the functional connectivity of the right caudate nucleus and MoCA scores in Parkinson's patient groups, but not in healthy control subjects. Interestingly, PDNC's functional connectivity of the right caudate was significantly higher than both PDLC and healthy controls, while PDLC and healthy controls were not significantly different from each other. We found that Alzheimer's disease-like metabolic/perfusion pattern score correlated with MoCA scores in healthy controls, but not in Parkinson's disease. Increased caudate connectivity may be related to a compensatory mechanism found in cognitively normal patients with Parkinson's disease. Our findings support and complement the dual syndrome hypothesis.

Tolerability and Efficacy of Customized IncobotulinumtoxinA Injections for Essential Tremor: A Randomized, Double-Blind, Placebo-Controlled Study.

In this first, double-blind, randomized, placebo-controlled exploratory trial, we evaluate the efficacy and safety of incobotulinumtoxinA and feasibility of using kinematic tremor assessment to aid in the planning of muscle selection in a multicenter setting. Reproducibility of the planning technology to other clinical sites was explored. In this trial (NCT02207946), patients with upper-limb essential tremor (ET) were randomized 2:1 to a single treatment cycle of incobotulinumtoxinA or placebo. A tremor kinematic analytics investigational device was used to define a customized muscle set for injection, related to the pattern of the wrist, forearm, elbow, and shoulder tremor for each patient, and the incobotulinumtoxinA dose per muscle (total ≤ 200 U). Fahn-Tolosa-Marin (FTM) Part B motor performance score, Global Impression of Change Scale (GICS), and kinematic analysis-based efficacy evaluations were assessed. Thirty patients were randomized (incobotulinumtoxinA, n = 19; placebo, n = 11). FTM motor performance scores showed greater improvement with incobotulinumtoxinA versus placebo at Week 4 (p= 0.003) and Week 8 (p= 0.031). The physician-rated GICS score indicated improvement with incobotulinumtoxinA versus placebo at Week 4 (p < 0.05). IncobotulinumtoxinA also decreased accelerometric hand-tremor amplitude versus placebo from baseline to Week 4 (p= 0.004) and Week 8 (p < 0.001), with persistent tremor reduction up to 24 weeks post-injection. IncobotulinumtoxinA produced a slight and transient reduction of maximal grip strength versus placebo; two patients reported localized finger muscle weakness. Customized incobotulinumtoxinA injections decreased tremor severity and improved hand motor function in patients with upper-limb ET after a single injection cycle, with a favorable tolerability profile. The study showed that tremor kinematic analytics technology could be successfully scaled for use in other clinical sites.

Blood Flow and Glucose Metabolism Dissociation in the Putamen Is Predictive of Levodopa Induced Dyskinesia in Parkinson's Disease Patients.

Background: The forefront treatment of Parkinson's disease (PD) is Levodopa. When patients are treated with Levodopa cerebral blood flow is increased while cerebral metabolic rate is decreased in key subcortical regions including the putamen. This phenomenon is especially pronounced in patients with Levodopa-induced dyskinesia (LID). Method: To study the effect of clinically-determined anti-parkinsonian medications, 10 PD patients (5 with LID and 5 without LID) have been scanned with FDG-PET (a probe for glucose metabolism) and perfusion MRI (a probe for cerebral blood flow) both when they are ON and OFF medications. Patients additionally underwent resting state fMRI to detect changes in dopamine-mediated cortico-striatal connectivity. The degree of blood flow-glucose metabolism dissociation was quantified by comparing the FDG-PET and perfusion MRI data. Results: A significant interaction effect (imaging modality × medication; blood flow-glucose metabolism dissociation) has been found in the putamen (p = 0.023). Post-hoc analysis revealed that anti-parkinsonian medication consistently normalized the pathologically hyper-metabolic state of the putamen while mixed effects were observed in cerebral blood flow changes. This dissociation was especially predominant in patients with LID compared to those without. Unlike the prior study, this differentiation was not observed when cortico-striatal functional connectivity was assessed. Conclusion: We confirmed striatal neurovascular dissociation between FDG-PET and perfusion MRI in response to clinically determined anti-parkinsonian medication. We further proposed a novel analytical method to quantify the degree of dissociation in the putamen using only the ON condition scans, Putamen-to-thalamus Hyper-perfusion/hypo-metabolism Index (PHI), which may have the potential to be used as a biomarker for LID (correctly classifying 8 out 10 patients). For wider use of PHI, a larger validation study is warranted.

Educational Needs and Considerations for a Visual Educational Tool to Discuss Parkinson's Disease.

BACKGROUND: In our clinical experience, people with Parkinson's disease (PwP) and their caregivers have difficulty understanding the complexities of the disease, which has a multitude of symptoms and involved therapies. We undertook a needs assessment to understand the need for, and to guide the development of, an educational tool. METHODS: We invited PwP, caregivers and health care providers (HCP) from across Canada to participate in an online survey to determine the need and desired content for such a tool. RESULTS: Respondents included 450 PwP, 335 caregivers, and 96 HCP from across Canada. 86.5% of HCP reported that it was "very important" for patients to understand issues in PD and 84.4% would use a visual aid to explain these issues. Results showed that 81.9-95.7% of caregivers and PwP were not "very satisfied" with the explanations of all domains in PD. Non-motor symptoms and cognitive issues were highly ranked by all groups as difficult to understand or explain. Older PwP (those with PD for less than 5 years and those who reported that their HCP spent less than 15 minutes counselling in each clinic visit) were less likely to fully understand and be satisfied with the explanations of most issues in PD. INTERPRETATION: There is a need for better patient education when discussing PD issues in the clinical setting. Older PwP that have been recently diagnosed have the greatest educational needs. Potential users indicate that a visual aid would help and non-motor symptoms, particularly cognitive issues, need to be a focus of such a tool.

Distinct brain metabolic patterns separately associated with cognition, motor function, and aging in Parkinson's disease dementia.

We explored whether patients with Parkinson's disease dementia (PDD) show a distinct spatial metabolic pattern that characterizes cognitive deficits in addition to motor dysfunction. Eighteen patients with PDD underwent 3 separate positron emission tomography sessions with [18F]fluorodeoxyglucose (for glucose metabolism), fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane (for dopamine transporter density) and Pittsburgh compound-B (for beta-amyloid load). We confirmed in PDD versus normal controls, overall hypometabolism in the posterior and prefrontal brain regions accompanied with hypermetabolism in subcortical structures and the cerebellar vermis. A multivariate network analysis then revealed 3 metabolic patterns that are separately associated with cognitive performance (p = 0.042), age (p = 0.042), and motor symptom severity (p = 0.039). The age-related pattern's association with aging was replicated in healthy controls (p = 0.047) and patients with Alzheimer's disease (p = 0.002). The cognition-related pattern's association with cognitive performance was observed, with a trend-level of correlation, in patients with dementia with Lewy bodies (p = 0.084) but not in patients with Alzheimer's disease (p = 0.974). We found no association with fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane and Pittsburgh compound-B positron emission tomography with patients' cognitive performance.

Caffeine as symptomatic treatment for Parkinson disease (Café-PD): A randomized trial.

OBJECTIVE: To assess effects of caffeine on Parkinson disease (PD). METHODS: In this multicenter parallel-group controlled trial, patients with PD with 1-8 years disease duration, Hoehn & Yahr stages I-III, on stable symptomatic therapy were randomized to caffeine 200 mg BID vs matching placebo capsules for 6-18 months. The primary research question was whether objective motor scores would differ at 6 months (Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale [MDS-UPDRS]-III, Class I evidence). Secondary outcomes included safety and tolerability, motor symptoms (MDS-UPDRS-II), motor fluctuations, sleep, nonmotor symptoms (MDS-UPDRS-I), cognition (Montreal Cognitive Assessment), and quality of life. RESULTS: Sixty patients received caffeine and 61 placebo. Caffeine was well-tolerated with similar prevalence of side effects as placebo. There was no improvement in motor parkinsonism (the primary outcome) with caffeine treatment compared to placebo (difference between groups -0.48 [95% confidence interval -3.21 to 2.25] points on MDS-UPDRS-III). Similarly, on secondary outcomes, there was no change in motor signs or motor symptoms (MDS-UPDRS-II) at any time point, and no difference on quality of life. There was a slight improvement in somnolence over the first 6 months, which attenuated over time. There was a slight increase in dyskinesia with caffeine (MDS-UPDRS-4.1+4.2 = 0.25 points higher), and caffeine was associated with worse cognitive testing scores (average Montreal Cognitive Assessment = 0.66 [0.01, 1.32] worse than placebo). CONCLUSION: Caffeine did not provide clinically important improvement of motor manifestations of PD (Class I evidence). Epidemiologic links between caffeine and lower PD risk do not appear to be explained by symptomatic effects. CLINICALTRIALSGOV IDENTIFIER: NCT01738178. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with PD, caffeine does not significantly improve motor manifestations.

High affinity hemoglobin and Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN) region of the midbrain. Oxidative damage in this region has been shown to play an important role in the pathogenesis of this disease. Human neurons have been discovered to contain hemoglobin, with an increased concentration seen in the neurons of the SN. High affinity hemoglobin is a clinical entity resulting from mutations that create a functional increase in the binding of hemoglobin to oxygen and an inability to efficiently unload it to tissues. This can result in a number of metabolic compensatory changes, including an elevation in circulating hemoglobin and an increase in the molecule 2,3-diphosphoglycerate (2,3-DPG). Population based studies have revealed that patients with PD have elevated hemoglobin as well as 2,3-DPG levels. Based on these observations, we hypothesize that the oxidative damage seen in PD is related to an underlying high affinity hemoglobin subtype.

Healthcare utilization in patients with Parkinson's disease: a population-based analysis.

PURPOSE: To investigate factors associated with healthcare utilization and prescription drug use for Parkinson's disease (PD) patients and matched controls. METHODS: A retrospective matched-group design was adopted using administrative data from Manitoba, Canada. PD cases (N = 1469) were identified from diagnoses in hospital records and physician billing claims and matched to controls (N = 2938) on age, sex, and region of residence. Sixteen measures of healthcare utilization were examined over a six-year period using generalized linear models. RESULTS: PD cases had greater healthcare utilization than controls for almost all investigated services, with the exception of visits to non-neurological specialists and hospital use for non-mental disorder diagnoses. For controls, utilization of all forms of healthcare increased with age; for PD cases the relationship was weak, except for specialist visits, where an inverse relationship was observed. A rural region of residence was associated with a lower rate of seeing a specialist or any medical doctor, with a higher rate of hospitalization than for urban cases or controls. Comorbidity was strongly associated with healthcare use for both groups. Over the six-year study period significant differences in the trend were observed for mental disorder hospitalizations, hospital days, and physician visits. CONCLUSIONS: Factors associated with healthcare utilization in PD patients differ from those without PD. This information may help to identify and optimize healthcare services and associated costs for PD patients.

Asymmetry in parkinsonism, spreading pathogens and the nose.

Parkinson's disease, as well as many other parkinsonisms, including most toxic, neurodegenerative and familial types are typically asymmetric. No explanation for this phenomenon exists. A summary of the frequency of asymmetry in a spectrum of parkinsonian disorders is provided. Evidence against asymmetry being the result of normal asymmetries of the substantia nigrais reviewed. Asymmetry either results from a greater susceptibility on one side or a spreading pathology entering or starting on one side of the CNS. With the increasing evidence for spreading pathologies (toxins, viruses, α-synuclein), knowledge of neuroanatomical connections, and literature implicating spreading pathogens from the enteric and olfactory nerves, potential explanations can be theorized and explored, including the possibility of a pathogen preferentially entering or originating in the olfactory bulb on one side, with subsequent involvement of the other side.

User evaluation of three wheelchair securement systems in large accessible transit vehicles.

Ease of use, comfort, security, and independent use of three types of wheelchair securement systems were evaluated in a large accessible transit vehicle by 20 wheelchair and scooter users. The securement systems included a 4-point tie-down system, a prototype autodocking system, and a prototype rear-facing wheelchair passenger (RF-WP) system. Study participants took a 15-minute city ride and completed a survey. Participants responded positively to the autodocking and RF-WP systems that were quicker and easier to use and allowed more independent use than the 4-point tie-down system (p < 0.001). There was concern regarding the RF-WP system that rear-facing travel made it more difficult to see upcoming stops and was less comfortable than a forward-facing ride and that the system may damage wheelchair wheels during use. The majority of participants preferred using an autodocking system because it allowed secure and independent forward-facing travel. Participants found it undesirable, however, that a wheelchair-mounted docking adaptor was needed to use the autodocking system. Study results indicate a need for improved securement systems for forward-facing use that do not require a wheelchair adaptation and can be easily and independently used by wheelchair and scooter users.

Development and testing of an innovative user-adjustable support surface for wheelchair seating discomfort.

Beginning in 2000, a study of discomfort experienced by wheelchair users and development of technology solutions were undertaken. This research culminated with the present study of a new technology targeting sitting discomfort. Support for development of the "Butt Scooter" prototype and its testing was provided through an NIH research grant. Investigators tested a prototype device, called the "Butt Scooter," and conducted a focus group to obtain expert clinical opinions about the potential usefulness of the prototype. Subject testing of the prototype device followed a single subject design (ABABA). Subjects self-administered the Tool for Assessing Wheelchair disComfort (TAWC) to evaluate their discomfort levels. Results from three subjects are reported. All three expert therapists participating in the focus group responded favorably to the prototype. In summary, results from subject testing were somewhat mixed with regard to discomfort management, however all subjects commented positively on the features of the device.

Socioeconomic variations in the prevalence and incidence of Parkinson's disease: a population-based analysis.

BACKGROUND: For many chronic conditions, lower socioeconomic status is associated with higher rates of disease. Previous research has not investigated whether this inverse relationship exists for Parkinson's disease (PD). The purpose was to investigate the association between socioeconomic status and prevalence and incidence of PD. METHODS: The study was conducted using population-based administrative data from Manitoba, Canada. PD cases were identified from diagnoses in hospital and physician records. Area-level census data on average household income and residential postal codes in health insurance registration files were used to assign PD cases to urban and rural income quintiles. Annual adjusted prevalence and incidence estimates were calculated for fiscal years 1987/88-2006/07. Hypotheses about differences between quintiles in average estimates and average rates of change were tested using generalised linear models with generalised estimating equations. RESULTS: The estimated prevalence of PD increased over the 20-year-period but incidence remained unchanged. In urban regions, average prevalence and incidence estimates were significantly higher for the lowest income quintile than the highest quintile. In rural regions, average prevalence estimates were significantly higher for the lowest quintile than for the highest quintile but incidence estimates were not significantly different. The annual rate of increase in the PD prevalence was significantly different for the lowest urban and rural income quintiles. CONCLUSIONS: There is a greater burden of PD in low-income areas. An understanding of socioeconomic inequalities is useful when formulating hypotheses about factors associated with disease onset and developing equity-oriented policies about access to healthcare resources.

State of the science workshop on wheelchair transportation safety.

The Rehabilitation Engineering Research Center on Wheelchair Transportation Safety held a state-of-the-science workshop on wheelchair transportation. The workshop had three purposes: reviewing and documenting the status of wheelchair transportation safety, identifying deficiencies, and formulating, discussing, and prioritizing recommendations for future action. The final goal was to disseminate the workshop outcomes for utilization in formatting future research priorities. A nominal group technique was used to facilitate focused open discussion by knowledgeable persons, resulting in the identification and ranking of existing deficiencies according to priority. Participants then formulated potential short-term solutions and speculated what wheelchair transportation safety should be in the future. This document presents four white papers, prepared prior to the workshop and modified according to participant feedback, and summarizes the outcomes of the workshop. The results identify and prioritize recommendations for future action.