Cognitive function in people with and without freezing of gait in Parkinson’s disease

Freezing of gait (FOG) is common in people with Parkinson’s disease (PD) which is extremely debilitating. One hypothesis for the cause of FOG episodes is impaired cognitive control, however, this is still in debate in the literature. We aimed to assess a comprehensive range of cognitive tests in older adults and people with Parkinson’s with and without FOG and associate FOG severity with cognitive performance. A total of 227 participants took part in the study which included 80 healthy older adults, 81 people with PD who did not have FOG and 66 people with PD and FOG. A comprehensive battery of neuropsychological assessments tested cognitive domains of global cognition, executive function/attention, working memory, and visuospatial function. The severity of FOG was assessed using the new FOG questionnaire and an objective FOG severity score. Cognitive performance was compared between groups using an ANCOVA adjusting for age, gender, years of education and disease severity. Correlations between cognitive performance and FOG severity were analyzed using partial correlations. Cognitive differences were observed between older adults and PD for domains of global cognition, executive function/attention, and working memory. Between those with and without FOG, there were differences for global cognition and executive function/attention, but these differences disappeared when adjusting for covariates. There were no associations between FOG severity and cognitive performance. This study identified no significant difference in cognition between those with and without FOG when adjusting for covariates, particularly disease severity. This may demonstrate that complex rehabilitation programs may be undertaken in those with FOG

Motor imagery of gait tasks in individuals with Parkinson disease

We developed a questionnaire to assess motor imagery (MI) of gait and administered it to 34 controls and 28 individuals with PD. Our goals were: 1) compare gait MI in individuals with and without PD, 2) determine whether walking performance relates to gait MI and 3) compare gait MI in individuals with PD with and without freezing of gait. Gait MI was not different between PD and controls. There was no correlation between walking performance and gait MI, and no difference in gait MI between freezers and nonfreezers. The gait imagery questionnaire may be useful for imaging studies involving imagined gait

Gait coordination in Parkinson disease: Effects of step length and cadence manipulations

BACKGROUND: Gait impairments are well documented in those with PD. Prior studies suggest that gait impairments may be worse and ongoing in those with PD who demonstrate FOG compared to those with PD who do not. PURPOSE: Our aim was to determine the effects of manipulating step length and cadence individually, and together, on gait coordination in those with PD who experience FOG, those with PD who do not experience FOG, healthy older adults, and healthy young adults. METHODS: Eleven participants with PD and FOG, 16 with PD and no FOG, 18 healthy older, and 19 healthy young adults walked across a GAITRite walkway under four conditions: Natural, Fast (+50% of preferred cadence), Small (−50% of preferred step length), and SmallFast (+50% cadence and −50% step length). Coordination (i.e. phase coordination index) was measured for each participant during each condition and analyzed using mixed model repeated measure ANOVAs. RESULTS: FOG was not elicited. Decreasing step length or decreasing step length and increasing cadence together affected coordination. Small steps combined with fast cadence resulted in poorer coordination in both groups with PD compared to healthy young adults and in those with PD and FOG compared to healthy older adults. CONCLUSIONS: Coordination deficits can be identified in those with PD by having them walk with small steps combined with fast cadence. Short steps produced at high rate elicit worse coordination than short steps or fast steps alone

Effects of levodopa on vividness of motor imagery in Parkinson disease

INTRODUCTION: Motor imagery during functional magnetic resonance imaging is commonly used to understand the neural underpinnings of complex movements. This approach has recently been applied to individuals with Parkinson disease (PD) to better understand how brain function may relate to movement dysfunction. However, the ability of individuals with PD to imagine movements when “Off” dopamine replacement medication is poorly understood. Therefore, the primary purpose of the current study is to test the ability of people with PD to imagine movements while “On” and “Off” anti-Parkinson medication. METHODS: Vividness of imagery was assessed in 28 individuals with mild to moderate PD (Hoehn and Yahr stages 1–3) via the Kinesthetic Visual Imagery Questionnaire (KVIQ-20) both “On” and “Off” anti-Parkinson medication. Vividness of imagery of 32 age-matched older adults was also assessed. RESULTS: No differences in vividness of imagery were observed between “Off” and “On” medication states (p=0.15). Imagery was similar between controls and PD both “Off” (p=0.25) and “On” (p=0.46) anti-Parkinson medication. A significant correlation was observed between imagery and disease severity while “On” anti-Parkinson medication (r= −0.49; p=0.008). DISCUSSION AND CONCLUSIONS: Vividness of movement imagery was not different between “Off” and “On” anti-Parkinson medications or between PD and controls. These results suggest that people with PD are able to imagine similarly to older adults both when “On” and “Off” anti-Parkinson medication, and supports the use of motor imagery in the “Off” medication state

Evidence for a relationship between bilateral coordination during complex gait tasks and freezing of gait in Parkinson\u27s disease

BACKGROUND: Freezing of gait is a debilitating and common gait disturbance observed in individuals with Parkinson’s disease (PD). Although the underlying mechanisms of freezing remain unclear, bilateral coordination of steps, measured as a phase coordination index, has been suggested to be related to freezing. Phase coordination index has not, however, been measured during tasks associated with freezing such as turning and backward walking. Understanding how bilateral coordination changes during tasks associated with freezing may improve our understanding of the causes of freezing. METHODS: Twelve individuals with PD who freeze (freezers), 19 individuals with PD who do not freeze (non-freezers), and 10 healthy, age-matched older adults participated. General motor disease severity and freezing severity were assessed. Phase coordination index was calculated for all subjects during forward walking, backward walking, continuous turning in small radius circles, and turning in large radius circles. RESULTS: Freezers and non-freezers had similar disease duration and general motor severity. Stepping coordination (measured as phase coordination index) was significantly worse in freezers compared to non-freezers and controls. Turning and backward walking, tasks related to freezing, resulted in worse coordination with respect to forward walking. Coordination was associated with severity of freezing scores such that worse coordination was correlated with more severe freezing. CONCLUSIONS: These results provide evidence that stepping coordination is related to freezing in people with PD. Identifying variables associated with freezing may provide insights into factors underlying this symptom, and may inform rehabilitative interventions to reduce its occurrence in PD

Lethal Mutagenesis of Poliovirus Mediated by a Mutagenic Pyrimidine Analogue

Lethal mutagenesis is the mechanism of action of ribavirin against poliovirus (PV) and numerous other RNA viruses. However, there is still considerable debate regarding the mechanism of action of ribavirin against a variety of RNA viruses. Here we show by using T7 RNA polymerase mediated production of PV genomic RNA, PV polymerase-catalyzed primer extension and cell-free PV synthesis that a pyrimidine ribonucleoside triphosphate analogue (rPTP) with ambiguous basepairing capacity is an efficient mutagen of the PV genome. The in vitro incorporation properties of rPTP are superior to ribavirin triphosphate. We observed a log-linear relationship between virus titer reduction and the number of rPMP molecules incorporated. A PV genome encoding a high-fidelity polymerase was more sensitive to rPMP incorporation, consistent with diminished mutational robustness of high-fidelity PV. The nucleoside (rP) did not exhibit antiviral activity in cell culture owing to the inability of rP to be converted to rPMP by cellular nucleotide kinases. rP was also a poor substrate for herpes simplex virus thymidine kinase. The block to nucleoside phosphorylation could be bypassed by treatment with the P nucleobase, which exhibited both antiviral activity and mutagenesis, presumably a reflection of rP nucleotide formation by a nucleotide salvage pathway. These studies provide additional support for lethal mutagenesis as an antiviral strategy, suggest that rPMP prodrugs may be highly efficacious antiviral agents, and provide a new tool to determine the sensitivity of RNA virus genomes to mutagenesis as well as interrogation of the impact of mutational load on the population dynamics of these viruses

A distributed data component for the Open Modeling Interface

As the volume of collected data continues to increase in the environmental sciences, so too does the need for effective means for accessing those data. We have developed an Open Modeling Interface (OpenMI) data component that retrieves input data for model components from environmental information systems and delivers output data to those systems. The adoption of standards for both model component input–output interfaces and web services make it possible for the component to be reconfigured for use with different linked models and various online systems. The data component employs three techniques tailored to the unique design of the OpenMI that enable efficient operation: caching, prefetching, and buffering, making it capable of scaling to large numbers of simultaneous simulations executing on a computational grid. We present the design of the component, an evaluation of its performance, and a case study demonstrating how it can be incorporated into modeling studies