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

Assessment of the ability of open- and closed-loop cueing to improve turning and freezing in people with Parkinson’s disease

Turning impairments are common in Parkinson's disease (PD) and can elicit freezing of gait (FoG). Extensive examination of open-loop cueing interventions has demonstrated that they can ameliorate gait deficits in PD; less is known about efficacy to improve turning. Here, we investigate the immediate effectiveness of open- and closed-loop cueing in improving turning characteristics in people with PD. Twenty-five subjects with and 18 subjects without FoG participated in the study. Subjects turned in place for one minute under single- and dual-task for 3 randomized conditions: (i) Baseline; (ii) Turning to the beat of a metronome (open-loop); and (iii) Turning with phase-dependent tactile biofeedback (closed-loop). Objective measures of freezing, such as % time spent freezing and FoG-ratio, significantly improved when turning with both open-loop and closed-loop cueing compared to baseline. Dual-tasking did not worsen FoG in freezers, but significantly slowed down turns in both groups. Both cueing modalities significantly improved turning smoothness in both groups, but reduced turning velocity and number of turns compared to baseline. Both open and closed-loop cueing markedly improved turning in people with PD. These preliminary observations warrant further exploration of vibrotactile closed-loop cueing to improve mobility in everyday life

Associations between mobility, cognition and callosal integrity in people with parkinsonism

Falls in people with parkinsonism are likely related to both motor and cognitive impairments. In addition to idiopathic Parkinson\u27s disease (PD), some older adults have lower body parkinsonism (a frontal gait disorder), characterized by impaired lower extremity balance and gait as well as cognition, but without tremor or rigidity. Neuroimaging during virtual gait suggests that interhemispheric, prefrontal cortex communication may be involved in locomotion, but contributions of neuroanatomy connecting these regions to objective measures of gait in people with parkinsonism remains unknown. Our objectives were to compare the integrity of fiber tracts connecting prefrontal and sensorimotor cortical regions via the corpus callosum in people with two types of parkinsonism and an age-matched control group and to relate integrity of these callosal fibers with clinical and objective measures of mobility and cognition. We recruited 10 patients with frontal gait disorders, 10 patients with idiopathic PD and 10 age-matched healthy control participants. Participants underwent cognitive and mobility testing as well as diffusion weighted magnetic resonance imaging to quantify white matter microstructural integrity of interhemispheric fiber tracts. People with frontal gait disorders displayed poorer cognitive performance and a slower, wider-based gait compared to subjects with PD and age-matched control subjects. Despite a widespread network of reduced white matter integrity in people with frontal gait disorders, gait and cognitive deficits were solely related to interhemispheric circuitry employing the genu of the corpus callosum. Current results highlight the importance of prefrontal interhemispheric communication for lower extremity control in neurological patients with cognitive dysfunction

Functional limits of stability and standing balance in people with Parkinson's disease with and without freezing of gait using wearable sensors

Background: People with from Parkinson's disease (PD) and freezing of gait (FoG) have more frequent falls compared to those who do not freeze but there is no consensus on which, specific objective measures of postural instability are worse in freezers (PD + FoG) than non-freezers (PD-FoG). Research question: Are functional limits of stability (fLoS) or postural sway during stance measured with wearable inertial sensors different between PD + FoG versus PD-FoG, as well as between PD versus healthy control subjects (HC)? Methods: Sixty-four PD subjects with FoG (MDS-UPDRS Part III: 45.9 +/- 12.5) and 80 PD subjects without FoG (MDS-UPDRS Part III: 36.2 +/- 10.9) were tested Off medication and compared with 79 HC. Balance was quantified with inertial sensors worn on the lumbar spine while performing the following balance tasks: 1) fLoS as defined by the maximum displacement in the forward and backward directions and 2) postural sway area while standing with eyes open on a firm and foam surface. An ANOVA, controlling for disease duration, compared postural control between groups. Results: PD + FoG had significantly smaller fLoS compared to PD-FoG (p = 0.004) and to healthy controls (p < 0.001). However, PD-FoG showed similar fLoS compared to healthy controls (p = 0.48). Both PD+FoG and PDFoG showed larger postural sway on a foam surface compared to healthy controls (p = 0.001) but there was no significant difference in postural sway between PD+FoG and PD-FoG. Significance: People with PD and FoG showed task-specific, postural impairments with smaller fLoS compared to non-freezers, even when controlling for disease duration. However, individuals with PD with or without FoG had similar difficulties standing quietly on an unreliable surface compared to healthy controls. Wearable inertial sensors can reveal worse fLoS in freezers than non-freezers that may contribute to FoG and help explain their more frequent falls

Effect of Bout Length on Gait Measures in People with and without Parkinson’s Disease during Daily Life

Although the use of wearable technology to characterize gait disorders in daily life is increasing, there is no consensus on which specific gait bout length should be used to characterize gait. Clinical trialists using daily life gait quality as study outcomes need to understand how gait bout length affects the sensitivity and specificity of measures to discriminate pathological gait as well as the reliability of gait measures across gait bout lengths. We investigated whether Parkinson’s disease (PD) affects how gait characteristics change as bout length changes, and how gait bout length affects the reliability and discriminative ability of gait measures to identify gait impairments in people with PD compared to neurotypical Old Adults (OA). We recruited 29 people with PD and 20 neurotypical OA of similar age for this study. Subjects wore 3 inertial sensors, one on each foot and one over the lumbar spine all day, for 7 days. To investigate which gait bout lengths should be included to extract gait measures, we determined the range of gait bout lengths available across all subjects. To investigate if the effect of bout length on each gait measure is similar or not between subjects with PD and OA, we used a growth curve analysis. For reliability and discriminative ability of each gait measure as a function of gait bout length, we used the intraclass correlation coefficient (ICC) and area under the curve (AUC), respectively. Ninety percent of subjects walked with a bout length of less than 53 strides during the week, and the majority (\u3e50%) of gait bouts consisted of less than 12 strides. Although bout length affected all gait measures, the effects depended on the specific measure and sometimes differed for PD versus OA. Specifically, people with PD did not increase/decrease cadence and swing duration with bout length in the same way as OA. ICC and AUC characteristics tended to be larger for shorter than longer gait bouts. Our findings suggest that PD interferes with the scaling of cadence and swing duration with gait bout length. Whereas control subjects gradually increased cadence and decreased swing duration as bout length increased, participants with PD started with higher than normal cadence and shorter than normal stride duration for the smallest bouts, and cadence and stride duration changed little as bout length increased, so differences between PD and OA disappeared for the longer bout lengths. Gait measures extracted from shorter bouts are more common, more reliable, and more discriminative, suggesting that shorter gait bouts should be used to extract potential digital biomarkers for people with PD

Laboratory versus daily life gait characteristics in patients with multiple sclerosis, Parkinson’s disease, and matched controls

Background and purpose Recent findings suggest that a gait assessment at a discrete moment in a clinic or laboratory setting may not reflect functional, everyday mobility. As a step towards better understanding gait during daily life in neurological populations, we compared gait measures that best discriminated people with multiple sclerosis (MS) and people with Parkinson’s Disease (PD) from their respective, age-matched, healthy control subjects (MS-Ctl, PD-Ctl) in laboratory tests versus a week of daily life monitoring. Methods We recruited 15 people with MS (age mean ± SD: 49 ± 10 years), 16 MS-Ctl (45 ± 11 years), 16 people with idiopathic PD (71 ± 5 years), and 15 PD-Ctl (69 ± 7 years). Subjects wore 3 inertial sensors (one each foot and lower back) in the laboratory followed by 7 days during daily life. Mann–Whitney U test and area under the curve (AUC) compared differences between PD and PD-Ctl, and between MS and MS-Ctl in the laboratory and in daily life. Results Participants wore sensors for 60–68 h in daily life. Measures that best discriminated gait characteristics in people with MS and PD from their respective control groups were different between the laboratory gait test and a week of daily life. Specifically, the toe-off angle best discriminated MS versus MS-Ctl in the laboratory (AUC [95% CI] = 0.80 [0.63–0.96]) whereas gait speed in daily life (AUC = 0.84 [0.69–1.00]). In contrast, the lumbar coronal range of motion best discriminated PD versus PD-Ctl in the laboratory (AUC = 0.78 [0.59–0.96]) whereas foot-strike angle in daily life (AUC = 0.84 [0.70–0.98]). AUCs were larger in daily life compared to the laboratory. Conclusions Larger AUC for daily life gait measures compared to the laboratory gait measures suggest that daily life monitoring may be more sensitive to impairments from neurological disease, but each neurological disease may require different gait outcome measures

Global access to surgical care: a modelling study

Background More than 2 billion people are unable to receive surgical care based on operating theatre density alone. The vision of the Lancet Commission on Global Surgery is universal access to safe, aff ordable surgical and anaesthesia care when needed. We aimed to estimate the number of individuals worldwide without access to surgical services as defi ned by the Commission’s vision. Methods We modelled access to surgical services in 196 countries with respect to four dimensions: timeliness, surgical capacity, safety, and aff ordability. We built a chance tree for each country to model the probability of surgical access with respect to each dimension, and from this we constructed a statistical model to estimate the proportion of the population in each country that does not have access to surgical services. We accounted for uncertainty with oneway sensitivity analyses, multiple imputation for missing data, and probabilistic sensitivity analysis. Findings At least 4·8 billion people (95% posterior credible interval 4·6–5·0 [67%, 64–70]) of the world’s population do not have access to surgery. The proportion of the population without access varied widely when stratifi ed by epidemiological region: greater than 95% of the population in south Asia and central, eastern, and western sub- Saharan Africa do not have access to care, whereas less than 5% of the population in Australasia, high-income North America, and western Europe lack access. Interpretation Most of the world’s population does not have access to surgical care, and access is inequitably distributed. The near absence of access in many low-income and middle-income countries represents a crisis, and as the global health community continues to support the advancement of universal health coverage, increasing access to surgical services will play a central role in ensuring health care for all

Prefrontal cortex activity and gait in Parkinson's disease with cholinergic and dopaminergic therapy

Objectives: Degradation of striatal dopamine in Parkinson’s disease (PD) may initially be supplemented by increased cognitive control mediated by cholinergic mechanisms. Shift to cognitive control of walking can be quantified by prefrontal cortex (PFC) activation. Levodopa improves certain aspects of gait and worsens others, and cholinergic augmentation influence on gait and PFC activity remains unclear. This study examined dopaminergic and cholinergic influence on gait and PFC activity while walking in PD. Methods: A single-site, randomized, double-blind, cross-over trial examined effects of levodopa and donepezil in PD. 20 PD participants were randomized and 19 completed the trial. Participants were randomized to either levodopa+donepezil (5mg) or levodopa+placebo treatments, with two-weeks with treatment and a two-week washout. The primary outcome was change in PFC activity while walking, and secondary outcomes were change in gait, dual-task performance and attention. Results: Levodopa decreased PFC activity compared to Off medication (effect size: -0.51), whereas the addition of donepezil reversed this decrease. Gait speed and stride length, under single and dual-task conditions, improved with combined donepezil and levodopa compared to Off medication (effect size: 1 for gait speed and 0.75 for stride length). Dual-task reaction time was quicker with levodopa compared to Off medication (effect size: -0.87), and accuracy improved with combined donepezil and levodopa (effect size: 0.47). Conclusions: Cholinergic therapy, specifically donepezil 5mg/day for two-weeks, can alter PFC activity when walking, and improve secondary cognitive task accuracy and gait in PD. Further studies will investigate whether higher PFC activity while walking is associated with gait changes

High-quality permanent draft genome sequence of <i>Rhizobium sullae</i> strain WSM1592; a <i>Hedysarum coronarium</i> microsymbiont from Sassari, Italy

Rhizobium sullae strain WSM1592 is an aerobic, Gram-negative, non-spore-forming rod that was isolated from an effective nitrogen (N2) fixing root nodule formed on the short-lived perennial legume Hedysarum coronarium (also known as Sulla coronaria or Sulla). WSM1592 was isolated from a nodule recovered from H. coronarium roots located in Ottava, bordering Sassari, Sardinia in 1995. WSM1592 is highly effective at fixing nitrogen with H. coronarium, and is currently the commercial Sulla inoculant strain in Australia. Here we describe the features of R. sullae strain WSM1592, together with genome sequence information and its annotation. The 7,530,820 bp high-quality permanent draft genome is arranged into 118 scaffolds of 118 contigs containing 7.453 protein-coding genes and 73 RNA-only encoding genes. This rhizobial genome is sequenced as part of the DOE Joint Genome Institute 2010 Genomic Encyclopedia for Bacteria and Archaea-Root Nodule Bacteria (GEBA-RNB) project