Quantitative Susceptibility Mapping Changes Relate to Gait Issues in Parkinson's Disease.

BACKGROUND: Quantitative susceptibility mapping (QSM) demonstrates elevated iron content in Parkinson's disease (PD) patients within the basal ganglia, though it has infrequently been studied in relation to gait difficulties including freezing of gait (FOG). Our purpose was to relate QSM of basal ganglia and extra-basal ganglia structures with qualitative and quantitative gait measures in PD. METHODS: This case-control study included PD and cognitively unimpaired (CU) participants from the Comprehensive Assessment of Neurodegeneration and Dementia study. Whole brain QSM was acquired at 3T. Region of interests (ROIs) were drawn blinded manually in the caudate nucleus, putamen, globus pallidus, pulvinar nucleus of the thalamus, red nucleus, substantia nigra, and dentate nucleus. Susceptibilities of ROIs were compared between PD and CU. Items from the FOG questionnaire and quantitative gait measures from PD participants were compared to susceptibilities. RESULTS: Twenty-nine participants with PD and 27 CU participants were included. There was no difference in susceptibility values in any ROI when comparing CU versus PD (p > 0.05 for all). PD participants with gait impairment (n = 23) had significantly higher susceptibility in the putamen (p = 0.008), red nucleus (p = 0.01), and caudate nucleus (p = 0.03) compared to those without gait impairment (n = 6). PD participants with FOG (n = 12) had significantly higher susceptibility in the globus pallidus (p = 0.03) compared to those without FOG (n = 17). Among quantitative gait measures, only stride time variability was significantly different between those with and without FOG (p = 0.04). CONCLUSION: Susceptibilities in basal ganglia and extra-basal ganglia structures are related to qualitative measures of gait impairment and FOG in PD.

Accidental substance-related acute toxicity deaths in older adults in 2016 and 2017: a national chart review study. / Décès accidentels liés à une intoxication aiguë due à une substance chez les aînés en 2016 et en 2017 : une étude nationale d'examen des dossiers.

INTRODUCTION: Limited research exists on substance-related acute toxicity deaths (ATDs) in older adults (≥60 years) in Canada. This study aims to examine and describe the sociodemographic characteristics, health histories and circumstances of death for accidental ATDs among older adults. METHODS: Following a retrospective descriptive analysis of all coroner and medical examiner files on accidental substance-related ATDs in older adults in Canada from 2016 to 2017, proportions and mortality rates for coroner and medical examiner data were compared with general population data on older adults from the 2016 Census. Chisquare tests were conducted for categorical variables where possible. RESULTS: From 2016 to 2017, there were 705 documented accidental ATDs in older adults. Multiple substances contributed to 61% of these deaths. Fentanyl, cocaine and ethanol (alcohol) were the most common substances contributing to death. Heart disease (33%), chronic pain (27%) and depression (26%) were commonly documented. Approximately 84% of older adults had contact with health care services in the year preceding their death. Only 14% were confirmed as having their deaths witnessed. CONCLUSIONS: Findings provide insight into the demographic, contextual and medical history factors that may influence substance-related ATDs in older adults and suggest key areas for prevention.

A comparison of the characteristics of accidental substance-related acute toxicity deaths in Canada across life stages, 2016-2017. / Comparaison des caractéristiques des décès accidentels attribuables à une intoxication aiguë due à une substance au Canada aux différents stades de la vie, 2016-2017.

The acute toxicity (sometimes called "overdose" or "poisoning") crisis has affected Canadians across all stages of life, including youth, adults and older adults. Our biological risks and exposures to substances change as we age. Based on a national chart review study of coroner and medical examiner data on acute toxicity deaths in 2016 and 2017, this analysis compares the burden of deaths and circumstances of death, locations of acute toxicity event and death, health history and substances contributing to death of people, by sex and life stage.

This analysis reveals key differences in the characteristics of acute toxicity deaths by sex and life stage, and suggests potential intervention points for each group. Many people across demographics were alone while using substances before the acute toxicity event, and many were alone when they died. Youth, particularly female youth, more often died in circumstances where someone might have been available to help by calling 911 or administering first aid and naloxone. For the people who were in contact with health care prior to their death, about one-quarter (24%­28%) of adults and older adults sought assistance for reasons related to pain. Youth more often sought assistance for a nonfatal acute toxicity event (13%­14%) or for mental health (particularly female youth, 21%) than people in other life stages. Multiple substances contributed to most deaths, and both pharmaceutical and nonpharmaceutical substances were common causes of death for all life stages and sexes. There are demographic differences in the specific substances contributing to death.

Cette analyse présente les différences clés des caractéristiques des décès attribuables à une intoxication aiguë par sexe et stade de la vie, et propose des interventions possibles pour chaque groupe. Dans toutes les catégories démographiques, plusieurs personnes étaient seules au moment de consommer des substances avant l'intoxication aiguë, et plusieurs d'entre elles étaient seules au moment du décès. Les jeunes, et en particulier les jeunes femmes, sont décédées le plus souvent dans des circonstances où quelqu'un aurait pu être disponible pour aider en appelant le 911 ou en administrant les premiers soins et la naloxone. Parmi les personnes qui étaient en contact avec le système de santé avant leur décès, environ le quart (24 % à 28 %) des adultes et des aînés ont sollicité de l'aide pour des raisons liées à la douleur. Les jeunes ont plus souvent sollicité de l'aide pour une intoxication aiguë non mortelle (13 % à 14 %) ou pour des raisons liées à la santé mentale (en particulier les jeunes femmes, 21 %) que les personnes à d'autres stades de la vie. La polyconsommation de substances était en cause pour la plupart des décès, et les substances pharmaceutiques et non pharmaceutiques étaient toutes deux des causes courantes de décès pour tous les stades de la vie et les sexes. Il existe des différences démographiques en lien avec les substances spécifiques ayant contribué aux décès.

Walking exercise alters pedunculopontine nucleus connectivity in Parkinson's disease in a dose-dependent manner.

Background: Gait disturbances are critical motor symptoms in Parkinson's disease (PD). The mechanisms of gait impairment in PD are not entirely understood but likely involve changes in the Pedunculopontine Nucleus (PPN), a critical locomotion center, and its associated connections. Exercise is universally accepted as helpful in PD, but the extent and intensity of exercise required for plastic changes are unclear. Methods: Twenty-seven PD subjects participated in a 3-month gait training intervention. Clinical assessments and resting-state functional magnetic resonance imaging were performed at baseline and 3 months after exercise. Functional connectivity of PPN was assessed by combining the methods of partial least squares, conditional dependence and partial correlation. In addition, paired t-tests were used to examine the effect of exercise on PPN functional connectivity and clinical measures, and Pearson's correlation was used to assess the association between altered PPN functional connectivity and clinical measures. Results: Exercise significantly improved Unified Parkinson's Disease Rating Scale-III (UPDRS-III). A significant increase in right PPN functional connectivity was observed after exercise, which did not correlate with motor improvement. However, the decrease in left PPN functional connectivity significantly correlated with the improvement in UPDRS-III and was linearly related to both number of walks and the duration of walks. In addition, exercise induced a significant increase in the laterality of PPN connectivity strength, which correlated with motor improvement. Conclusion: PPN functional connectivity is modifiable by walking exercise in both a dose-independent (right PPN and laterality of PPN connectivity strength) and dose-dependent (left PPN) manner. The PPN may contribute to pathological and compensatory processes in PD gait control. The observed gait improvement by walking exercise is most likely due to the reversal of the maladaptive compensatory mechanism. Altered PPN functional connectivity can be a marker for exercise-induced motor improvement in PD.

The Effects of Music-Contingent Gait Training on Cognition and Mood in Parkinson Disease: A Feasibility Study.

Background. In Parkinson disease (PD), gait impairments often coexist with nonmotor symptoms such as anxiety and depression. Biofeedback training may improve gait function in PD, but its effect on nonmotor symptoms remains unclear. This study explored the cognitive and global effects of Ambulosono, a cognitive gait training method utilizing step size to contingently control the real-time play of motivational music. Objective. This study examined the feasibility of music-contingent gait training and its effects on neuropsychological test performance and mood in persons with PD. Methods. A total of 30 participants with mild to moderate PD were semirandomized via sequential alternating assignment into an experimental training group or control music group. The training group received 12 weeks of music-contingent training, whereby music play was dependent on the user achieving a set stride length, adjusted online based on individual performance. The control group received hybrid training beginning with 6 weeks of noncontingent music walking, whereby music played continuously regardless of step size, followed by 6 weeks of music-contingent training. Global cognition, memory, executive function, attention, and working memory assessments were completed by blinded assessors at baseline, 6 weeks, and 12 weeks. Motor function, mood, and anxiety were assessed. Results. Average training adherence was 97%, with no falls occurring during training sessions. Improvements on cognitive measures were not clinically significant; however, significant decreases in depression and anxiety were observed in both groups over time (P < .05). Conclusions. Music-contingent gait training is feasible and safe in individuals with PD. Further investigation into potential therapeutic applications of this technology is recommended.

Frailty Prevalence in the COMPASS-ND Study of Neurodegenerative Disorders.

BACKGROUND: Frailty is characterized by increased vulnerability to adverse health outcomes. The prevalence of frailty across neurodegenerative disorders (NDD) is largely unknown. Symptoms of frailty and NDD overlap, calling into question a tautology in some frailty instruments. Our objectives were 1) to construct a Frailty Index (FI) independent of NDD symptoms, and 2) to estimate frailty prevalence in a broad NDD cohort using both the Frailty Phenotype (FP) and the constructed FI as measures. METHODS: Data from the Canadian COMPASS-ND cohort study were assessed for applicability to FI construction. Frailty status according to FI and FP criteria were ascertained for each participant. RESULTS: 81 items were selected for the FI. In the cohort (150 participants; 46% women; mean age 73.6±7.0; 10 NDD subgroups), frailty was identified in 11% and 14% of participants according to the FI and FP, respectively. The difference between estimates was not significant. The FP classified most participants (84%) as pre-frail. CONCLUSION: The presence of frailty elements, regardless of whether they are part of NDD, is likely to influence health status. Given the FP identified a large proportion of the cohort as pre-frail or frail, it is likely worthwhile to identify frailty in the context of NDD.

Differentiating cognitive or motor dimensions associated with the perception of fall-related self-efficacy in Parkinson's disease.

In Parkinson's disease (PD), concurrent declines in cognitive and motor domain function can severely limit an individual's ability to conduct daily tasks. Current diagnostic methods, however, lack precision in differentiating domain-specific contributions of cognitive or motor impairments based on a patients' clinical manifestation. Fear of falling (FOF) is a common clinical manifestation among the elderly, in which both cognitive and motor impairments can lead to significant barriers to a patients' physical and social activities. The present study evaluated whether a set of analytical and machine-learning approaches could be used to help delineate boundary conditions and separate cognitive and motor contributions to a patient's own perception of self-efficacy and FOF. Cognitive and motor clinical scores, in conjunction with FOF, were collected from 57 Parkinson's patients during a multi-center rehabilitation intervention trial. Statistical methodology was used to extract a subset of uncorrelated cognitive and motor components associated with cognitive and motor predictors, which were then used to independently identify and visualize cognitive and motor dimensions associated with FOF. We found that a central cognitive process, extracted from tests of executive, attentional, and visuoperceptive function, was a unique and significant independent cognitive predictor of FOF in PD. In addition, we provide evidence that the approaches described here may be used to computationally discern specific types of FOF based on separable cognitive or motor models. Our results are consistent with a contemporary model that the deterioration of a central cognitive mechanism that modulates self-efficacy also plays a critical role in FOF in PD.