Evaluating the importance of a core competency and capability framework for advanced practice physiotherapy: A cross-sectional survey.

INTRODUCTION: The need for a global core competency and capability framework for advanced practice physiotherapy is important due to the rapidly changing nature of health care delivery internationally and the need to standardize advanced practice physiotherapy. OBJECTIVE: To determine the importance of a proposed international core competency and capability framework for advanced practice physiotherapy. METHODS: We conducted a cross-sectional online survey of advanced practice physiotherapists across seven countries. The importance of each competency and capability was rated on a five-point agreement Likert scale. Participants were from the United Kingdom, Ireland, Australia, New Zealand, Canada, Switzerland and Argentina. RESULTS: A total of 99 participants completed the survey, comprising 63% (57/90) females and 33% (30/90) males. Sixty percent, 60% (54/90), had over 20 years of experience. The survey participants represented a diverse geographic distribution, with 25% (23/90) from Australia, 25% (23/90) from Canada, 18% (6/90) from New Zealand, and 18% (6/90) from the United Kingdom. Four percent 4% (4/90) from Ireland, and 4% (4/90) from other countries (Switzerland and Argentina). The survey revealed a strong consensus among participants, with all competencies and capabilities ranked as high and considered important to advanced practice. CONCLUSION: This study demonstrates a consensus among advanced practice physiotherapists across seven countries on the importance of a proposed competency and capability framework. The findings highlight the need for a global standard in advanced practice physiotherapy, particularly in light of the rapidly changing healthcare landscape.

"I Had to Know About It, I Had to Find It, I Had to Know How to Access it": Experiences of Access to Rehabilitation Services Among People Living with Long COVID.

Purpose: The aim of this qualitative study is to understand the need for, access to, and quality of rehabilitation services for people living with Long COVID. Little is known about the experiences of people living with Long COVID accessing rehabilitation services. Therefore, we explored health concerns leading people living with Long COVID to seek help to address functional concerns and their experiences with accessing and participating in rehabilitation. Method: Interpretive description guided exploration of participants' experiences with Long COVID rehabilitation in Alberta, Canada. Semi-structured interviews were completed with 56 participants recruited from: three publicly funded Long COVID clinics, a specialized private physiotherapy clinic, a telephone-based rehabilitation advice line, and a Workers' Compensation Board-funded Long COVID rehabilitation program. Recruitment through mass media coverage allowed us to include people who did not access rehabilitation services. Data analysis was informed by Braun and Clarke's reflexive thematic analysis. Results: Four themes were identified: (1) the burden of searching for guidance to address challenges with functioning and disability; (2) supportive relationships promote engagement in rehabilitation; (3) conditions for participation in safe rehabilitation; and (4) looking forward - provision of appropriate interventions at the right time. Conclusions: Our findings highlight the experiences of accessing rehabilitation services for people living with Long COVID. Results suggest approaches to Long COVID rehabilitation should be accessible, multi-disciplinary, flexible, and person-centred.

Objectif: étude qualitative pour comprendre les besoins en services de réadaptation des personnes qui vivent avec la COVID longue, l'accès à ces services et leur qualité. On sait peu de choses sur les expériences des personnes qui vivent avec la COVID longue et accèdent à des services de réadaptation. C'est pourquoi les auteurs ont exploré les inquiétudes qui incitent ces personnes à demander de l'aide pour répondre à leurs problèmes fonctionnels et les expériences qu'elles ont vécues en matière d'accès à la réadaptation et de participation aux services qui y sont associés. Méthodologie: exploration guidée de la description interprétative des expériences des participants qui suivent une réadaptation à cause de la COVID longue en Alberta, au Canada. Les chercheurs ont procédé à des entrevues semi-structurées auprès de 56 participants recrutés dans trois cliniques de COVID longue financées par le gouvernement, une clinique de physiothérapie spécialisée privée, une ligne téléphonique de conseils en réadaptation et un programme de réadaptation après la COVID longue remboursé par la commission des accidents de travail. Le recrutement dans les médias de masse a permis d'inclure des personnes qui n'avaient pas accédé aux services de réadaptation. L'examen des données reposait sur l'analyse thématique réflexive de Braun et Clarke. Résultats: les chercheurs ont relevé quatre thèmes : 1) le fardeau de la recherche de conseils pour répondre aux problèmes de fonctionnement et d'incapacité; 2) les relations de soutien qui favorisent la participation à la réadaptation; 3) les conditions nécessaires pour participer à une réadaptation sécuritaire et 4) pour l'avenir, la prestation d'interventions appropriées au bon moment. Conclusions: les constatations des auteurs font ressortir les expériences d'accès aux services de réadaptation chez les personnes qui vivent avec la COVID longue. Selon les résultats, les approches de réadaptation après la COVID longue devraient être accessibles, multidisciplinaires, flexibles et axées sur l'individu.

Developing an international competency and capability framework for advanced practice physiotherapy: a scoping review with narrative synthesis.

INTRODUCTION: The need to address increasing numbers of people seeking care, insufficient numbers of physicians, and providing high-value and sustainable care has contributed to changing physiotherapy practice across the world, often referred to as advanced practice physiotherapy. Currently, there is no internationally standardized competency and capability framework to support advanced practice physiotherapy. OBJECTIVES: This scoping review has two aims; 1) To identify and map out the competencies of advanced practice physiotherapy available in the literature. 2) To develop a competency and capability framework by mapping the competencies identified from the review. DESIGN: The Arksey and O'Malley framework and the PRISMA Scoping review methodology were used. Databases searched included CINAHL Plus, MEDLINE Ovid, PubMed, and Scopus. The competency and capability framework was developed through a narrative synthesis approach. RESULTS: Nineteen documents were included in the final review, with 13 grey literature (government reports, policy documents, thesis) and six research papers. Included publications came from the United Kingdom, Ireland, Australia, New Zealand, and Canada. The included documents covered predominantly musculoskeletal practice (n = 17). The others focused on cardiorespiratory care, incontinence and pelvic health. Through narrative synthesis, 27 competencies and capabilities were identified and grouped under seven domains. CONCLUSION: The synthesis of this scoping review provides the first competency and capability framework for advanced practice physiotherapy that integrates competencies and capabilities from five different countries. With the expansion of advanced practice physiotherapy, the framework developed from this review is the first step towards international recognition, standardization and consistency of education and training of practitioners. CONTRIBUTION OF THE PAPER.

"None of us are lying": an interpretive description of the search for legitimacy and the journey to access quality health services by individuals living with Long COVID.

BACKGROUND: Understanding of Long COVID has advanced through patient-led initiatives. However, research about barriers to accessing Long COVID services is limited. This study aimed to better understand the need for, access to, and quality of, Long COVID services. We explored health needs and experiences of services, including ability of services to address needs. METHODS: Our study was informed by the Levesque et al.'s (2013) "conceptual framework of access to health care." We used Interpretive Description, a qualitative approach partly aimed at informing clinical decisions. We recruited participants across five settings. Participants engaged in one-time, semi-structured, virtual interviews. Interviews were transcribed verbatim. We used reflexive thematic analysis. Best practice to ensure methodological rigour was employed. RESULTS: Three key themes were generated from 56 interviews. The first theme illustrated the rollercoaster-like nature of participants' Long COVID symptoms and the resulting impact on function and health. The second theme highlighted participants' attempts to access Long COVID services. Guidance received from healthcare professionals and self-advocacy impacted initial access. When navigating Long COVID services within the broader system, participants encountered barriers to access around stigma; appointment logistics; testing and 'normal' results; and financial precarity and affordability of services. The third theme illuminated common factors participants liked and disliked about Long COVID services. We framed each sub-theme as the key lesson (stemming from all likes and dislikes) that, if acted upon, the health system can use to improve the quality of Long COVID services. This provides tangible ways to improve the system based directly on what we heard from participants. CONCLUSION: With Long COVID services continuously evolving, our findings can inform decision makers within the health system to better understand the lived experiences of Long COVID and tailor services and policies appropriately.

Developing a core competency and capability framework for advanced practice physiotherapy: A qualitative study.

INTRODUCTION: There is an urgent need to develop an international competency and capability framework to support standardization of education and roles in advanced practice physiotherapy (APP). This need arose due to the rapid growth of the APP model of care, implemented out of necessity in the absence of agreement as to the competencies and capabilities or formal education required for the roles. This study explores the views and perceptions of practitioners and key stakeholders on a draft competency and capability framework for advanced practice physiotherapists. OBJECTIVES: The purpose of this study was to: 1) gather feedback from key stakeholders (advanced practice physiotherapists, researchers, and leaders) on a draft competency and capability framework and 2) use that feedback to revise and improve the draft framework. DESIGN: Qualitative study using a series of four multi-national online focus groups. Thematic analysis was conducted according to Braun and Clarke. RESULTS: Sixteen participants from the United Kingdom, Ireland, Canada, Australia, and New Zealand participated in the study. Five themes were generated after data analysis: clinical expert, experienced communicator, strong leader, collaborator, and knowledge creator). A modified competency and capability framework was developed based on feedback from the focus groups and input from subject matter experts (SMEs). CONCLUSION: This study provides a modified core competency and capability framework comprising 24 competencies grouped under six domains. This study is a step toward international standardization of advanced practice physiotherapy based on a commonly agreed framework for the education and training of advanced practice physiotherapists.

Return-to-Work Following Occupational Rehabilitation for Long COVID: Descriptive Cohort Study.

BACKGROUND: Emerging evidence suggests that worldwide, between 30% and 50% of those who are infected with COVID-19 experience long COVID (LC) symptoms. These symptoms create challenges with return-to-work (RTW) in a high proportion of individuals with LC. To tailor rehabilitation programs to LC sequelae and help improve RTW outcomes, more research on LC rehabilitation program outcomes is needed. OBJECTIVE: This study describes the characteristics and outcomes of workers who participated in an LC occupational rehabilitation program. METHODS: A cohort study was conducted. Descriptive variables included demographic and occupational factors as well as patient-reported outcome measures (PROMs, ie, the Fatigue Severity Scale [FSS], the Post-COVID Functional Scale [PCFS], the 36-item Short Form Health Survey [SF-36], the Pain Disability Index [PDI], the pain Visual Analogue Scale [VAS], the 9-item Patient Health Questionnaire [PHQ-9], the 7-item Generalized Anxiety Disorder Questionnaire [GAD-7], and the Diagnostic and Statistical Manual for Mental Disorders Fifth Edition [DSM-5] posttraumatic stress disorder [PTSD] checklist [PCL-5]). The main outcome variable was the RTW status at discharge. Descriptive statistics were calculated. Logistic regression examined predictors of RTW. RESULTS: The sample consisted of 81 workers. Most workers were female (n=52, 64%) and from health-related occupations (n=43, 53%). Only 43 (53%) individuals returned to work at program discharge, with 40 (93%) of these returning to modified duties. Although there were statistically significant improvements on the pain VAS (mean 11.1, SD 25.6, t31=2.5, P=.02), the PDI (mean 9.4, SD 12.5, t32=4.3, P<.001), the FSS (mean 3.9, SD 8.7, t38=2.8, P=.01), the SF-36 PCS (mean 4.8, SD 8.7, t38=-3.5, P=.001), the PHQ-9 (mean 3.7, SD 4.0, t31=5.2, P<.001), and the GAD-7 (mean 1.8, SD 4.4, t22=1.8, P=.03), there were no significant improvements in the PCFS, the overall mental component score (MCS) of the SF-36, or on the PCL-5. The availability of modified duties (odds ratio [OR] 3.38, 95% CI 1.26-9.10) and shorter time between infection and admission for rehabilitation (OR 0.99, 95% CI 0.99-1.00) predicted RTW even when controlling for age and gender. CONCLUSIONS: Workers undergoing LC rehabilitation reported significant but modest improvements on a variety of PROMs, but only 43 (53%) returned to work. Outcomes would likely improve with increased availability of modified duties and timelier rehabilitation. Additional research is needed, including larger observational cohorts as well as randomized controlled trials to evaluate the effectiveness of LC rehabilitation.

Rapid Standardized CT-Based Method to Determine Lean Body Mass SUV for PET-A Significant Improvement Over Prediction Equations.

In 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) studies, maximum standardized uptake value (SUVmax) is the parameter commonly used to provide a measurement of the metabolic activity of a tumor. SUV normalized by body mass is affected by the proportions of body fat and lean tissue, which present high variability in patients with cancer. SUV corrected by lean body mass (LBM), denoted as SUL, is recommended to provide more accurate, consistent, and reproducible SUV results; however, LBM is frequently estimated rather than measured. Given the increasing importance of a quantitative PET parameter, especially when comparing PET studies over time to evaluate disease response clinically, and its use in oncological clinical trials, we set out to evaluate the commonly used equations originally derived by James (1976) and Janmahasatian et al. (2005) against computerized tomography (CT)-derived measures of LBM. Methods: Whole-body 18F-FDG PET images of 195 adult patients with cancer were analyzed retrospectively. Representative liver SUVmean was normalized by total body mass. SUL was calculated using a quantitative determination of LBM based on the CT component of the PET/CT study (LBMCT) and compared against the equation-estimated SUL. Bland and Altman plots were generated for SUV-SUL differences. Results: This consecutive sample of patients undergoing usual care (men, n = 96; women, n = 99) varied in body mass (38-127 kg) and in Body Mass Index (BMI) (14.7-47.2 kg/m2). LBMCT weakly correlated with body mass (men, r2 = 0.32; women, r2 = 0.22), and thus SUV and SULCT were also weakly correlated (men, r2 = 0.24; women, r2 = 0.11). Equations proved inadequate for the assessment of LBM. LBM estimated by James' equation showed a mean bias (overestimation of LBM compared with LBMCT) in men (+6.13 kg; 95% CI 4.61-7.65) and in women (+6.32 kg; 95% CI 5.26-7.39). Janmahasatian's equation provided similarly poor performance. Conclusions: CT-based LBM determinations incorporate the patient's current body composition at the time of a PET/CT study, and the information garnered can provide care teams with information with which to more accurately determine FDG uptake values, allowing comparability over multiple scans and treatment courses and will provide a robust basis for the use of PET Response Criteria in Solid Tumors (PERCIST) in clinical trials.

Pedunculopontine Nucleus Dysconnectivity Correlates With Gait Impairment in Parkinson's Disease: An Exploratory Study.

Background: Gait impairment is a debilitating and progressive feature of Parkinson's disease (PD). Increasing evidence suggests that gait control is partly mediated by cholinergic signaling from the pedunculopontine nucleus (PPN). Objective: We investigated whether PPN structural connectivity correlated with quantitative gait measures in PD. Methods: Twenty PD patients and 15 controls underwent diffusion tensor imaging to quantify structural connectivity of the PPN. Whole brain analysis using tract-based spatial statistics and probabilistic tractography were performed using the PPN as a seed region of interest for cortical and subcortical target structures. Gait metrics were recorded in subjects' medication ON and OFF states, and were used to determine if specific features of gait dysfunction in PD were related to PPN structural connectivity. Results: Tract-based spatial statistics revealed reduced structural connectivity involving the corpus callosum and right superior corona radiata, but did not correlate with gait measures. Abnormalities in PPN structural connectivity in PD were lateralized to the right hemisphere, with pathways involving the right caudate nucleus, amygdala, pre-supplementary motor area, and primary somatosensory cortex. Altered connectivity of the right PPN-caudate nucleus was associated with worsened cadence, stride time, and velocity while in the ON state; altered connectivity of the right PPN-amygdala was associated with reduced stride length in the OFF state. Conclusion: Our exploratory analysis detects a potential correlation between gait dysfunction in PD and a characteristic pattern of connectivity deficits in the PPN network involving the right caudate nucleus and amygdala, which may be investigated in future larger studies.

Life-Space Mobility and Parkinson's Disease. A Multiple-Methods Study.

Background: Life-space mobility (LSM) captures a broad spectrum of mobility in physical and social environments; however, it has not been extensively studied in Parkinson's disease. Using a multiple-methods approach, individual, social and environmental factors that impact LSM were explored in PD. Methods: Two hundred twenty-seven participants with PD (n = 113) and a comparative group without PD (n = 114) were recruited from the community. Within a cross-sectional survey, LSM (University of Alabama Birmingham Life-Space Assessment, LSA) was compared in the two groups. Using multiple linear regression, socio-demographics, lifestyle behaviors, medical, mobility and social factors were examined to identify factors that explained LSM. A qualitative narrative inquiry was completed to augment the findings from the survey; 10 participants with PD were interviewed regarding facilitators and barriers to mobility. Results: The mean overall LSA-composite score for the PD group was 64.2 (SD = 25.8) and 70.3 (SD = 23.1) for the community comparative group (mean difference = 6 points, 95%CI:-0.4, 12.5) indicating most participants moved independently beyond their neighborhoods. A higher proportion of the PD group required assistance with mobility than the community comparison group. Not driving, receiving caregiving, lower social participation, and lower monthly family finances were associated with restricted LSM in the PD group. Data from qualitative interviews supported quantitative findings and offered insights into the features of the built environment that facilitate and restrict mobility. Conclusion: Individual, social and environmental factors are associated with the LSM among persons with PD. Clinicians and policy-makers should include both individual and community-based factors when developing interventions to encourage the LSM of the PD population.

Advanced practice in physiotherapy: a global survey.

INTRODUCTION: Advanced practice in physiotherapy represents a development in the practice of physiotherapy and has developed in different ways around the world. There is growing evidence to support advanced physiotherapy practice. In May 2019, the member organisations adopted the first World Physiotherapy policy on advanced practice in physiotherapy. However, to date, there is no evidence on the nature and extent of this practice globally. OBJECTIVES: To investigate the extent to which advanced practice is present within the global physiotherapy community, to document the titles used, to describe the pathway to become an advanced physiotherapy practitioner and to investigate the barriers and facilitators to the development of the roles. DESIGN: An online cross-sectional survey was sent to the various national associations of the World Physiotherapy. PARTICIPANTS: Participants were the member organisations of World Physiotherapy. INSTRUMENT: The survey comprised 14 questions. The questions were developed based on a review of the evidence around advanced practice and in-depth discussions with the expert group set up by World Physiotherapy. RESULTS: A total of 82/112 MOs responded to the survey representing a 73% response rate. Fourteen respondents (14/82, 17%) indicated that they had formal roles in their country/territory. The terms specialist and advanced physiotherapy practitioner were often used interchangeably and were a source of confusion. Seventy-nine (11/14, 79%) percent stated that most advanced physiotherapy practitioners have a combination of clinical practice and a Master's or Doctoral degree. The major facilitators to the development and sustainability of the role were the research evidence, advocacy by the professional organisation, the need to reduce cost and the support received by the advanced physiotherapy practitioners from their employers. CONCLUSION: The outcomes of this study provide a clearer understanding of how member organisations of World Physiotherapy defined advanced practice in physiotherapy and what titles are used. It provides insights into the barriers and facilitators to the development of advanced practice in physiotherapy.

Subcortical microstructural diffusion changes correlate with gait impairment in Parkinson's disease.

BACKGROUND: Gait impairments are common in Parkinson's Disease (PD) and are likely caused by degeneration in multiple brain circuits, including the basal ganglia, thalamus and mesencephalic locomotion centers (MLC). Diffusion tensor imaging (DTI) assesses fractional anisotropy (FA) and mean diffusivity (MD) that reflect the integrity of neuronal microstructure. We hypothesized that DTI changes in motor circuits correlate with gait changes in PD. OBJECTIVE: We aimed to identify microstructural changes of brain locomotion control centers in PD via DTI and their correlations with clinical and quantitative measures of gait. METHODS: Twenty-one PD patients reporting gait impairment and 15 controls were recruited. Quantitative gait and clinical tests were recorded in PD subjects' medication ON and OFF states. Region of Interest (ROI) analysis of the thalamus, basal ganglia and MLC was performed using ExploreDTI. Correlations between FA/MD with clinical gait parameters were examined. RESULTS: Microstructural changes were seen in the thalamus, caudate and MLC in the PD compared to the control group. Thalamic microstructural changes significantly correlated with gait parameters in the pace domain including the Timed Up and Go in the ON state. Caudate changes correlated with cadence and stride time in the OFF state. CONCLUSIONS: Our pilot study suggests that PD is associated with a characteristic regional pattern of microstructural degradation in the thalamus, caudate and MLC. The DTI changes may represent subcortical locomotion network failure. Overall, DTI ROI analyses might provide a useful tool for assessing PD for functional status and specific motor domains, such as gait, and potentially could serve as an imaging marker.

Parkinson Disease: The Relationship Between Non-motor Symptoms and Motor Phenotype.

BACKGROUND: Parkinson disease (PD) presents with motor and non-motor symptoms (NMS). The NMS often precede the onset of motor symptoms, but may progress throughout the disease course. Tremor dominant, postural instability gait difficulty (PIGD), and indeterminate phenotypes can be distinguished using Unified PD Rating scales (UPDRS-III). We hypothesized that the PIGD phenotype would be more likely to develop NMS, and that the non-dopamine-responsive axial signs would correlate with NMS severity. METHODS: We conducted a retrospective cross-sectional chart review to assess the relationship between NMS and PD motor phenotypes. PD patients were administered the NMS Questionnaire, the UPDRS-III, and the Mini-Mental State Examination score. The relationship between NMS burden and PD subtypes was examined using linear regression models. The prevalence of each NMS among difference PD motor subtypes was analyzed using chi-square test. RESULTS: PD patients with more advanced disease based on their UPDRS-III had higher NMS Questionnaire scores. The axial component of UPDRS-III correlated with higher NMS. There was no correlation between NMS and tremor scores. There was a significant correlation between PIGD score and higher NMS burden. PIGD group had higher prevalence in most NMS domains when compared with tremor dominant and indeterminate groups independent of disease duration and severity. CONCLUSIONS: NMS profile and severity vary according to motor phenotype. We conclude that in the PD population, patients with a PIGD phenotype who have more axial involvement, associated with advanced disease and poor motor response, have a higher risk for a higher NMS burden.

Freezing of gait in early Parkinson's disease: Nigral iron content estimated from magnetic resonance imaging.

PURPOSE: Freezing of gait is a major source of disability associated with the progression of Parkinson's disease (PD). Our objective was to determine whether evolving changes in nigral iron content in association with declining motor function in early PD differentiates subjects who develop freezing from those who do not. METHODS: A cohort of previously untreated individuals with early PD (n=19) was followed for 36 months clinically and with MRI. The cohort was divided into two groups based on the development of freezing during follow-up. A multiple gradient echo MRI sequence provided an index of basal ganglia iron content. RESULTS: There were significant baseline differences between those who developed freezing (n=7) and those who did not (n=12) in Unified Parkinson's Disease Rating Scale motor scores, time to complete a 14 m walk and timed up and go. There was a significant correlation between the measured change in transverse relaxation in the lateral substantia nigra pars compacta and the change in motor score from baseline to 36 months (p=0.002). The freezing group showed a greater change in motor score and iron content than did the non-freezing group. CONCLUSIONS: Individuals destined to develop freezing early in PD have more motor impairment at baseline, more rapid deterioration in motor function, and pars compacta changes suggestive of increased iron content in comparison to those who do not.

Longitudinal midbrain changes in early Parkinson's disease: iron content estimated from R2*/MRI.

OBJECTIVE: To determine whether, in patients with early Parkinson's disease (PD), longitudinal changes in midbrain iron content are associated with declining motor function over a period of three years. METHODS: Nineteen untreated subjects with early PD and 13 age- and sex-matched controls were followed clinically for 36 months. MRI with a 3 T magnet was performed at baseline, 18 months and 36 months with a multiple gradient echo sequence designed for rapid single-scan mapping of the proton transverse relaxation rate R2*. R2* was calculated for midbrain and forebrain basal ganglia regions. RESULTS: A difference in R2* between patients and controls was observed at baseline (p = 0.035) but not at 18 or 36 months in the lateral substantia nigra pars compacta (SNc). Linear regression indicated significant correlations between the change in R2* in the lateral SNc and the change score in UPDRS III (p = 0.008) and the PDQ-39 -mobility sub-score (p = 0.03) from baseline to 36 months. R2* tended to increase in those with more advanced disease and to decrease in those with milder disease. CONCLUSIONS: High field MRI demonstrates lateral SNc abnormalities that progress over 3 years in early PD consistent with increased iron content in those with more advanced disease, corresponding to the known distribution of neuronal loss occurring in this disorder, and correlating with motor symptomatology. Larger and longer investigations with more precise mapping of iron-containing midbrain structures are needed to fully evaluate the potential of R2* as a biomarker of disease progression in PD.

Coexistence of Huntington's disease and amyotrophic lateral sclerosis: a clinicopathologic study.

We report a retrospective case series of four patients with genetically confirmed Huntington's disease (HD) and sporadic amyotrophic lateral sclerosis (ALS), examining the brain and spinal cord in two cases. Neuropathological assessment included a polyglutamine recruitment method to detect sites of active polyglutamine aggregation, and biochemical and immunohistochemical assessment of TDP-43 pathology. The clinical sequence of HD and ALS varied, with the onset of ALS occurring after the mid-50's in all cases. Neuropathologic features of HD and ALS coexisted in both cases examined pathologically: neuronal loss and gliosis in the neostriatum and upper and lower motor neurons, with Bunina bodies and ubiquitin-immunoreactive skein-like inclusions in remaining lower motor neurons. One case showed relatively early HD pathology while the other was advanced. Expanded polyglutamine-immunoreactive inclusions and TDP-43-immunoreactive inclusions were widespread in many regions of the CNS, including the motor cortex and spinal anterior horn. Although these two different proteinaceous inclusions coexisted in a small number of neurons, the two proteins did not co-localize within inclusions. The regional distribution of TDP-43-immunoreactive inclusions in the cerebral cortex partly overlapped with that of expanded polyglutamine-immunoreactive inclusions. In the one case examined by TDP-43 immunoblotting, similar TDP-43 isoforms were observed as in ALS. Our findings suggest the possibility that a rare subset of older HD patients is prone to develop features of ALS with an atypical TDP-43 distribution that resembles that of aggregated mutant huntingtin. Age-dependent neuronal dysfunction induced by mutant polyglutamine protein expression may contribute to later-life development of TDP-43 associated motor neuron disease in a small subset of patients with HD.

Incidence and mortality of Parkinson's disease in older Canadians.

OBJECTIVE: To estimate the age-specific incidence of Parkinson's disease (PD) in elderly persons in the Canadian province of British Columbia (BC). All-cause and injury mortalities and relative risk of death for those persons with PD were also examined. METHODS: A historical cohort study was conducted using 5 provincial administrative databases from 1991/92 to 2000/2001. A series of algorithms based on the databases were created for case ascertainment of PD for persons 65 years or older. Crude and age-specific incidence and mortality rates were calculated using person-years of follow-up as the denominator. The impact of PD on all-cause and injury mortalities was examined using multivariate Cox regression models to provide adjusted hazard ratios. RESULTS: 10,910 incidence cases over 6,051,682 person-years of follow-up were identified. The crude annual incidence rate was 252 per 100,000 person-years. Over the nine year period, age standardized incidence for males ranged from 207 to 396 per 100,000 person-years and 127 to 259 per 100,000 person-years for females. Persons with PD were at a 43% greater risk of all-cause mortality and specifically, 51% greater risk of injury mortality. CONCLUSIONS: Incidence of PD is substantially higher in advanced age with age adjusted increases for both all-cause and injury mortalities. These findings also highlight falls as a primary factor for injury mortality in PD.

Temporal lobe changes in early, untreated Parkinson's disease.

The purpose of this study was to determine if focal cortical abnormalities may occur in early Parkinson's disease (PD). We studied 26 untreated patients with early PD and 14 healthy control subjects, with cognitive screening and magnetic resonance imaging (MRI). Voxel-based morphometry was used to assess for the presence of localized cortical grey matter (GM) and/or subcortical white matter (WM) changes. Patient and control groups showed no differences in age or gender distribution. Females had a greater GM% than males (P = 0.001). Comparison of patients and controls revealed no difference in local GM volumes. In PD, however, there was decreased WM volume in the anterior right fusiform gyrus and superior temporal gyrus. There were no correlations between the California Verbal Learning Test long delay free recall, Judgment of Line Orientation, Trail Making A or B and either the GM or WM localized volumes. These results suggest that right anterior temporal lobe changes occur in untreated patients with PD. The earliest changes may occur in subcortical white matter rather than temporal cortex.

Intact presupplementary motor area function in early, untreated Parkinson's disease.

Although motor symptoms of Parkinson's disease (PD) are initially responsive to dopamine replacement therapy, nonresponsive features develop over time, suggesting that impaired dopaminergic function alone may not be wholly responsible for all the motor features of the disease. Previous studies suggest impaired function in the presupplementary motor area (pre-SMA) in PD. Our objective was to determine whether pre-SMA abnormalities are present in untreated patients with early disease. We measured N-acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios in pre-SMA in 26 untreated patients with early PD (disease duration 3.0 +/- 2.0 yr) and 15 control subjects with single voxel magnetic resonance spectroscopy. Neither NAA/Cr nor Cho/Cr ratios differed significantly between groups. These observations suggest that, although pre-SMA function is impaired in moderately advanced PD, it is relatively spared in early disease. We suggest that pre-SMA dysfunction is in part responsible for the dopamine nonresponsive features associated with disease progression.