Study protocol for the iMarkHD study in individuals with Huntington's disease.

Huntington's disease (HD) is still often defined by the onset of motor symptoms, inversely associated with the size of the CAG repeat expansion in the gene. Although the cause of HD is known, much remains unknown about mechanisms underlying clinical symptom development, disease progression, and specific clinical subtypes/endophenotypes. In the iMarkHD study, we aim to investigate four discrete molecular positron emission tomography (PET) tracers and magnetic resonance imaging (MRI) markers as biomarkers for disease and symptom progression.

Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction.

The spectrum, pathophysiology and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the 1-year cognitive, serum biomarker and neuroimaging findings from a prospective, national study of cognition in 351 COVID-19 patients who required hospitalization, compared with 2,927 normative matched controls. Cognitive deficits were global, associated with elevated brain injury markers and reduced anterior cingulate cortex volume 1 year after COVID-19.

Utilising accessible and reproducible neurological assessments in clinical studies: Insights from use of the Neurological Impairment Scale in the multi-centre COVID-CNS study.

Reproducible and standardised neurological assessment scales are important in quantifying research outcomes. These scales are often performed by non-neurologists and/or non-clinicians and must be robust, quantifiable, reproducible and comparable to a neurologist's assessment. COVID-CNS is a multi-centre study which utilised the Neurological Impairment Scale (NIS) as a core assessment tool in studying neurological outcomes following COVID-19 infection.

The Prevalence of Parkinson's Disease in Poland: Regional and Sex-Related Differences.

Background: Given the growing evidence for an environmental contribution to the etiology of Parkinson's disease (PD), searching for local and regional differences in PD prevalence in multiple areas across the world may further clarify the role of environmental toxins.

Objective: To provide local and regional prevalence estimates of PD in Poland.

Methods: We analyzed the prevalence of PD and its trend over the last decade (2010 to 2019) based on data from the National Health Fund in Poland.

Accessibility of Device-Aided Therapies for Persons With Parkinson's Disease in Poland.

Objective: Access to care for people with Parkinson's disease (PD), particularly to device-aided therapies (DAT), is not equally distributed. The objective was to analyze accessibility to DAT (deep brain stimulation, intraduodenal levodopa pump therapy, and apomorphine pump therapy) in Poland.

Methods: We analyzed the distribution of DAT use in Poland by determining the number of persons with PD receiving one of the three DATs during 2015-2021.

Future Directions for Developing Non-dopaminergic Strategies for the Treatment of Parkinson's Disease.

The symptomatic treatment of Parkinson's disease (PD) has been dominated by the use of dopaminergic medication, but significant unmet need remains, much of which is related to non-motor symptoms and the involvement of non-dopaminergic transmitter systems. As such, little has changed in the past decades that has led to milestone advances in therapy and significantly improved treatment paradigms and patient outcomes, particularly in relation to symptoms unresponsive to levodopa. This review has looked at how pharmacological approaches to treatment are likely to develop in the near and distant future and will focus on two areas: 1) novel non-dopaminergic pharmacological strategies to control motor symptoms; and 2) novel non-dopaminergic approaches for the treatment of non-motor symptoms.

The real-life effect of catechol-O-methyltransferase inhibition on non-motor symptoms in levodopa-treated Parkinson's disease: opicapone versus entacapone.

Objective: To evaluate the long-term, real-life effects on non-motor symptoms (NMS) of opicapone compared to entacapone in levodopa-treated people with Parkinson's disease (PwP).

Methods: A retrospective data analysis, with pre- and post-opicapone initiation data of 17 PwP with motor fluctuations compared to a comparable group of 18 PwP introduced on entacapone. The primary outcome was changes in the NMS Scale (NMSS) total score after 1-year follow-up.

The multimodal effect of circadian interventions in Parkinson's disease: A narrative review.

Background: The circadian system and its dysfunction in persons with Parkinson's disease (PwP) has a clear impact on both motor and non-motor symptoms. Examples include circadian patterns in motor disability, with worsening of symptoms throughout the day, but also the existence of similar patterns in non-motor symptoms.

Objective: In this narrative review, we discuss the role of the circadian system, we address the role of dopamine in this system, and we summarise the evidence that supports the use of circadian system treatments for motor and non-motor symptoms in PwP.

Characterization of Non-Motor Fluctuations Using the Movement Disorder Society Non-Motor Rating Scale.

Background: Non-motor fluctuations (NMF) in people with Parkinson's disease (PwP) are clinically important yet understudied.

Objective: To study NMF in PwP using both the Movement Disorder Society Non-Motor Rating Scale (MDS-NMS) NMF subscale and wearable sensors.

Methods: We evaluated differences in overall burden of NMF and of specific NMF across disease durations: <2 years (n = 33), 2-5 years (n = 35), 5-10 years (n = 33), and > 10 years (n = 31).

Why do 'OFF' periods still occur during continuous drug delivery in Parkinson's disease?

Continuous drug delivery (CDD) is used in moderately advanced and late-stage Parkinson's disease (PD) to control motor and non-motor fluctuations ('OFF' periods). Transdermal rotigotine is indicated for early fluctuations, while subcutaneous apomorphine infusion and levodopa-carbidopa intestinal gel are utilised in advanced PD. All three strategies are considered examples of continuous dopaminergic stimulation achieved through CDD.

Covid-19 and Parkinson's disease: Acute clinical implications, long-COVID and post-COVID-19 parkinsonism.

The Coronavirus Disease 2019 (Covid-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has led to unprecedented challenges for the delivery of healthcare and has had a clear impact on people with chronic neurological conditions such as Parkinson's disease (PD). Acute worsening of motor and non-motor symptoms and long-term sequalae have been described during and after SARS-CoV-2 infections in people with Parkinson's (PwP), which are likely to be multifactorial in their origin. On the one hand, it is likely that worsening of symptoms has been related to the viral infection itself, whereas social restrictions imposed over the course of the Covid-19 pandemic might also have had such an effect.

Impact of Covid-19 on research and training in Parkinson's disease.

The Coronavirus Disease 2019 (Covid-19) pandemic and the consequent restrictions imposed worldwide have posed an unprecedented challenge to research and training in Parkinson's disease (PD). The pandemic has caused loss of productivity, reduced access to funding, an oft-acute switch to digital platforms, and changes in daily work protocols, or even redeployment. Frequently, clinical and research appointments were suspended or changed as a solution to limit the risk of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) spread and infection, but since the care and research in the field of movement disorders had traditionally been performed at in-person settings, the repercussions of the pandemic have even been more keenly felt in these areas.

Parkinson's disease and Covid-19: The effect and use of telemedicine.

As a result of the Coronavirus Disease 2019 (Covid-19) pandemic the use of telemedicine and remote assessments for patients has increased exponentially, enabling healthcare professionals to reduce the need for in-person clinical visits and, consequently, reduce the exposure to the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This development has been aided by increased guidance on digital health technologies and cybersecurity measures, as well as reimbursement options within healthcare systems. Having been able to continue to connect with people with Parkinson's Disease (PwP, PD) has been crucial, since many saw their symptoms worsen over the pandemic.

Advances in the Pharmacological and Non-pharmacological Management of Non-motor Symptoms in Parkinson's Disease: An Update Since 2017.

Background: Non-motor symptoms (NMS) are an important and ubiquitous determinant of quality of life in Parkinson's disease (PD). However, robust evidence for their treatment is still a major unmet need.

Objective: This study aimed to provide an updated review on advances in pharmacological, nonpharmacological, and exercise-based interventions for NMS in PD, covering the period since the publication of the MDS Task Force Recommendations.

Personalised Advanced Therapies in Parkinson's Disease: The Role of Non-Motor Symptoms Profile.

Device-aided therapies, including levodopa-carbidopa intestinal gel infusion, apomorphine subcutaneous infusion, and deep brain stimulation, are available in many countries for the management of the advanced stage of Parkinson's disease (PD). Currently, selection of device-aided therapies is mainly focused on patients' motor profile while non-motor symptoms play a role limited to being regarded as possible exclusion criteria in the decision-making process for the delivery and sustenance of a successful treatment. Differential beneficial effects on specific non-motor symptoms of the currently available device-aided therapies for PD are emerging and these could hold relevant clinical implications.

Digital health technology for non-motor symptoms in people with Parkinson's disease: Futile or future?

Introduction: There is an ongoing digital revolution in the field of Parkinson's disease (PD) for the objective measurement of motor aspects, to be used in clinical trials and possibly support therapeutic choices. The focus of remote technologies is now also slowly shifting towards the broad but more "hidden" spectrum of non-motor symptoms (NMS).

Methods: A narrative review of digital health technologies for measuring NMS in people with PD was conducted.

Disentangling the PIGD classification for the prediction of cognitive impairment in de novo Parkinson's disease.

Background: Postural Instability and Gait difficulties (PIGD) subtype has been associated with worse cognitive performance in Parkinson's disease (PD).

Objective: To investigate whether PIGD subtype classification or PIGD-related clinical features predict the development of cognitive decline in de novo PD patients.

Methods: Data from 422 PD patients with de novo PD were obtained from the PPMI database.

Hypothalamic pathology in Huntington disease.

Huntington's disease (HD), an autosomal dominant hereditary disorder associated with the accumulation of mutant huntingtin, is classically associated with cognitive decline and motor symptoms, notably chorea. However, growing evidence suggests that nonmotor symptoms are equally prevalent and debilitating. Some of these symptoms may be linked to hypothalamic pathology, demonstrated by findings in HD animal models and HD patients showing specific changes in hypothalamic neuropeptidergic populations and their associated functions.

Cross-sectional analysis of the Parkinson's disease Non-motor International Longitudinal Study baseline non-motor characteristics, geographical distribution and impact on quality of life.

Growing evidence suggests that non-motor symptoms (NMS) in Parkinson's disease (PD) have differential progression patterns that have a different natural history from motor progression and may be geographically influenced. We conducted a cross-sectional analysis of 1607 PD patients of whom 1327 were from Europe, 208 from the Americas, and 72 from Asia. The primary objective was to assess baseline non-motor burden, defined by Non-Motor Symptoms Scale (NMSS) total scores.

Constipation is Associated with Development of Cognitive Impairment in de novo Parkinson's Disease: A Longitudinal Analysis of Two International Cohorts.

Background: Constipation is regarded as one of the prodromal features of Parkinson's disease (PD) and there is emerging evidence linking gastrointestinal dysfunction and cognitive impairment (CI) in PD.

Objective: We explored whether constipation is associated with development of CI in two independent cohorts of de novo PD patients (n = 196 from the Non-motor International Longitudinal Study [NILS] and n = 423 from the Parkinson's Progression Markers Initiative [PPMI] study).

Methods: Constipation was clinically defined using the Non-Motor Symptoms Scale (NMSS) item-21 [NILS] and Scales for Outcomes in PD-Autonomic (SCOPA-AUT) item-5 [PPMI].

Nonmotor symptom burden grading as predictor of cognitive impairment in Parkinson's disease.

Background: Identifying predictors of incident cognitive impairment (CI), one of the most problematic long-term outcomes, in Parkinson's disease (PD) is highly relevant for personalized medicine and prognostic counseling. The Nonmotor Symptoms Scale (NMSS) provides a global clinical assessment of a range of NMS, reflecting NMS burden (NMSB), and thus may assist in the identification of an "at-risk" CI group based on overall NMSB cutoff scores.

Methods: To investigate whether specific patterns of PD NMS profiles predict incident CI, we performed a retrospective longitudinal study on a convenience sample of 541 nondemented PD patients taking part in the Nonmotor Longitudinal International Study (NILS) cohort, with Mini-Mental State Examination (MMSE), NMSS, and Scales for Outcomes in PD Motor Scale (SCOPA Motor) scores at baseline and last follow-up (mean 3.

How Time Rules: Diurnal Motor Patterns in de novo Parkinson's Disease.

Background: Several small-scale studies have shown that motor performance in Parkinson's disease (PD) fluctuates throughout the day. Studies specifically focusing on de novo patients are, however, lacking.

Objective: To evaluate the effect of clock time on motor performance in de novo drug-naïve patients with PD.

Cost-Effectiveness of Device-Aided Therapies in Parkinson's Disease: A Structured Review.

Background: Despite optimal dopaminergic treatment most patients in moderate to advanced stages of Parkinson's disease (PD) experience progressively increasing disabilities, necessitating a shift from oral medication to device-aided therapies, including deep brain stimulation (DBS), intrajejunal levodopa-carbidopa infusion (IJLI), and continuous subcutaneous apomorphine infusion (CSAI). However, these therapies are costly, limiting their implementation.

Objectives: To perform a systematic review on cost-effectiveness analyses for device-aided therapies in PD.