Bridging Huntington's disease research with big data science: Harmonized neuroimaging datasets from multiple studies.

Multiple neuroimaging datasets from Huntington's disease (HD) studies are publicly available, but these datasets are in various formats, omit imaging metadata, and sometimes contain corrupt scans. We have created a platform to curate, harmonize, and distribute neuroimaging datasets from eight different studies: TRACK-HD, TRACKOn-HD, PREDICT-HD, IMAGE-HD, HD-YAS, SHIELD-HD, PEARL-HD, and LONGPDE10. The platform is organized into three conceptual levels to serve the research community with both raw and processed data.

Utilizing MCID for evaluating clinical relevance of AD therapeutic interventions.

Unlabelled: With the recent approval of disease-modifying treatments for mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) by the United States Food and Drug Administration (FDA), Medicines and Healthcare products Regulatory Agency (MHRA), European Medicine Agency's Committee for Medicinal Products for Human Use (EMA/CHMP) entities, there is a growing sense of urgency and renewed efforts to reassess and understand what constitutes a clinically meaningful benefit in the context of new treatments for AD care, despite the discordance between regulatory entities in regulatory decision-making. While the concept of minimal clinically important difference (MCID) was introduced many years ago, there remains an ongoing debate about how best to evaluate and define clinical benefit in the context of emerging and new therapies for dementia. In this perspective piece, we assess how MCID can be applied to common endpoints and identify areas where MCID application or generation could be useful to enable a better valuation of therapeutic innovation.

PET imaging with [¹¹C]CHDI-00485180-R, designed as radioligand for aggregated mutant huntingtin, in people with Huntington's disease.

Purpose: [C]CHDI-00485180-R ([C]CHDI-180R) is a novel PET radioligand developed to image aggregated mutant huntingtin (mHTT). Data from mouse models of Huntington's disease (HD) and biodistribution studies in healthy volunteers suggested that [C]CHDI-180R is a promising candidate for in vivo determination of cerebral aggregated mHTT levels using PET. In the iMagemHTT study reported here, we investigated [C]CHDI-180R kinetic properties and suitability to quantify aggregated mHTT in brains of people with HD (pwHD).

Modeling Disease Progression and Placebo Response in Huntington Disease: Insights From Enroll-HD and GENERATION HD1 Cohorts.

Background And Objectives: Huntington disease is a rare neurodegenerative disorder with no disease-modifying therapies. This study aimed to quantify longitudinal changes in Unified Huntington's Disease Rating Scale (UHDRS) scores and evaluate their susceptibility to placebo response, enhancing our understanding of disease progression and ability to optimize future trials.

Methods: We used data from the Enroll-HD natural history study (NCT01574053) and the GENERATION HD1 phase 3 clinical trial (NCT03761849) to model disease progression and placebo response for UHDRS scores, which are commonly used to evaluate disease progression in clinical trials.

Functional Rating Scale 2.0 (FuRST 2.0): A patient-reported outcome measure of function for Huntington's disease.

BackgroundCurrent functional rating scales are not sensitive to the earliest functional changes in Huntington's disease (HD).ObjectiveThe Functional Rating Scale 2.0 (FuRST 2.

Sleep quality and associated factors in teachers.

Sleep is an essential part of life, accounting for about one third of an individual's life expectancy and plays an important role in quality of life and professional performance. This study focuses specifically on primary school teachers, a group that often faces high levels of stress. Restorative sleep is vital for dealing with this stress, and when its quality is unsatisfactory, it can contribute to the development of burnout.

Update on Treatments for Parkinson's Disease Motor Fluctuations - An International Parkinson and Movement Disorder Society Evidence-Based Medicine Review.

Objective: To update evidence-based medicine recommendations for treating motor fluctuations of Parkinson's disease (PD).

Background: The International Parkinson and Movement Disorder Society (MDS) Evidence Based Medicine in Movement Disorders Committee recommendations for the treatments of PD were first published in 2002 and regularly updated. The current review uses a new methodology, including the Cochrane Risk of Bias tool and a modified version of GRADE (Grading of Recommendations, Assessment, Development, and Evaluations).

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.

Increased Mortality Risk in Patients with Illicit Substance Use and COVID-19: Analysis of a Large Brazilian Sample.

Background: Illicit substance use (ISU) may be a potential predisposing factor for severe COVID-19 outcomes.

Objective: To conduct a propensity score-matching analysis to assess and compare the mortality rate of individuals who reported ISU among a sizable cohort of hospitalized COVID-19 patients in Brazil.

Methods: This population-based retrospective cohort study analyzed a nationwide Brazilian database of patients hospitalized for COVID-19.

Lack of Evidence for Kynurenine Pathway Dysfunction in Huntington's Disease: CSF and Plasma Analyses from the HDClarity Study.

Background: Evidence from animal studies and post-mortem studies of brains from people with Huntington's disease (PwHD) has suggested that the kynurenine pathway (KP) may be dysregulated in Huntington's disease (HD).

Objective: To determine whether there are differences in KP metabolites in the CSF and plasma of PwHD versus healthy controls enrolled in the HDClarity study.

Methods: CSF and plasma samples from 141 PwHD with mild and moderate manifest disease and 75 healthy controls were analyzed for 3-hydroxykynurenine (3-OH-KYN), quinolinic acid, kynurenine, anthranilic acid, kynurenic acid, and tryptophan concentrations using validated high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) methods.

Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington's disease decades before clinical motor diagnosis.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with the age at which characteristic symptoms manifest strongly influenced by inherited HTT CAG length. Somatic CAG expansion occurs throughout life and understanding the impact of somatic expansion on neurodegeneration is key to developing therapeutic targets. In 57 HD gene expanded (HDGE) individuals, ~23 years before their predicted clinical motor diagnosis, no significant decline in clinical, cognitive or neuropsychiatric function was observed over 4.

Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation.

There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas.

Time to Functional Loss as an Endpoint in Huntington's Disease Trials: Enrichment and Sample Size.

Background: Clinical trial scenarios can be modeled using data from observational studies, providing critical information for design of real-world trials. The Huntington's Disease Integrated Staging System (HD-ISS) characterizes disease progression over an individual's lifespan and allows for flexibility in the design of trials with the goal of delaying progression. Enrichment methods can be applied to the HD-ISS to identify subgroups requiring smaller estimated sample sizes.

The impact of smoking on COVID-19-related mortality: a Brazilian national cohort study.

Introduction: Current evidence suggests the potential heightened vulnerability of smokers to severe coronavirus disease (COVID-19) outcomes.

Aims: This study aimed to analyze the clinical outcomes and mortality related to tobacco use in a cohort of hospitalized Brazilian COVID-19 patients.

Methods: This retrospective cohort study analyzed adults hospitalized for COVID-19 in Brazil using the SIVEP-Gripe database (official data reported by public and private healthcare facilities for monitoring severe acute respiratory syndrome cases in Brazil).

Therapeutic itineraries of quilombola women in northern Minas Gerais, Brazil.

Quilombolas are ethnic-racial groups, of black ancestry, and had their territories consolidated in Brazil in regions with difficult access and far from large centers. The objective of this study is to know the therapeutic itinerary (IT) adopted by quilombola women in traditional communities located in the North of the state of Minas Gerais. This is a qualitative study with the theoretical model using the Arthur Kleinman health care system.

Therapeutic itineraries in health care in Quilombola communities.

This article aimed to map therapeutic itineraries in health care within rural Quilombola communities in the north of Minas Gerais, Brazil. This is a section of a qualitative research conducted in six visited communities. The data was collected through 18 individual interviews, analyzed using the theoretical-methodological framework of Therapeutic Itineraries, and organized into three empirical themes.

Large-scale screening of clinical assessments to distinguish between states in the Integrated HD Progression Model (IHDPM).

Background: Understanding the sensitivity and utility of clinical assessments across different HD stages is important for study/trial endpoint selection and clinical assessment development. The Integrated HD Progression Model (IHDPM) characterizes the complex symptom progression of HD and separates the disease into nine ordered disease states.

Objective: To generate a temporal map of discriminatory clinical measures across the IHDPM states.