Participant-reported personal utility of genetic testing for Parkinson's disease and interest in clinical trial participation.

Genetic testing for Parkinson's disease (PD) is infrequently performed due to perceptions of low utility. We investigated the personal utility in PD GENEration and how results lead to enrollment in additional research studies. Participants (n = 972) underwent genetic testing, results disclosure, genetic counseling, and completed a survey examining the perceived personal utility of their results and interest in participating in additional studies.

Parkinson's disease variant detection and disclosure: PD GENEration, a North American study.

Variants in seven genes (LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7 and VPS35) have been formally adjudicated as causal contributors to Parkinson's disease; however, individuals with Parkinson's disease are often unaware of their genetic status since clinical testing is infrequently offered. As a result, genetic information is not incorporated into clinical care, and variant-targeted precision medicine trials struggle to enrol people with Parkinson's disease. Understanding the yield of genetic testing using an established gene panel in a large, geographically diverse North American population would help patients, clinicians, clinical researchers, laboratories and insurers better understand the importance of genetics in approaching Parkinson's disease.

Improving Parkinson's Disease Care through Systematic Screening for Depression.

Background: Depression is common in Parkinson's disease (PD) but is underrecognized clinically. Although systematic screening is a recommended strategy to improve depression recognition in primary care practice, it has not been widely used in PD care.

Methods: The 15-item Geriatric Depression Scale (GDS-15) was implemented at 5 movement disorders clinics to screen PD patients.

Providing genetic testing and genetic counseling for Parkinson's disease to the community.

Purpose: To evaluate the feasibility and impact of offering genetic testing and counseling to patients with Parkinson's disease (PD), with the potential to enroll in gene-targeted clinical trials and improve clinical care.

Methods: A multicenter, exploratory pilot study at 7 academic hospital sites in the United States tracked enrollment and randomized participants to receive results and genetic counseling at local sites or by genetic counselors, remotely. Follow-up surveys measured participant/provider satisfaction, knowledge, and psychological impact.

Association of women-specific health factors in the severity of Parkinson's disease.

Parkinson's disease (PD) is an age-related neurological disorder known for the observational differences in its risk, progression, and severity between men and women. While estrogen has been considered to be a protective factor in the development of PD, there is little known about the role that fluctuations in hormones and immune responses from sex-specific health experiences have in the disease's development and severity. We sought to identify women-specific health experiences associated with PD severity, after adjusting for known PD factors, by developing and distributing a women-specific questionnaire across the United States and creating multivariable models for PD severity.

Racial and Ethnic Differences in Health-Related Quality of Life for Individuals With Parkinson Disease Across Centers of Excellence.

Background And Objectives: Racial and ethnic minorities have been underrepresented in Parkinson disease (PD) research, limiting our understanding of treatments and outcomes across all non-White groups. The goal of this research is to investigate variability in health-related quality of life (HRQoL) and other outcomes in patients with PD across different races and ethnicities.

Methods: This was a retrospective, cross-sectional and longitudinal, cohort study of individuals evaluated at PD Centers of Excellence.

Differential serum microRNAs in premotor LRRK2 G2019S carriers from Parkinson's disease.

The LRRK2 G2019S pathogenic mutation causes LRRK2-associated Parkinson's disease (L2PD) with incomplete penetrance. LRRK2 non-manifesting carriers (L2NMC) are at PD high risk but predicting pheno-conversion is challenging given the lack of progression biomarkers. To investigate novel biomarkers for PD premotor stages, we performed a longitudinal microRNA (miRNA) assessment of serum samples from G2019S L2NMC followed-up over 8 years.

Study in Parkinson's disease of exercise phase 3 (SPARX3): study protocol for a randomized controlled trial.

Background: To date, no medication has slowed the progression of Parkinson's disease (PD). Preclinical, epidemiological, and experimental data on humans all support many benefits of endurance exercise among persons with PD. The key question is whether there is a definitive additional benefit of exercising at high intensity, in terms of slowing disease progression, beyond the well-documented benefit of endurance training on a treadmill for fitness, gait, and functional mobility.

The commercial genetic testing landscape for Parkinson's disease.

Introduction: There have been no specific guidelines regarding which genes should be tested in the clinical setting for Parkinson's disease (PD) or parkinsonism. We evaluated the types of clinical genetic testing offered for PD as the first step of our gene curation.

Methods: The National Institutes of Health (NIH) Genetic Testing Registry (GTR) was queried on 12/7/2020 to identify current commercial PD genetic test offerings by clinical laboratories, internationally.

Personality traits of alexithymia and perfectionism in impaired awareness of hypoglycemia in adults with type 1 diabetes - An exploratory study.

Objective: Severe hypoglycemia complicates insulin therapy for type 1 diabetes, with impaired awareness of hypoglycemia (IAH) being a major risk factor. We explored associations between the personality traits, alexithymia and perfectionism, and cognitive barriers to hypoglycemia avoidance described in IAH, and evaluated their prevalence in people with and without IAH.

Methods: Cross-sectional exploratory study.

Genetic Testing for Parkinson Disease: Are We Ready?

Purpose Of Review: With the advent of precision medicine and demand for genomic testing information, we may question whether it is time to offer genetic testing to our patients with Parkinson disease (PD). This review updates the current genetic landscape of PD, describes what genetic testing may offer, provides strategies for evaluating whom to test, and provides resources for the busy clinician.

Recent Findings: Patients with PD and their relatives, in various settings, have expressed an interest in learning their PD genetic status; however, physicians may be hesitant to widely offer testing due to the perceived low clinical utility of PD genetic test results.

Expediting telehealth use in clinical research studies: recommendations for overcoming barriers in North America.

Despite data supporting the rapid adoption of telehealth in the delivery of clinical care in North America, the implementation of telehealth visits in clinical research studies has faced critical barriers. These challenges include: (1) variations in state licensure requirements for telehealth; (2) disparities in access to telehealth among disadvantaged populations; (3) lack of consistency among individual Investigational Review Boards (IRBs). Each barrier prevents the systematic conversion of research protocols to include telehealth visits.

The Role of Genetic Testing for Parkinson's Disease.

Purpose Of Review: To describe current practices and attitudes about genetic testing for Parkinson's disease (PD) among neurologists, highlight the changing scene of genetic testing for PD, and provide guidance on facilitating PD genetic testing in a clinical practice.

Recent Findings: Since the 1990s, researchers have discovered several major gene variants contributing to PD etiology. A large body of literature now exists supporting the frequency of these variants in different populations and their effects on phenotype and clinical course.

Correction: Genetic testing for Parkinson disease: current practice, knowledge, and attitudes among US and Canadian movement disorders specialists.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genetic testing for Parkinson disease: current practice, knowledge, and attitudes among US and Canadian movement disorders specialists.

Purpose: Genetic testing for Parkinson disease (PD) has not been widely used in clinical practice. In preparation for upcoming precision medicine-designed clinical trials for GBA and LRRK2, we evaluated movement disorders specialists' current practice, knowledge, attitudes, and barriers to genetic testing in PD.

Methods: An anonymous questionnaire was sent to movement disorders specialists at 146 Parkinson Study Group (PSG) sites in the United States (n = 131) and Canada (n = 15) to assess their knowledge and attitudes about genetic testing for PD.

Motor phenotype classification in moderate to advanced PD in BioFIND study.

Background: Three motor phenotypes have been described in PD: postural instability and gait difficulty (PIGD) dominant, tremor-dominant (TD), and indeterminate (IND) subtype. These phenotypes have been associated with different cognitive trajectories, motor outcomes, and biomarkers profiles. However, whether motor subtype classifications change with treatment and disease progression is not well established.

Congenital extrahepatic portosystemic shunt with progressive myelopathy and encephalopathy.

Portosystemic encephalopathy commonly occurs in patients with portal hypertension caused by end-stage liver disease or portal vein thrombosis. Congenital extrahepatic portosystemic shunt (CEPS) is an underdiagnosed and treatable condition that can cause encephalopathy and various neuropsychiatric symptoms. We report an unusual case of type 2 CEPS in a 29-year-old woman who presented with progressive myelopathy and fluctuating encephalopathy on a background of congenital cardiac disease.

Finding useful biomarkers for Parkinson's disease.

The recent advent of an "ecosystem" of shared biofluid sample biorepositories and data sets will focus biomarker efforts in Parkinson's disease, boosting the therapeutic development pipeline and enabling translation with real-world impact.

Cerebrospinal fluid, plasma, and saliva in the BioFIND study: Relationships among biomarkers and Parkinson's disease Features.

Objective: Examine relationships among neurodegenerative biomarkers and PD motor and nonmotor symptoms.

Background: CSF alpha-synuclein is decreased in PD versus healthy controls, but whether plasma and saliva alpha-synuclein differentiate these groups is controversial. Correlations of alpha-synuclein among biofluids (CSF, plasma, saliva) or biomarkers (eg, beta-amyloid, tau [total, phosphorylated]) are not fully understood.

Preclinical development of moxidectin as a novel therapeutic for alcohol use disorder.

Current pharmacotherapies for alcohol used disorder (AUD) are few and relatively ineffective illustrating the need for the development of new, effective medications. Using a translational approach, our laboratory reported that ivermectin, an FDA-approved, human and animal anti-parasitic agent, can significantly reduce ethanol intake in male and female mice across different drinking paradigms. Extending this line of investigation, the current paper investigated the utility of moxidectin (MOX), an analogue of ivermectin, to reduce ethanol intake.

Glycine and GABA(A) ultra-sensitive ethanol receptors as novel tools for alcohol and brain research.

A critical obstacle to developing effective medications to prevent and/or treat alcohol use disorders is the lack of specific knowledge regarding the plethora of molecular targets and mechanisms underlying alcohol (ethanol) action in the brain. To identify the role of individual receptor subunits in ethanol-induced behaviors, we developed a novel class of ultra-sensitive ethanol receptors (USERs) that allow activation of a single receptor subunit population sensitized to extremely low ethanol concentrations. USERs were created by mutating as few as four residues in the extracellular loop 2 region of glycine receptors (GlyRs) or γ-aminobutyric acid type A receptors (GABA(A)Rs), which are implicated in causing many behavioral effects linked to ethanol abuse.