Midlife Vascular Risk Factors, Parkinson Disease, and Parkinson Disease-Dementia: The ARIC Study.

Background And Objectives: Vascular risk factors (VRFs) such as smoking, hypertension, obesity, and diabetes are associated with dementia, but their importance in Parkinson disease (PD) and PD-dementia (PDD) is less well understood. Previous studies demonstrated that smoking may be protective of PD, but its role in PDD is unclear. The primary objective was to examine the association between midlife VRFs and the risk of developing PD and PDD in older adults.

Lewy body dementia promotion by air pollutants.

Evidence links air pollution to dementia, yet its role in Lewy body dementia (LBD) remains unclear. In this work, we showed in a cohort of 56.5 million individuals across the United States that fine particulate matter (PM) exposure raises LBD risk.

Content Validity of the Spinocerebellar Ataxia Composite Score as a Measure of Disease Progression in Patients with Spinocerebellar Ataxia.

Spinocerebellar ataxia (SCA) composite score (SCACOMS) is a statistically-derived composite measure comprising weighted items that are sensitive to change during early-stage disease. SCACOMS items and weights include the functional Scale for the Assessment and Rating of Ataxia Gait (12%), Stance (17%), Sitting (8%), and Speech (10%) items, and the Clinician Global Impression of Change (CGI) (53%). The content validity of SCACOMS is yet to be established.

Practice Recommendations for Genetic Testing of Ataxias.

Objective: Over the past decade, significant advances in genetic testing for ataxia have improved diagnostic accuracy, informed clinical trial eligibility, guided treatment decisions, and enabled cascade testing of at-risk relatives. While guidance exists for other neurogenetic conditions, there are no standardized guidelines on genetic counseling and testing for individuals with unexplained ataxia.

Methods: We conducted a comprehensive literature review on genetic counseling and testing in ataxia, identifying 7362 articles.

Cerebellum mitochondrial DNA copy number is increased in Parkinson's disease.

Bioinformatics methods can be used to quantify mitochondrial DNA copy number from whole genome sequencing (WGS) data. We evaluated mitochondrial DNA copy number from human brain-derived WGS data using the fastMitoCalc tool. 341 Parkinson's Disease cerebellum samples were compared with 74 age-matched controls from the North American Brain Expression Consortium.

A plasma proteomics-based candidate biomarker panel predictive of amyotrophic lateral sclerosis.

Identifying a reliable biomarker for amyotrophic lateral sclerosis (ALS) is crucial for clinical practice. Here, in this cross-sectional study, we used the Olink Explore 3072 platform to investigate plasma proteomics as a biomarker tool for this neurodegenerative condition. Thirty-three proteins were differentially abundant in the plasma of patients with ALS (n = 183) versus controls (n = 309).

Vesicular monoamine transport inhibitors: current uses and future directions.

Advancements over the past decade in understanding vesicular monoamine transporter 2 (VMAT2) inhibitors highlight their key role in the treatment of movement and neuropsychiatric disorders. VMAT2 is crucial for packaging neurotransmitters such as serotonin, dopamine, and norepinephrine into synaptic vesicles, facilitating their release and reuptake in synaptic transmission. VMAT2 inhibitors, such as tetrabenazine, deutetrabenazine, and valbenazine, show therapeutic efficacy in managing hyperkinetic movement disorders, including Huntington's disease, tardive dyskinesia, and Tourette's syndrome.

Discovery and validation of biomarkers for Parkinson's disease from human cerebrospinal fluid using mass spectrometry-based proteomics analysis.

Background: Proteomic biomarkers for Parkinson's disease (PD) are critical for identifying new targets for disease-modifying therapies and expanding our understanding of disease pathophysiology.

Methods: Deep proteome analysis of a cerebrospinal fluid (CSF) cohort (40 PD, 40 controls) coupled with previous data from the substantia nigra (SN) proteome was used to discover low abundance biomarkers involved in PD pathogenesis. We validated our findings using parallel reaction monitoring mass spectrometry with an independent cohort of CSF samples (80 PD, 80 controls).

The Natural History Study and Biomarker Collection of the Clinical Research Consortium for the Study of Cerebellar Ataxia (CRC-SCA).

Hereditary ataxias are progressive neurodegenerative disorders primarily affecting the cerebellum. Since 2009, the Clinical Research Consortium for the Study of Cerebellar Ataxias (CRC-SCA) has studied the natural history of common types of spinocerebellar ataxias (SCAs). The CRC-SCA is a 17-site academic collaboration supported by the National Ataxia Foundation.

Development and Validation of PARCOMS Composite Scales for Assessing Disease Progression and Treatment Effects in Parkinson's Disease.

Introduction: Measures designed to comprehensively assess Parkinson's disease (PD) irrespective of disease stage and treatment status may be unable to capture nuances in disease progression, particularly in early-stage PD. The objective of this paper is to develop PARkinson's COMposite Scales (PARCOMS) with increased responsiveness to clinical decline using items of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) for three discrete cohorts of patients.

Methods: Patients with confirmed PD from the Parkinson's Progression Markers Initiative (PPMI) data were assigned to three cohorts based on use of dopaminergic treatment, stage of disease, and presence of motor complication.

Automated Imaging Differentiation for Parkinsonism.

Importance: Magnetic resonance imaging (MRI) paired with appropriate disease-specific machine learning holds promise for the clinical differentiation of Parkinson disease (PD), multiple system atrophy (MSA) parkinsonian variant, and progressive supranuclear palsy (PSP). A prospective study is needed to test whether the approach meets primary end points to be considered in a diagnostic workup.

Objective: To assess the discriminative performance of Automated Imaging Differentiation for Parkinsonism (AIDP) using 3-T diffusion MRI and support vector machine (SVM) learning.

Spinocerebellar Ataxia Progression Measured with the Patient-Reported Outcome Measure of Ataxia.

Background: The Patient-Reported Outcome Measure of Ataxia (PROM-Ataxia) has been validated cross-sectionally but not longitudinally.

Objective: We aimed to validate PROM-Ataxia as a measure of patient experience of disease over time, examine overall and domain-specific progression, and test convergent validity with other clinical outcome assessments (COAs).

Methods: We derived PROM-Ataxia data from 176 patients with spinocerebellar ataxia types 1, 2, 3, 6, 7, 8, or 10 in the Clinical Research Consortium for the Study of Cerebellar Ataxia at baseline and 1 year.

Longitudinal Changes in Patient- and Clinical-Reported Outcomes in Early Spinocerebellar Ataxia Types 1, 2, 3, and 6 from the IDEA Study.

Background: Clinical outcomes assessments (COAs) in spinocerebellar ataxia (SCA) need to be standardized, ataxia-specific, sensitive to change, clinically relevant, and meaningful to patients.

Objectives: To evaluate the longitudinal 1- and 2-year performances of different patient reported outcomes, including the Patient Reported Outcome Measure of Ataxia (PROM-Ataxia), and clinician reported outcomes, including FARS and SARA, in those with early manifest symptoms of SCA 1, 2, 3, and 6.

Methods: We studied 53 patients with early stage SCA1-3 and SCA6 from The Instrumented Data Exchange for Ataxia Study and 24 age-matched healthy controls.

Content Validity of the Friedreich Ataxia Rating Scale in Patients with Spinocerebellar Ataxia.

Introduction: The Friedreich Ataxia Rating Scale-Activities of Daily Living (FARS-ADL) is a validated and highly utilized measure for evaluating patients with Friedreich Ataxia. While construct validity of FARS-ADL has been shown for spinocerebellar ataxia (SCA), content validity has not been established.

Methods: Individuals with SCA1 or SCA3 (n = 7) and healthcare professionals (HCPs) with SCA expertise (n = 8) participated in qualitative interviews evaluating the relevance, clarity, and clinical meaningfulness of FARS-ADL for assessment of individuals with SCA.

Differential functional change in olfactory bulb and olfactory eloquent areas in Parkinson's disease.

Olfactory dysfunction, or hyposmia, frequently occurs as a prodromal symptom and ongoing sign of Parkinson's disease. Functional MRI is a powerful tool for studying functional changes in the olfactory brain regions in patients with Parkinson's disease. However, existing studies show inconsistent results and no study has measured olfactory functional MRI abnormalities in the human olfactory bulb directly.

α-Synuclein Strain Dynamics Correlate with Cognitive Shifts in Parkinson's Disease.

α-Synuclein (α-syn) strains can serve as discriminators between Parkinson's disease (PD) from other α-synucleinopathies. The relationship between α-syn strain dynamics and clinical performance as patients transition from normal cognition (NC) to cognitive impairment (CI) is not known. Here, we show that the biophysical properties and neurotoxicity of α-syn strains change as PD cognitive status transitions from NC to mild cognitive impairment (PD-MCI) and dementia (PD-D).

Biomarker discovery in progressive supranuclear palsy from human cerebrospinal fluid.

Background: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder often misdiagnosed as Parkinson's Disease (PD) due to shared symptoms. PSP is characterized by the accumulation of tau protein in specific brain regions, leading to loss of balance, gaze impairment, and dementia. Diagnosing PSP is challenging, and there is a significant demand for reliable biomarkers.

The Parkinson's Disease Composite of Executive Functioning: A Measure for Detecting Cognitive Decline in Clinical Trials.

Background And Objectives: Executive functioning is one of the first domains to be impaired in Parkinson disease (PD), and the majority of patients with PD eventually develop dementia. Thus, developing a cognitive endpoint measure specifically assessing executive functioning is critical for PD clinical trials. The objective of this study was to develop a cognitive composite measure that is sensitive to decline in executive functioning for use in PD clinical trials.

Content Validity of the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) Instrument in Spinocerebellar Ataxia.

The functional Scale for the Assessment and Rating of Ataxia (f-SARA) assesses Gait, Stance, Sitting, and Speech. It was developed as a potentially clinically meaningful measure of spinocerebellar ataxia (SCA) progression for clinical trial use. Here, we evaluated content validity of the f-SARA.