Replication and reliability of Parkinson's disease clinical subtypes.

Background: We recently identified three distinct Parkinson's disease subtypes: "motor only" (predominant motor deficits with intact cognition and psychiatric function); "psychiatric & motor" (prominent psychiatric symptoms and moderate motor deficits); "cognitive & motor" (cognitive and motor deficits).

Objective: We used an independent cohort to replicate and assess reliability of these Parkinson's disease subtypes.

Methods: We tested our original subtype classification with an independent cohort (N = 100) of Parkinson's disease participants without dementia and the same comprehensive evaluations assessing motor, cognitive, and psychiatric function.

PET Quantification of [F]VAT in Human Brain and Its Test-Retest Reproducibility and Age Dependence.

Molecular imaging of brain vesicular acetylcholine transporter provides a biomarker to explore cholinergic systems in humans. We aimed to characterize the distribution of, and optimize methods to quantify, the vesicular acetylcholine transporter-specific tracer (-)-(1-(8-(2-[F]fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-piperidin-4-yl)(4-fluorophenyl)methanone ([F]VAT) in the brain using PET. Fifty-two healthy participants aged 21-97 y had brain PET with [F]VAT.

Neocortical Lewy Body Pathology Parallels Parkinson's Dementia, but Not Always.

Objective: The objective of this study was to evaluate the relationship between Parkinson's disease (PD) with dementia and cortical proteinopathies in a large population of pathologically confirmed patients with PD.

Methods: We reviewed clinical data from all patients with autopsy data seen in the Movement Disorders Center at Washington University, St. Louis, between 1996 and 2019.

Proteinopathy and Longitudinal Cognitive Decline in Parkinson Disease.

Background And Objectives: People with Parkinson disease (PD) commonly experience cognitive decline, which may relate to increased α-synuclein, tau, and β-amyloid accumulation. This study examines whether the different proteins predict longitudinal cognitive decline in PD.

Methods: All participants (PD n = 152, controls n = 52) were part of a longitudinal study and completed a lumbar puncture for CSF protein analysis (α-synuclein, total tau [tau], and β-amyloid [β-amyloid]), a β-amyloid PET scan, and/or provided a blood sample for genotype (ε4+, ε4-), which is a risk factor for β-amyloid accumulation.

Quantifying regional α -synuclein, amyloid β, and tau accumulation in lewy body dementia.

Objective: Parkinson disease (PD) is defined by the accumulation of misfolded α-synuclein (α-syn) in Lewy bodies and Lewy neurites. It affects multiple cortical and subcortical neuronal populations. The majority of people with PD develop dementia, which is associated with Lewy bodies in neocortex and referred to as Lewy body dementia (LBD).

Distinct progression patterns across Parkinson disease clinical subtypes.

Objective: To examine specific symptom progression patterns and possible disease staging in Parkinson disease clinical subtypes.

Methods: We recently identified Parkinson disease clinical subtypes based on comprehensive behavioral evaluations, "Motor Only," "Psychiatric & Motor," and "Cognitive & Motor," which differed in dementia and mortality rates. Parkinson disease participants ("Motor Only": n = 61, "Psychiatric & Motor": n = 17, "Cognitive & Motor": n = 70) and controls (n = 55) completed longitudinal, comprehensive motor, cognitive, and psychiatric evaluations (average follow-up = 4.

Functional Connectivity of Vermis Correlates with Future Gait Impairments in Parkinson's Disease.

Background: Dysfunction of cerebellar vermis contributes to gait abnormalities in multiple conditions and may play a key role in gait impairment in Parkinson's disease (PD).

Objective: The purpose of this study was to investigate whether altered resting-state functional connectivity of the vermis relates to subsequent impairment of specific domains of gait in PD.

Methods: We conducted morphometric and resting-state functional connectivity MRI analyses contrasting 45 PD and 32 age-matched healthy participants.

Resting-state functional connectivity associated with gait characteristics in people with Parkinson's disease.

Introduction: Parkinson's disease (PD) is a movement disorder caused by dysfunction in the basal ganglia (BG). Clinically relevant gait deficits, such as decreased velocity and increased variability, may be caused by underlying neural dysfunction. Reductions in resting-state functional connectivity (rs-FC) between networks have been identified in PD compared to controls; however, the association between gait characteristics and rs-FC of brain networks in people with PD has not yet been explored.

Functional genomic analyses uncover APOE-mediated regulation of brain and cerebrospinal fluid beta-amyloid levels in Parkinson disease.

Alpha-synuclein is the main protein component of Lewy bodies, the pathological hallmark of Parkinson's disease. However, genetic modifiers of cerebrospinal fluid (CSF) alpha-synuclein levels remain unknown. The use of CSF levels of amyloid beta, total tau, and phosphorylated tau as quantitative traits in genetic studies have provided novel insights into Alzheimer's disease pathophysiology.

Regional, not global, functional connectivity contributes to isolated focal dystonia.

Objective: To test the hypothesis that there is shared regional or global functional connectivity dysfunction in a large cohort of patients with isolated focal dystonia affecting different body regions compared to control participants. In this case-control study, we obtained resting-state MRI scans (three or four 7.3-minute runs) with eyes closed in participants with focal dystonia (cranial [17], cervical [13], laryngeal [18], or limb [10]) and age- and sex-matched controls.

Parkinson disease clinical subtypes: key features & clinical milestones.

Objectives: Based on multi-domain classification of Parkinson disease (PD) subtypes, we sought to determine the key features that best differentiate subtypes and the utility of PD subtypes to predict clinical milestones.

Methods: Prospective cohort of 162 PD participants with ongoing, longitudinal follow-up. Latent class analysis (LCA) delineated subtypes based on score patterns across baseline motor, cognitive, and psychiatric measures.

Removal of high frequency contamination from motion estimates in single-band fMRI saves data without biasing functional connectivity.

Denoising fMRI data requires assessment of frame-to-frame head motion and removal of the biases motion introduces. This is usually done through analysis of the parameters calculated during retrospective head motion correction (i.e.

Little Change in Functional Brain Networks Following Acute Levodopa in Drug-Naïve Parkinson's Disease.

Objective: The objective of this study was to investigate the effects of levodopa on functional brain networks in Parkinson's disease.

Methods: We acquired resting state functional magnetic resonance imaging in 30 drug-naïve participants with Parkinson's disease and 20 age-matched healthy controls. Each participant was studied following administration of a single oral dose of either levodopa or placebo in a randomized, double-blind, crossover design.

Proteinopathy and longitudinal changes in functional connectivity networks in Parkinson disease.

Objective: To evaluate resting-state functional connectivity as a potential prognostic biomarker of Parkinson disease (PD) progression. The study examined longitudinal changes in cortical resting-state functional connectivity networks in participants with PD compared to controls as well as in relation to baseline protein measures and longitudinal clinical progression.

Methods: Individuals with PD without dementia (n = 64) and control participants (n = 27) completed longitudinal resting-state MRI scans and clinical assessments including full neuropsychological testing after overnight withdrawal of PD medications ("off").

Cognitive correlates of cerebellar resting-state functional connectivity in Parkinson disease.

Objective: To investigate in a cross-sectional study the contributions of altered cerebellar resting-state functional connectivity (FC) to cognitive impairment in Parkinson disease (PD).

Methods: We conducted morphometric and resting-state FC-MRI analyses contrasting 81 participants with PD and 43 age-matched healthy controls using rigorous quality assurance measures. To investigate the relationship of cerebellar FC to cognitive status, we compared participants with PD without cognitive impairment (Clinical Dementia Rating [CDR] scale score 0, n = 47) to participants with PD with impaired cognition (CDR score ≥0.

Detecting associations between intact connectomes and clinical covariates using recursive partitioning object-oriented data analysis.

Many neuroscientists are interested in how connectomes (graphical representations of functional connectivity between areas of the brain) change in relation to covariates. In statistics, changes like this are analyzed using regression, where the outcomes or dependent variables are regressed onto the covariates. However, when the outcome is a complex object, such as connectome graphs, classical regression models cannot be used.

Thalamic and ventricular volumes predict motor response to deep brain stimulation for Parkinson's disease.

Background: Brain atrophy frequently occurs with Parkinson's disease (PD) and relates to increased motor symptoms of PD. The predictive value of neuroimaging-based measures of global and regional brain volume on motor outcomes in deep brain stimulation (DBS) remains unclear but potentially could improve patient selection and targeting.

Objectives: To determine the predictive value of preoperative volumetric MRI measures of cortical and subcortical brain volume on motor outcomes of subthalamic nucleus (STN) DBS in PD.

ESM-CT: a precise method for localization of DBS electrodes in CT images.

Background: Deep brain stimulation (DBS) of the subthalamic nucleus produces variable effects in Parkinson disease. Variation may result from different electrode positions relative to target. Thus, precise electrode localization is crucial when investigating DBS effects.

Mapping movement, mood, motivation and mentation in the subthalamic nucleus.

The anatomical connections of the subthalamic nucleus (STN) have driven hypotheses about its functional anatomy, including the hypothesis that the precise anatomical location of STN deep brain stimulation (DBS) contributes to the variability of motor and non-motor responses across patients with Parkinson's disease (PD). We previously tested the hypothesis using a three-dimensional (3D) statistical method to interpret the acute effects of unilateral DBS at each patient's clinically optimized DBS settings and active contact. Here, we report a similar analysis from a new study in which DBS parameters were standardized and DBS locations were chosen blind to clinical response.

Emergent Functional Network Effects in Parkinson Disease.

The hallmark pathology underlying Parkinson disease (PD) is progressive synucleinopathy, beginning in caudal brainstem that later spreads rostrally. However, the primarily subcortical pathology fails to account for the wide spectrum of clinical manifestations in PD. To reconcile these observations, resting-state functional connectivity (FC) can be used to examine dysfunction across distributed brain networks.

7T MRI subthalamic nucleus atlas for use with 3T MRI.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces motor symptoms in most patients with Parkinson disease (PD), yet may produce untoward effects. Investigation of DBS effects requires accurate localization of the STN, which can be difficult to identify on magnetic resonance images collected with clinically available 3T scanners. The goal of this study is to develop a high-quality STN atlas that can be applied to standard 3T images.