Glymphatic dysfunction is related to motor disability fully mediated by gray matter degeneration in early-stage Parkinson's disease.

Background: Glymphatic dysfunction plays a critical role in Parkinson's disease (PD), but its impact on neurodegeneration and clinical symptoms in the early-stage remains unclear. This study investigates the relationship between glymphatic dysfunction, gray matter (GM) degeneration, and clinical deterioration in early-stage PD.

Methods: A total of 249 early-stage PD patients and 114 healthy controls (HC) underwent T1-weighted and DTI scans, along with clinical assessments.

Robust computation of subcortical functional connectivity guided by quantitative susceptibility mapping: An application in Parkinson's disease diagnosis.

Previous resting state functional MRI (rs-fMRI) analyses of the basal ganglia in Parkinson's disease heavily relied on T1-weighted imaging (T1WI) atlases. However, subcortical structures are characterized by subtle contrast differences, making their accurate delineation challenging on T1WI. In this study, we aimed to introduce and validate a method that incorporates quantitative susceptibility mapping (QSM) into the rs-fMRI analytical pipeline to achieve precise subcortical nuclei segmentation and improve the stability of RSFC measurements in Parkinson's disease.

Identifying brain degeneration patterns in early-stage Parkinson's disease: a multimodal MRI study.

Parkinson's disease (PD) is a highly heterogeneous neurodegenerative disorder. This study aimed to identify different patterns of early brain degeneration in PD patients and investigate their clinical relevance. 179 early-stage PD patients and 115 healthy controls were included.

Arterial spin labeling MRI based perfusion pattern related to motor dysfunction and L-DOPA reactivity in Parkinson's disease.

Objective: Identifying intrinsic pattern of Parkinson's disease (PD) helps to better understand of PD and provide insights to disease identification and treatment monitoring. Here we confirmed the PD-related covariance pattern (PDRP) by using arterial spin labelling technology (ASL-PDRP) and explore its potential for predicting motor progression and levodopa (L-DOPA) reactivity reduction.

Methods: Data from an original cohort of 179 PD and 62 normal controls (NC) and a validation cohort including 36 PD and 19 NC to construct and validate the ASL-PDRP.

Gradients of Nigrostriatal Iron Deposition in Healthy Aging and Synucleinopathies.

Aims: To investigate the gradients of nigrostriatal iron deposition in aging, Parkinson's disease (PD), and multiple system atrophy (MSA).

Methods: This study included 100 young healthy controls, 171 old healthy controls (OHC), 231 PD, and 24 MSA patients. The brain iron content was quantified by quantitative susceptibility mapping.

Aberrant functional connectome gradient and its neurotransmitter basis in Parkinson's disease.

Patients with Parkinson's disease (PD) exhibit heterogenous clinical deficits not only in motor function, other deficits in both sensory and higher-order cognitive processing are also involved. Connectome studies have suggested a primary-to-transmodal gradient and a primary-to-primary gradient in functional brain networks, supporting the spectrum from sensation to cognition. However, whether these gradients are altered in PD patients and how these alterations associate with neurotransmitter profiles remain unknown.

LRRK2 mutation contributes to decreased free water in the nucleus basalis of Meynert in manifest and premanifest Parkinson's disease.

Background: Free-water imaging can predict and monitor dopamine system degeneration in patients with Parkinson's disease (PD). However, brain cholinergic function has not been investigated to date in LRRK2 mutation carriers with or without PD using free-water imaging.

Objectives: To investigate the effect of LRRK2 mutations on the cholinergic system in manifest and premanifest stages of PD using free-water imaging.

Wider and faster degeneration of white matter in Parkinson's disease with possible REM sleep behaviour disorder.

Background: In Parkinson's disease (PD), rapid eye movement (REM) sleep behaviour disorder (RBD) signifies a poorer prognosis, yet its impact on white matter (WM) degeneration remains unclear. The study examined the effect of RBD on WM alterations in PD progression.

Methods: The study included 45 PD patients with possible RBD (PD-pRBD), 38 PD patients without possible RBD (PD-npRBD), and 79 healthy controls (HC).

Unsupervised definition of two clinical subtypes of Essential tremor and the underlying brain topology.

Background: Essential tremor (ET) is one of the most prevalent neurological diseases varying considerably in clinical manifestations and prognosis, which indicates the existence of subtypes. Identifying ET subtypes is crucial for explaining clinical heterogeneity. This study aimed to identify ET subtypes using unsupervised clustering analysis based on clinical manifestations and explore underlying brain topology within both functional and structural networks.

Spatiotemporal neurodegeneration of the substantia nigra and its connecting cortex and subcortex in Parkinson's disease.

Background And Purpose: Neurodegeneration is uneven in Parkinson's disease (PD). This study aimed to investigate spatiotemporal neurodegeneration in functional subregions of the substantia nigra (SN) and their connected cortex and subcortex in people with PD.

Methods: A total of 120 patients with early-stage PD, 45 patients with advanced PD, and 120 healthy controls (HCs) were enrolled.

Glymphatic system dysfunction and risk of clinical milestones in patients with Parkinson disease.

Background And Purpose: Glymphatic dysfunction may play a significant role in the development of neurodegenerative diseases. We aimed to evaluate the association between glymphatic dysfunction and the risk of malignant event/clinical milestones in Parkinson disease (PD).

Methods: This study included 236 patients from August 2014 to December 2020.

Assessing the Role of Locus Coeruleus Degeneration in Essential Tremor and Parkinson's Disease with Sleep Disorders.

Background: Previous studies have demonstrated the importance of the locus coeruleus (LC) in sleep-wake regulation. Both essential tremor (ET) and Parkinson's disease (PD) share common sleep disorders, such as poor quality of sleep (QoS). LC pathology is a feature of both diseases.

Differential influences of rest tremor on brain fiber architecture in essential tremor and Parkinson's disease.

Background: Rest tremor is a movement disorder commonly found in diseases like Parkinson's disease (PD) and essential tremor (ET). Rest tremor typically shows slower progression in PD, but more severe progression in ET. However, the underlying white matter organization of rest tremor behind PD and ET remains unclear.

Microstructural alterations of the hypothalamus in Parkinson's disease and probable REM sleep behavior disorder.

Background: Whether there is hypothalamic degeneration in Parkinson's disease (PD) and its association with clinical symptoms and pathophysiological changes remains controversial.

Objectives: We aimed to quantify microstructural changes in hypothalamus using a novel deep learning-based tool in patients with PD and those with probable rapid-eye-movement sleep behavior disorder (pRBD). We further assessed whether these microstructural changes associated with clinical symptoms and free thyroxine (FT4) levels.

Neurovascular coupling alteration in drug-naïve Parkinson's disease: The underlying molecular mechanisms and levodopa's restoration effects.

Background: Parkinson's disease (PD) patients exhibit an imbalance between neuronal activity and perfusion, referred to as abnormal neurovascular coupling (NVC). Nevertheless, the underlying molecular mechanism and how levodopa, the standard treatment in PD, regulates NVC is largely unknown.

Material And Methods: A total of 52 drug-naïve PD patients and 49 normal controls (NCs) were enrolled.

The effect of dopamine replacement therapy on cortical structure in Parkinson's disease.

Aims: To explore the cortical structural reorganization in Parkinson's disease (PD) patients under chronic dopamine replacement therapy (DRT) in cross-sectional and longitudinal data and determine whether these changes were associated with clinical alterations.

Methods: A total of 61 DRT-treated, 60 untreated PD patients, and 61 normal controls (NC) were retrospectively included. Structural MRI scans and neuropsychological tests were conducted.

Cholinergic basal forebrain system degeneration underlies postural instability/gait difficulty and attention impairment in Parkinson's disease.

Background And Purpose: The specific pathophysiological mechanisms underlying postural instability/gait difficulty (PIGD) and cognitive function in Parkinson's disease (PD) remain unclear. Both postural and gait control, as well as cognitive function, are associated with the cholinergic basal forebrain (cBF) system.

Methods: A total of 84 PD patients and 82 normal controls were enrolled.

Predictability of inter-regional cerebral perfusion similarity on dopamine responsiveness and the moderation role of cognition in PD patients.

Background: Large heterogeneity can be found in dopamine responsiveness of patients with Parkinson's disease (PD). Instantly and objectively understanding dopamine responsiveness of patients may help clinical practice.

Purpose: This PD study explored the predictability of off-state inter-regional cerebral blood flow (CBF) perfusion similarity on patient's dopamine responsiveness and tested whether the predictive power could be moderated by patient's cognitive status.

Aberrant dentato-rubro-thalamic pathway in action tremor but not rest tremor: A multi-modality magnetic resonance imaging study.

Aims: The purpose of this study was to clarify the dentato-rubro-thalamic (DRT) pathway in action tremor in comparison to normal controls (NC) and disease controls (i.e., rest tremor) by using multi-modality magnetic resonance imaging (MRI).

Functional connectome predicting individual gait function and its relationship with molecular architecture in Parkinson's disease.

Gait impairment is a common symptom of Parkinson's disease (PD), but its neural signature remains unclear due to the interindividual variability of gait performance. Identifying a robust gait-brain correlation at the individual level would provide insight into a generalizable neural basis of gait impairment. In this context, this study aimed to detect connectome that can predict individual gait function of PD, and follow-up analyses assess the molecular architecture underlying the connectome by relating it to the neurotransmitter-receptor/transporter density maps.

Regional white matter hyperintensity volume in Parkinson's disease and associations with the motor signs.

Objective: To determine whether white matter hyperintensity (WMH) volumes in specific regions are associated with Parkinson's disease (PD) compared to non-PD controls, and to assess their impact on motor signs through cross-sectional and longitudinal analyses.

Methods: A total of 50 PD participants and 47 age- and gender-matched controls were enrolled. All PD participants were followed up for at least 2 years.

Functional connectomes of akinetic-rigid and tremor within drug-naïve Parkinson's disease.

Aims: To detect functional connectomes of akinetic-rigid (AR) and tremor and compare their connection pattern.

Methods: Resting-state functional MRI data of 78 drug-naïve PD patients were enrolled to construct connectomes of AR and tremor via connectome-based predictive modeling (CPM). The connectomes were further validated with 17 drug-naïve patients to verify their replication.

Normalization effect of dopamine replacement therapy on brain functional connectome in Parkinson's disease.

Dopamine replacement therapy (DRT) represents the standard treatment for Parkinson's disease (PD), however, instant and long-term medication influence on patients' brain function have not been delineated. Here, a total of 97 drug-naïve patients, 43 patients under long-term DRT, and 94 normal control (NC) were, retrospectively, enrolled. Resting-state functional magnetic resonance imaging data and motor symptom assessments were conducted before and after levodopa challenge test.

Presence but not the timing of onset of REM sleep behavior disorder distinguishes evolution patterns in Parkinson's disease.

Background: Rapid eye movement (REM) sleep behavior disorder (RBD) could develop preceding or come after motor symptoms during Parkinson's disease (PD). It remains unknown that whether PD with different timing of RBD onset relative to motor symptoms suggests different spatiotemporal sequence of neurodegeneration. This study aimed to explore the sequence of disease progression in crucially involved brain regions in PD with different timing of RBD onset.