IGLON5 Frequency in Idiopathic REM Sleep Behavior Disorder: A Multicenter Study.

Background And Objectives: Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD.

Neuromelanin-sensitive MRI correlates of cognitive and motor function in Parkinson's disease with freezing of gait.

Substantia nigra pars compacta (SNc) and locus coeruleus (LC) are neuromelanin-rich nuclei implicated in diverse cognitive and motor processes in normal brain function and disease. However, their roles in aging and neurodegenerative disease mechanisms have remained unclear due to a lack of tools to study them . Preclinical and post-mortem human investigations indicate that the relationship between tissue neuromelanin content and neurodegeneration is complex.

Validation of the RBD Symptom Severity Scale in the North American Prodromal Synucleinopathy Consortium.

Background And Objectives: REM sleep behavior disorder (RBD) is a parasomnia characterized by dream enactment. The International RBD Study Group developed the RBD Symptom Severity Scale (RBDSSS) to assess symptom severity for clinical or research use. We assessed the psychometric and clinimetric properties of the RBDSSS in participants enrolled in the North American Prodromal Synucleinopathy (NAPS) Consortium for RBD.

Frequency of Orthostatic Hypotension in Isolated REM Sleep Behavior Disorder.

Background And Objectives: Although orthostatic hypotension (OH) can be an early feature of autonomic dysfunction in isolated REM sleep behavior disorder (iRBD), no large-scale studies have examined the frequency of OH in iRBD. In this study, we prospectively evaluated the frequency of OH in a large multicenter iRBD cohort.

Methods: Participants 18 years or older with video polysomnogram-confirmed iRBD were enrolled through the North American Prodromal Synucleinopathy consortium.

Nigral volume loss in prodromal, early, and moderate Parkinson's disease.

The loss of melanized neurons in the substantia nigra pars compacta (SNc) is a hallmark pathology in Parkinson's disease (PD). Melanized neurons in SNc can be visualized using magnetization transfer (MT) effects. Nigral volume was extracted in data acquired with a MT-prepared gradient echo sequence in 33 controls, 83 non-manifest carriers (42 LRRK2 and 41 GBA nonmanifest carriers), 65 prodromal hyposmic participants, 105 PD patients and 26 48-month PD patients from the Parkinson's Progressive Markers Initiative.

Neuromelanin-sensitive MRI correlates of cognitive and motor function in Parkinson's disease with freezing of gait.

Substantia nigra pars compacta (SNc) and locus coeruleus (LC) are neuromelanin-rich nuclei implicated in diverse cognitive and motor processes in normal brain function and disease. However, their roles in aging and neurodegenerative disease mechanisms have remained unclear due to a lack of tools to study them . Preclinical and post-mortem human investigations indicate that the relationship between tissue neuromelanin content and neurodegeneration is complex.

In vivo detection of substantia nigra and locus coeruleus volume loss in Parkinson's disease using neuromelanin-sensitive MRI: Replication in two cohorts.

Patients with Parkinson's disease undergo a loss of melanized neurons in substantia nigra pars compacta and locus coeruleus. Very few studies have assessed substantia nigra pars compacta and locus coeruleus pathology in Parkinson's disease simultaneously with magnetic resonance imaging (MRI). Neuromelanin-sensitive MRI measures of substantia nigra pars compacta and locus coeruleus volume based on explicit magnetization transfer contrast have been shown to have high scan-rescan reproducibility in controls, but no study has replicated detection of Parkinson's disease-associated volume loss in substantia nigra pars compacta and locus coeruleus in multiple cohorts with the same methodology.

Baseline characteristics of the North American prodromal Synucleinopathy cohort.

Objective: Rapid eye movement (REM) sleep behavior disorder (RBD) is widely considered a prodromal synucleinopathy, as most with RBD develop overt synucleinopathy within ~10 years. Accordingly, RBD offers an opportunity to test potential treatments at the earliest stages of synucleinopathy. The North American Prodromal Synucleinopathy (NAPS) Consortium has created a multisite RBD participant, primarily clinic-based cohort to better understand characteristics at diagnosis, and in future work, identify predictors of phenoconversion, develop synucleinopathy biomarkers, and enable early stage clinical trial enrollment.

Nigral volumetric and microstructural measures in individuals with scans without evidence of dopaminergic deficit.

Introduction: Striatal dopamine transporter (DAT) imaging using I-ioflupane single photon positron emitted computed tomography (SPECT) (DaTScan, GE) identifies 5-20% of newly diagnosed Parkinson's disease (PD) subjects enrolling in clinical studies to have scans without evidence of dopaminergic deficit (SWEDD). These individuals meet diagnostic criteria for PD, but do not clinically progress as expected, and they are not believed to have neurodegenerative Parkinsonism. Inclusion of SWEDD participants in PD biomarker studies or therapeutic trials may therefore cause them to fail.

Nigral diffusivity, but not free water, correlates with iron content in Parkinson's disease.

The loss of melanized neurons in the substantia nigra pars compacta is a primary feature in Parkinson's disease. Iron deposition occurs in conjunction with this loss. Loss of nigral neurons should remove barriers for diffusion and increase diffusivity of water molecules in regions undergoing this loss.

Impact of Locus Coeruleus and Its Projections on Memory and Aging.

Locus coeruleus (LC) is the primary source of norepinephrine to the brain and its efferent projections innervate many brain regions, including the thalamus. The LC degrades with normal aging, but not much is known regarding whether its structural connectivity evolves with age or predicts aspects of cognition. Here, we use high-resolution diffusion tensor imaging-based tractography to examine structural connectivity between LC and the thalamus in younger and older adults.

Rationale and Design of the PAIRED Trial: Partnered Dance Aerobic Exercise as a Neuroprotective, Motor, and Cognitive Intervention in Parkinson's Disease.

Parkinson's disease (PD), an intractable condition impairing motor and cognitive function, is imperfectly treated by drugs and surgery. Two priority issues for many people with PD are OFF-time and cognitive impairment. Even under best medical management, three-fourths of people with PD experience "OFF-time" related to medication-related motor fluctuations, which severely impacts both quality of life and cognition.

Multimodal assessment of nigrosomal degeneration in Parkinson's disease.

Background: Approximately forty percent of all dopaminergic neurons in SNpc are located in five dense neuronal clusters, named nigrosomes. T- or T*-weighted images are used to delineate the largest nigrosome, named nigrosome-1. In these images, nigrosome-1 is a hyperintense region in the caudal and dorsal portion of the T- or T*-weighted substantia nigra.

Increased iron-deposition in lateral-ventral substantia nigra pars compacta: A promising neuroimaging marker for Parkinson's disease.

Background: To date there are no validated MRI biomarkers to assist diagnosis of Parkinson's disease (PD). Our aim was to investigate PD related iron changes in the substantia nigra pars compacta (SNpc) as defined by neuromelanin-sensitive MR contrast.

Methods: Thirty-nine PD participants and 33 healthy controls were scanned at 3.

Reproducible detection of nigral iron deposition in 2 Parkinson's disease cohorts.

Background: Previous studies investigating nigral iron accumulation used T or T *-weighted contrasts to define the regions of interest (ROIs) in the substantia nigra with mixed results. Because these contrasts are not sensitive to neuromelanin, ROIs may have inadvertently missed the SNpc. An approach sensitive to neuromelanin should yield consistent results.

Improved Neuroimaging Atlas of the Dentate Nucleus.

The dentate nucleus (DN) of the cerebellum is the major output nucleus of the cerebellum and is rich in iron. Quantitative susceptibility mapping (QSM) provides better iron-sensitive MRI contrast to delineate the boundary of the DN than either T-weighted images or susceptibility-weighted images. Prior DN atlases used T-weighted or susceptibility-weighted images to create DN atlases.

In vivo detection of lateral-ventral tier nigral degeneration in Parkinson's disease.

The objective of this study was to measure neuromelanin-sensitive MRI contrast changes in the lateral-ventral tier of substantia nigra pars compacta in Parkinson's disease (PD). Histopathological studies of PD have demonstrated both massive loss of melanized dopamine neurons and iron accumulation in the substantia nigra pars compacta. Neurodegeneration is most profound in the lateral-ventral tier of this structure.

Parkinson's disease-related increase of T2*-weighted hypointensity in substantia nigra pars compacta.

Background: In PD, at the time of diagnosis, approximately 50% of melanized dopaminergic neurons in SNpc have died, yet ongoing neuronal death and neuromelanin release with associated neuroinflammation and microglial activation continue, as does local iron accumulation. Previous studies investigating nigral iron accumulation used T / T2*-weighted contrasts to define the regions of interest in the SN. Given that T / T2*-weighted contrasts lack sensitivity to neuromelanin and thereby SNpc, neuromelanin-sensitive MRI provides better delineation of SNpc and allows the examination of increased iron deposition in SNpc more specifically and accurately.

Reproducibility of locus coeruleus and substantia nigra imaging with neuromelanin sensitive MRI.

Objectives: The purpose of this study was to assess the reproducibility of substantia nigra pars compacta (SNpc) and locus coeruleus (LC) delineation and measurement with neuromelanin-sensitive MRI.

Materials And Methods: Eleven subjects underwent two neuromelanin-sensitive MRI scans. SNpc and LC volumes were extracted for each scan.

Multimodal Imaging Signatures of Parkinson's Disease.

Parkinson's disease (PD) is a complex neurodegenerative disorder that manifests through hallmark motor symptoms, often accompanied by a range of non-motor symptoms. There is a putative delay between the onset of the neurodegenerative process, marked by the death of dopamine-producing cells, and the onset of motor symptoms, creating an urgent need to develop biomarkers that may yield early PD detection. Neuroimaging offers a non-invasive approach to examining the potential utility of a vast number of functional and structural brain characteristics as biomarkers.

Diffusion tensor imaging of the substantia nigra in Parkinson's disease revisited.

Objective: To analyze diffusion tensor imaging (DTI) data in the substantia nigra (SN) using a more consistent region of interest (ROI) defined by neuromelanin-sensitive MRI in order to assess Parkinson's disease (PD) related changes in diffusion characteristics in the SN.

Methods: T1 -weighted and DTI data were obtained in a cohort of 37 subjects (17 control subjects and 20 subjects with PD). The subjects in the PD group were clinically diagnosed PD patients with an average Unified Parkinsonian Disease Rating Scale (UPDRS)-III score of 23.

A multicontrast approach for comprehensive imaging of substantia nigra.

We characterize the contrast behavior of substantia nigra (SN) in both magnetization transfer (MT) imaging, which is believed to be sensitive to neuromelanin (NM), and susceptibility weighted imaging (SWI). Images were acquired with a MT prepared dual echo gradient echo sequence. The first echo was taken as the MT contrast image and the second was used to generate the SWI image.

Simultaneous imaging of locus coeruleus and substantia nigra with a quantitative neuromelanin MRI approach.

Quantitative MRI of neuromelanin (NM) containing structures (referred to as NM-MRI) in the brainstem, namely the locus coeruleus (LC) and substantia nigra (SN), may assist with the early detection of Parkinson's disease (PD) and Alzheimer's disease (AD) as well as differential diagnosis in the early disease stages. In this study, two gradient echo (GRE) sequences with magnetization transfer contrast (MTC) preparation pulses were developed to simultaneously image the LC and SN. This has been a challenge with NM-MRI techniques used in previous studies due to the relatively high specific absorption rate (SAR) induced by these techniques.