Best Practices in the Clinical Management of Progressive Supranuclear Palsy and Corticobasal Syndrome: A Consensus Statement of the CurePSP Centers of Care.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS; the most common phenotype of corticobasal degeneration) are tauopathies with a relentless course, usually starting in the mid-60s and leading to death after an average of 7 years. There is as yet no specific or disease-modifying treatment. Clinical deficits in PSP are numerous, involve the entire neuraxis, and present as several discrete phenotypes. They center on rigidity, bradykinesia, postural instability, gait freezing, supranuclear ocular motor impairment, dysarthria, dysphagia, incontinence, sleep disorders, frontal cognitive dysfunction, and a variety of behavioral changes. CBS presents with prominent and usually asymmetric dystonia, apraxia, myoclonus, pyramidal signs, and cortical sensory loss. The symptoms and deficits of PSP and CBS are amenable to a variety of treatment strategies but most physicians, including many neurologists, are reluctant to care for patients with these conditions because of unfamiliarity with their multiplicity of interacting symptoms and deficits. CurePSP, the organization devoted to support, research, and education for PSP and CBS, created its CurePSP Centers of Care network in North America in 2017 to improve patient access to clinical expertise and develop collaborations. The directors of the 25 centers have created this consensus document outlining best practices in the management of PSP and CBS. They formed a writing committee for each of 12 sub-topics. A 4-member Steering Committee collated and edited the contributions. The result was returned to the entire cohort of authors for further comments, which were considered for incorporation by the Steering Committee. The authors hope that this publication will serve as a convenient guide for all clinicians caring for patients with PSP and CBS and that it will improve care for patients with these devastating but manageable disorders.

Semi-automated approaches to optimize deep brain stimulation parameters in Parkinson's disease.

BACKGROUND: Deep brain stimulation (DBS) is a treatment option for Parkinson's disease patients when medication does not sufficiently manage their symptoms. DBS can be a highly effect therapy, but only after a time-consuming trial-and-error stimulation parameter adjustment process that is susceptible to clinician bias. This trial-and-error process will be further prolonged with the introduction of segmented electrodes that are now commercially available. New approaches to optimizing a patient's stimulation parameters, that can also handle the increasing complexity of new electrode and stimulator designs, is needed. METHODS: To improve DBS parameter programming, we explored two semi-automated optimization approaches: a Bayesian optimization (BayesOpt) algorithm to efficiently determine a patient's optimal stimulation parameter for minimizing rigidity, and a probit Gaussian process (pGP) to assess patient's preference. Quantified rigidity measurements were obtained using a robotic manipulandum in two participants over two visits. Rigidity was measured, in 5Hz increments, between 10-185Hz (total 30-36 frequencies) on the first visit and at eight BayesOpt algorithm-selected frequencies on the second visit. The participant was also asked their preference between the current and previous stimulation frequency. First, we compared the optimal frequency between visits with the participant's preferred frequency. Next, we evaluated the efficiency of the BayesOpt algorithm, comparing it to random and equal interval selection of frequency. RESULTS: The BayesOpt algorithm estimated the optimal frequency to be the highest tolerable frequency, matching the optimal frequency found during the first visit. However, the participants' pGP models indicate a preference at frequencies between 70-110 Hz. Here the stimulation frequency is lowest that achieves nearly maximal suppression of rigidity. BayesOpt was efficient, estimating the rigidity response curve to stimulation that was almost indistinguishable when compared to the longer brute force method. CONCLUSIONS: These results provide preliminary evidence of the feasibility to use BayesOpt for determining the optimal frequency, while pGP patient's preferences include more difficult to measure outcomes. Both novel approaches can shorten DBS programming and can be expanded to include multiple symptoms and parameters.

REM Sleep Without Atonia and Gait Impairment in People with Mild-to-Moderate Parkinson's Disease.

BACKGROUND: Subtle gait deficits can be seen in people with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD), a prodromal stage of Parkinson's disease (PD) and related alpha-synucleinopathies. It is unknown if the presence and level of REM sleep without atonia (RSWA, the electromyographic hallmark of RBD) is related to the severity of gait disturbances in people with PD. OBJECTIVE: We hypothesized that gait disturbances in people with mild-to-moderate PD would be greater in participants with RSWA compared to those without RSWA and matched controls, and that gait impairment would correlate with measures of RSWA. METHODS: Spatiotemporal characteristics of gait were obtained from 41 people with PD and 21 age-matched controls. Overnight sleep studies were used to quantify muscle activity during REM sleep and group participants with PD into those with RSWA (PD-RSWA+, n = 22) and normal REM sleep muscle tone (PD-RSWA-, n = 19). Gait characteristics were compared between groups and correlated to RSWA. RESULTS: The PD-RSWA+ group demonstrated significantly reduced gait speed and step lengths and increased stance and double support times compared to controls, and decreased speed and cadence and increased stride velocity variability compared to PD-RSWA- group. Larger RSWA scores were correlated with worse gait impairment in the PD group. CONCLUSION: The presence and level of muscle tone during REM sleep is associated with the severity of gait disturbances in PD. Pathophysiological processes contributing to disordered gait may occur earlier and/or progress more rapidly in people with PD and RBD.

REM sleep without atonia is associated with increased rigidity in patients with mild to moderate Parkinson's disease.

OBJECTIVE: Increased muscle activity during rapid eye movement (REM) sleep (i.e. REM sleep without atonia) is common in people with Parkinson's disease (PD). This study tested the hypotheses that people with PD and REM sleep without atonia (RSWA) would present with more severe and symmetric rigidity compared to individuals with PD without RSWA and age-matched controls. METHODS: Sixty-one individuals participated in this study (41 PD, 20 controls). An overnight sleep study was used to classify participants with PD as having either elevated (PD-RSWA+) or normal muscle activity (PD-RSWA-) during REM sleep. Quantitative measures of rigidity were obtained using a robotic manipulandum that passively pronated and supinated the forearm. RESULTS: Quantitative measures of forearm rigidity were significantly higher in the PD-RSWA+ group compared to the control group. Rigidity was significantly more asymmetric between limbs in the PD-RSWA- group compared with controls, while there was no significant difference in symmetry between the control and PD-RSWA+ groups. CONCLUSION: In people with mild to moderate PD, RSWA is associated with an increased and more symmetric presentation of upper limb rigidity. SIGNIFICANCE: Dysfunction of brainstem systems that control muscle tone during REM sleep may contribute to increased rigidity during wakefulness in people with PD.

The Transition from Standing to Walking Is Affected in People with Parkinson's Disease and Freezing of Gait.

BACKGROUND: It has been hypothesized that freezing of gait (FOG) in people with Parkinson's disease (PD) is due to abnormal coupling between posture and gait. OBJECTIVE: In this study, we examined the relationship between anticipatory postural adjustments (APAs) preceding gait initiation and the kinematics of the first two steps between people with FOG and without FOG. METHODS: The kinetics and kinematics of self-initiated gait were recorded in 25 people with PD (11 with FOG, 14 without FOG). Outcome variables included the amplitude and timing of the ground reaction forces (GRFs), center of pressure (CoP) shifts and the spatial and temporal characteristics of the first and second steps. RESULTS: The magnitude and timing of the APA phase of gait initiation were not significantly different between participants with and without FOG, yet the first step in the FOG group was distinguished by a significantly wider and less variable first step width, followed by a subsequent wider and shortened second step with reduced toe clearance. Multiple linear regression showed that the relationship between the initial conditions (stance width), APAs (posterior shift of the CoP) and the kinematics of the first step were different between groups with a significantly increased slope in the FOG group. CONCLUSION: These findings demonstrate that the transition from standing to walking is different between those with and without FOG and that alterations in the initial conditions or APAs are more likely to impact the execution of the two steps in people with FOG.

GBA1 mutations: Prospects for exosomal biomarkers in α-synuclein pathologies.

The discovery that patients with Gaucher Disease (GD), a rare lysosomal storage disorder, were developing symptoms similar to Parkinson's disease (PD) led to investigation of the relationship between the two seemingly unrelated pathologies. GD, an autosomal recessive disorder, is the result of a biallelic mutation in the gene GBA1, which encodes for the enzyme glucocerebrosidase (GCase). Since the observation of its relation to PD, GBA1 mutations have become recognized as the most common genetic risk factor for development of synucleinopathies such as PD and dementia with Lewy bodies. Although the exact mechanism by which GBA1 mutations promote PD is unknown, current understanding suggests that impaired GCase inhibits lysosomal activity and decreases the overall ability of the cell to degrade proteins, specifically the neuronal protein α-synuclein. Decreased elimination of α-synuclein can lead to its abnormal accumulation and aggregation, an important component of PD development. Further understanding of how decreased GCase activity increases risk for α-synuclein pathology can assist with the development of clinical biomarkers for early detection of synucleinopathies, as well as promote novel treatments tailored for people with a GBA1 mutation. Historically, α-synuclein has not been a reliable biomarker for PD. However, recent research on α-synuclein content within exosomes, which are small vesicles released by cells that carry specific cellular cargo, has yielded encouraging results. Moreover, decreased GCase activity has been shown to influence exosomal contents. Exosomes have emerged as a promising new avenue for the identification of novel biomarkers and therapeutic targets aimed at improving neuronal GCase function and limiting the development of synucleinopathies.

Neurochemical abnormalities in patients with type 1 Gaucher disease on standard of care therapy.

Type 1 Gaucher disease (GD1), a glycosphingolipid storage disorder caused by deficient activity of lysosomal glucocerebrosidase, is classically considered non-neuronopathic. However, current evidence challenges this view. Multiple studies show that mutations in GBA1 gene and decreased glucocerebrosidase activity are associated with increased risk for Parkinson disease. We tested the hypothesis that subjects with GD1 will show neurochemical abnormalities consistent with cerebral involvement. We performed Magnetic Resonance Spectroscopy at 7 T to quantify neurochemical profiles in participants with GD1 (n = 12) who are on stable therapy. Age and gender matched healthy participants served as controls (n = 13). Neurochemical profiles were obtained from parietal white matter (PWM), posterior cingulate cortex (PCC), and putamen. Further, in the GD1 group, the neurochemical profiles were compared between individuals with and without a single L444P allele. We observed significantly lower levels of key neuronal markers, N-acetylaspartate, γ-aminobutyric acid, glutamate and glutamate-to-glutamine ratio in PCC of participants with GD1 compared to healthy controls (P < .015). Glutamate concentration was also lower in the putamen in GD1 (P = .01). Glucose + taurine concentration was significantly higher in PWM (P = .04). Interestingly, individuals without L444P had significantly lower aspartate and N-acetylaspartylglutamate in PCC (both P < .001), although this group was 7 years younger than those with an L444P allele. This study demonstrates neurochemical abnormalities in individuals with GD1, for which clinical and prognostic significance remains to be determined. Further studies in a larger cohort are required to confirm an association of neurochemical levels with mutation status and glucocerebrosidase structure and function. SYNOPSIS: Ultrahigh field magnetic resonance spectroscopy reveals abnormalities in neurochemical profiles in patients with GD1 compared to matched healthy controls.

Corrigendum: Multi-modal Brain MRI in Subjects with PD and iRBD.

[This corrects the article on p. 709 in vol. 11, PMID: 29311789.].

The effects of anodal tDCS over the supplementary motor area on gait initiation in Parkinson's disease with freezing of gait: a pilot study.

OBJECTIVE: We investigated if anodal transcranial direct current stimulation (A-tDCS), applied over the supplementary motor areas (SMAs), could improve gait initiation in Parkinson's disease (PD) with freezing of gait (FOG). METHODS: In this double-blinded cross-over pilot study, ten PD with FOG underwent two stimulation sessions: A-tDCS (1 mA, 10 min) and sham stimulation. Eight blocks of gait initiation were collected per session: (1) pre-tDCS, with acoustic cueing; (2) pre-tDCS, self-initiated (no cue); and (3-8) post-tDCS, self-initiated. Gait initiation kinetics were analyzed with two-way repeated measures ANOVAs for the effects of A-tDCS. RESULTS: A-tDCS did not significantly improve the magnitude or timing of anticipatory postural adjustments or the execution of the first step during self-initiated gait compared with baseline measures (p > .13). The lack of significant change was not due to an inability to generate functional APAs since external cueing markedly improved gait initiation (p < .01). CONCLUSIONS: A single dose of A-tDCS over the SMAs did not improve self-initiated gait in PD and FOG. Alternative approaches using a different dose or cortical target are worthy of exploration since individuals demonstrated the capacity to improve. SIGNIFICANCE: Neuromodulation strategies tailored to facilitate SMA activity may be ineffective for the treatment of gait initiation impairment in people with PD and FOG.

Somatosensory Training Improves Proprioception and Untrained Motor Function in Parkinson's Disease.

Background: Proprioceptive impairment is a common feature of Parkinson's disease (PD). Proprioceptive function is only partially restored with anti-parkinsonian medication or deep brain stimulation. Behavioral exercises focusing on somatosensation have been promoted to overcome this therapeutic gap. However, conclusive evidence on the effectiveness of such somatosensory-focused behavioral training for improving somatosensory function is lacking. Moreover, it is unclear, if such training has any effect on motor performance in PD. Objective: To investigate, whether proprioception improves with a somatosensory focused, robot-aided training in people with PD (PWPs), and whether enhanced proprioception translates to improved motor performance. Method: Thirteen PWPs of mild-moderate clinical severity were assessed and trained ON medication using a robotic wrist exoskeleton. Thirteen healthy elderly participants served as controls. Training involved making increasingly accurate, continuous, precise small amplitude wrist flexion/extension movements. Wrist position sense acuity, as a marker of proprioception function, and spatial error during wrist pointing, as a marker of untrained motor performance, were recorded twice before and once after training. Functional hand writing kinematics exhibited during training were evaluated in the PD group for determining training-induced changes. Results: Training improved position sense acuity in all PWPs (mean change: 28%; p < 0.001) and healthy controls (mean change: 23%; p < 0.01). Second, 10/13 PD participants and 10/13 healthy control participants had reduced spatial movement error in the untrained wrist pointing task after training. Third, spatial error for the functional handwriting tasks (line tracing and tracking) did not improve with training in the PD group. Conclusion: Proprioceptive function in mild to moderate PD is trainable and improves with a somatosensory-focused motor training. Learning showed a local transfer within the trained joint degree-of-freedom as improved spatial accuracy in an unpracticed motor task. No learning gains were observed for the untrained functional handwriting task, indicating that training may be specific to the trained joint degree-of-freedom.

Repeated-Dose Oral N-Acetylcysteine in Parkinson's Disease: Pharmacokinetics and Effect on Brain Glutathione and Oxidative Stress.

Parkinson's disease (PD) is associated with oxidative stress and decreased nigral glutathione (GSH), suggesting that therapies that boost GSH may have a disease-modifying effect. Intravenous administration of a high dose of N-acetylcysteine (NAC), a well-known antioxidant and GSH precursor, increases blood and brain GSH in individuals with PD and with Gaucher disease and in healthy controls. To characterize the pharmacokinetics of repeated high oral doses of NAC and their effect on brain and blood oxidative stress measures, we conducted a 4-week open-label prospective study of oral NAC in individuals with PD (n = 5) and in healthy controls (n = 3). Brain GSH was measured in the occipital cortex using 1 H-MRS at 3 and 7 tesla before and after 28 days of 6000 mg NAC/day. Blood was collected prior to dosing and at predetermined collection times before and after the last dose to assess NAC, cysteine, GSH, catalase, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) concentrations and the reduced-to-oxidized GSH ratio (GSH/ glutathione disulfide [GSSG]). Symptomatic adverse events were reported by 3 of the 5 subjects with PD. NAC plasma concentration-time profiles were described by a first-order absorption, 1-compartment pharmacokinetic model. Although peripheral antioxidant measures (catalase and GSH/GSSG) increased significantly relative to baseline, indicators of oxidative damage, that is, measures of lipid peroxidation (4-HNE and MDA) were unchanged. There were no significant increases in brain GSH, which may be related to low oral NAC bioavailability and small fractional GSH/GSSG blood responses. Additional studies are needed to further characterize side effects and explore the differential effects of NAC on measures of antioxidant defense and oxidative damage.

Effect of Cue Timing and Modality on Gait Initiation in Parkinson Disease With Freezing of Gait.

OBJECTIVE: To examine the effects of cue timing, across 3 sensory modalities, on anticipatory postural adjustments (APAs) during gait initiation in people with Parkinson disease (PD). DESIGN: Observational study. SETTING: Biomechanics research laboratory. PARTICIPANTS: Individuals with idiopathic PD (N=25; 11 with freezing of gait [FOG]) were studied in the off-medication state (12-h overnight withdrawal). INTERVENTIONS: Gait initiation was tested without cueing (self-initiated) and with 3 cue timing protocols: fixed delay (3s), random delay (4-12s), and countdown (3-2-1-go, 1-s intervals) across 3 sensory modalities (acoustic, visual, and vibrotactile). MAIN OUTCOME MEASURES: The incidence and spatiotemporal characteristics of APAs during gait initiation were analyzed, including vertical ground reaction forces and center of pressure. RESULTS: All cue timings and modalities increased the incidence and amplitude of APAs compared with self-initiated stepping. Acoustic and visual cues, but not vibrotactile stimulation, improved the timing of APAs. Fixed delay or countdown timing protocols were more effective at decreasing APA durations than random delay cues. Cue-evoked improvements in APA timing, but not amplitude, correlated with the level of impairment during self-initiated gait. Cues did not improve the late push-off phase in the FOG group. CONCLUSIONS: External cueing improves gait initiation in PD regardless of cue timing, modality, or clinical phenotype (with and without FOG). Acoustic or visual cueing with predictive timing provided the greatest improvements in gait initiation; therefore, these protocols may provide the best outcomes when applied by caregivers or devices.

Multi-modal Brain MRI in Subjects with PD and iRBD.

Idiopathic rapid eye movement sleep behavior disorder (iRBD) is a condition that often evolves into Parkinson's disease (PD). Therefore, by monitoring iRBD it is possible to track the neurodegeneration of individuals who may progress to PD. Here we aimed at piloting the characterization of brain tissue properties in mid-brain subcortical regions of 10 healthy subjects, 8 iRBD, and 9 early-diagnosed PD. We used a battery of magnetic resonance imaging (MRI) contrasts at 3 T, including adiabatic and non-adiabatic rotating frame techniques developed by our group, along with diffusion tensor imaging (DTI) and resting-state fMRI. Adiabatic T1ρ and T2ρ, and non-adiabatic RAFF4 (Relaxation Along a Fictitious Field in the rotating frame of rank 4) were found to have lower coefficient of variations and higher sensitivity to detect group differences as compared to DTI parameters such as fractional anisotropy and mean diffusivity. Significantly longer T1ρ were observed in the amygdala of PD subjects vs. controls, along with a trend of lower functional connectivity as measured by regional homogeneity, thereby supporting the notion that amygdalar dysfunction occurs in PD. Significant abnormalities in reward networks occurred in iRBD subjects, who manifested lower network strength of the accumbens. In agreement with previous studies, significantly longer T1ρ occurred in the substantia nigra compacta of PD vs. controls, indicative of neuronal degeneration, while regional homogeneity was lower in the substantia nigra reticulata. Finally, other trend-level findings were observed, i.e., lower RAFF4 and T2ρ in the midbrain of iRBD subjects vs. controls, possibly indicating changes in non-motor features as opposed to motor function in the iRBD group. We conclude that rotating frame relaxation methods along with functional connectivity measures are valuable to characterize iRBD and PD subjects, and with proper validation in larger cohorts may provide pathological signatures of iRBD and PD.

N-Acetylcysteine boosts brain and blood glutathione in Gaucher and Parkinson diseases.

OBJECTIVE: This study aimed to determine if the antioxidant N-acetylcysteine (NAC) is able to alter peripheral and central redox capabilities in patients with Parkinson disease (PD) or Gaucher disease (GD). METHODS: The study included nondemented adult subjects: 3 with PD, 3 with GD, and 3 healthy controls. Baseline brain glutathione (GSH) concentrations were measured using 7-T magnetic resonance spectroscopy (MRS). Baseline blood reduced-to-oxidized GSH ratios were determined for each subject. Brain GSH concentrations and blood redox ratios were then determined during and at specified time points after a single, 150-mg/kg NAC infusion. RESULTS: N-acetylcysteine increased blood GSH redox ratios in those with PD and GD and healthy controls, which was followed by an increase in brain GSH concentrations in all subjects. CONCLUSIONS: This is the first demonstration that with MRS, it is possible to directly measure and monitor increases in brain GSH levels in the human brain in response to a single, intravenous administration of NAC. This work shows the potential utility of MRS monitoring, which could assist in determining dosing regimens for clinical trials of this potentially useful antioxidant therapy for PD disease, GD, and other neurodegenerative disorders.

Magnetic Resonance Imaging (MRI) in Parkinson's Disease.

Recent developments in brain imaging methods are on the verge of changing the evaluation of people with Parkinson's disease (PD). This includes an assortment of techniques ranging from diffusion tensor imaging (DTI) to iron-sensitive methods such as T2*, as well as adiabatic methods R1ρ and R2ρ, resting-state functional MRI, and magnetic resonance spectroscopy (MRS). Using a multi-modality approach that ascertains different aspects of the pathophysiology or pathology of PD, it may be possible to better characterize disease phenotypes as well as provide a surrogate of disease and a potential means to track disease progression.

Elevated pontine and putamenal GABA levels in mild-moderate Parkinson disease detected by 7 tesla proton MRS.

BACKGROUND: Parkinson disease (PD) is characterized by the degeneration of nigrostriatal dopaminergic neurons. However, postmortem evidence indicates that the pathology of lower brainstem regions, such as the pons and medulla, precedes nigral involvement. Consistently, pontomedullary damage was implicated by structural and PET imaging in early PD. Neurochemical correlates of this early pathological involvement in PD are unknown. METHODOLOGY/PRINCIPAL FINDING: To map biochemical alterations in the brains of individuals with mild-moderate PD we quantified neurochemical profiles of the pons, putamen and substantia nigra by 7 tesla (T) proton magnetic resonance spectroscopy. Thirteen individuals with idiopathic PD (Hoehn & Yahr stage 2) and 12 age- and gender-matched healthy volunteers participated in the study. γ-Aminobutyric acid (GABA) concentrations in the pons and putamen were significantly higher in patients (N = 11, off medications) than controls (N = 11, p<0.001 for pons and p<0.05 for putamen). The GABA elevation was more pronounced in the pons (64%) than in the putamen (32%). No other neurochemical differences were observed between patients and controls. CONCLUSION/SIGNIFICANCE: The GABA elevation in the putamen is consistent with prior postmortem findings in patients with PD, as well as with in vivo observations in a rodent model of PD, while the GABA finding in the pons is novel. The more significant GABA elevation in the pons relative to the putamen is consistent with earlier pathological involvement of the lower brainstem. This study provides in vivo evidence for an alteration in the GABAergic tone in the lower brainstem and striatum in early-moderate PD, which may underlie disease pathogenesis and may provide a biomarker for disease staging.

Magnetization transfer and adiabatic R 1ρ MRI in the brainstem of Parkinson's disease.

BACKGROUND: In addition to classic midbrain pathology, Parkinson's disease (PD) is accompanied by changes in pontine and medullary brainstem structures. These additional abnormalities may underlie non-motor features as well as play a role in motor disability. METHODS: Using novel magnetic resonance imaging (MRI) methods based on rotating frame adiabatic R(1ρ) (i.e., measurements of longitudinal relaxation during adiabatic full passage pulses) and modified magnetization transfer (MT) MRI mapping, we sought to identify brainstem alterations in nine individuals with mild-moderate PD (off medication) and ten age-matched controls at 4 T. RESULTS: We discovered significant differences in MRI parameters between midbrain and medullary brainstem structures in control subjects as compared to PD patients. CONCLUSIONS: These findings support the presence of underlying functional/structural brainstem changes in mild-moderate PD.

Impulsive behavior and associated clinical variables in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a degenerative brain disorder accompanied by the loss of dopaminergic neurons and the presence of motor and non-motor symptoms. OBJECTIVE: We performed a cross-sectional, questionnaire-based analysis of impulsive behavior in our PD clinic population to assess prevalence and associated characteristics. RESULTS: We found a higher prevalence of impulsive behavior (29.7%) than previously reported, and found multiple, concurrent impulsive behaviors in 26% of subjects reporting impulsive behavior. CONCLUSIONS: Our findings contribute to the growing awareness of impulsive behavior in PD, and support the need for longitudinal studies to assess changes in impulsive behaviors in Parkinson's patients.

T1rho and T2rho MRI in the evaluation of Parkinson's disease.

Prior work has shown that adiabatic T(1rho) and T(2rho) relaxation time constants may have sensitivity to cellular changes and the presence of iron, respectively, in Parkinson's disease (PD). Further understanding of these magnetic resonance imaging (MRI) methods and how they relate to measures of disease severity and progression in PD is needed. Using T(1rho) and T(2rho) on a 4T MRI scanner, we assessed the substantia nigra (SN) of nine non-demented moderately affected PD and ten gender- and age-matched control participants. When compared to controls, the SN of PD subjects had increased T(1rho) and reduced T(2rho). We also found a significant correlation between asymmetric motor features and asymmetry based on T(1rho). This study provides additional validation of T(1rho) and T(2rho) as a means to separate PD from control subjects, and T(1rho) may be a useful marker of asymmetry in PD.