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. All participants underwent 3-minute orthostatic stand testing to assess the frequency of OH, and a Δ heart rate/Δ systolic blood pressure (ΔHR/ΔSBP) ratio <0.5 was used to define reduced HR augmentation, suggestive of neurogenic OH. All participants completed a battery of assessments, including the Scales for Outcomes in Parkinson Disease-Autonomic Dysfunction (SCOPA-AUT) and others assessing cognitive, motor, psychiatric, and sensory domains. RESULTS: Of 340 iRBD participants (65 ± 10 years, 82% male), 93 (27%) met criteria for OH (ΔHR/ΔSBP 0.37 ± 0.28; range 0.0-1.57), and of these, 72 (77%) met criteria for OH with reduced HR augmentation (ΔHR/ΔSBP 0.28 ± 0.21; range 0.0-0.5). Supine hypertension (sHTN) was present in 72% of those with OH. Compared with iRBD participants without OH, those with OH were older, reported older age of RBD symptom onset, and had worse olfaction. There was no difference in autonomic symptom scores as measured by SCOPA-AUT. DISCUSSION: OH and sHTN are common in iRBD. However, as patients may have reduced autonomic symptom awareness, orthostatic stand testing should be considered in clinical evaluations. Longitudinal studies are needed to clarify the relationship between OH and phenoconversion risk in iRBD. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT03623672; North American Prodromal Synucleinopathy Consortium.

Prevalence and impact of neuropsychiatric symptoms in normal aging and neurodegenerative syndromes: A population-based study from Latin America.

BACKGROUND: Neuropsychiatric symptoms (NPSs) are common in neurodegenerative diseases; however, little is known about the prevalence of NPSs in Hispanic populations. METHODS: Using data from community-dwelling participants age 65 years and older enrolled in the 10/66 study (N = 11,768), we aimed to estimate the prevalence of NPSs in Hispanic populations with dementia, parkinsonism, and parkinsonism-dementia (PDD) relative to healthy aging. The Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to assess NPSs. RESULTS: NPSs were highly prevalent in Hispanic populations with neurodegenerative disease; approximately 34.3%, 56.1%, and 61.2% of the participants with parkinsonism, dementia, and PDD exhibited three or more NPSs, respectively. NPSs were the major contributor to caregiver burden. DISCUSSION: Clinicians involved in the care of elderly populations should proactively screen for NPSs, especially in patients with parkinsonism, dementia, and PPD, and develop intervention plans to support families and caregivers. Highlights Neuropsychiatric symptoms (NPSs) are highly prevalent in Hispanic populations with neurodegenerative diseases. In healthy Hispanic populations, NPSs are predominantly mild and not clinically significant. The most common NPSs include depression, sleep disorders, irritability, and agitation. NPSs explain a substantial proportion of the variance in global caregiver burden.

Sleep symptoms signaling the menopausal transition.

STUDY OBJECTIVES: To describe changes in sleep quality and associated sleep symptoms as women begin menopausal transition compared with premenopausal controls. METHODS: In a repeated-measures design, we analyzed data collected every 2-6 months from a community-based sample of 223 women aged 40-50 (45.6 ± 2.3) years old over a 2-year period. Each 6-month visit included urinary follicle-stimulating hormone (FSH) as a marker of ovarian function and the Pittsburgh Sleep Quality Index (PSQI) and other questionnaires (Center for Epidemiological Studies-Depression Scale; Perceived Stress Scale). Menstrual cycle and vasomotor symptoms (Seattle Women's Health Symptom Checklist) were tracked every 2 months by phone. For women entering menopausal transition (n = 68) we used data from the two consecutive visits prior to their FSH rise and the next two visits. Data from the last four consecutive visits were used for controls remaining premenopausal (n = 155). RESULTS: The transition group did not differ from controls on age, vasomotor symptoms (hot flashes/night sweats), stress, or depression but did have a higher body mass index. Measures were stable over time for controls. However, the transition group experienced an increase in PSQI scores (initial PSQI = 5.7 ± 3.2 and final PSQI = 6.3 ± 3.8; P = .030) and frequency of trouble sleeping because of feeling too hot (P = .016), which lagged the FSH rise by 6 months with no notable change in report of hot flashes/night sweats. CONCLUSIONS: Trouble sleeping because of feeling too hot, distinct from awareness of vasomotor symptoms, was the only uniform contribution to higher PSQI scores after the initial FSH increase and may signal the onset of the menopausal transition. CITATION: Zak R, Zitser J, Jones HJ, Gilliss CL, Lee KA. Sleep symptoms signaling the menopausal transition. J Clin Sleep Med. 2023;19(8):1513-1521.

Ambulatory Detection of Isolated Rapid-Eye-Movement Sleep Behavior Disorder Combining Actigraphy and Questionnaire.

BACKGROUND: Isolated rapid-eye-movement sleep behavior disorder (iRBD) is in most cases a prodrome of neurodegenerative synucleinopathies, affecting 1% to 2% of middle-aged and older adults; however, accurate ambulatory diagnostic methods are not available. Questionnaires lack specificity in nonclinical populations. Wrist actigraphy can detect characteristic features in individuals with RBD; however, high-frequency actigraphy has been rarely used. OBJECTIVE: The aim was to develop a machine learning classifier using high-frequency (1-second resolution) actigraphy and a short patient survey for detecting iRBD with high accuracy and precision. METHODS: The method involved analysis of home actigraphy data (for seven nights and more) and a nine-item questionnaire (RBD Innsbruck inventory and three synucleinopathy prodromes of subjective hyposmia, constipation, and orthostatic dizziness) in a data set comprising 42 patients with iRBD, 21 sleep clinic patients with other sleep disorders, and 21 community controls. RESULTS: The actigraphy classifier achieved 95.2% (95% confidence interval [CI]: 88.3-98.7) sensitivity and 90.9% (95% CI: 82.1-95.8) precision. The questionnaire classifier achieved 90.6% accuracy and 92.7% precision, exceeding the performance of the Innsbruck RBD Inventory and prodromal questionnaire alone. Concordant predictions between actigraphy and questionnaire reached a specificity and precision of 100% (95% CI: 95.7-100.0) with 88.1% sensitivity (95% CI: 79.2-94.1) and outperformed any combination of actigraphy and a single question on RBD or prodromal symptoms. CONCLUSIONS: Actigraphy detected iRBD with high accuracy in a mixed clinical and community cohort. This cost-effective fully remote procedure can be used to diagnose iRBD in specialty outpatient settings and has potential for large-scale screening of iRBD in the general population. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Autoimmune Encephalitis Misdiagnosis in Adults.

Importance: Autoimmune encephalitis misdiagnosis can lead to harm. Objective: To determine the diseases misdiagnosed as autoimmune encephalitis and potential reasons for misdiagnosis. Design, Setting, and Participants: This retrospective multicenter study took place from January 1, 2014, to December 31, 2020, at autoimmune encephalitis subspecialty outpatient clinics including Mayo Clinic (n = 44), University of Oxford (n = 18), University of Texas Southwestern (n = 18), University of California, San Francisco (n = 17), University of Washington in St Louis (n = 6), and University of Utah (n = 4). Inclusion criteria were adults (age ≥18 years) with a prior autoimmune encephalitis diagnosis at a participating center or other medical facility and a subsequent alternative diagnosis at a participating center. A total of 393 patients were referred with an autoimmune encephalitis diagnosis, and of those, 286 patients with true autoimmune encephalitis were excluded. Main Outcomes and Measures: Data were collected on clinical features, investigations, fulfillment of autoimmune encephalitis criteria, alternative diagnoses, potential contributors to misdiagnosis, and immunotherapy adverse reactions. Results: A total of 107 patients were misdiagnosed with autoimmune encephalitis, and 77 (72%) did not fulfill diagnostic criteria for autoimmune encephalitis. The median (IQR) age was 48 (35.5-60.5) years and 65 (61%) were female. Correct diagnoses included functional neurologic disorder (27 [25%]), neurodegenerative disease (22 [20.5%]), primary psychiatric disease (19 [18%]), cognitive deficits from comorbidities (11 [10%]), cerebral neoplasm (10 [9.5%]), and other (18 [17%]). Onset was acute/subacute in 56 (52%) or insidious (>3 months) in 51 (48%). Magnetic resonance imaging of the brain was suggestive of encephalitis in 19 of 104 patients (18%) and cerebrospinal fluid (CSF) pleocytosis occurred in 16 of 84 patients (19%). Thyroid peroxidase antibodies were elevated in 24 of 62 patients (39%). Positive neural autoantibodies were more frequent in serum than CSF (48 of 105 [46%] vs 7 of 91 [8%]) and included 1 or more of GAD65 (n = 14), voltage-gated potassium channel complex (LGI1 and CASPR2 negative) (n = 10), N-methyl-d-aspartate receptor by cell-based assay only (n = 10; 6 negative in CSF), and other (n = 18). Adverse reactions from immunotherapies occurred in 17 of 84 patients (20%). Potential contributors to misdiagnosis included overinterpretation of positive serum antibodies (53 [50%]), misinterpretation of functional/psychiatric, or nonspecific cognitive dysfunction as encephalopathy (41 [38%]). Conclusions and Relevance: When evaluating for autoimmune encephalitis, a broad differential diagnosis should be considered and misdiagnosis occurs in many settings including at specialized centers. In this study, red flags suggesting alternative diagnoses included an insidious onset, positive nonspecific serum antibody, and failure to fulfill autoimmune encephalitis diagnostic criteria. Autoimmune encephalitis misdiagnosis leads to morbidity from unnecessary immunotherapies and delayed treatment of the correct diagnosis.

Pittsburgh Sleep Quality Index (PSQI) responses are modulated by total sleep time and wake after sleep onset in healthy older adults.

OBJECTIVES: To investigate the objective sleep influencers behind older adult responses to subjective sleep measures, in this case, the Pittsburgh Sleep Quality Index (PSQI). Based on previous literature, we hypothesized that SE would be associated with PSQI reported sleep disruption. Furthermore, because SOL increases progressively with age and it tends to be easily remembered by the patients, we also expected it to be one of the main predictors of the perceived sleep quality in the elderly. METHODS: We studied 32 cognitively healthy community-dwelling older adults (age 74 ± 0.3 years) who completed an at-home sleep assessment (Zeo, Inc.) and the PSQI. Linear mixed models were used to analyze the association of the objective sleep parameters (measured by the Zeo) with the PSQI total score and sub-scores, adjusting for age, gender, years of education and likelihood of sleep apnea. RESULTS: Objective sleep parameters did not show any association with the PSQI total score. We found that objective measures of Wake after sleep onset (WASO, % and min) were positively associated with the PSQI sleep disturbance component, while SE and Total Sleep Time (TST) were negatively associated with PSQI sleep disturbance. Lastly, objective SE was positively associated with PSQI SE. CONCLUSIONS: Our findings showed that WASO, SE and TST, are associated with PSQI sleep disturbance, where the greater WASO, overall lower SE and less TST, were associated with increased subjective report of sleep disturbance. As expected, subjective (PSQI) and objective measures of SE were related. However, PSQI total score did not relate to any of the objective measures. These results suggest that by focusing on the PSQI total score we may miss the insight this easily administered self-report tool can provide. If interpreted in the right way, the PSQI can provide further insight into cognitively healthy older adults that have the likelihood of objective sleep disturbance.

Sleep Self-Report and Actigraphy Measures in Healthy Midlife Women: Validity of the Pittsburgh Sleep Quality Index.

Background: Validity of the Pittsburgh Sleep Quality Index (PSQI) has not been established for midlife women before menopause, and evidence suggests that two-factor or three-factor models may be more informative than the PSQI global score derived from its seven components. We hypothesized that the PSQI and its factor structure would be valid in premenopausal women. Materials and Methods: We performed a validation study of the PSQI against wrist actigraphy in a community-based convenience sample of 71 healthy premenopausal women (aged 40-50 years). For convergent validity, PSQI and its component scores were compared with homologous actigraphy measures. For discriminant validity, characteristics known to affect sleep quality were compared, including body mass index, exercise, menopausal status, menopausal symptoms, and depressive symptoms measured with the Center for Epidemiological Studies-Depression (CES-D) Scale. Results: The PSQI global score and Components 1 (quality) and 5 (disturbance) were correlated (p < 0.05) with actigraphy-measured wake after sleep onset. The PSQI global score and Components 1 (quality) and 7 (daytime dysfunction) were correlated with CES-D scores. PSQI Components 2 (onset latency) and 4 (efficiency) were not congruent with homologous actigraphy measures, while component 3 (duration) was congruent with actigraphy duration. The single-factor PSQI global score had a higher McDonald's omega (0.705) and Cronbach's alpha (0.702) than the two-factor or three-factor models. Conclusions: The PSQI global score is a valid measure of sleep quality in healthy midlife women, performing better than two-factor or three-factor models. However, overlapping CES-D and PSQI scores warrant further clinical assessment and research to better differentiate poor sleep quality from depression.

Clinical, neuroimaging, and neuropathological characterization of a patient with Alzheimer's disease syndrome due to Pick's pathology.

The most common neurodegenerative syndrome associated with Pick's disease pathology (PiD) is behavioral variant frontotemporal dementia (bvFTD), which features profound social behavioral changes. Rarely, PiD can manifest as an Alzheimer's disease (AD)-type dementia with early memory impairment. We describe a patient with AD-type dementia and pure PiD pathology who showed slowly progressive memory impairment, early social changes, and paucity of motor symptoms. Atrophy and PiD were found mainly in frontotemporal regions underlying social behavior. This report may help predict the pathology of patients with atypical AD, which will ultimately be critical for enrolling suitable subjects into disease-modifying clinical trials.

Biomarkers of conversion to α-synucleinopathy in isolated rapid-eye-movement sleep behaviour disorder.

Patients with isolated rapid-eye-movement sleep behaviour disorder (RBD) are commonly regarded as being in the early stages of a progressive neurodegenerative disease involving α-synuclein pathology, such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Abnormal α-synuclein deposition occurs early in the neurodegenerative process across the central and peripheral nervous systems and might precede the appearance of motor symptoms and cognitive decline by several decades. These findings provide the rationale to develop reliable biomarkers that can better predict conversion to clinically manifest α-synucleinopathies. In addition, biomarkers of disease progression will be essential to monitor treatment response once disease-modifying therapies become available, and biomarkers of disease subtype will be essential to enable prediction of which subtype of α-synucleinopathy patients with isolated RBD might develop.

Cutaneous α-synuclein is correlated with autonomic impairment in isolated rapid eye movement sleep behavior disorder.

STUDY OBJECTIVES: To define the clinical implications of cutaneous phosphorylated α-synuclein (p-syn) and its association with subjective and objective measures of autonomic impairment and clinical features including antidepressant use in isolated rapid eye movement (REM) sleep behavior disorder (iRBD). METHODS: Twenty-five iRBD patients had quantified neurological and cognitive examinations, olfactory testing, questionnaires, autonomic function testing, and 3 punch skin biopsies (distal thigh, proximal thigh, neck). Skin biopsies were stained for the pan-axonal marker PGP 9.5 and co-stained with p-syn, and results were compared to 28 patients with Parkinson's disease (PD) and 18 healthy controls. Equal numbers of iRBD patients on and off antidepressants were recruited. The composite autonomic severity scale (CASS) was calculated for all patients. RESULTS: P-syn was detected in 16/25 (64%) of iRBD patients, compared to 27/28 (96%) of PD and 0/18 controls. The presence of p-syn at any biopsy site was correlated with both sympathetic (CASS adrenergic r = 0.6, p < 0.05) and total autonomic impairment (CASS total r = 0.6, p < 0.05) on autonomic reflex testing in iRBD patients. These results were independent of the density of p-syn at each site. There was no correlation between p-syn and antidepressant use. CONCLUSIONS: In patients with iRBD, the presence of cutaneous p-syn was detected in most patients and was associated with greater autonomic dysfunction on testing. Longitudinal follow-up will aid in defining the predictive role of both skin biopsy and autonomic testing in determining phenoconversion rates and future disease status.

Mild Motor Signs Matter in Typical Brain Aging: The Value of the UPDRS Score Within a Functionally Intact Cohort of Older Adults.

Objectives: To characterize the clinical correlates of subclinical Parkinsonian signs, including longitudinal cognitive and neural (via functional connectivity) outcomes, among functionally normal older adults. Methods: Participants included 737 functionally intact community-dwelling older adults who performed prospective comprehensive evaluations at ~15-months intervals for an average of 4.8 years (standard deviation 3.2 years). As part of these evaluations, participants completed the Unified Parkinson's Disease Rating Scale (UPDRS) longitudinally and measures of processing speed, executive functioning and verbal episodic memory. T1-weighted structural scans and task-free functional MRI scans were acquired on 330 participants. We conducted linear mixed-effects models to determine the relationship between changes in UPDRS with cognitive and neural changes, using age, sex, and education as covariates. Results: Cognitive outcomes were processing speed, executive functioning, and episodic memory. Greater within-person increases in UPDRS were associated with more cognitive slowing over time. Although higher average UPDRS scores were significantly associated with overall poorer executive functions, there was no association between UPDRS and executive functioning longitudinally. UPDRS scores did not significantly relate to longitudinal memory performances. Regarding neural correlates, greater increases in UPDRS scores were associated with reduced intra-subcortical network connectivity over time. There were no relationships with intra-frontoparietal or inter-subcortical-frontoparietal connectivity. Conclusions: Our findings add to the aging literature by indicating that mild motor changes are negatively associated with cognition and network connectivity in functionally intact adults.

The role of tissue biopsy as a biomarker in REM sleep behavior disorder.

Patients with idiopathic REM-sleep behavior disorder (iRBD) are at substantial risk of progressive neurodegenerative disease of α-synuclein pathology. Longitudinal studies have demonstrated that abnormal α-synuclein deposition occurs early in the course of disease and may precede the appearance of motor symptoms by several decades. This provides rationale for the use of a reliable biomarker to both follow disease progression and to assess treatment response, once disease-modifying treatments become available. Tissue α-synuclein has emerged as a promising candidate, however the utility of α-synuclein detection in tissues accessible to biopsy in iRBD remains unclear. This article summarizes the current literature on the role of tissue biopsy in iRBD, with specific focus on its potential role as a biomarker of disease progression and its role in future clinical trials.

Sleep duration over 28 years, cognition, gray matter volume, and white matter microstructure: a prospective cohort study.

STUDY OBJECTIVES: To examine the association between sleep duration trajectories over 28 years and measures of cognition, gray matter volume, and white matter microstructure. We hypothesize that consistently meeting sleep guidelines that recommend at least 7 hours of sleep per night will be associated with better cognition, greater gray matter volumes, higher fractional anisotropy, and lower radial diffusivity values. METHODS: We studied 613 participants (age 42.3 ± 5.03 years at baseline) who self-reported sleep duration at five time points between 1985 and 2013, and who had cognitive testing and magnetic resonance imaging administered at a single timepoint between 2012 and 2016. We applied latent class growth analysis to estimate membership into trajectory groups based on self-reported sleep duration over time. Analysis of gray matter volumes was carried out using FSL Voxel-Based-Morphometry and white matter microstructure using Tract Based Spatial Statistics. We assessed group differences in cognitive and MRI outcomes using nonparametric permutation testing. RESULTS: Latent class growth analysis identified four trajectory groups, with an average sleep duration of 5.4 ± 0.2 hours (5%, N = 29), 6.2 ± 0.3 hours (37%, N = 228), 7.0 ± 0.2 hours (45%, N = 278), and 7.9 ± 0.3 hours (13%, N = 78). No differences in cognition, gray matter, and white matter measures were detected between groups. CONCLUSIONS: Our null findings suggest that current sleep guidelines that recommend at least 7 hours of sleep per night may not be supported in relation to an association between sleep patterns and cognitive function or brain structure.

Repeated Intravenous Amantadine Infusions in Advanced Parkinsonism: Experience of a Large Movement Disorder Center.

BACKGROUND: The effect of repeated intravenous amantadine (IVAM) in advanced Parkinsonism has not been studied in depth. OBJECTIVES: To report the experience of our medical center with repeated IVAM infusions in patients with advanced Parkinsonism. METHODS: Thirty patients with advanced Parkinsonism of various etiologies were enrolled in an open-label retrospective study. All patients were treated with IVAM infusions in a neurological daycare center. Treatment was initiated with a loading dose of 200/400 mg per day for 5 days followed by a once-daily maintenance dose of 200/400 mg every 1 to 3 weeks. Patients and their caregivers participated in a structured interview and independently completed a clinical global impression of changes scale questionnaire on various motor and non-motor symptoms. RESULTS: Patient mean age was 73.3 ± 9.7 years, average disease duration was 6.2 ± 5.7 years, and mean Hoehn and Yahr score was 3.2 ± 0.84. Mean duration of the IVAM treatment was 15.1 ± 11.6 months. An improvement in general function was reported by 91% of the patients and 89% of the caregivers. Most of the patients reported improvement in tremor and rigidity, as well as in gait stability, freezing of gait, and reduced falls. The treatment was safe with few side effects. CONCLUSIONS: Our data suggest that repeated IVAM infusions could be an effective treatment against various motor symptoms and for improvement of mobility in patients with advanced Parkinsonism. Further randomized clinical trials with a larger sample size using objective measures are warranted to validate our results.

Autonomic impairment as a potential biomarker in idiopathic REM-sleep-behavior disorder.

Autonomic dysfunction is common in REM-sleep behavior disorder (RBD). Several studies have demonstrated abnormalities in heart rate variability, cardiac scintigraphy, and cardiovascular autonomic reflex testing. In addition, the type and severity of these abnormalities may correlate with rate of phenoconversion from idiopathic RBD (iRBD) to manifest neurodegenerative disease. This article summarizes the current literature on autonomic impairment in iRBD, with specific focus on the role of autonomic impairment as a potential biomarker of disease progression. REM sleep physiology and relevant anatomy is also discussed in relation to the central autonomic network and autonomic neurodegeneration.

Dysphagia characteristics in Huntington's disease patients: insights from the Fiberoptic Endoscopic Evaluation of Swallowing and the Swallowing Disturbances Questionnaire.

BACKGROUND: Huntington's disease (HD) is a neurodegenerative disease characterized by increasing dysphagia as the disease progresses. Specific characteristics of the HD dysphagia are not well defined. OBJECTIVE: To characterize the swallowing disturbances of HD patients, to evaluate the feasibility of Fiberoptic Endoscopic Evaluation of Swallowing (FEES) in assessing dysphagia in HD patients, and to discern the relation between FEES findings and patients' self-report on dysphagia symptoms and swallowing related quality of life (SWAL-QOL). METHOD: A retrospective case series in a tertiary referral center. All recruited HD patients underwent Bed Side Swallowing Evaluation (BSE), FEES, the Unified Huntington's Disease Rating Scale (UHDRS), and the Montreal Cognitive Assessment (MoCA). All completed the Swallowing Disturbances Questionnaire (SDQ) and the SWAL-QOL questionnaire. RESULTS: Fourteen HD patients were recruited. All were able to complete the FEES study. The FEES demonstrated delayed swallowing reflex, solid food residues, and pre/post swallowing spillage in most patients (50%, 53.5%, 83.3%, and 87.5%, respectively). The mean SDQ score was 13.2. Significant correlations were found between the SWAL-QOL fear of eating score; the SDQ oral, pharyngeal, and total scores; and the FEES parameters of pureed and solid food bolus flow time. Significant correlations were also found between the total UHDRS score, the volitional cough score, and the SWAL-QOL disease burden score. CONCLUSION: HD patients exhibit prominent unique oropharyngeal dysphagia features that may serve as a marker of disease progression. The FEES and the SDQ are valuable tools for detecting these features in HD patients with swallowing disturbance.

Validation of the Hebrew version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale.

BACKGROUND: The Movement Disorders Society (MDS) published the English new Unified Parkinson's Disease Rating Scale (MDS-UPDRS) as the official benchmark scale for Parkinson's disease (PD) in 2008. We aimed to validate the Hebrew version of the MDS-UPDRS, explore its dimensionality and compare it to the original English one. METHODS: The MDS-UPDRS questionnaire was translated to Hebrew and was tested on 389 patients with PD, treated at the Movement Disorders Unit at Tel-Aviv Medical Center. The MDS-UPDRS is made up of four sections. The higher the score, the worst the clinical situation of the patient is. Confirmatory and explanatory factor analysis were applied to determine if the factor structure of the English version could be confirmed in the Hebrew version. RESULTS: The Hebrew version of the MDS-UPDRS showed satisfactory clinimetric properties. The internal consistency of the Hebrew-version was satisfactory, with Cronbach's alpha values 0.79, 0.90, 0.93, 0.80, for parts 1 to 4 respectively. In the confirmatory factor analysis, all four parts had high (greater than 0.90) comparative fit index (CFI) in comparison to the original English MDS-UPDRS with high factor structure (0.96, 0.99, 0.94, 1.00, respectively), thus confirming the pre-specified English factor structure. Explanatory factor analysis yielded that the Hebrew responses differed from the English one within an acceptable range: in isolated item differences in factor structure and in the findings of few items having cross loading on multiple factors. CONCLUSIONS: The Hebrew version of the MDS-UPDRS meets the requirements to be designated as the Official Hebrew Version of the MDS-UPDRS.