Journal of Movement Disorders

Original Articles

Distinct and Combined Cognitive Profiles associated with Depression and Anxiety in Early Parkinson's Disease: Hak-Loh Lee, Seong-Min Choi, Soo Hyun Cho, Byeong C. Kim; Received March 13, 2026 Accepted June 12, 2026 Published online June 12, 2026; DOI: https://doi.org/10.14802/jmd.26076 [Accepted]

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Abstract PDF: Objective
Cognitive impairment is a major non-motor manifestation of Parkinson's disease (PD), and mood disorders, including depression and anxiety, are increasingly recognized as potentially modifiable contributors to cognitive decline. However, studies simultaneously evaluating the individual and combined effects of depression and anxiety on specific cognitive domains in PD remain limited.
Methods
One hundred forty-nine patients with early-to-mid-stage PD were stratified by depression (BDI ≥ 14) and anxiety (BAI ≥ 8) status. Cognitive performance was evaluated using the Seoul Neuropsychological Screening Battery (SNSB). Group differences were analyzed using ANCOVA, adjusting for education, H–Y stage, and MDS-UPDRS motor scores, followed by Bonferroni correction for multiple testing.
Results
After adjustment for covariates, depression was associated with impaired verbal recognition memory (p = 0.009), although this did not survive Bonferroni correction. Conversely, anxiety-related deficits immediate visual recall (p = 0.006) and inhibitory executive control (p = 0.016) remained robustly significant even after rigorous correction. Patients with comorbid depression and anxiety exhibited the most pervasive cognitive impairment, including statistically resilient deficits in both visual memory and frontal executive function (all adjusted p < 0.05).
Conclusion
Depression and anxiety exert distinct yet additive detrimental effects on cognition in early PD. While anxiety and comorbid symptoms show robust associations with visuospatial and executive deficits, the impact of isolated depression appears less statistically stable under conservative thresholds. These findings underscore the importance of early neuropsychiatric screening and targeted intervention, which may be associated with the maintenance of cognitive health in PD.

Serum Neuronal Extracellular vesicles for RT-QuIC assay to detect Pathological α-Synuclein in Synucleinopathies: Hye Joung Choi, Dong Gyun Ko, JeKuk Yu, Nguyen Thi Hai Thanh, Hyeo-il Ma, Young Eun Kim; Received February 19, 2026 Accepted May 20, 2026 Published online May 20, 2026; DOI: https://doi.org/10.14802/jmd.26054 [Accepted]

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Abstract PDF: Background
Pathological α-synuclein aggregates are key finding of synucleinopathies, including Parkinson’s disease (PD), dementia with Lewy bodies, and multiple system atrophy. The Real-Time Quaking-Induced Conversion (RT-QuIC) assay using cerebrospinal fluid (CSF) can sensitively detect pathological α-syn aggregates with strong biologic rationale. Because of limitation by the invasive nature of CSF collection, blood-based RT-QuIC assay is now attended with small evidence and showed good performance discriminating PD and control. This study investigated pathological α-syn aggregates using the neuronal extracellular vesicles (nEVs) from serum in patients with synucleinopathies, and healthy controls (HC).
Methods
Serum were collected from the patients diagnosed with synucleinopathies and HC without neurological disorders. Total extracellular vesicles (tEVs) were isolated from serum using ExoQuick kit, followed by nEVs isolation via L1-Cell Adhesion Molecule (L1CAM) immunocapture. The identity of nEVs was confirmed by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting. Pathological α-synuclein aggregates in EVs were assessed by western blotting, dot blot, and RT-QuIC assay.
Results
The concentration and abundance of EVs were comparable between PD and HC groups. TEM and NTA confirmed extracellular vesicle morphology, and size distribution, and western blotting validated neuronal quality of nEVs. Higher levels of phosphorylated or aggregated α-synuclein were detected in nEVs from synucleinopathy patients compared to HC. Optimized RT-QuIC conditions achieved 100% sensitivity without false positives. Distinct RT-QuIC kinetic profiles were observed between synucleinopathy and HC samples.
Conclusion
Serum-derived nEVs represent a promising, minimally invasive seed source for RT-QuIC assays, offering robust diagnostic performance for the detection of synucleinopathy and potential applicability in broader clinical settings.

The Clinical Significance of Thyroid Uptake in ¹²³I- meta-iodobenzylguanidine Scintigraphy in Parkinson’s disease: Sang-Won Yoo, Dong-Woo Ryu, Yoonsang Oh, Seunggyun Ha, Joong-Seok Kim; Received February 13, 2026 Accepted May 4, 2026 Published online May 5, 2026; DOI: https://doi.org/10.14802/jmd.26046 [Accepted]

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Abstract PDF: Background
The thyroid gland receives sympathetic innervation. ¹²³I-meta-iodobenzylguanidine (¹²³I-MIBG) is a noradrenaline analog taken up by adrenergic nerve terminals. Although thyroid uptake can be seen on ¹²³I-MIBG scintigraphy, its quantitative value is poorly understood. This study examined the clinical relevance of thyroid ¹²³I-MIBG uptake in Parkinson’s disease (PD).
Methods
A total of 233 de novo patients were enrolled in a longitudinal cohort and underwent ¹²³I-MIBG scintigraphy. Early and late heart-to-mediastinum ratio (HMR) and early thyroid-to-mediastinum ratio (TMR) were calculated. Baseline TMR was estimated using a mixed model after verifying the empirical linear decline over time. Observed and model-implied uptake ratios were analyzed in relation to adrenergic blood pressure (BP) control, motor and non-motor burdens, and quality of life (QoL). Baseline thyroid uptake was further assessed for its influence on longitudinal disease progression.
Results
Patients were assessed from early PD (mean age, 68.7 ± 8.7 years; median disease duration, 1.0 year). Mean follow-up was 57.3 ± 22.1 months. Lower baseline HMR correlated with greater orthostatic BP changes, autonomic symptom burden, and worsening motor, non-motor functions, and QoL. The TMR showed no significant correlations overall; however, it was associated with a higher occurrence of supine hypertension, orthostatic hypotension, and non-dipper or nocturnal hypertension. Thyroid uptake did not influence longitudinal changes in motor, non-motor, cognitive, and QoL measure, though higher uptake showed trends toward slower cognitive decline and better QoL.
Conclusions
Thyroid ¹²³I-MIBG uptake did not predict disease progression, but may indicate early blood pressure dysregulation, and could reflect non-motor vulnerability in PD.

Review Article

Digital Technology for Sleep Symptoms in Parkinson’s Disease: A Scoping Review: Kye Won Park, Ki-Young Jung, Han-Joon Kim, Jung Hwan Shin; J Mov Disord. 2026;19(2):119-134. Published online April 14, 2026; DOI: https://doi.org/10.14802/jmd.26098

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Abstract PDF Supplementary Material: Sleep disturbances are highly prevalent and clinically significant nonmotor features of Parkinson’s disease (PD). Although in-laboratory polysomnography remains the gold standard method for investigating these disturbances, its limited scalability and ecological validity constrain longitudinal and real-world assessments. Recent advances in digital health technologies have introduced a broad spectrum of portable, wearable, and contactless tools for sleep monitoring. In this scoping review, we systematically map the landscape of digital sleep technologies in PD by using a tiered framework based on technical maturity and clinical validation (Tiers 1–4); moreover, we further classify them by signal modality and sleep symptom domain. Through a systematic review of the literature, we identified 19 studies (Tiers 2–4) that applied digital biomarkers to assess sleep disturbances in PD, including REM sleep behavior disorder, nocturnal immobility, insomnia, circadian rhythm disturbances, excessive daytime sleepiness, and sleep-related respiratory and movement disorders. We additionally contextualize these findings against the rapid expansion of multimodal and AI-driven Tier 3–4 platforms in the general population. Despite this technological progress, a major translational gap persists in PD, which is characterized by limited disease-specific validation, small cohort sizes, and insufficient multimodal benchmarking. Multimodal systems leveraging machine learning offer a promising direction by enabling the more precise characterization of complex and overlapping sleep phenotypes. Emerging contactless systems further expand the potential for continuous, low-burden monitoring, although their clinical validity remains to be established. Future development of digital sleep biomarkers in PD will require prospective validation against established standards and the integration of multimodal data to enable scalable, longitudinal phenotyping and clinical trial applications.

Original Articles

Cognitive Impairment Alters Cortical Adaptation and Gait Regulation During Obstacle Walking in Patients With Parkinson’s Disease: Evidence From Temporal fNIRS and Gait Dynamics: Pei-Ling Wong, Yea-Ru Yang, Chen-Wei Hung, Nai-Chen Yeh, Shih-Jung Cheng, Ray-Yau Wang; Received December 25, 2025 Accepted March 3, 2026 Published online March 3, 2026; DOI: https://doi.org/10.14802/jmd.25346 [Epub ahead of print]

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Abstract PDF: Objective
Obstacle crossing during walking poses a major risk of falling among individuals with Parkinson’s disease (PD), particularly those with cognitive impairment. Although cognitive decline worsens gait, its specific effects on gait performance and cortical activation during obstacle walking remain unclear. The dynamic interaction between brain activity and gait across different walking phases is especially understudied in PD patients with mild cognitive impairment (PD-MCI) compared with those without cognitive impairment (PD-non-MCI).
Methods
Nineteen PD-non-MCI and fifteen PD-MCI participants performed obstacle walking, and functional near-infrared spectroscopy was used to measure activation in the prefrontal cortex (PFC), supplementary motor area (SMA), and premotor cortex (PMC). Gait parameters (speed, cadence, stride length, and stride time) and obstacle crossing metrics (crossing speed, stride length, stride time, and step width) were analyzed across early (5–20 s) and late (20–40 s) phases. Generalized estimating equations were used to examine group, phase, and interaction effects. Brain–gait associations were assessed using Spearman’s correlations.
Results
PD-MCI participants exhibited poorer obstacle walking performance than PD-non-MCI participants, but no significant phase-related behavioral change was observed. Both groups showed higher PFC, SMA, and PMC activation during the early phase, reflecting greater neural engagement at task onset. However, SMA and PMC activation decreased more steeply across phases in the PD-MCI group. In PD-MCI patients, obstacle walking performance correlated negatively with early-phase PMC and late-phase PFC activation.
Conclusion
PD-MCI participants had poorer gait and greater cortical activation, indicating increased neural effort and reduced efficiency. These results highlight altered brain–gait coupling in PD-MCI patients and emphasize the need for interventions that increase neural efficiency during complex walking.

Association between vestibulo-ocular reflex and cognitive function in de novo Parkinson’s disease: Hyun Joo Kim, Mincheol Park, Chan-Nyoung Lee, Kun-Woo Park, Sun-Uk Lee, Kyoungwon Baik; Received August 28, 2025 Accepted February 20, 2026 Published online February 23, 2026; DOI: https://doi.org/10.14802/jmd.25230 [Accepted]

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Abstract PDF: Objective
Vestibulo-ocular reflex (VOR) impairment has been reported in Parkinson’s disease (PD). However, the clinical implications, particularly for cognition remains unclear. We investigated canal-specific VOR changes and their associations with cognitive function, motor symptoms, gaits, and dopamine transporter (DAT) uptake in de-novo PD.
Methods
We prospectively enrolled 127 patients with de- novo PD who underwent video head-impulse tests (video-HITs), comprehensive neuropsychological assessment, gait analysis, and FP-CIT PET. Associations between VOR gains and clinical characteristics of PD were evaluated using general linear models adjusted for age, sex, and education. Cognitive analyses were performed after stratifying patients into PD with normal cognition (PD-NC) and PD with mild cognitive impairment (PD-MCI). Partial correlation analyses assessed relationships between VOR gains and regional DAT uptake.
Results
Decreased VOR gain in at least one canal was observed in 22 patients (17.3%). Horizontal canal (HC) gain was positively associated with the Montreal Cognitive Assessment (p=0.040), anterior canal (AC) gain had negative association with the base of support (p=0.018). Patterns of association between VOR gains and neuropsychological measures differed between PD-NC and PD-MCI. In addition, VOR-cognition relationships were canal-specific: HC gain was positively related to visuospatial function, whereas AC and posterior canal gains were negatively related to language and frontal-executive functions. DAT uptake in the locus coeruleus was positively correlated with HC gain (p=0.020).
Conclusion
VOR integrity is associated with cognitive and gait function in patients with PD. Video-HITs may serve as a potential biomarker for disease monitoring in PD.

The Amnesia Light and Brief Assessment (ALBA) and the door PICture Naming and Immediate Recall (PICNIR) brief tests for identifying mild cognitive impairment in Parkinson's disease: Kateřina Stolaríková, Aleš Bartoš, Kateřina Menšíková, Helena Kisvetrová, Jana Zapletalová, Sandra Kurčová, Raymond Rosales, Petr Kaňovský; Received October 11, 2025 Accepted February 13, 2026 Published online February 13, 2026; DOI: https://doi.org/10.14802/jmd.25271 [Accepted]

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Abstract PDF: Objective
To identify mild cognitive impairment (MCI) in Parkinson's disease (PD) using two brief tests the Amnesia Light and Brief Asssment (ALBA) and the door Picture Naming and Immediate Recall (dPICNIR) in 6–8 minutes.
Methods
The ALBA, the dPICNIR and the third version of the Addenbrooke’s Cognitive Examination III (ACE-III) were administered to 124 participants, equally divided into PD patients and socio-demographically matched normal controls (NC). The PD group was divided into those with normal cognitive functions (PD-CN) and with MCI (PD-MCI) using neuropsychological tests.
Results
Cognitive impairment in the PD group was mild, with significantly lower ACE-III scores than in NC (91 vs. 96 points). Despite these subtle deficits, gesture recall in the ALBA was significantly lower even in the PD-CN group compared to the NC. PD-MCI patients had other significant deficits in the ALBA and PICNIR tests. In the PD group, the gesture recall in the ALBA and correctly recalled pictures in the dPICNIR correlated with the results of verbal fluency and trail making tests, followed by memory tests and all ACE-III scores except visuospatial one. In contrast, correctly recalled sentence words in the ALBA correlated with the memory and language scores in the ACE-III test and memory test scores.
Conclusions
Subtle cognitive changes in PD can be detected through gesture recall test, even in those with normal cognition. The ALBA and PICNIR tests are effective in identifying MCI in PD and provide a brief and valid assessment of cognitive functions. They are freely available at www.abadeco.cz.

Neuropsychiatric and Cognitive Safety of Subcutaneous Foslevodopa/Foscarbidopa in Advanced Parkinson’s Disease: Insights From a Real-World Cohort: Clément Desjardins, Hélène de Saint Vaulry, Quentin Salardaine, Céline Rosset, Jean-Philippe Brandel, Guillaume Baille; J Mov Disord. 2026;19(2):178-186. Published online January 26, 2026; DOI: https://doi.org/10.14802/jmd.25304

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Abstract PDF Supplementary Material

Objective
Continuous subcutaneous foslevodopa/foscarbidopa infusion (CSFLI) represents a transformative therapy for advanced Parkinson’s disease (aPD), but real-world neuropsychiatric safety data remain limited, particularly in populations typically excluded from clinical trials. This study aimed to assess the frequency, clinical patterns, and predictors of neuropsychiatric and/or cognitive worsening in a real-world CSFLI-treated cohort.
Methods
We performed a retrospective observational study involving 36 consecutive aPD patients who underwent CSFLI with a six-month follow-up. Neuropsychiatric/cognitive worsening was defined as any clinically meaningful increase in the Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part I or the Parkinson’s Disease Questionnaire-8 (PDQ-8) cognitive/psychiatric subscores. Patients were classified as “worsening” versus “no worsening” and compared with respect to baseline characteristics. Predictors were identified using univariable and exploratory multivariable analyses.
Results
Seventeen patients (47.2%) experienced neuropsychiatric/cognitive worsening within six months. Critically, patients with prior confusion or hallucinations who were managed with baseline clozapine had significantly better outcomes: confusion history was common in 57.9% of the patients in the stable group versus 11.8% in the worsening group (p=0.006), with clozapine use corresponding to 63.2% of the patients versus 23.5% (p=0.023). Conversely, catechol-O-methyltransferase inhibitor (COMT-I) use was more frequent in the worsening group (70.6% vs. 21.1%, p=0.006). Motor outcomes remained stable at 6 months regardless of the patient’s neuropsychiatric status.
Conclusion
In a vulnerable real-world aPD population, neuropsychiatric/cognitive worsening under CSFLI was more frequent than it was in pivotal trials (47% vs. 7%–17%) but was generally mild and not associated with motor deterioration. Importantly, proactive clozapine use enabled safe CSFLI treatment in patients with psychiatric histories traditionally considered high risk. COMT-I emerged as a modifiable risk factor. These findings support broader CSFLI use with structured neuropsychiatric monitoring and proactive clozapine in selected patients.

Citations

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Sex Differences in the Treatment of People with Parkinson’s Disease with a Device-Aided Therapy: A Prospective Real-World Study
Diego Santos García, Ángela Solleiro Vidal, Marta Blázquez Estrada, Pablo Mir, Nuria López Ariztegui, Déborah Alonso Modino, Inés Legarda, Alejandro Peral, Rocío García-Ramos, Iria Cabo, Pilar Sánchez Alonso, Jorge Hernández-Vara, Javier Ruíz Martínez, Ma
Medical Sciences.2026; 14(2): 217. CrossRef
Real-world outcomes and early discontinuation of foslevodopa/foscarbidopa in Parkinson’s disease
Takashi Tsuboi, Katsuo Kimura, Kensuke Ikenaka, Toru Baba, Keita Matsuura, Yuta Kajiyama, Daiki Kamiyama, Takashi Uematsu, Katsuya Abe, Keita Kakuda, Hiroyuki Takenaka, Koichi Miyashita, Akiko Saito, Masahito Mihara, Akihiro Shindo, Takafumi Hasegawa, Yas
Journal of Neurology.2026;[Epub] CrossRef

Brief communication

Endurance and Efficiency of Cycling and Manual Wheelchairs in Late-Stage Parkinson’s Disease: A Preliminary Study: Mayura Konzo, Masaru Narita, Masaki Naito, Ayumi Ide, Taiyo Kai, Dai Wakabayashi, Wataru Fujita, Tomohiro Shibata, Yohei Okada; J Mov Disord. 2026;19(2):203-207. Published online January 21, 2026; DOI: https://doi.org/10.14802/jmd.25317

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Abstract PDF Supplementary Material: Objective
In late-stage Parkinson’s disease (PD), wheelchair mobility becomes essential, yet little is known about the endurance and efficiency of wheelchairs. For individuals who struggle with manual wheelchair (MW) propulsion, a cycling wheelchair (CW) may provide an alternative. In this study, endurance and efficiency were compared between MWs and CWs during continuous driving, including turning tasks, in late-stage PD.
Methods
Nine participants with late-stage PD performed the 6-minute push test using both MWs and CWs. Total distance, average speed, and the Physiological Cost Index (PCI) were measured. The PCI was calculated from the pre- and post-driving heart rates.
Results
Compared with the use of MWs, the use of CWs resulted in a significantly greater total distance and a lower PCI, and similar patterns were observed among participants at Hoehn and Yahr stage V (n=6).
Conclusion
Compared with MW use, CW use may enable more enduring and efficient mobility in late-stage PD. Further studies are needed to validate these preliminary findings.

Original Articles

Longitudinal Implications of the BDNF rs6265 Polymorphism for Motor and Nonmotor Features of Parkinson’s Disease in the Korean Population: Sang-Won Yoo, Yun Joong Kim, Dong-Woo Ryu, Yoonsang Oh, Seunggyun Ha, Joong-Seok Kim; J Mov Disord. 2026;19(2):167-177. Published online January 20, 2026; DOI: https://doi.org/10.14802/jmd.25300

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Abstract PDF Supplementary Material

Objective
Brain-derived neurotrophic factor (BDNF) has been suggested to support the endurance and dopamine release of dopaminergic neurons. Its Val66Met polymorphism might modify Parkinson’s disease (PD) evolution, although evidence in Asian populations remains limited. This study aimed to explore how the BDNF rs6265 genotype is associated with the clinical characteristics and longitudinal progression patterns of PD patients in a Korean population.
Methods
A total of 247 patients were enrolled and followed for a mean duration of 50.9±23.9 months. Baseline and/or periodic assessments captured motor severity, nonmotor burden, cognition, orthostatic stress, cardiac denervation, and presynaptic dopamine transporter availability. The repeated measures were manipulated to infer any genotypic differences in the trajectories of each clinical domain.
Results
The genotype frequencies were 31.2% (77/247) for Val/Val carriers and 68.8% (170/247) for Met-allele carriers. Baseline clinical characteristics and presynaptic dopamine transporter availability were comparable between genotypes. Initially, Val homozygotes showed more preserved myocardial innervation and poorer nonfrontal cognitive performance. Longitudinal analyses demonstrated genotype-specific increases in motor and cognitive severity. Compared with Met-allele carriers, the homozygous Val group exhibited accelerated motor progression and a more rapid decline in the frontal domain after 3 years of follow-up.
Conclusion
The differences in myocardial denervation at diagnosis, cognitive profiles, and motor progression might suggest a potential modulatory role of BDNF polymorphisms in PD progression in the Korean population.

Citations

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Commentary for “Longitudinal Implications of the BDNF rs6265 Polymorphism for Motor and Nonmotor Features of Parkinson’s Disease in the Korean Population”
Sun Ju Chung
Journal of Movement Disorders.2026; 19(2): 242. CrossRef

Association Between Statin Use and Mortality in Adults With Parkinson’s Disease: A Nationwide Cohort Study: Mincheol Park, Hokyung Lee, Yeonju Jin, Sanghee Yoo, Sung-Woo Kim, Sojeong Park, Jiwon Hong, Jin Yong Hong, Ickpyo Hong, Min Seok Baek; J Mov Disord. 2026;19(2):157-166. Published online January 20, 2026; DOI: https://doi.org/10.14802/jmd.25240

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Abstract PDF Supplementary Material

Objective
The impact of statin use on the progression and survival of patients with Parkinson’s disease (PD) remains unclear. Moreover, evidence in Asian populations is limited. This study aimed to assess the associations between statin prescription, cumulative dosage, and all-cause mortality in PD patients.
Methods
This retrospective cohort study was conducted using sample data obtained from the Korean National Health Insurance Service (KNHIS) claims database. The study included 3,152 adults who were diagnosed with PD and whose history of statin use and cumulative dose information were obtained from claims records. Data were collected from the KNHIS database, and all eligible participants were followed longitudinally to determine all-cause mortality. The primary outcome was all-cause mortality, and the exposures were statin use (yes or no) and cumulative dose. The analysis was conducted using Cox proportional hazards regression adjusted for relevant covariates.
Results
Statin use was associated with a lower risk of all-cause mortality (hazard ratio [HR], 0.600; 95% confidence interval [CI], 0.521–0.691). Among statin users, a higher cumulative statin dose was linked to a further reduction in mortality (HR, 0.800; 95% CI, 0.761–0.842).
Conclusion
Statin use and increased cumulative exposure were associated with reduced all-cause mortality in patients with PD, and these findings suggest a potential survival benefit and warrant further investigation in diverse populations.

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Lovastatin Potentiates the Function of α7-Nicotinic Acetylcholine Receptors
Dmytro Isaev, Keun-Hang Susan Yang, Murat Oz
Pharmaceuticals.2026; 19(6): 849. CrossRef

Brief communication

Opicapone for the Treatment of Nocturnal Hypokinesia in Patients With Parkinson’s Disease: An Open-Label Pilot Clinical Trial: Chaewon Shin, Jong-Min Kim; J Mov Disord. 2026;19(1):81-85. Published online November 19, 2025; DOI: https://doi.org/10.14802/jmd.25250

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Abstract PDF Supplementary Material: Nocturnal hypokinesia (NH) is common in patients with moderate-stage Parkinson’s disease (PD). This open-label, single-arm pilot study aimed to assess the effect of bedtime opicapone administration on NH and to evaluate the clinical utility of the Nocturnal Hypokinesia Questionnaire (NHQ). The primary endpoint was the change in the NHQ score from baseline to week 6. Fifteen patients were included. The mean change in the NHQ score after the 6-week treatment was -0.9 points (95% confidence interval [CI]: -2.4, 0.5; p=0.187), which was not statistically significant. However, NHQ domain 2 (getting out of bed) significantly improved, with a mean change of -0.3 points (95% CI: -0.6, -0.1; p=0.025). The administration of opicapone in patients with PD and NH did not result in a significant improvement in NH, although it was associated with an improvement in the single domain of getting out of bed. Further studies are needed to establish the efficacy of opicapone for treating NH.

Original Articles

Effects of MAO-B and COMT Inhibitors on Sleep Disturbances in Patients With Parkinson’s Disease: A Network Meta-Analysis: Seon-Min Lee, Sung Ryul Shim, Kyum-Yil Kwon, Taeho Greg Rhee, Yu Jin Jung; J Mov Disord. 2026;19(1):67-75. Published online November 7, 2025; DOI: https://doi.org/10.14802/jmd.25253

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Abstract PDF Supplementary Material: Objective
Sleep disturbances are common and debilitating nonmotor symptoms (NMS) in Parkinson’s disease (PD) patients and profoundly affect quality of life. Despite emerging evidence suggesting that monoamine oxidase B (MAO-B) and catechol-O-methyltransferase (COMT) inhibitors may alleviate NMS, their specific effects on sleep remain unclear. The aim of this network meta-analysis (NMA) was to compare the efficacy of these inhibitors related to sleep problems in PD patients.
Methods
Following a systematic search of PubMed, Cochrane, and Embase, studies comparing MAO-B or COMT inhibitors and assessing sleep outcomes in PD patients were identified. An NMA was conducted using data from the seven studies that met our inclusion criteria. The outcomes included subjective sleep quality, daytime sleepiness, and objective polysomnography (PSG) parameters.
Results
No statistically significant differences were found between the effects of the MAO-B and COMT inhibitors on improving subjective sleep quality or daytime sleepiness. However, analyses of objective PSG data revealed that, compared with rasagiline and placebo, safinamide significantly increased rapid eye movement sleep duration (mean difference, 5.70 min [95% CI, 2.26 to 9.14]) and decreased wake time after sleep onset (mean difference, -10.20 min [-19.38 to -1.02]).
Conclusion
These findings suggest that safinamide may offer additional value for managing sleep disruptions beyond its known motor benefits in patients with PD. Given the limited number and small scale of available trials, the overall evidence should be interpreted cautiously. Nonetheless, this analysis highlights the need for future high-quality trials focused on sleep outcomes to guide the personalized use of MAO-B and COMT inhibitors for sleep disturbances in PD patients.

Impact of Additional Occipital Involvement in Parkinson’s Disease With Posterior Cortical Hypoperfusion: Chan Wook Park, Su Hong Kim, Phil Hyu Lee, Yun Joong Kim, Young H. Sohn, Yong Jeong, Seok Jong Chung; J Mov Disord. 2026;19(1):58-66. Published online November 7, 2025; DOI: https://doi.org/10.14802/jmd.25231

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Abstract PDF Supplementary Material: Objective
This study aims to investigate the clinical relevance of occipital hypoperfusion in patients with Parkinson’s disease (PD) with respect to clinical phenotype and the risk of dementia conversion.
Methods
We enrolled 349 patients with newly diagnosed PD and 48 healthy controls who underwent dual-phase ¹⁸F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (¹⁸F-FP-CIT) positron emission tomography (PET). Patients with PD were classified into three groups based on posterior cortical perfusion patterns on early-phase ¹⁸F-FP-CIT PET images: PD with preserved posterior cortical perfusion (n=186), PD with parieto-temporal hypoperfusion (n=84), and PD with parieto-temporo-occipital hypoperfusion (n=79). Baseline clinical features and dementia conversion risk were compared across PD groups.
Results
Patients with preserved posterior cortical perfusion were younger than those in the other PD groups. Compared with the other groups, the parieto-temporo-occipital hypoperfusion group tended to have lower Cross-Cultural Smell Identification Test scores, a higher prevalence of rapid eye movement sleep behavior disorder, higher Unified PD Rating Scale motor scores, and more severe reductions in striatal dopamine transporter availability. The risk of dementia conversion was lower in patients with preserved posterior cortical perfusion than in those with posterior cortical hypoperfusion. However, the risk of dementia conversion did not differ between the parieto-temporal and parieto-temporo-occipital hypoperfusion groups.
Conclusion
Additional occipital hypoperfusion was not associated with an imminent risk of dementia conversion in patients with PD with posterior cortical hypoperfusion. Nonetheless, occipital involvement may serve as an indicator of the diffuse malignant subtype of PD.

Conceptualizing a Personalized Care Pathway for Parkinson’s Disease Using Wearable Sensors in Muslim Patients: The Ramadan Regime: Vinod Metta, Huzaifa Ibrahim, Haidar Dafsari, Rajinder K. Dhamija, Hani T. S. Benamer, Tom Loney, Mishal Abu Al-Melh, Hasna Hussain, Afsal Nalarekttil, Guy Chung-Faye, Gloria Tanjung, Bushra Alblooshi, Shaikha Almazrouei, Bassam Darwish, Mohamed Al Mheiri, Mohamed Elmahdy, Rukmini Mridula, Sai Sampath Kumar, Vinay Goyal, Karolina Popławska-Domaszewicz, Cristian Falup Pecurariu, Prashanth Kukle, Jacob Chacko, Rupam Borgohain, Kallol Ray Chaudhuri; J Mov Disord. 2026;19(1):39-48. Published online September 30, 2025; DOI: https://doi.org/10.14802/jmd.25198

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Abstract PDF: Objective
Parkinson’s disease (PD) affects approximately 2% of individuals over the age of 60. With more than two billion Muslims observing Ramadan, individuals with PD encounter specific challenges, such as deteriorating motor skills, sleep disturbances, and an increased risk of falls during fasting.
Methods
Our study focused on 75 patients with idiopathic PD divided into two groups: the Ramadan Regime group, which consisted of 50 patients whose medication was adjusted to twice daily at Suhoor and Iftar, and the Nontreatment group, which included 25 patients who abstained from medication for religious reasons. Both groups were instructed to wear a Parkinson’s KinetiGraph (PKG) wrist device.
Results
The study findings revealed that motor function worsened in the Nontreatment group (p<0.001) but improved in the Ramadan Regime group (p=0.007). Daytime sleepiness also significantly increased in the Nontreatment group (p<0.001).
Conclusion
Overall, the findings suggest that the Ramadan regime significantly enhances patient health and quality of life.

Differential Peripheral NLRP3 Inflammasome Expression in Patients With Parkinson’s Disease and Patients With Multiple System Atrophy: Jeongjae Lee, Han-Joon Kim, Huu Dat Nguyen, Suk Jun Song, Trung Nguyen Thanh, In Hee Kwak, Hye Joung Choi, Hyeo-il Ma, Young Eun Kim; J Mov Disord. 2026;19(1):31-38. Published online September 30, 2025; DOI: https://doi.org/10.14802/jmd.25124

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Abstract PDF Supplementary Material: Objective
The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome has been proposed to be a downstream mediator of neuroinflammation in individuals with Parkinson’s disease (PD). However, its involvement across disease stages and related synucleinopathies, such as multiple system atrophy (MSA), remains unclear. We aimed to analyze the peripheral mRNA expression of NLRP3-related genes and cytokines across individuals with isolated REM sleep behavior disorder (iRBD), early-stage PD, late-stage PD, and MSA.
Methods
Peripheral blood mononuclear cells (PBMCs) were collected from 151 participants: 35 healthy controls (HCs), 31 patients with iRBD, 41 patients with early-stage PD, 21 patients with late-stage PD, and 23 patients with MSA. mRNA expression was measured using quantitative real-time polymerase chain reaction. Statistical comparisons were performed using analysis of variance (ANOVA) or Welch’s ANOVA, and associations with clinical variables were analyzed through stepwise multiple linear regression.
Results
NLRP3 expression was significantly lower in patients with iRBD (p=0.0263) and patients with early-stage PD (p= 0.0101) than in HCs. NIMA-related kinase 7 (NEK7) expression progressively decreased across the disease spectrum (HCs vs. patients with early-stage PD, p=0.0008; vs. patients with late-stage PD, p<0.0001). In contrast, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 were elevated in patients with PD, especially those in the late stages. Levels of patients with MSA resembled those of HCs but differed from those of patients with PD. Interleukin (IL)-1β and IL-18 levels were not significantly different. In patients with early-stage PD, NLRP3 expression was negatively correlated with disease duration, the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale Part II score, and the cognitive score.
Conclusion
Our findings challenge the prevailing hypothesis that NLRP3 inflammasome activation directly contributes to PD pathogenesis. Instead, the observed increase in ASC and caspase-1 expression suggests the potential involvement of alternative inflammasome pathways during disease progression.

Brief communication

Feasibility and Preliminary Efficacy of Digital Cognitive Training in Parkinson’s Disease With Mild Cognitive Impairment: A Pilot Study: Dongje Lee, Hang-Rai Kim, Yu Jeong Park, Yisuh Ahn, Daeho Lee, Jungyeun Lee, Su Jin Chung, Seung Yeon Kim, Yeji Hwang, Ji Young Yun, Jin Whan Cho, Kyum-Yil Kwon, Seong-Beom Koh, Sung Hoon Kang; J Mov Disord. 2026;19(1):76-80. Published online August 26, 2025; DOI: https://doi.org/10.14802/jmd.25135

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Abstract PDF Supplementary Material

Objective
Cognitive impairment is common in patients with Parkinson’s disease (PD), and few pharmacological options are available for treating this condition. We evaluated the effects of a digital cognitive training program (SUPERBRAIN), which was previously shown to be effective in populations at risk of Alzheimer’s disease, on cognitive function in individuals with PD.
Methods
Twenty-three individuals with PD and mild cognitive impairment (PD-MCI) from four clinics were randomized to the intervention (n=16) or control (n=7) groups. The intervention group completed a 12-week, home-based, tablet-based cognitive training program (25–30 min/day, 7 days/week). Cognitive outcomes were assessed using the Seoul Neuropsychological Screening Battery pre- and post-intervention.
Results
The adherence rate was 79.36%. The intervention group showed significant improvements in the Seoul Verbal Learning Test (SVLT) delayed recall and the Controlled Oral Word Association Test, while no changes were observed in the control group. Analysis of covariance confirmed greater SVLT improvement in the intervention group (F statistic=7.15, p=0.015, partial η²=0.28).
Conclusion
SUPERBRAIN is feasible and can improve cognitive function in individuals with PD-MCI.

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Integrated bio-cooperative robotic platform for virtual cognitive training in Parkinson's disease: design and methodology of the OPERA project
Cristina Polito, Giulia Martinelli, Sara Della Bella, Eleonora Pavan, Ylenia Crocetto, Simona Abagnale, Cristiana Rondoni, Alfonso Voscarelli, Marco Pirini, Francesco Scotto di Luzio, Loredana Zollo, Anna Estraneo
Frontiers in Neurology.2026;[Epub] CrossRef
Adherence to non-pharmacological interventions in patients with mild cognitive impairment: A scoping review
Qiuxia Qian, Jia Li, Ying Zhu, Yidan Li, Xuedan Wang, Jinhan Nan, Yu Zhu, Jianxun Cao, Yuxia Ma
Neuropsychological Rehabilitation.2026; : 1. CrossRef

Original Articles

Clinical Profile and Genetic Composition of Patients With Juvenile Parkinsonism From a Single Tertiary Care Center in India: Madathum Kuzhiyil Farsana, Vikram V Holla, Prashant Phulpagar, Nitish Kamble, Babylakshmi Muthusamy, Ravi Yadav, Pramod Kumar Pal; J Mov Disord. 2026;19(1):19-30. Published online August 19, 2025; DOI: https://doi.org/10.14802/jmd.25132

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Abstract PDF: Objective
Studies outlining the genetic architecture of Parkinson’s disease in India are sparse, and juvenile parkinsonism is underrepresented in the literature. The objective was to study the clinical, therapeutic, and genetic profiles of patients with juvenile parkinsonism and to correlate their phenotypic–genotypic characteristics.
Methods
This retrospective chart review was conducted in patients with suspected genetically mediated juvenile parkinsonism (onset ≤21 years) who underwent genetic testing at a tertiary care center in India from 2015–2024. The available phenotypic–genotypic characteristics were evaluated and compared between Gene (+) and Gene (-) patients.
Results
Forty patients (22 males, 55.0%) with juvenile parkinsonism were included, with mean ages at onset and presentation of 15.85±4.96 years and 26.37±10.11 years, respectively. The mean duration of illness was 10.43±10.49 years. A positive family history was present in 40.0% of the participants, and consanguinity was present in 45%. Bradykinesia was the most common motor symptom (95.0%), and cognitive impairment was the most common nonmotor symptom (17.5%). Pathogenic/likely pathogenic variants were identified in 27 patients (67.5%), with variants in PRKN being the most common (n=8 patients), followed by those in PLA2G6 (n=7 patients). Gene (+) patients had significantly more severe disease with a better levodopa response and more frequent familial consanguinity, oculomotor abnormalities, motor fluctuations, and dyskinesia. Compared with PARK-PRKN patients, PARK-PLA2G6 patients had significantly more dystonia, gaze restriction, and pyramidal signs and more severe disease at presentation, with a lower levodopa equivalent daily dose and fewer motor fluctuations.
Conclusion
More than two-thirds (67.5%) of the juvenile parkinsonism patients in our cohort had an underlying monogenic cause. PARK-PRKN, PARK-PLA2G6, and PARK-SYNJ1 are the common causes of genetically mediated juvenile parkinsonism in India.

Muscle Ultrasonography as a Diagnostic Tool for Assessing Sarcopenia in Parkinson’s Disease: Lay San Lim, Cheng-Hsien Lu, Yun-Ru Lai, Na-Ning Kan, Chien-Chang Liao, Sieh Yang Lee; J Mov Disord. 2025;18(4):347-354. Published online August 19, 2025; DOI: https://doi.org/10.14802/jmd.25072

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Abstract PDF Supplementary Material: Objective
This study aimed to evaluate the feasibility of muscle ultrasonography (US) as a diagnostic tool for assessing sarcopenia in patients with Parkinson’s disease (PD) to facilitate early detection and intervention to help prevent falls and enhance quality of life.
Methods
This prospective single-center study evaluated the diagnostic accuracy of US for identifying sarcopenia, using the Asian Working Group for Sarcopenia 2019 criteria as the reference. A total of 85 patients with PD, were recruited between June 2022 and August 2024, consisting of 31 individuals in the sarcopenic group and 54 in the nonsarcopenic group. We compared muscle thickness (MT), cross-sectional area (CSA), and shear wave velocity of the rectus femoris (RF), anterior tibialis (AT), and biceps brachii (BB) between the two groups. Statistical analyses included univariate analysis, correlation analysis, and binary logistic regression to develop a prediction model for sarcopenia.
Results
The sarcopenic group exhibited lower MT_BB, MT_AT, and CSA_AT than the nonsarcopenic group (all p<0.05). MT_BB, CSA_BB, and CSA_AT were significantly correlated with the appendicular skeletal muscle mass index and functional measures (all p<0.05). The prediction model, which included age, body mass index, and MT_BB as predictors, achieved an area under the curve of 0.857, with a sensitivity of 80.6% and a specificity of 79.6%.
Conclusion
US is a reliable and effective diagnostic tool for assessing sarcopenia in patients with PD, providing a practical approach for early identification of this condition.

Review Article

Cardiac ¹²³I-Meta-Iodobenzylguanidine Imaging as a Biomarker for Body-First Parkinson’s Disease: Linking Peripheral α-Synuclein to Clinical Subtyping: Dong-Woo Ryu, Sang-Won Yoo, Yoonsang Oh, Joong-Seok Kim; J Mov Disord. 2026;19(1):1-10. Published online August 4, 2025; DOI: https://doi.org/10.14802/jmd.25137

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Abstract PDF

Recent neuropathological and imaging studies support the concept of “brain-first vs. body-first” Parkinson’s disease (PD), which is based on the α-synuclein origin site and connectome model. The body-first phenotype is characterized by early involvement of the peripheral autonomic nervous system, particularly the cardiac sympathetic nerves and enteric nerves. ¹²³I-meta-iodobenzylguanidine (¹²³I-MIBG) myocardial scintigraphy is a well-established method for evaluating cardiac sympathetic innervation. This review explores the potential of ¹²³I-MIBG scintigraphy as a biomarker to differentiate the body-first phenotype from the brain-first phenotype. Reduced ¹²³I-MIBG uptake has been observed in idiopathic rapid eye movement (REM) sleep behavior disorder, pure autonomic failure, and incidental Lewy body disease—conditions strongly associated with prodromal or early-stage PD. Postmortem and biopsy evidence indicates α-synuclein accumulation in cardiac nerves and other peripheral sites, which is consistent with bottom-up progression. α-Synuclein seed amplification assays further corroborate the association between the peripheral α-synuclein burden and reduced ¹²³I-MIBG uptake. While ¹²³I-MIBG myocardial scintigraphy is a promising tool, its limitations include cost, limited availability, and potential confounding from underlying cardiac conditions. Nonetheless, early detection of cardiac sympathetic denervation via ¹²³I-MIBG imaging may enhance diagnosis, support subtype classification, and improve the understanding of PD pathogenesis.

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Letter to the editor: B-type natriuretic peptide in Parkinson's disease: a novel biomarker of dysautonomia
Manxing Zhou, Tianmei Zhou
Parkinsonism & Related Disorders.2026; 142: 108123. CrossRef
Human and Mouse Alpha-Synuclein Fibrillation: Impact on h-FTAA Binding and Advancing Strain-Specific Biomarkers in PD Animal Models
Priyanka Swaminathan, Vasileios Theologidis, Hjalte Gram, Debdeep Chatterjee, Per Hammarström, Nathalie Van Den Berge, Mikael Lindgren
International Journal of Molecular Sciences.2026; 27(9): 3807. CrossRef

Original Articles

Retro-Walking and Cholinergic Network Correlates in Parkinson’s Disease: Alexis Griggs, Giulia Carli, Taylor Brown, Prabesh Kanel, Stiven Roytman, Chatkaew Pongmala, Miriam van Emde Boas, Nicolaas Ida Bohnen; J Mov Disord. 2025;18(4):337-346. Published online July 30, 2025; DOI: https://doi.org/10.14802/jmd.25109

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Abstract PDF

Objective
To investigate the cholinergic underpinnings of forward and retro-walking in patients with Parkinson’s disease (PwP) using [¹⁸F]fluoroethoxybenzovesamicol ([¹⁸F]FEOBV) positron emission tomography (PET), which binds to the vesicular acetylcholine transporter.
Methods
We retrospectively included 44 PwP who underwent [¹⁸F]FEOBV PET imaging and forward- and retro-walking gait assessments. Voxelwise correlation analyses were performed to examine associations between gait velocities and [¹⁸F]FEOBV binding, controlling for levodopa equivalent dose and disease duration. Linear regression and mediation analyses were used to investigate the contribution of postural instability and gait disorder symptoms—measured using MDS-UPDRS items and the Mini-Balance Evaluation Systems Test (MiniBESTest)—as well as cognitive performance (attention, memory, executive, language, and visuospatial domains) to the observed associations.
Results
Slower retro-walking velocity was associated with lower [¹⁸F]FEOBV uptake in a subcortical–frontal–temporal cluster, including the bilateral middle frontal cortex, anterior cingulate, insula, basal forebrain, and striatal regions. No significant associations were found for forward walking time. Linear regression analyses revealed that MiniBESTest total score, reactive postural control subscore, and attention domain score were associated with both cholinergic uptake in the identified cluster and retro-walking velocities. Mediation analyses revealed that attention and reactive postural control mediated the relationship between [¹⁸F]FEOBV binding and retro-walking performance.
Conclusion
Our findings indicate that retro-walking places greater demands on brain cholinergic synaptic integrity involving subcortical-frontal and temporal cortical regions, subserving balance—particularly reactive postural control—and attentional resources compared to forward walking. Our results suggest that retro-walking might serve as part of an intervention strategy to improve balance and cognition in PwP.

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Utility of the 4-meter backward walking speed test in older adults with neurodegenerative diseases
Kubra Altunkalem Seydi, Derya Kaya, Idil Yavuz, Alev Cam Mahser, Feyza Mutlay, Fatma Sena Dost, Ahmet Turan Isik
Irish Journal of Medical Science (1971 -).2026;[Epub] CrossRef

Connectivity-Based Analysis of the Stimulation Effects of Globus Pallidus Interna Deep Brain Stimulation in Parkinson’s Disease: A Focus on Freezing of Gait: Sungyang Jo, Moongwan Choi, Jihyun Lee, Sangjin Lee, Hwon Heo, Chong Hyun Suh, Woo Hyun Shim, Junhyung Kim, Sang Ryong Jeon, Hyunna Lee, Sun Ju Chung; J Mov Disord. 2025;18(4):327-336. Published online July 30, 2025; DOI: https://doi.org/10.14802/jmd.25005

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Abstract PDF Supplementary Material

Objective
Freezing of gait (FOG) significantly affects quality of life and increases the risk of falls in patients with Parkinson’s disease (PD). Although deep brain stimulation (DBS) of the globus pallidus interna (GPi) is effective in managing motor complications, its efficacy in treating FOG remains inconsistent. This study aimed to determine whether preoperative structural brain connectivity can predict both the presence of FOG and its postoperative improvement following GPi DBS.
Methods
We retrospectively analyzed 58 patients with PD who underwent GPi DBS. Preoperative diffusion tensor imaging was used to assess structural connectivity between the volume of activated tissue (VAT) and 82 cortical regions. Machine learning models were developed to predict baseline FOG and postoperative FOG improvement (defined as a ≥1- or ≥2-point reduction) using demographic and connectivity features.
Results
Machine learning models incorporating structural connectivity features between the VAT and cortical regions—including the prefrontal, cingulate, and premotor cortices—outperformed models based solely on demographic variables in predicting both the presence of preoperative FOG and postoperative improvement. For example, the support vector machine model to predict FOG improvement (≥1-point improvement) achieved an accuracy of 0.65 with demographic data alone, which increased to 0.77 with the addition of structural connectivity features. Similar performance enhancements were observed in sensitivity analyses using stricter FOG thresholds (≥2-point improvement).
Conclusion
Preoperative structural connectivity between the GPi and key cortical regions involved in cognitive control and motor planning predicts FOG responsiveness to DBS. These results highlight the utility of connectomic biomarkers for personalizing DBS strategies and optimizing therapeutic outcomes in patients with advanced PD.

Citations

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Predictors of motor outcome with pallidal stimulation for Parkinson’s disease from the CSP468 cohort
Shawn D’Souza, Aashish Batheja, Jeffrey Chen, Harsh P. Shah, Vikram Seshadri, Nina Opem, Omar Al-Dulaimi, Jamie Toms, Pierre D’Haese, Benoit M. Dawant, Rui Li, Paul Koch, Paul Larson, Kathryn L. Holloway
npj Parkinson's Disease.2026;[Epub] CrossRef

Subtyping of Parkinson’s Disease by Longitudinal Trajectories of Levodopa Equivalent Daily Dose: Young-gun Lee, Kyoungwon Baik, Mincheol Park, Sung Woo Kang, So Hoon Yoon; J Mov Disord. 2025;18(4):317-326. Published online July 18, 2025; DOI: https://doi.org/10.14802/jmd.25099

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Abstract PDF Supplementary Material: Objective
Clinical heterogeneity exists in the optimal timing and dosage of symptomatic treatments for Parkinson’s disease (PD). This study aimed to cluster PD patients on the basis of longitudinal trajectories of levodopa equivalent daily dose (LEDD) and evaluate the clinical features and progression associated with these clusters.
Methods
From the Parkinson’s Progression Markers Initiative database, we enrolled 301 PD patients who were followed up for at least 3 years after the initiation of antiparkinsonian medications. On the basis of the longitudinal trajectories of the LEDD increment, the participants were classified into three clusters: slow-increment, initial-increment, and rapid-increment. The outcomes were initial and longitudinal changes in motor phenotype, on-time motor symptoms, and the efficacy of antiparkinsonian medications.
Results
The initial-increment cluster exhibited the greatest symptomatic improvements following the administration of higher doses of LEDD, although the motor improvement per unit of LEDD was comparable across clusters. Longitudinally, motor phenotypes changed rapidly in the initial-increment cluster. The initial-increment cluster showed continuous worsening of on-time motor symptoms, with limited LEDD efficacy. In contrast, the rapid-increment cluster exhibited stable on-time motor symptoms, whereas the efficacy of antiparkinsonian medications declined over time. The risk of disability related to walking and balance milestones and motor complications was twice as high in the initial-increment and rapid-increment clusters than in the slow-increment cluster.
Conclusion
Heterogeneity is noted in the increase in the use of antiparkinsonian medications, which is driven by changes in motor phenotype, medication efficacy, and the occurrence of PD-relevant milestones. Subtyping patients on the basis of LEDD trajectories may provide insight into clinical heterogeneity for future research on individualized treatment strategies for patients with PD.

Brief communication

The Effects of Biofeedback Therapy on Anxiety and Depression in Parkinson’s Disease: A Pilot Study: Justus Chun-Yu Chen, Tzu-Yun Tseng, Jong-Ling Fuh, Yu-Hsiang Cheng, Dai-Wei Lin, Han-Lin Chiang; J Mov Disord. 2025;18(4):360-364. Published online July 14, 2025; DOI: https://doi.org/10.14802/jmd.25097

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Abstract PDF Supplementary Material: Objective
This pilot study aimed to evaluate the feasibility and potential effects of biofeedback therapy (BT) on anxiety and depression among patients with Parkinson’s disease (PD).
Methods
A randomized waitlist-controlled trial was conducted involving 19 patients with PD and comorbid anxiety and/or depression. Anxiety and depression were assessed at baseline, posttreatment, and 1-month follow-up.
Results
All 19 patients completed the study. Compared with those of the control group, significant improvements in the Hamilton Depression Rating Scale and the anxiety subscale (but not the depression subscale) of the Hospital Anxiety and Depression Scale were observed immediately after BT. In the pooled analysis, the anxiolytic effect persisted at the 1-month follow-up, with greater improvements observed in those with more severe baseline anxiety.
Conclusion
These preliminary findings suggest that BT may help reduce anxiety symptoms among PD patients. Future studies with larger, more severely affected cohorts are needed to confirm these findings.

Review Articles

Longitudinal Multimodal Functional Imaging: An Essential Tool for Visualizing Pathologic Progression in Parkinson’s Disease: Antonio Martín-Bastida, María Cruz Rodríguez-Oroz; J Mov Disord. 2025;18(3):197-207. Published online June 8, 2025; DOI: https://doi.org/10.14802/jmd.24257

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Abstract PDF: Research on the pathophysiology of Parkinson’s disease (PD) has traditionally been performed with functional magnetic resonance imaging (fMRI); however, only a few studies have been conducted in longitudinal cohorts. In the present literature review, we aim to summarize the most recent progress in functional fMRI studies in prospective cohorts and, more specifically, in combination with other biomarkers to track the disease progression of PD. This review focuses on the potential application of multimodal longitudinal functional approaches based on the current evidence for the purpose of understanding disease progression and monitoring future therapeutic interventions.

MRI-Guided Focused Ultrasound in Parkinson’s Disease and Essential Tremor: Incisionless but Invasive. A Narrative Review: Vinod Metta, Hani Taha Sherif Benamer, Georgios Kapsas, Rukmini Mridula, Rajesh Alugolu, Hasna Hussain, Afsal Nalarakettil, Sampath Kumar Natuva Sai, Mohamed Elmahdy, Rupam Borgohain, Kallol Ray Chaudhuri; J Mov Disord. 2025;18(4):289-303. Published online June 4, 2025; DOI: https://doi.org/10.14802/jmd.25042

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Abstract PDF

Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging and promising technology for treating movement disorders, such as essential tremors and tremor-dominant Parkinson’s disease. MRgFUS utilizes advanced ultrasound transducer emitters to condense sound waves at a precisely defined point. This technology can target various brain areas, such as the pallidothalamic tract, thalamus, and pallidum, to ameliorate some of the symptoms of Parkinson’s disease and other movement disorders, such as dystonic and action-induced tremors. We review the current status of preclinical and clinical trials on the clinical use, treatment outcomes, and indications of MRgFUS.

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The quality and reliability of YouTube video resources concerning patient education for Parkinson’s disease: An electronic media-based study
Xin Liu, Shuaiyan Wang, LiZhen Gan, Yuhang Wang, Longkui Jiang
Journal of International Medical Research.2026;[Epub] CrossRef
Efficacy and safety of MRI-guided focused ultrasound lesioning for tremor-dominant Parkinson Disease: A systematic review and meta-analysis
Chao Sun, Yuejun Lin, Lingling Wang, Ying Wang
Neurosurgical Review.2026;[Epub] CrossRef
Levodopa–entacapone–carbidopa intestinal gel in advanced Parkinson’s disease: an analysis of interim data for Romanian patients enrolled in the ELEGANCE study
József Attila Szász, Alina Vasilica Blesneag, Traian Flavius Dan, Viorelia Adelina Constantin, Dafin Fior Mureşanu, Dragoş Cătălin Jianu, Any Axelerad, Delia Tulbă, Bogdan Ovidiu Popescu
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Tremor: Clinical Frameworks, Network Dysfunction and Therapeutics
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Brain Sciences.2025; 15(8): 799. CrossRef

Original Articles

Factors Associated With the Response to Exercise in Patients With Parkinson’s Disease: Myung Jun Lee, Jinse Park, Dong-Woo Ryu, Dallah Yoo, Sang-Myung Cheon; J Mov Disord. 2025;18(4):308-316. Published online May 16, 2025; DOI: https://doi.org/10.14802/jmd.25068

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Abstract PDF Supplementary Material: Objective
Exercises have been proposed as adjuvants for the treatment of Parkinson’s disease (PD); however, responses to exercise interventions have shown inconsistent results. We investigated the clinical factors associated with improvements in motor deficits after exercise.
Methods
A total of 85 patients with PD were enrolled from five tertiary hospitals and classified into four exercise groups: home exercise, strength training, Tai Chi, and yoga groups. Clinical measurements of the motor and nonmotor features of patients with PD were performed at baseline and 12 weeks after the exercise intervention. We employed principal component analysis (PCA) to reduce variables into ten factors and then examined associations of baseline characteristics with percentage improvement in the Movement Disorder Society sponsored Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS III) score via a Bayesian regression model.
Results
In the multivariate Bayesian regression model including ten PCA-derived factors, the percentage improvement in the MDS-UPDRS III score was associated with factors including prominent motor deficits (posterior interval [mean±standard deviation]: 2.5±1.5) and nonmotor symptoms such as depression, anxiety, and subjective memory impairment (3.3±1.7). Another factor related to functional impairments in gait and postural control was associated with less improvement after the exercise intervention (-3.9±1.7). According to the subgroup analyses, motor features were associated with improvements in the home exercise and strength training groups, whereas mood disturbance, fatigue, and subjective cognitive impairment were related to changes in the home exercise and Tai Chi groups.
Conclusion
Our results suggest that the individual phenotypes of patients with PD may be associated with clinical improvement following exercise.

Efficacy of Levodopa/Benserazide Dispersible Tablets on “Delayed ON ” to the First Morning Dose in Patients With Parkinson’s Disease With Motor Fluctuations: A Multicenter, Randomized, Open-Label, Crossover Trial: Hee Jin Chang, Jongkyu Park, Sohee Oh, Chaewon Shin, Ji Won Kim, Jin Whan Cho, Jee-Young Lee; J Mov Disord. 2025;18(3):244-252. Published online May 7, 2025; DOI: https://doi.org/10.14802/jmd.25031

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Abstract PDF Supplementary Material: Objective
Delayed ON is a condition in which Parkinson’s disease (PD) patients do not experience the effect of levodopa in time after taking the dosage. The ability of various oral levodopa regimens to overcome this problem has been poorly investigated. To evaluate the efficacy of levodopa/benserazide dispersible tablets in PD patients with delayed ON to the first morning dose.
Methods
This multicenter, randomized, crossover trial involved 40 eligible PD patients with delayed ON. The participants were randomized to receive either levodopa/benserazide 100 mg dispersible or regular tablets for 4 weeks, followed by a one-week wash-out interval and an alternate drug for another 4 weeks. Participants took the investigational drug with the first morning dose of their antiparkinsonian medications. Other medications were not changed during the trial. The primary outcome was changes in time-to-ON after the first-morning dose recorded in a special diary before and after each therapy. We also evaluated changes in parkinsonism, motor fluctuations, and dyskinesia using the Unified PD Rating Scale and the Unified Dyskinesia Rating Scale. Finally, we investigated whether efficacy was affected by Helicobacter pylori status via baseline serum samples from every participant.
Results
Nine patients dropped out during the trial. The time-to-ON was significantly reduced by the dispersible tablet compared with the regular tablet (-34.72 vs. -23.81 minutes, p=0.014). There were no significant changes in parkinsonian severity or dyskinesia with either drug. The dispersible formulation was beneficial for both Helicobacter pylori-positive and -negative groups.
Conclusion
Levodopa/benserazide dispersible formulations can improve time-to-ON without exacerbating dyskinesia in PD patients suffering from delayed ON.

Brief communication

Safety and Efficacy of Istradefylline in Parkinson’s Disease Patients With and Without Preexisting Dyskinesia: Pooled Analysis of 8 Randomized Controlled Trials: Nobutaka Hattori, Lawrence Elmer, Stuart H. Isaacson, Rajesh Pahwa, Olivier Rascol, Kapil Sethi, Fabrizio Stocchi, Yu Nakajima, Hannah Cummings, Lia Kostiuk; J Mov Disord. 2025;18(3):262-267. Published online April 25, 2025; DOI: https://doi.org/10.14802/jmd.25047

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Abstract PDF Supplementary Material: Objective
To evaluate the efficacy of istradefylline in Parkinson’s disease patients experiencing motor fluctuations with and without dyskinesia and characterize potential predictors for treatment-emergent dyskinesia with istradefylline.
Methods
Pooled analysis of 8 phase 2b/3 trials of istradefylline (20 or 40 mg/day) versus placebo.
Results
Data from 2,719 patients, 56% of whom presented with baseline dyskinesia, were analyzed post hoc. The presence of baseline dyskinesia did not affect the mean decrease in “OFF” time with dyskinesia, increase in “ON” time without troublesome dyskinesia, or improvement in the Unified Parkinson’s Disease Rating Scale motor score associated with istradefylline treatment. Dyskinesia was reported in 17% of patients receiving istradefylline, with higher rates for women (21%), patients with a BMI <18.5 kg/m² (22%), and patients receiving catechol-o-methyltransferase inhibitors plus dopamine agonists (22%) and monoamine oxidase B inhibitors (25%).
Conclusion
Istradefylline treatment resulted in greater reductions in total “OFF” hours/day and increases in “ON” time without troublesome dyskinesia than did placebo, regardless of the presence or absence of preexisting dyskinesia.

Original Articles

Factors Associated With the Decline in Daytime Bed Mobility Independence in Patients With Parkinson’s Disease: A Cross-Sectional Study: Masaru Narita, Kosuke Sakano, Yuichi Nakashiro, Fumio Moriwaka, Shinsuke Hamada, Yohei Okada; J Mov Disord. 2025;18(3):231-243. Published online April 25, 2025; DOI: https://doi.org/10.14802/jmd.25035

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Abstract PDF

Objective
People with Parkinson’s disease (PwPD) experience a gradual decline in bed mobility independence as the disease progresses. Identifying factors associated with nonindependence in daytime bed mobility is crucial for developing effective interventions to increase independence. We investigated factors associated with nonindependence in daytime bed mobility in PwPD.
Methods
This cross-sectional study included 109 PwPD (Hoehn and Yahr [HY] stage 2–4). Patients’ bed mobility ability (turning in bed, supine-to-sitting, and sitting-to-supine) was assessed during the daytime, and they were categorized into independent and nonindependent groups. Potential factors associated with bed mobility independence, including components of the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (rigidity, bradykinesia, tremor, axial symptoms), neck/trunk/hip strength, the Mini-Mental State Examination, and the Trail Making Test-A and B, were evaluated.
Results
The nonindependent group presented significantly increased axial symptoms, increased rigidity in the upper and lower limbs and neck, increased upper limb bradykinesia, and decreased trunk flexion/extension strength in all bed mobility tasks (p<0.05). Multivariate regression analyses revealed that axial symptoms, upper limb rigidity, and trunk extension strength were highly discriminative for nonindependence in turning in bed (the area under the curve [AUC]=0.84). Similarly, upper limb rigidity and axial symptoms were predictive of nonindependence in supine-to-sitting and sitting-to-supine movements (AUC=0.78, 0.92). A significant difference in axial symptoms between the HY stage 4 subgroups was observed only in the sitting-to-supine movement.
Conclusion
Our findings indicate that axial symptoms and upper limb rigidity are key factors contributing to nonindependence in daytime bed mobility tasks among PwPD. Targeting these factors in rehabilitation may help mitigate the decline in bed mobility independence in PwPD.

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Influence of Age on the Effectiveness of Lee Silverman Voice Treatment® BIG in Patients with Parkinson’s Disease: A Retrospective Exploratory Observational Study
Masanobu Iwai, Kazuya Takeda, Soichiro Koyama, Ikuo Motoya, Yuichi Hirakawa, Hiroaki Sakurai, Yoshikiyo Kanada, Nobutoshi Kawamura, Mami Kawamura, Shigeo Tanabe
Geriatrics.2026; 11(3): 63. CrossRef

Comparison of the Impact of Various Exercise Modalities on Parkinson’s Disease: Jinse Park, Sang-Myung Cheon, Myung Jun Lee, Dong-Woo Ryu, Dallah Yoo; J Mov Disord. 2025;18(3):222-230. Published online April 15, 2025; DOI: https://doi.org/10.14802/jmd.25038

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Abstract PDF Supplementary Material

Objective
Exercise is a critical nonpharmacological intervention for Parkinson’s disease (PD); however, comparative evidence on the efficacy of different exercise modalities is limited. This study aimed to compare the effects of tai chi, strength training, yoga, and home-based exercises on motor function in patients with PD.
Methods
In this multicenter, open-label, randomized clinical trial, 99 patients with PD were allocated to one of four exercise interventions: tai chi, strength training, yoga, or home-based exercises. Each intervention consisted of 12 weeks of supervised sessions, followed by 12 weeks of independent practice. The primary outcomes included the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III and timed up-and-go (TUG) test parameters. The assessed secondary outcomes included physical activity (measured via short physical performance battery and the 6-minute walking test [6MWT]), balance (measured via the Mini-BEST), and freezing of gait (measured via the New Freezing of Gait Questionnaire).
Results
Home exercise and tai chi demonstrated significant improvements in the MDS-UPDRS Part III scores over 24 weeks. The 6MWT was improved by home exercises and tai chi; additionally, the Mini-BEST test scores were enhanced by strength exercises and yoga. The total duration and forward movement of the TUG test, as well as the turning duration measured via the wearable sensor, were markedly improved in the yoga group.
Conclusion
Our results support the notion that various types of adherence to and outcomes of exercise can be observed in real-world settings, even though the effectiveness of exercise is well established. These findings highlight the importance of tailoring exercise regimens by considering individual patients in PD management.

Citations

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Telerehabilitation for Parkinson’s disease: a systematic review and meta-analysis based on randomized controlled trials
Renfei Li, Lili Wang, Jian Zhang
Neurological Sciences.2026;[Epub] CrossRef
Comparative Efficacy of 17 Rehabilitation Therapies Combined With Medication for Improving Gait Disorders and Quality of Life in Parkinson's Disease: A Network Meta-Analysis of 137 RCTs
Xinyu Lin, Haojie Li, Xie Wu
Archives of Physical Medicine and Rehabilitation.2026;[Epub] CrossRef
Instrumented Timed Up and Go (iTUG): A Systematic Review of Parameters Across Healthy, Older, and Neurological Populations
Piotr Szaflik, Katarzyna Nowakowska-Lipiec
Journal of Clinical Medicine.2026; 15(9): 3307. CrossRef
Summary of the best evidence for non-pharmaceutical interventions for mild cognitive impairment in Parkinson’s disease
Yud Dan Liu, Hui Fang Li, Ya Xian Zhai, Yun Xia Shen, Jinmei Yang, Li Mei He, Ting Shen
Frontiers in Neurology.2025;[Epub] CrossRef
Symptom Networks and Associations with Quality of Life in Patients with Early to Mid-Stage Parkinson’s Disease: A Network Analysis
Qiu Deng, Yaoling Duan, Zhengting Yang, Puqing Wang, Ziwei Liu, Min Zhou
Degenerative Neurological and Neuromuscular Disease.2025; Volume 15: 101. CrossRef
Factors Associated With the Response to Exercise in Patients With Parkinson’s Disease
Myung Jun Lee, Jinse Park, Dong-Woo Ryu, Dallah Yoo, Sang-Myung Cheon
Journal of Movement Disorders.2025; 18(4): 308. CrossRef

Brief communication

Current Status of Pelvic Lateral Shift in Patients With Parkinson’s Disease and Its Relationship With Lateral Trunk Flexion: Kyohei Mikami, Makoto Shiraishi, Akika Yoshimoto, Tsutomu Kamo; J Mov Disord. 2025;18(3):253-256. Published online April 15, 2025; DOI: https://doi.org/10.14802/jmd.25017

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Abstract PDF Supplementary Material: Objective
A lack of standardized methods for evaluating postural abnormalities hinders treatment progress. The role of pelvic lateral shift (PLS) in patients with Parkinson’s disease (PwP) exhibiting lateral trunk flexion (LTF) remains unclear. We hypothesized that PLS is related to LTF and investigated its characteristics and relationship with the LTF angle.
Methods
PwP attending outpatient rehabilitation (March 2018–March 2023) were assessed via still images. The PLS direction, its relationship with the LTF angle, and the LTF angle on the PLS side were analyzed.
Results
Among 158 patients, PLS was contralateral in 80 (50.6%), ipsilateral in 43 (27.2%), and absent in 35 (22.2%). In the contralateral PLS, but not in the ipsilateral PLS, the PLS angle was correlated with the LTF angle (r=0.48, p<0.001). The LTF angle was greater in the contralateral shift (8.5°±9.6°) than in the ipsilateral shift (2.8°±4.2°, p<0.001).
Conclusion
Based on the positive relationship between the LTF angle and contralateral shift angle, evaluation criteria that include PLS are needed for PwP with LTF.

Original Articles

Shoulder Dysfunction in Parkinson’s Disease: Implications of Motor Subtypes, Disease Severity, and Spinopelvic Alignment: Sieh Yang Lee, Lay San Lim, Yun-Ru Lai, Cheng-Hsien Lu; J Mov Disord. 2025;18(3):213-221. Published online April 8, 2025; DOI: https://doi.org/10.14802/jmd.25032

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Abstract PDF Supplementary Material

Objective
To investigate shoulder function and muscle alterations in patients with Parkinson’s disease (PD) and determine their associations with spinopelvic parameters and clinical status.
Methods
This prospective cohort study included 62 PD patients, divided into postural instability and gait difficulty (PIGD) (n=30) and non-PIGD (n=32) groups, as well as 35 controls. The American Shoulder and Elbow Surgeons (ASES) score, shoulder range of motion (ROM), and shoulder muscle stiffness were assessed for each group. Clinical demographics, PD severity, and shoulder-related parameters were extracted and analyzed.
Results
Compared with the control group, the PIGD group had significantly lower total and subscored ASESs (all p<0.05). Compared with the controls, both the PIGD and non-PIGD groups demonstrated reduced abduction and forward flexion (all p<0.05). Compared with the non-PIGD group and the control group, the PIGD group also presented decreased external rotation (all p<0.05). Infraspinatus muscle stiffness was greater in the PIGD group than in the control group (p=0.012). Correlation analysis revealed that shoulder condition was significantly associated with PD severity and the PIGD score, whereas muscle stiffness was linked to spinopelvic alignment and the PIGD score. Various clinical factors, including PD severity, the PIGD score, the tremor score, and spinopelvic alignment, were significantly correlated with shoulder ROM.
Conclusion
PD patients experience shoulder dysfunction in various ways, including decreased ASES scores, limited ROM, and increased shoulder muscle stiffness. Our study highlighted the impact of PD motor subtype, disease severity, and spinopelvic alignment on the development of shoulder dysfunction, offering deeper insights into the pathophysiological basis of shoulder disorders in PD.

Citations

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Efficacy of Suprascapular Nerve Block and Pulsed Radiofrequency for Chronic Shoulder Pain in Parkinson’s Disease
Atak Karabacak, Tuğçe Gezer Karabacak, Banu Özen Barut, Massimiliano Valeriani
Pain Research and Management.2026;[Epub] CrossRef

Feasibility of a Multidomain Intervention for Safe Mobility in People With Parkinson’s Disease and Recurrent Falls: Natalie E Allen, Lina Goh, Colleen G Canning, Catherine Sherrington, Lindy Clemson, Jacqueline CT Close, Stephen R Lord, Simon J G Lewis, Simone Edwards, Susan Harkness, Roslyn Savage, Lyndell Webster, Genevieve Zelma, Serene S Paul; J Mov Disord. 2025;18(2):149-159. Published online March 14, 2025; DOI: https://doi.org/10.14802/jmd.24237

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Abstract PDF Supplementary Material

Objective
Mobility limitations and falls are common in people with Parkinson’s disease (PwP). Compared with exercise alone, a tailored, multidomain intervention has the potential to be more effective in improving mobility safety and preventing falls. This study aimed to explore the feasibility and potential effectiveness of a multidomain fall prevention intervention (Integrate) designed for PwP who experience frequent falls.
Methods
The home-based intervention was delivered over a span of 6 months by occupational therapists and physiotherapists. The personalized intervention included home fall hazard reduction, exercise, and safer mobility behavior training. The participants received 8 to 12 home visits and were supported by care-partners (when necessary) to participate in the intervention.
Results
Twenty-nine people (recruitment rate: 49%; drop-out rate: 10%) with moderate to advanced Parkinson’s disease, a history of recurrent falls, and mild to moderate cognitive impairment participated in the study, with 26 people completing the study. A moderate-to-high adherence to the intervention was observed, and there were no adverse events related to the intervention. Twenty-one (81%) participants met or exceeded their safer mobility goal based on the Goal Attainment Scale. The participants exhibited a median 1.0-point clinically meaningful improvement according to the Short Physical Performance Battery. An exploratory analysis revealed that fall rates were reduced by almost 50% in the 6-month follow-up period (incidence rate ratio: 0.51; 95% confidence interval 0.28–0.92).
Conclusion
A multidomain occupational therapy and physiotherapy intervention for PwP experiencing recurrent falls was feasible and appeared to improve mobility safety. A randomized trial powered to detect the effects of the intervention on falls and mobility is warranted.

Citations

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Effects of a specific rehabilitation protocol on muscle mass and function in Parkinson’s disease: a multicenter prospective study
Alessandro de Sire, Nicola Marotta, Emanuele Prestifilippo, Claudio Curci, Lorenzo Lippi, Roberta Zito, Federica Pisani, Marco Invernizzi, Antonio Ammendolia, Kamal Mezian
Disability and Rehabilitation.2026; 48(7): 2104. CrossRef
A scoping review of safer mobility behaviour assessment and intervention: implications for people with Parkinson’s disease
Daniel Cheung, Jacqueline Wesson, Serene S. Paul, Lynette Mackenzie, Lina Goh, Colleen G. Canning, Lorena Rosa S. Almeida, Michael Enright, Natalie E. Allen
Disability and Rehabilitation.2026; 48(11): 3248. CrossRef
Shed Syndecans (1–3), ELA-32, BDNF, NLR, and hs-CRP in Parkinson’s Disease: Appropriate Diagnostic and Prognostic Biomarkers When Combined in a Unique Panel
Carmela Rita Balistreri, Daniele Magro, Letizia Scola, Paolo Aridon, Paolo Ragonese, Felipe Augusto Dos Santos Mendes, Giuseppe Schirò, Marco D’Amelio
International Journal of Molecular Sciences.2025; 26(10): 4503. CrossRef
Acceptability of a programme for safer mobility (INTEGRATE): Perspectives of people with Parkinson’s disease and their care-partners
Natalie E Allen, Annabel Darmali, Cecelia Koch, Sammi Tran, Serene S Paul, Colleen G Canning, Simone Edwards, Susan Harkness, Roslyn Savage, Lyndell Webster, Genevieve Zelma, Lina Goh
Clinical Rehabilitation.2025; 39(10): 1378. CrossRef

The Association between the Triglyceride-Glucose Index and the Incidence Risk of Parkinson’s Disease: A Nationwide Cohort Study: Yoonkyung Chang, Ju-young Park, Ji Young Yun, Tae-Jin Song; J Mov Disord. 2025;18(2):138-148. Published online February 27, 2025; DOI: https://doi.org/10.14802/jmd.24131

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Abstract PDF Supplementary Material

Objective
We aimed to investigate the associations of the triglyceride-glucose index, which measures insulin resistance, and the incidence of Parkinson’s disease.
Methods
Our study used the Health Screening Cohort database of the National Health Insurance Service of South Korea (2002–2019). We included 310,021 participants who had no previous history of Parkinson’s disease and for whom more than 3 triglyceride-glucose index measurements were available. A diagnosis of Parkinson’s disease was determined via the International Classification of Diseases Tenth edition (G20) with a specific reimbursement code for rare intractable diseases and a history of prescriptions for anti-Parkinsonism drugs.
Results
During a median of 9.64 years (interquartile range 8.72–10.53), 4,587 individuals (1.5%) had Parkinson’s disease. Based on a multivariable time-dependent Cox proportional hazards model, a per-unit increase in triglyceride-glucose index score was associated with a significantly increased risk of Parkinson’s disease (hazard ratio [HR]: 1.062; 95% confidence interval [CI] 1.007–1.119). In a sensitivity analysis, the triglyceride-glucose index was associated with the incidence of Parkinson’s disease in a non–diabetes mellitus cohort (HR: 1.093; 95% CI 1.025–1.165), but not in the diabetes mellitus cohort (HR: 0.990; 95% CI 0.902–1.087). In a restricted cubic spline analysis, the association between the triglyceride-glucose index and the incidence risk of Parkinson’s disease showed a nonlinear increasing (J-shaped) trend.
Conclusion
Our study demonstrated that higher triglyceride-glucose index scores were associated with the incidence of Parkinson’s disease in the general population, particularly in a nondiabetic mellitus cohort.

Citations

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Association between the triglyceride-glucose frailty index and Parkinson's disease in middle-aged and older adults: a comparative cross-national analysis of NHANES and CHARLS
Changze Ou, Binbin Chen, Haidong Yu, Jun Deng, Huajun Long
Parkinsonism & Related Disorders.2026; 145: 108240. CrossRef
Insulin Resistance Surrogates and Cognitive Impairment in Parkinson’s Disease: A Cross-Sectional Study with Interpretable Machine Learning
Hongming Liang, Yuru Jia, Hui Zhang, Danlei Wang, Haoheng Yu, Yongwen Yan, Jingyi Li, Liangkai Chen, Zheng Xue
Biomedicines.2026; 14(3): 493. CrossRef
Association between the triglyceride-glucose index and disease severity in non-diabetic Parkinson’s disease patients
Deyan Zeng, Min Luo, Baojun Zhang, Yan Zhang, Ailan Pang, Xinglong Yang
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Metabolic dysfunction and insulin resistance across major dementias: A comprehensive narrative review of the TyG index as a predictive marker
Moein Mirzai, Seyed Parsa Marouf, MohammadPooyan Eslami, Mohammad Hossein Nabian
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The interplay between obesity and triglyceride-glucose index in modulating Parkinson's disease risk: A cross-sectional NHANES study of middle-aged and young adults
Jincheng Ma, Mimi Li, Zhendong Lei
Parkinsonism & Related Disorders.2025; 140: 108070. CrossRef
Revisiting the Triglyceride–Glucose Index in Parkinson’s Disease: Risk Ractor or Disease Marker?
Shweta Prasad, Tarunya Nagaraj, Shubha GS Bhat, Mahima Bhardwaj, Pooja Mailankody, Rohan R Mahale, Nitish Kamble, Vikram Venkappayya Holla, Ravi Yadav, Pramod Kumar Pal
Journal of Movement Disorders.2025; 18(4): 389. CrossRef
Association of triglyceride glucose-waist to height ratio index with Parkinson’s disease and the mediating role of systemic inflammatory response index: A cross-sectional study
Keyu Shi, Zikai Pei, Sijie Quan, Yue Shi, Yi Zhou
Medicine.2025; 104(52): e46737. CrossRef

Review Article

Drug Repositioning and Repurposing for Disease-Modifying Effects in Parkinson’s Disease: Seong Ho Jeong, Phil Hyu Lee; J Mov Disord. 2025;18(2):113-126. Published online February 7, 2025; DOI: https://doi.org/10.14802/jmd.25008

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Abstract PDF

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder and is characterized by progressive dopaminergic and nondopaminergic neuronal loss and the presence of Lewy bodies, which are primarily composed of aggregated α-synuclein. Despite advancements in symptomatic therapies, such as dopamine replacement and deep brain stimulation, no disease-modifying therapies (DMTs) have been identified to slow or arrest neurodegeneration in patients with PD. Challenges in DMT development include disease heterogeneity, the absence of reliable biomarkers, and the multifaceted pathophysiology of PD, encompassing neuroinflammation, mitochondrial dysfunction, lysosomal impairment, and oxidative stress. Drug repositioning and repurposing strategies using existing drugs for new therapeutic applications offer promising approaches to accelerate the development of DMTs for PD. These strategies minimize time, cost, and risk by using compounds with established safety profiles. Prominent candidates include glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, ambroxol, calcium channel blockers, statins, iron-chelating agents, c-Abl inhibitors, and memantine. Although preclinical and early clinical studies have demonstrated encouraging results, numerous phase III trials have yielded unfavorable outcomes, elucidating the complexity of PD pathophysiology and the need for innovative trial designs. This review evaluates the potential of prioritized repurposed drugs for PD, focusing on their mechanisms, preclinical evidence, and clinical trial outcomes, and highlights the ongoing challenges and opportunities in this field.

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A Collaborative Approach to Creating Knowledge-Building Resources for the Early-Stage Parkinson’s Disease Community
Soania Mathur, Harold de Wit, Becky Jones, Evelyn Stevens, Angels Costa, Alexander Klein, Kate Trenam
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Automated ROI detection allows rapid quantification of synaptic activity across tens of thousands of synapses in cell culture
John Carl Begley, Harald Prüss, Paul Turko, Camin Dean
Frontiers in Synaptic Neuroscience.2026;[Epub] CrossRef
Teneligliptin, a DPP4 inhibitor protects dopaminergic neurons in PD models via inhibiting of oxidative stress and ferroptosis
Linting Huang, Jiakai Pi, Liqin Gu, Zirou Liao, Wenya Wang
European Journal of Pharmacology.2025; 1002: 177782. CrossRef
Deciphering the Janus‐Faced Nature of the Apolipoprotein Superfamily in Parkinsonian Neurodegeneration: Molecular Crosstalk Between the Astroglial Secretome and Neuronal Homeostasis
Yingying Dai, Mingxia Bi, Qian Jiao, Xixun Du, Xi Chen, Chunling Yan, Hong Jiang
Movement Disorders.2025; 40(11): 2299. CrossRef
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Therapeutic innovation through drug repurposing: A multidimensional approach toward treating Parkinson's disease
Saswati Swagatika Sahoo, Sudhir Kumar Paidesetty, Pratap Kumar Sahu, Swagata Pattanaik, Rambabu Dandela
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Brief communication

Modified Ratio of Tremor/Postural Instability Gait Difficulty Score as an Indicator of Short-Term Outcomes of Subthalamic Nucleus Deep Brain Stimulation in Parkinson’s Disease: Chakradhar Reddy, Kanchana Pillai, Shejoy Joshua, Anup Nair, Harshad Chavotiya, Manas Chacko, Asha Kishore; J Mov Disord. 2025;18(2):165-169. Published online January 2, 2025; DOI: https://doi.org/10.14802/jmd.24175

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Abstract PDF Supplementary Material: Objective
The outcomes of motor and nonmotor features of Parkinson’s disease (PD) following deep brain stimulation (DBS) vary among its subtypes. We tested whether preoperative motor subtyping using the modified tremor/postural instability and gait difficulty ratio (T/P ratio) could indicate the short-term motor, nonmotor and quality of life (QOL) outcomes of subthalamic nucleus (STN) DBS.
Methods
In this prospective study, 39 consecutive STN DBS patients were assessed in the drug-OFF state before surgery and subtyped according to the T/P ratio. Patients were reassessed 6 months after surgery in the stimulation ON-drug-OFF state, and the percentage changes in motor, nonmotor and QOL scores (Parkinson’s Disease Quality of Life Questionnaire [PDQ-39]) were calculated.
Results
The modified T/P ratio was moderately and positively correlated with the percentage change in the Unified Parkinson’s Disease Rating Scale III score in the OFF state, the sum of cardinal motor signs, the Non-Motor Symptom Scale score, and QOL (PDQ-39).
Conclusion
Preoperative PD motor subtyping can be used as an indicator of the short-term outcomes of STN DBS in PD patients.

Original Article

Gait Instability and Compensatory Mechanisms in Parkinson’s Disease Patients With Camptocormia: An Exploratory Study: Hideyuki Urakami, Yasutaka Nikaido, Yuta Okuda, Yutaka Kikuchi, Ryuichi Saura, Yohei Okada; J Mov Disord. 2025;18(2):127-137. Published online December 27, 2024; DOI: https://doi.org/10.14802/jmd.24226

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Abstract PDF Supplementary Material

Objective
Camptocormia contributes to vertical gait instability and, at times, may also lead to forward instability in experimental settings in Parkinson’s disease (PD) patients. However, these aspects, along with compensatory mechanisms, remain largely unexplored. This study comprehensively investigated gait instability and compensatory strategies in PD patients with camptocormia (PD+CC).
Methods
Ten PD+CC patients, 30 without camptocormia (PD-CC), and 27 healthy controls (HCs) participated. Self-paced gait tasks were analyzed using three-dimensional motion capture systems to assess gait stability as well as spatiotemporal and kinematic parameters. Unique cases with pronounced forward gait stability or instability were first identified, followed by group comparisons. Correlation analysis was performed to examine associations between trunk flexion angles (lower/upper) and gait parameters. The significance level was set at 0.05.
Results
Excluding one unique case, the PD+CC group presented a significantly lower vertical center of mass (COM) position (p=0.019) increased mediolateral COM velocity (p=0.004) and step width (p=0.013), compared to the PD-CC group. Both PD groups presented greater anterior‒posterior margins of stability than did the HCs (p<0.001). Significant correlations were found between lower/upper trunk flexion angles and a lower vertical COM position (r=-0.690/-0.332), as well as increased mediolateral COM velocity (r=0.374/0.446) and step width (r=0.580/0.474).
Conclusion
Most PD+CC patients presented vertical gait instability, increased fall risk, and adopted compensatory strategies involving greater lateral COM shift and a wider base of support, with these trends intensifying as trunk flexion angles increased. These findings may guide targeted interventions for gait instability in PD+CC patients.

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Immediate Effects of a Jewett Brace on Posture and Dynamic Balance in Parkinson’s Disease-Associated Camptocormia: A Case Report
Chisato Nakamoto, Kyota Bando, Yohei Mukai, Yuji Takahashi, Kazuhiko Seki, Takatoshi Hara
Cureus.2026;[Epub] CrossRef
How are we representing the trunk? A narrative review on marker sets for kinematics analysis of neurological conditions.
María B. Sánchez, Alberto Javier Fidalgo-Herrera, Bruno Mazuquin
Clinical Biomechanics.2026; 137: 106843. CrossRef

Brief communication

Spatiotemporal Gait Parameters During Turning and Imbalance in Parkinson’s Disease: Video-Based Analysis From a Single Camera: HoYoung Jeon, Jung Hwan Shin, Ri Yu, Min Kyung Kang, Seungmin Lee, Seoyeon Kim, Bora Jin, Kyung Ah Woo, Han-Joon Kim, Beomseok Jeon; J Mov Disord. 2025;18(1):87-92. Published online December 23, 2024; DOI: https://doi.org/10.14802/jmd.24210

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Abstract PDF Supplementary Material

Objective
This study aims to objectively evaluate turning gait parameters in Parkinson’s disease (PD) patients using 2D-RGB video-based analysis and explore their relationships with imbalance.
Methods
We prospectively enrolled PD patients for clinical assessment, balance analysis and gait with 180º turning. Spatiotemporal gait parameters during turning were derived using video-based analysis and correlated with modified Hoehn and Yahr (mHY) stages and center of pressure (COP) oscillations.
Results
A total of 64 PD patients were enrolled. The PD patients with higher mHY stages (≥2.5) had significantly longer turning times, greater numbers of steps, wider step bases and less variability in step length during turns. COP oscillations were positively correlated with the mean turning time on both the anterior-posterior and right-left axes.
Conclusion
Spatiotemporal gait parameter during turning, derived from video-based gait analysis, may represent apromising biomarker for monitoring postural instability in PD patients.

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Francesco Castelli Gattinara Di Zubiena, Alessandro Zampogna, Martina Patera, Giovanni Cusolito, Ludovica Apa, Ilaria Mileti, Antonio Cannuli, Antonio Suppa, Marco Paoloni, Zaccaria Del Prete, Eduardo Palermo
Sensors.2025; 25(16): 5054. CrossRef
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Danyeong Kim, Da-Eun Jeong, Hyunkyung Yi, Min Ju Kang
Dementia and Neurocognitive Disorders.2025; 24(4): 259. CrossRef
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Seungmin Lee, Minchul Kim, Kyu Sung Choi, Chanhee Jeong, Ri Yu, Jee-Young Lee, Jung Hwan Shin, Han-Joon Kim, Beomseok Jeon
Scientific Reports.2025;[Epub] CrossRef

Review Article

Non-Motor Fluctuations in Parkinson’s Disease: Underdiagnosed Yet Important: Iro Boura, Karolina Poplawska-Domaszewicz, Cleanthe Spanaki, Rosabel Chen, Daniele Urso, Riaan van Coller, Alexander Storch, Kallol Ray Chaudhuri; J Mov Disord. 2025;18(1):1-16. Published online December 20, 2024; DOI: https://doi.org/10.14802/jmd.24227

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Abstract PDF

Non-motor fluctuations (NMFs) in Parkinson’s disease (PD) significantly affect patients’ well-being. Despite being identified over two decades ago, NMFs remain largely underrecognized, undertreated, and poorly understood. While they are often temporally associated with motor fluctuations (MFs) and can share common risk factors and pathophysiologic mechanisms, NMFs and MFs are currently considered distinct entities. The prevalence and severity of NMFs, often categorized into neuropsychiatric, sensory, and autonomic subtypes, vary significantly across studies due to the heterogeneous PD populations screened and the diverse evaluation tools applied. The consistent negative impact of NMFs on PD patients’ quality of life underscores the importance of further investigations via focused and controlled studies, validated assessment instruments and novel digital technologies. High-quality research is essential to illuminate the complex pathophysiology and clinical nuances of NMFs, ultimately enhancing clinicians’ diagnostic and treatment options in routine clinical practice.

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Jing Chen, Xiaotong Feng, Danhua Zhao, Baoyu Chen, Chaobo Bai, Qi Wang, Yuan Li, Junyi Chen, Xintong Guo, Jinjin Wang, Lin Zhang, Junliang Yuan
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Post hoc exploratory analysis of the effect of foslevodopa/foscarbidopa continuous subcutaneous infusion on nocturia in patients with Parkinson’s disease
K. Ray Chaudhuri, Manon Bouchard, Eric Freire-Alvarez, Rajesh Pahwa, Lars Bergmann, Resmi Gupta, Pavnit Kukreja, Megha B. Shah, Stuart H. Isaacson
Clinical Parkinsonism & Related Disorders.2025; 12: 100330. CrossRef
Motor fluctuations in Parkinson disease – a mini-review of emerging drugs
Priti Gros, Laura Armengou Garcia, Susan H. Fox
Expert Opinion on Emerging Drugs.2025; 30(3): 179. CrossRef
Neuropsychiatric disorders in Parkinson’s disease
Beatrice Heim, Atbin Djamshidian
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Oscar Arias-Carrión, Emmanuel Ortega-Robles
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Ann Subota, Veronica Bruno
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Original Articles

Video-Oculography for Enhancing the Diagnostic Accuracy of Early Oculomotor Dysfunction in Progressive Supranuclear Palsy: Harshad Chovatiya, Kanchana Pillai, Chakradhar Reddy, Amiya Thalakkattu, Ayana Avarachan, Manas Chacko, Asha Kishore; J Mov Disord. 2025;18(1):77-86. Published online December 9, 2024; DOI: https://doi.org/10.14802/jmd.24171

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Objective
Oculomotor impairment is an important diagnostic feature of progressive supranuclear palsy (PSP) and PSP subtypes. We assessed the role of video-oculography (VOG) in confirming clinically suspected slow saccades in PSP and differentiating PSP from Parkinson’s disease (PD). We also measured the correlation of both saccadic velocity and latency in PSP patients with scores on the PSP Rating Scale, Montreal Cognitive Assessment, and frontal assessment battery. We assessed the frequency of apraxia of eyelid opening (ALO) and reflex blepharospasm in PSP and PD patients.
Methods
A total of 112 PSP patients with slow saccades but not gaze palsy, 50 PD patients, and 50 healthy controls (HCs) were recruited. The Movement Disorders Society task force-PSP and PD criteria were used for the diagnoses. All the subjects underwent VOG.
Results
Horizontal and vertical saccadic velocities and latencies differentiated PSP patients from PD patients and HCs (p<0.001). Vertical saccadic velocity and latency accurately differentiated PSP with predominant parkinsonism (PSP-P) patients from PD patients (p<0.001 and 0.012, respectively). A couple of vertical and horizontal saccadic velocities differentiated PSP-Richardson’s syndrome (PSP-RS) patients from PSP-P patients (vertical velocity of left eye: p=0.024; horizontal velocity of right eye: p=0.030). In vertical gaze, the mean velocity cutoff showed good sensitivity and specificity in differentiating PSP patients from HCs and PD patients. Prolonged horizontal gaze latency was associated with more severe PSP and worse global cognitive and frontal dysfunction. ALO and reflex blepharospasm were observed only in PSP patients.
Conclusion
VOG is useful for confirming slow saccades in PSP-RS and PSP-P patients and for differentiating PSP-P patients from PD patients. Prolonged horizontal gaze latency was associated with more severe PSP and worse cognitive dysfunction. ALO and reflex blepharospasm were observed only in PSP patients.

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Exploring eye movement abnormalities as objective biomarkers for Parkinson’s disease utilizing virtual reality-based eye tracking
Tingting Zhang, Chenhui Pei, Feng Jin, Yifan Zhou, Lina Tan, Jiaojiao Li, Da Wang, Huiling Zhou, Zhanhua Liang
BMC Neurology.2026;[Epub] CrossRef
Advances in ocular motor and pupil biomarkers for neurological disorders
Ana Coito, Dominik Brügger, Tatiana Brémovà-Ertl, Pia Massatsch, Mathias Abegg, Konrad P Weber, Anke Salmen
Brain Communications.2026;[Epub] CrossRef
Eye movement abnormalities in normal pressure hydrocephalus: a video-oculographic study
Alessio Facchin, Jolanda Buonocore, Giulia Sgrò, Alessia Cristofaro, Marianna Crasà, Chiara Camastra, Maria Grazia Vaccaro, Aldo Quattrone, Andrea Quattrone
Journal of Neurology.2025;[Epub] CrossRef
Toward Biology-Driven Diagnosis of Atypical Parkinsonian Disorders
Oscar Arias-Carrión, Elizabeth Romero-Gutiérrez, Emmanuel Ortega-Robles
NeuroSci.2025; 6(4): 107. CrossRef

Adjustability of Gait Speed in Clinics and Free-Living Environments for People With Parkinson’s Disease: Yuki Nishi, Shintaro Fujii, Koki Ikuno, Yuta Terasawa, Shu Morioka; J Mov Disord. 2024;17(4):416-424. Published online September 23, 2024; DOI: https://doi.org/10.14802/jmd.24167

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Objective
Gait speed is regulated by varying gait parameters depending on the diverse contexts of the environment. People with Parkinson’s disease (PwPD) have difficulty adapting to gait control in their environment; however, the relationships between gait speed and spatiotemporal parameters in free-living environments have not been clarified. This study aimed to compare gait parameters according to gait speed in clinics and free-living environments.
Methods
PwPD were assessed at the clinic and in a free-living environment using an accelerometer on the lower back. By fitting a bimodal Gaussian model to the gait speed distribution, gait speed was divided into lower and higher speeds. We compared the spatiotemporal gait parameters using a 2 × 2 (environment [clinic/free-living] × speed [lower/higher]) repeated-measures analysis of variance. Associations between Parkinson’s disease symptoms and gait parameters were evaluated using Bayesian Pearson’s correlation coefficients.
Results
In the 41 PwPD included in this study, spatiotemporal gait parameters were significantly worse in free-living environments than in clinics and at lower speeds than at higher speeds. The fit of the walking speed distribution to the bimodal Gaussian model (adjustability of gait speed) in free-living environments was related to spatiotemporal gait parameters, severity of Parkinson’s disease, number of falls, and quality of life.
Conclusion
The findings suggest that gait control, which involves adjusting gait speed according to context, differs between clinics and free-living environments in PwPD. Gait assessments for PwPD in both clinical and free-living environments should interpret gait impairments in a complementary manner.

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Risk of Falls and Need of Walking Aid in Parkinson's Disease: Incidence and Impact of Comorbidities
Louise‐Laure Mariani, Benjamin Dano, Marion Houot, Graziella Mangone, Fernando Pico, Olivier Rascol, Ana Marques, Pascal Derkinderen, Marie Vidailhet, Alexis Brice, Jean‐Christophe Corvol
Movement Disorders Clinical Practice.2026;[Epub] CrossRef
Multimodal machine learning mobility assessment in Parkinson’s disease within supervised and unsupervised settings
Y. Celik, H. Kuduz, F. V. Engin, F. Kacar, E. Tarakci, L. T. Pearson-Noseworthy, J. Das, S. Stuart, W. L. Woo, A. Godfrey
Journal of NeuroEngineering and Rehabilitation.2026;[Epub] CrossRef
Machine learning model to estimate momentary status of activities of daily living in people with early-stage Parkinson’s disease: an experimental study in home setting
Takazumi Ono, Shunsuke Maruoka, Yuya Yamaguchi, Junya Ogawa, Misato Nihei
Disability and Rehabilitation: Assistive Technology.2026; : 1. CrossRef
Gait Instability and Compensatory Mechanisms in Parkinson’s Disease Patients With Camptocormia: An Exploratory Study
Hideyuki Urakami, Yasutaka Nikaido, Yuta Okuda, Yutaka Kikuchi, Ryuichi Saura, Yohei Okada
Journal of Movement Disorders.2025; 18(2): 127. CrossRef
The Impact of Atrial Fibrillation on Physical Performance in Older Adults: A Longitudinal Study in Relation to Cognitive Function
Chiara Ceolin, Eleonora Mizzon, Marianna Noale, Adele Ravelli, Sabrina Pigozzo, Chiara Curreri, Bruno Micael Zanforlini, Enzo Manzato, Alessandra Coin, Maria Devita, Giuseppe Sergi, Marina De Rui
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A systematic review of real-world gait-related digital mobility outcomes in Parkinson’s disease
Cameron Kirk, Emma Packer, Ashley Polhemus, Mhairi K. MacLean, Harry Bailey, Felix Kluge, Heiko Gaßner, Lynn Rochester, Silvia Del Din, Alison J. Yarnall
npj Digital Medicine.2025;[Epub] CrossRef
Body composition, bone mineral density, and functional impairment in axial spondyloarthritis: a 36-month longitudinal study
Chiara Ceolin, Sara Bindoli, Giacomo Cozzi, Benedetta di Marzio, Mariagrazia Lorenzin, Marina De Rui, Paolo Sfriso, Andrea Doria, Giuseppe Sergi, Roberta Ramonda
BMC Musculoskeletal Disorders.2025;[Epub] CrossRef

Brief communications

Monitoring Cognitive Functions During Deep Brain Stimulation Interventions by Real Time Neuropsychological Testing: Ilaria Guarracino, Christian Lettieri, Massimo Mondani, Stanislao D’Auria, Giovanni Sciacca, Flavia Lavezzi, Miran Skrap, Serena D’Agostini, Gian Luigi Gigli, Mariarosaria Valente, Barbara Tomasino; J Mov Disord. 2024;17(4):442-446. Published online September 23, 2024; DOI: https://doi.org/10.14802/jmd.24102

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Objective
We monitored cognition in 14 Parkinson’s disease (PD) patients during deep brain stimulation (DBS) surgery when the electrode was positioned at the target subthalamic nucleus (STN) (i.e., the STN motor area).
Methods
We present the DBS-real-time neuropsychological testing (DBS-RTNT) protocol and our preliminary experience with it; we also compared the intraoperative patient performance with the baseline data.
Results
Compared with the baseline data, patients undergoing DBS-RTNT in the target area demonstrated a significantly decreased performance on some tasks belonging to the memory and executive function domains. Patients undergoing right hemisphere DBS-RTNT had significantly lower short-term memory and sequencing scores than did patients undergoing left hemisphere DBS-RTNT.
Conclusion
PD patient cognitive performance should be monitored during DBS surgery, as STN-DBS may induce changes. These preliminary data contribute to improving our understanding of the anatomo-functional topography of the STN during DBS surgery, which will enable the identification of the best site for producing positive motor effects without causing negative cognitive and/or emotional changes in individual patients in the future. In principle, medications (i.e., patients who underwent surgery in a levodopa-off state) could have influenced our results; therefore, future studies are needed to address the possible confounding effects of levodopa use.

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Use of a Novel Intraoperative Neurocognitive Monitoring Task During Awake Craniotomy for Tumor Resection in the Language-Dominant Parietal Lobe
Mercy H. Mazurek, Amy J. Maguire, James D. Sixkiller, Timothy R. West, Nicole A. Perez, Ethan A. Wetzel, Alexander F. Wang, Zsombor T. Gal, Reiner B. See, Eva K. Ritzl, Otto Rapalino, Bryan D. Choi, Brian V. Nahed
Operative Neurosurgery.2026;[Epub] CrossRef

Clinico-Genetic Profiles of Seven Patients With PINK1-Related Parkinson’s Disease: A Case Series From a Tertiary Care Centre in India and a Review of the Literature: Aravind Gunasekaran, Vikram V Holla, Prashant Phulpagar, Sneha D Kamath, Nitish Kamble, Ravi Yadav, Babylakshmi Muthusamy, Pramod Kumar Pal; J Mov Disord. 2024;17(4):436-441. Published online September 19, 2024; DOI: https://doi.org/10.14802/jmd.24157

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Abstract PDF Supplementary Material

Objective
Recessive variants in the PINK1 gene are known causes of early-onset Parkinson’s disease (EOPD). To describe the clinical features and genetic profiles of patients with PINK1-related Parkinson’s disease (PARK-PINK1) mutations.
Methods
We conducted a retrospective chart review of the demographic, clinical and genetic details of patients from our database carrying biallelic PINK1 variants.
Results
A total of 7 patients whose median age at onset was 33 years (range: 20–49) were recruited. All had asymmetrical onset, tremors were present in 4 patients, abnormal posturing was present in 2 patients, and slowness was present in 1 patient. The parkinsonism phenotype was noted in 6 patients (with dystonia in four) and isolated dystonia in one. Among the 6 patients with parkinsonism, five had rest tremors, all had good levodopa responses, and four had motor fluctuations with choreiform dyskinesia. Exome sequencing revealed biallelic pathogenic/likely pathogenic variants, five of which were novel.
Conclusion
PARK-PINK1 presents as an EOPD with tremor-predominant phenotype, good levodopa-responsiveness, early motor fluctuation and dyskinesia. We describe five novel variants in PINK1 gene.

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Genetic Sketch of Parkinson’s Disease in India
Suvorit S Bhowmick, Soaham D Desai
Annals of Indian Academy of Neurology.2025; 28(4): 495. CrossRef

Original Articles

Effect of Positional Changes on Cerebral Perfusion in Parkinson’s Disease Patients With Orthostatic Hypotension: Jae Young Joo, Dallah Yoo, Jae-Myoung Kim, Chaewon Shin, Tae-Beom Ahn; J Mov Disord. 2024;17(4):408-415. Published online September 9, 2024; DOI: https://doi.org/10.14802/jmd.24104

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Objective
Orthostatic hypotension (OH) is one of the most common autonomic dysfunctions in Parkinson’s disease (PD) patients. However, many patients with OH are asymptomatic. Conversely, orthostatic dizziness (OD) is not always associated with OH. We investigated the effects of positional changes on cerebral perfusion in patients with PD and OH.
Methods
We enrolled 42 patients, comprising 31 PD patients and 11 healthy controls. All the subjects underwent the following clinical assessments: the OH questionnaire, head-up tilt test (HUTT) with transcranial Doppler (TCD), near-infrared spectroscopy, measurement of the change in oxygenated hemoglobin (ΔHb_oxy) during the squat-to-stand test (SST), measurement of the time derivative of total hemoglobin (DHb_tot), and time taken to reach the peak (peak time [PT]) of DHb_tot after restanding.
Results
The mean flow velocity change (ΔMFV) in the TCD during the HUTT failed to differentiate between the PD-OH(+) and PD-OH(-) groups. The change in oxygenated hemoglobin ΔHb_oxy was greater in the PD-OH(+) group, which persisted for 9 min until the end of the HUTT only in the left hemisphere. During SST, PT was significantly delayed in the left hemisphere in PD-OH(+) patients.
Conclusion
Although TCD demonstrated no significant difference in ΔMFV, the parameters measured by near-infrared spectroscopy, such as ΔHb_oxy during HUTT and PT during the SST, significantly increased ΔHb_oxy or delayed PT in the left hemisphere of PD-OH(+). Positional changes have a detrimental effect on cerebral hemodynamics in patients with PD and OH, especially in the left hemisphere.

Citations

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Orthostatic hypotension in Parkinson’s disease: effects on clinical features and disease severity-a systematic review and meta-analysis
Hui Wang, Chi Zhang, Dongxun Xu
Frontiers in Aging Neuroscience.2025;[Epub] CrossRef
Prevalence and impact of orthostatic hypotension in Parkinson’s disease: a systematic review and meta-analysis
Hui Wang, Chi Zhang, Dongxun Xu
Clinical Autonomic Research.2025; 35(6): 697. CrossRef
Intersection of Autonomic Dysfunction and Parkinson’s Disease: Insights Into Neurogenic and Classical Orthostatic Hypotension
Jamir Pitton Rissardo, Masoumeh Rashidi, Fatemeh Rashidi, Khalil I Hmedat, Ibrahim Khalil, Hania Moharam, Mallak Bahar, Ali Dway, Omesh Prathiraja, Ana Leticia Fornari Caprara, Maleesha Jayasinghe
Cureus.2025;[Epub] CrossRef
Mapping cerebral blood flow in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and orthostatic intolerance: insights from a systematic review
Elena M. Christopoulos, Darcy Tantanis, Katherine Huang, Elena K. Schneider-Futschik, Paul R. Gooley, Kegan J. Moneghetti, Christopher W. Armstrong
Journal of Translational Medicine.2025;[Epub] CrossRef
The current state of wearable device use in Parkinson's disease: a survey of individuals with Parkinson's
Siegfried Hirczy, Cyrus Zabetian, Yi-Han Lin
Frontiers in Digital Health.2024;[Epub] CrossRef

Ocular Vestibular-Evoked Myogenic Potential Assists in the Differentiation of Multiple System Atrophy From Parkinson’s Disease: Keun-Tae Kim, Kyoungwon Baik, Sun-Uk Lee, Euyhyun Park, Chan-Nyoung Lee, Tonghoon Woo, Yukang Kim, Seoui Kwag, Hyunsoh Park, Ji-Soo Kim; J Mov Disord. 2024;17(4):398-407. Published online July 9, 2024; DOI: https://doi.org/10.14802/jmd.24120

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Objective
Vestibular-evoked myogenic potentials (VEMPs) can help in assessing otolithic neural pathway in the brainstem, which may also contribute to the cardiovascular autonomic function. Parkinson’s disease (PD) is associated with altered VEMP responses; however, the associations between VEMP abnormalities and multiple system atrophy (MSA) remain unknown. Therefore, we compared the extent of otolith dysfunction using ocular (oVEMP) and cervical VEMPs between patients with MSA and PD.
Methods
We analyzed the clinical features, VEMP, and head-up tilt table test (HUT) findings using the Finometer in 24 patients with MSA and 52 with de novo PD who had undergone neurotologic evaluation at a referral-based university hospital in South Korea from January 2021 to March 2023.
Results
MSA was associated with bilateral oVEMP abnormalities (odds ratio [95% confidence interval] = 9.19 [1.77–47.76], p = 0.008). The n1–p1 amplitude was negatively correlated with the Unified Multiple System Atrophy Rating Scale I-II score in patients with MSA (r = -0.571, p = 0.033), whereas it did not correlate with the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale-III score in patients with PD (r = -0.051, p = 0.687). The n1 latency was negatively correlated with maximum changes in systolic blood pressure within 15 s during HUT in patients with PD (r = -0.335, p = 0.040) but not in those with MSA (r = 0.277, p = 0.299).
Conclusion
Bilaterally abnormal oVEMP responses may indicate the extent of brainstem dysfunction in MSA. oVEMP reflects the integrity of otolith-autonomic interplay, reliably assists in differentiating between MSA and PD, and helps infer clinical decline.

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Balance biomarker for early differentiation of Parkinson’s disease and multiple system atrophy with parkinsonian type
Hee Jin Chang, Jong Ho Kim, Han-Wook Song, Sanghyun Lee, Eunjin Kwon, Seong-Hae Jeong, Eungseok Oh
Journal of Neurology.2026;[Epub] CrossRef
Saccadic variability in patients with Parkinson’s disease
Kyoungwon Baik, Seoyeon Byun, Seoui Kwag, Sarah Hyunsoh Park, Yukang Kim, Tonghoon Woo, Sun-Uk Lee, Chan-Nyoung Lee, Gerard J. Kim, Byung-Jo Kim, Ji-Soo Kim, Kun-Woo Park
Journal of Neurology.2026;[Epub] CrossRef
Vestibular Evoked Myogenic Potentials (VEMPs) in Parkinson’s Disease Patients with Monopolar Deep Brain Stimulation
Kim E. Hawkins, John Holden, Elodie Chiarovano, Simon J. G. Lewis, Ian S. Curthoys, Hamish G. MacDougall
Signals.2025; 6(1): 10. CrossRef
Update on Clinical Physiology and Pathomechanisms for Vestibulo-Autonomic Interplay
Sun-Uk Lee, Jeong-Yoon Choi
The Cerebellum.2025;[Epub] CrossRef
Selective otolithic dysfunction in patients presenting with acute spontaneous vertigo: consideration based on MRI
Keun-Tae Kim, Sangeun Park, Sun-Uk Lee, Euyhyun Park, Byungjun Kim, Ji-Soo Kim
Frontiers in Neurology.2024;[Epub] CrossRef

Pain Characteristics of Parkinson’s Disease Using Validated Arabic Versions of the King’s Parkinson’s Disease Pain Scale and Questionnaire: A Multicenter Egyptian Study: Ali Shalash, Salma R. Mohamed, Marwa Y. Badr, Shimaa Elgamal, Shaimaa A. Elaidy, Eman A. Elhamrawy, Hayam Abdel-Tawab, Haidy Elshebawy, Heba Samir Abdelraheem, Tamer Roushdy, Wafik S. Bahnasy, Haitham H. Salem, Ehab A. El-Seidy, Hatem S. Shehata, Hazem Marouf, K. Ray Chaudhuri, Eman Hamid; J Mov Disord. 2024;17(4):387-397. Published online June 25, 2024; DOI: https://doi.org/10.14802/jmd.24088

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Objective
Pain is one of the most common nonmotor symptoms in Parkinson’s disease (PD), with variable characteristics among populations. This multicenter Egyptian study aimed to translate and validate the King’s Parkinson’s Disease Pain Scale (KPPS) and Questionnaire (KPPQ) into Arabic versions and to investigate the pain characteristics in Egyptian people with PD (PWP).
Methods
A total of 192 PWP and 100 sex- and age-matched controls were evaluated by the KPPS-Arabic and KPPQ-Arabic. Both tools were assessed for test–retest reliability, floor or ceiling effects, construct validity and convert validity. PWP were also assessed by the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr scale (H&Y), Non-Motor Symptom Scale (NMSS), PD Questionnaire-39, and Non-Motor Fluctuation Assessment (NoMoFA).
Results
The KPPS-Arabic and KPPQ-Arabic showed inter- and intrarater consistency and high validity, with an acceptable ceiling effect. A total of 188 PWP (97.9%) reported at least 1 type of pain (p < 0.001). The severity and prevalence of all pain domains in the KPPS-Arabic were significantly higher among PWP than among controls (p < 0.001). Fluctuation-related and musculoskeletal pains were the most common (81.3% and 80.7%, respectively). In the PD group, the total and domains of KPPS-Arabic were significantly correlated to the MDS-UPDRS total score and the scores of Parts I, II, III, postural instability gait disorder, axial, and H&Y but not with age or age of onset. The predictors of KPPS-Arabic scores included the total MDS-UPDRS, the part III-OFF, disease duration, the total NMSS, and the NoMoFA scores.
Conclusion
The current multicenter study provided validated Arabic versions of the KPPS and KPPQ, which exhibited high reliability and validity, and demonstrated a high prevalence and severity of pain within Egyptian PWP and characterized its determinants.

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Clinical Outcome Assessments in Parkinson's Disease: A Scoping Review of Current Rating Scales and Future Needs
Evita Papathoma, Panagiota Tsitsi, Nirosen Vijiaratnam, Camila Aquino, Stephen R. Duma, Norbert Kovacs, Kigocha Lameck Okeng'o, Aparna Wagle Shukla, Roongroj Bhidayasiri, Tiago A. Mestre, Alvaro Sanchez Ferro, Alberto J. Espay, Michelle H.S. Tosin, Matej
Movement Disorders Clinical Practice.2026; 13(5): 1124. CrossRef
Test-retest reliability and construct validity of the King's Parkinson's Disease Pain Scale – Brazilian version
Rafaela Moura Santos Rocha, Iza de Faria-Fortini, Paula Luciana Scalzo
Clinical Neurology and Neurosurgery.2025; 251: 108814. CrossRef
Redefining Non-Motor Symptoms in Parkinson’s Disease
Laura Peña-Zelayeta, Karen M. Delgado-Minjares, Marcos M. Villegas-Rojas, Karen León-Arcia, Alberto Santiago-Balmaseda, Jesús Andrade-Guerrero, Isaac Pérez-Segura, Emmanuel Ortega-Robles, Luis O. Soto-Rojas, Oscar Arias-Carrión
Journal of Personalized Medicine.2025; 15(5): 172. CrossRef

Association Between Exposure to Particulate Matter and the Incidence of Parkinson’s Disease: A Nationwide Cohort Study in Taiwan: Ting-Bin Chen, Chih-Sung Liang, Ching-Mao Chang, Cheng-Chia Yang, Hwa-Lung Yu, Yuh-Shen Wu, Winn-Jung Huang, I-Ju Tsai, Yuan-Horng Yan, Cheng-Yu Wei, Chun-Pai Yang; J Mov Disord. 2024;17(3):313-321. Published online June 18, 2024; DOI: https://doi.org/10.14802/jmd.24003

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Objective
Emerging evidence suggests that air pollution exposure may increase the risk of Parkinson’s disease (PD). We aimed to investigate the association between exposure to fine particulate matter (PM2.5) and the risk of incident PD nationwide.
Methods
We utilized data from the Taiwan National Health Insurance Research Database, which is spatiotemporally linked with air quality data from the Taiwan Environmental Protection Administration website. The study population consisted of participants who were followed from the index date (January 1, 2005) until the occurrence of PD or the end of the study period (December 31, 2017). Participants who were diagnosed with PD before the index date were excluded. To evaluate the association between exposure to PM2.5 and incident PD risk, we employed Cox regression to estimate the hazard ratio and 95% confidence interval (CI).
Results
A total of 454,583 participants were included, with a mean (standard deviation) age of 63.1 (9.9) years and a male proportion of 50%. Over a mean follow-up period of 11.1 (3.6) years, 4% of the participants (n = 18,862) developed PD. We observed a significant positive association between PM2.5 exposure and the risk of PD, with a hazard ratio of 1.22 (95% CI, 1.20–1.23) per interquartile range increase in exposure (10.17 μg/m³) when adjusting for both SO₂ and NO₂.
Conclusion
We provide further evidence of an association between PM2.5 exposure and the risk of PD. These findings underscore the urgent need for public health policies aimed at reducing ambient air pollution and its potential impact on PD.

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Analysis of the spatial-temporal variability of PM2.5 mass and fine-ultrafine particle concentration in two sites of Southern Italy
A. Dinoi, F. Unga, A. Pennetta, D. Cesari, G. DeLuca, E. Bloise, P. Semeraro, A. Mangone, L. Giotta, M.G. Lionetto, M.R. Guascito, D. Contini
Atmospheric Environment: X.2026; 30: 100472. CrossRef
Environmental toxicants and Parkinson's disease: recent evidence, risks, and prevention opportunities
E Ray Dorsey, Briana R De Miranda, Sarrah Hussain, Bastiaan R Bloem, Alexis Elbaz, Jorge Llibre-Guerra, Raymond Y Lo, Samuel M Goldman, Caroline M Tanner
The Lancet Neurology.2025; 24(11): 976. CrossRef
A PLAN to address the Parkinson pandemic
E Ray Dorsey, Michael S Okun, Bastiaan R Bloem
Journal of Parkinson’s Disease.2025; 15(8): 1322. CrossRef

Fatigue in Parkinson’s Disease Is Due to Decreased Efficiency of the Frontal Network: Quantitative EEG Analysis: Min Seung Kim, Sanguk Park, Ukeob Park, Seung Wan Kang, Suk Yun Kang; J Mov Disord. 2024;17(3):304-312. Published online June 10, 2024; DOI: https://doi.org/10.14802/jmd.24038

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Objective
Fatigue is a common, debilitating nonmotor symptom of Parkinson’s disease (PD), but its mechanism is poorly understood. We aimed to determine whether electroencephalography (EEG) could objectively measure fatigue and to explore the pathophysiology of fatigue in PD.
Methods
We studied 32 de novo PD patients who underwent EEG. We compared brain activity between 19 PD patients without fatigue and 13 PD patients with fatigue via EEG power spectra and graphs, including the global efficiency, characteristic path length, clustering coefficient, small-worldness, local efficiency, degree centrality, closeness centrality, and betweenness centrality.
Results
No significant differences in absolute or relative power were detected between PD patients without or with fatigue (all p > 0.02, Bonferroni-corrected). According to our network analysis, brain network efficiency differed by frequency band. Generally, the brain network in the frontal area for theta and delta bands showed greater efficiency, and in the temporal area, the alpha1 band was less efficient in PD patients without fatigue (p < 0.0001, p = 0.0011, and p = 0.0007, respectively, Bonferroni-corrected).
Conclusion
Our study suggests that PD patients with fatigue have less efficient networks in the frontal area than PD patients without fatigue. These findings may explain why fatigue is common in PD, a frontostriatal disorder. Increased efficiency in the temporal area in PD patients with fatigue is assumed to be compensatory. Brain network analysis using graph theory is more valuable than power spectrum analysis in revealing the brain mechanism related to fatigue.

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Sohaila Alshimemeri, Abdullah M. Shadid, Ibrahim A. Alsannat, Nada K. Alamri, Raghad A. Almuslih
Neurological Sciences.2026;[Epub] CrossRef
Behavioral disorders in Parkinson disease: current view
Kurt A. Jellinger
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Functional connectivity in burnout syndrome: a resting-state EEG study
Natalia Afek, Dmytro Harmatiuk, Magda Gawłowska, João Miguel Alves Ferreira, Krystyna Golonka, Sergii Tukaiev, Anton Popov, Tadeusz Marek
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Pain and fatigue in Parkinson’s disease: advances in diagnosis and management
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The Impact of LRRK2 G2019S on Parkinson’s Disease: Clinical Phenotype and Treatment in Tunisian Patients: Guedi Ali Barreh, Ikram Sghaier, Youssef Abida, Alya Gharbi, Amina Nasri, Saloua Mrabet, Amira Souissi, Mouna Ben Djebara, Sameh Trabelsi, Imen Kacem, Amina Gargouri-Berrechid, Riadh Gouider; J Mov Disord. 2024;17(3):294-303. Published online April 23, 2024; DOI: https://doi.org/10.14802/jmd.23276

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Abstract PDF Supplementary Material

Objective
LRRK2-G2019S is the most frequent mutation in North African Parkinson’s disease (PD) patients. Data on its impact on disease progression and treatment response remain elusive. Therefore, we investigated the clinical features, treatments, and complications of PD in Tunisian patients according to their LRRK2-G2019S profile.
Methods
This longitudinal retrospective study was performed in the Department of Neurology, Razi University Hospital. We included clinically diagnosed PD patients according to the Movement Disorders Society criteria and reviewed their medical records for clinical, treatment, and neuropsychological assessments. All patients were screened for the LRRK2-G2019S mutation using Sanger sequencing. The correlation between LRRK2-G2019S and clinical PD features was evaluated.
Results
We included 393 PD patients, 41.5% of whom had LRRK2-G2019S mutations. Patients with mutations were younger (p = 0.017), and female PD patients had a greater mutation frequency (p = 0.008). Mutation carriers exhibited distinct clinical features, with a greater frequency of postural instability gait difficulty forms (adjusted-p < 0.001). During disease progression, carriers showed a faster annual progression in the Unified Parkinson’s Disease Rating Scale Section III scores (adjusted-p = 0.009), and significantly higher levodopa equivalent dose values in later stages (1060.81 vs. 877.83 for 6-8 years). Motor complications, such as dyskinesia (adjusted-p < 0.001) and motor fluctuations (31.9% vs. 25.7%, adjusted-p < 0.001), were more prevalent in carriers, particularly in the later stages. LRRK2-G2019S carriers also exhibited a lower prevalence of non-motor symptoms, including episodic memory (adjusted-p < 0.001), attention (adjusted-p < 0.001), and dysexecutive disorders (adjusted-p = 0.038), as well as neuropsychiatric symptoms and dysautonomic signs.
Conclusion
The present study demonstrated that the variability of the clinical profile among Tunisian PD patients was explained by the incomplete penetrance of LRRK2-G2019S, which increased with age. Further studies using biomarker and disease progression data are necessary to improve PD management.

Citations

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