Search Results (239)

Background/Objectives: Spatio-temporal gait parameters have been proposed as surrogate markers for objective, remote monitoring of global motor status in Parkinson’s disease (PD). Our observational, cross-sectional pilot study tested whether gait metrics, derived from wearable sensors, reflect dopaminergic responsiveness in both axial and appendicular functions. Methods: Twenty-two PD patients were evaluated both under and not under L-Dopa (ON and OFF states, respectively). Motor performance was assessed using wearable inertial sensors during standardized tasks involving gait and upper/lower limb movements. From the recorded kinematics, measures of movement amplitude, speed, rhythm, and consistency were extracted, and dopaminergic response was compared in appendicular and axial functions. Results: Treatment effects were more pronounced on the more affected body side. Improvements in appendicular amplitude, speed, and consistency closely matched those observed in spatio-temporal gait parameters. In contrast, rhythm measures displayed a divergent pattern, with reduced gait cadence but increased hand movement frequency, showing an inverse correlation. No significant correlations emerged between axial and appendicular domains for amplitude, velocity, or consistency, whereas improvements in step length and gait velocity were associated with MDS-UPDRS III motor scores. Conclusions: These findings overall suggest that specific gait metrics, particularly those reflecting amplitude and velocity, may provide reliable, sensor-based indicators of overall motor status in PD, supporting their use in remote monitoring. Full article

Background: This study aims to investigate the association between the presence and severity of non-motor symptoms (constipation, REM sleep behavior disorder [RBD], hyposmia, and depression) and the severity of motor impairment in Parkinson’s disease (PD). Methods: We used data from Parkinson’s Progression Markers Initiative (PPMI), comprising patients with established PD, prodromal PD, and healthy controls. Motor disability was evaluated with the MDS-UPDRS part III. Non-motor symptoms were assessed with standardized scales for constipation (MDS-UPDRS part I sub-item), depression (15-item GDS), RBD questionnaire (RBDQ), and hyposmia (UPSIT). The relationships between non-motor symptoms and motor severity were explored using linear regression models (adjusted for age/sex). Results: Constipation was significantly more prevalent in PD and prodromal PD and independently associated with greater motor severity in both groups (p < 0.001). Constipation also correlated with increased freezing and falls. Depressive symptoms were similar across groups, but in prodromal PD, higher GDS scores were associated with worse UPDRS III scores (p = 0.02), as well as higher freezing and fall scores. Hyposmia was strongly reduced in PD and prodromal PD compared with controls but was not independently associated with motor severity. Higher RBDQ scores were associated with worse motor impairment in PD, but not in prodromal PD after adjustment. Conclusions: Constipation and REM sleep behavioral disorder were independent correlates of worse motor severity in prodromal and established PD, whereas depressive symptoms predicted more severe parkinsonism only within the prodromal phase. Full article

Background/Objectives: Parkinson’s disease (PD) affects both articulatory and phonatory subsystems, leading to characteristic speech changes known as hypokinetic dysarthria. However, few studies have jointly analyzed these subsystems within the same participants using interpretable deep-learning-based measures. Methods: Speech data from the PC-GITA corpus, including 50 Colombian Spanish speakers with PD and 50 age- and sex-matched healthy controls were analyzed. We combined phonological feature posteriors—probabilistic indices of articulatory constriction derived from the Phonet deep neural network—with harmonics-to-noise ratio (HNR) as a laryngeal measure. Linear mixed-effects models tested how these measures related to disease severity (UPDRS, UPDRS-speech, and Hoehn and Yahr), age, and sex. Results: PD participants showed significantly higher [continuant] posteriors, especially for dental stops, reflecting increased spirantization and articulatory weakening. In contrast, [sonorant] posteriors did not differ from controls, indicating reduced oral constriction without a shift toward more open, approximant-like articulations. HNR was predicted by vowel height and sex but did not distinguish PD from controls, likely reflecting ON-medication recordings. Conclusions: These findings demonstrate that deep-learning-derived articulatory features can capture early, subphonemic weakening in PD speech—particularly for coronal consonants—while single-parameter laryngeal indices such as HNR are less sensitive under medicated conditions. By linking spectral energy patterns to interpretable phonological categories, this approach provides a transparent framework for detecting subtle articulatory deficits and developing feature-level biomarkers of PD progression. Full article

The LRRK2+ SAA− cohort of Parkinson’s disease (PD), characterized by the absence of hallmark α-synuclein pathology, remains under-explored. This limits opportunities for early detection and targeted intervention. This study analyzes data from this under-characterized subgroup and compares it with the LRRK2+ SAA+ cohort using longitudinal data from the Parkinson’s Progression Markers Initiative (PPMI). The PPMI dataset includes 115 LRRK2+ patients (70 SAA+, 45 SAA−) across 52 features encompassing clinical assessments, cognitive scores, DaTScan SPECT imaging, and motor severity. DaTScan binding ratios were selected as imaging-based indicators of early dopaminergic loss, while NP3TOT (MDS-UPDRS Part III total score) was used as a gold-standard clinical measure of motor symptom severity. Linear mixed-effects models were then applied to evaluate longitudinal predictors of DaTScan decline and NP3TOT progression, and statistical analyses of group comparisons revealed distinct drivers of symptoms differentiating SAA− from SAA+ patients. In SAA− patients, a decline in DaTScan was significantly associated with thermoregulatory impairment (p-value = 0.019), while NP3TOT progression was predicted by constipation (p-value = 0.030), sleep disturbances (p-value = 0.046), and longitudinal time effects (p-value = 0.043). In contrast, SAA+ patients showed significantly lower DaTScan values compared to SAA− (p-value = 0.0004) and stronger coupling with classical motor impairments, including freezing of gait (p-value = 0.016), rising from a chair (p-value = 0.007), and turning in bed (p-value = 0.016), along with cognitive decline (MoCA clock-hands test, p-value = 0.037). These findings support the hypothesis that LRRK2+ SAA− patients follow a distinct pathophysiological course, where progression is influenced more by autonomic and non-motor symptoms than by typical motor dysfunction. This study establishes a robust, multimodal modeling framework for examining heterogeneity in genetic PD and highlights the utility of combining DaTScan, NP3TOT, and symptom-specific features for early subtype differentiation. These findings have direct clinical implications, as stratifying LRRK2 carriers by SAA status may enhance patient monitoring, improve prognostic accuracy, and guide the design of targeted clinical trials for disease-modifying therapies. Full article

Background and Objectives: Apathy and sleep problems are frequently observed among non-motor symptoms (NMSs) in Parkinson’s disease (PD), but the relationship between the two has not been well investigated. This study aimed to determine the extent to which apathy and sleep disturbances are present in people with early PD and whether apathy affects sleep quality. Materials and Methods: Patients diagnosed with early PD, defined as modified Hoehn and Yahr (mHY) stages 1-3 and a disease duration of no more than 5 years, were included in the study. Demographic characteristics were collected, and motor and NMSs including apathy and sleep disturbance were investigated with relevant scales. Results: Of 302 patients with PD, apathy was found in 97 (32.1%) patients. Patients with apathetic PD had significantly less formal education, a more advanced mHY stage, and higher scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) part II, total Non-Motor Symptom Scale (NMSS), Beck Depression Inventory (BDI), Apathy Evaluation Scale (AES), and Pittsburgh Sleep Quality Index (PSQI) global scores than patients with non-apathetic PD. The PSQI global score showed significant associations with years of education, UPDRS-II, total NMSS, Mini-Mental State Examination, BDI, and AES scores. For each component of the PSQI, only sleep latency was different between patients with apathetic and non-apathetic PD. Partial correlation analyses for determining the association between apathy and sleep disturbance revealed a significant positive correlation. Conclusions: Apathy is common and associated with poor sleep quality in patients with early PD. These findings suggest that recognizing and addressing apathy may be relevant for managing sleep disturbances in this population. Full article

Background/Objective: Few treatment options improve symptoms and the quality of life of Parkinson’s disease (PD); more treatment choices are needed. This study examined the effectiveness of photobiomodulation therapy (PBMt) combined with exercise to improve PD symptoms and quality of life. Methods: Participants were randomised into Active (n = 32) or Sham (n = 31) PBMt groups. Stage 1 was an 8-week double-blind, randomised, placebo-controlled trial using either active or sham PBMt to the head, back of the neck and abdomen three times weekly at home, followed by a 4-week washout. Stage 2 was 8 weeks of active PBMt for all participants. In Stage 3, participants chose to continue active PBMt treatment (‘continuers’) or receive no PBMt treatment (‘non-continuers’) for up to 48 weeks. Participants continued vigorous exercise throughout the study. Participants were assessed on enrolment and after each stage. The primary outcome measure was timed up-and-go, with a range of secondary motor and non-motor outcomes, including UPDRS. Results: There was no significant difference between the Active and Sham Groups after Stages 1 or 2, apart from minimal increase in MoCA score/cognition (Sham Group) in Stage 1. After Stage 3, continuers showed a significant improvement in the primary outcome measure compared to non-continuers. Anxiety and the motor experiences of daily living (MDS-UPDRS Part II) were also significantly improved, while other outcomes approached significance, including MDS-UPDRS Total score (p = 0.062). Conclusions: As the largest study to date, results add increasing weight to previous clinical trials and highlight potential for at-home, scalable treatment as adjunctive therapy alongside medication and exercise. Full article

Parkinson’s disease (PD) is one of the fastest-growing neurodegenerative disorders; its cardinal motor signs—tremor, bradykinesia, and rigidity—substantially impair quality of life. Conventional clinician-rated scales can be subjective and exhibit limited interrater reliability, underscoring the need for objective and reliable quantification. We present an integrated evaluation framework that leverages surface electromyography (sEMG) with multimodal sensing. For representation learning, we combine time–frequency descriptors with Mini-ROCKET features. Grading is performed by an sEMG-based Unified Parkinson’s Disease Rating Scale (UPDRS) model (LDA-SV) that produces per-segment probabilities for ordinal scores (0–3) and aggregates them via soft voting to assign item-level ratings. Participants completed a standardized protocol spanning gait, seated rest, and upper-limb tasks (forearm pronation–supination, finger-to-nose, fist clench, and thumb–index pinch). Using the aforementioned dataset, we report task-wise performance with 95% confidence intervals and compare the proposed model against CNN, LSTM, and InceptionTime using McNemar tests and log-odds ratios. The results indicate that the proposed model outperforms the three baseline models overall. These findings demonstrate the effectiveness and feasibility of the proposed approach, suggesting a viable pathway for the objective quantification of PD motor symptoms and facilitating broader clinical adoption of sEMG in diagnosis and treatment. Full article

Background: Parkinson’s disease (PD) is a neurodegenerative condition that affects quality of life due to motor (gait, balance) and cognitive alterations, raising the risk of falling. Virtual reality (RV) and dancing have shown benefits for speed of walking, balance, and postural stability, as well as decreased risk of falls. Objective: The goal of this study was to analyze the effectiveness of RV and dancing using a Kinect Xbox 360 video game to improve walking speed and motor performance and reduce the risk of falls in patients with PD. Method: This is a pre-experimental study with a simple pre-post design, involving a single group of 14 patients diagnosed with PD in stages 1 to 4 of the Hoehn and Yahr (H and Y) scale, from the National Institute of Neurology (INNN). Before and after the intervention, motor tests, the Unified Parkinson’s Disease Rating Scale (UPDRS-III), the Timed Up and Go (TUG) test, and the Tinetti were applied. The intervention consisted of 16 bi-weekly sessions, which included warm-up, coordination exercises, 10 songs, and cool-down. Results: Effects of the RV intervention were observed on improvements in motor tests (z = −2.640, p = 0.008), gait (z = −3.316, p = 0.001), balance (TUG) (z = −2.966, p = 0.001), and on the UPDRS-III scale (total index) (z = −3.048, p = 0.002). An increase in the difficulty level of dancing was also observed (X² = 144.13, p < 0.01). Conclusions: The virtual reality intervention with dancing improved motor performance, including increased walking speed, enhanced postural stability, reduced stiffness and bradykinesia, and a decreased risk of falls Full article

Deep brain stimulation (DBS) is an established neurosurgical treatment for Parkinson’s disease (PD), mainly targeting motor symptoms resistant to pharmacological therapy. This review examines strategies to optimize DBS using advanced anatomical, functional, and imaging approaches. The subthalamic nucleus (STN) remains the principal target for alleviating bradykinesia and rigidity, while recent evidence highlights the dentato-rubro-thalamic tract (DRTt) as an additional promising target, especially for tremor control. Clinical data demonstrate that co-stimulation of both STN and DRTt via electrode electric fields results in superior motor outcomes, including greater reductions in UPDRS-III scores and lower levodopa requirements. The review highlights the use of high-resolution MRI and diffusion tensor imaging tractography in visualizing STN and DRTt with high precision. These methods support accurate targeting and individualized treatment planning. Electric field modelling is discussed as a tool to quantify stimulation overlap with target structures and predict clinical efficacy. Anatomical variability in DRTt positioning relative to the STN is emphasized, supporting the need for patient-specific DBS approaches. Alternative and emerging DBS targets—including the pedunculopontine nucleus, zona incerta, globus pallidus internus, and nucleus basalis of Meynert—are discussed for their potential in treating axial and cognitive symptoms. The review concludes with a forward-looking discussion on network-based DBS paradigms, the integration of adaptive stimulation technologies, and the potential of multimodal imaging and electrophysiological biomarkers to guide therapy. Together, these advances support a paradigm shift from focal to network-based neuromodulation in PD management. Full article

Parkinson’s disease (PD) is characterized by motor symptoms, with key diagnostic features, such as rigidity, traditionally assessed through subjective clinical scales. This study proposes a novel hybrid framework integrating model-driven biomechanical features (damping ratio, decay rate) and data-driven statistical features (maximum detail coefficient) from wearable sensor data during a modified pendulum test to quantify shoulder girdle rigidity objectively. Using weak supervision, these features were unified to generate robust labels from limited data, achieving a 10% improvement in PD/healthy control classification accuracy (0.71 vs. 0.64) over data-driven methods and matching model-driven performance (0.70). The damping ratio and decay rate, aligning with Wartenberg pendulum test metrics like relaxation index, revealed velocity-dependent aspects of rigidity, challenging its clinical characterization as velocity-independent. Outputs correlated strongly with UPDRS rigidity scores (r = 0.78, p < 0.001), validating their clinical utility as novel biomechanical biomarkers. This framework enhances interpretability and scalability, enabling remote, objective rigidity assessment for early diagnosis and telemedicine, advancing PD management through innovative sensor-based neurotechnology. Full article

Autonomic dysfunction is a key non-motor feature of Parkinson’s disease (PD) and may influence motor performance, particularly gait. While heart rate variability (HRV) has been associated with freezing of gait, its relationship with broader gait parameters remains unclear. The objective was to investigate correlations between resting-state HRV time-domain measures and spatiotemporal gait parameters during comfortable and fast walking in patients with idiopathic PD. Twenty-eight PD patients (mean age 68 ± 9 years) were evaluated at Campus Bio-Medico University Hospital. HRV was recorded at rest using the e-Sense pule™ portable sensor, including the Baevsky’s Stress Index a measure increasing with sympathetic burden. Gait parameters were assessed via the 10 m Timed Up and Go (TUG) test using the Mon4t™ smartphone app at comfortable and fast pace. Clinical data included UPDRS III, MoCA, and disease characteristics. Gait metrics significantly changed between walking conditions. HRV parameters clustered separately from gait metrics but intersected with significant correlations. Higher Stress Index values, reflecting sympathetic dominance, were associated with poorer gait performance, including prolonged transition times, shorter steps, and increased variability (p < 0.001, r = 0.57–0.61). MoCA scores inversely correlated with the Stress Index (r = −0.52, p = 0.004), linking cognitive and autonomic status. UPDRS III and MoCA were related to TUG metrics but not HRV. Time-domain HRV measures, particularly the Stress Index, are significantly associated with spatiotemporal gait features in PD, independent of gait speed. These findings suggest that impaired autonomic regulation contributes to functional mobility deficits in PD and supports the role of HRV as a biomarker in motor assessment. Full article

Background: Alterations in peripheral red blood cell (RBC) indices have been proposed as potential biomarkers for Parkinson’s disease (PD), but their diagnostic utility and relation to clinical features remain uncertain. Methods: We conducted a pilot case–control study involving 70 PD patients and 122 controls from two neurology centers in Mexico. Standardized hematology analyses provided RBC indices, and neuropsychiatric assessments included the Hamilton Depression Rating Scale (HAM-D) and Mini-Mental State Examination (MMSE). Associations between RBC indices and PD were tested using multivariable logistic regression adjusted for age, sex, and smoking. Diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analysis. Subgroup analyses stratified PD patients by age at onset, disease duration, and Hoehn and Yahr (HY) stage. Results: PD patients exhibited significantly higher mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) than controls. Elevated MCHC was independently associated with PD (OR = 1.68, 95% CI 1.35–2.09; p < 0.001). Sex-stratified models confirmed consistent associations in women (OR = 1.57) and men (OR = 1.79). ROC analysis demonstrated fair diagnostic accuracy for MCHC (AUC 0.72, 95% CI 0.65–0.80; cutoff 33.9 g/dL, sensitivity 62.9%, specificity 72.1%). Sex-specific thresholds improved sensitivity in women (90.6%) and specificity in men (74.6%). Within the PD group, MCHC did not differ by HY stage or disease duration, and showed no correlation with UPDRS, HAM-D, or MMSE scores. Early-onset cases (<50 years) showed numerically higher MCHC, though numbers were limited. Conclusions: This pilot study confirms that an elevated MCHC is independently associated with PD, a finding consistent across both sexes and independent of disease severity. MCHC demonstrates fair diagnostic performance, supporting its potential as a low-cost, accessible biomarker. Larger longitudinal studies integrating RBC indices with inflammatory and iron-regulatory markers are warranted to establish their role in the diagnosis and differential diagnosis of PD. Elevated MCHC was associated with PD, and an MCHC-based index (cutoff 33.9 g/dL; AUC 0.72, sensitivity 62.9%, specificity 72.1%) showed potential as a simple diagnostic marker. Full article

We investigated associations between apolipoprotein E (APOE) alleles and motor manifestations in Alzheimer’s dementia (AD) capitalizing on National Alzheimer’s Coordinating Center data: the baseline evaluations of older adults (≥60 years) with a diagnosis of AD were analyzed. Those with a concomitant diagnosis Parkinson’s disease or other parkinsonian syndrome, and those treated with anti-parkinsonian agents were excluded. Three APOE groups were formed: APOE2 (APOE2 carriers), APOE3 (APOE3/APOE3) and APOE4 (APOE4/APOE4, APOE4/APOE3). UPDRS-III was used to assess the presence or absence of motor signs in 9 domains. Adjusted binary logistic models featuring the three APOE groups as exposures and motor domains as outcomes were estimated. There were 389 individuals in the APOE2, 1799 in the APOE3 and 2791 in the APOE4 groups. Compared to the APOE2 group, individuals in the APOE4 group had lower odds of having at least one motor sign [0.64 (0.50–0.82)]. Among motor signs, rigidity [0.53 (0.34–0.81)], bradykinesia [0.56 (0.40–0.77)], impaired chair rise [0.54 (0.37–0.78)] and impaired posture-gait [0.54 (0.36, 0.81)] exhibited significant associations. Exploratory analyses featuring APOE genotypes suggested dose–response relationships for both APOE2 and APOE4. In conclusion, APOE2 confers a risk towards motor (mainly parkinsonian) signs in AD. APOE4 may have a protective effect. Full article

Tavapadon, a novel oral dopamine-D1R/D5R partial agonist, has been studied in recent years for the treatment of late-stage development Parkinson’s disease (PD). Levodopa, a dopamine precursor that currently remains the gold-standard first-line therapy for PD motor symptoms, serves as a benchmark against emerging dopaminergic agents. By selectively activating D1-family receptors on direct-pathway medium neurons, Tavapadon differs in that it delivers levodopa-level motor benefit while avoiding its many D2R/D3R-mediated adverse effects. In placebo-controlled trials, Tavapadon produced clear, clinically meaningful gains in motor function and day-to-day activities, as captured by the Unified Parkinson’s Disease Rating Scale (UPDRS). Recent late-stage results have revealed that Tavapadon maintains superior UPDRS outcomes in de novo patients and, when added to levodopa, extended “ON” time periods of reliable motor control free of troublesome dyskinesia, without introducing new safety concerns. In studies, nausea, headache, and somnolence were the most frequent adverse events. Hallucinations, orthostatic hypotension, and impulse-control disorders remained comparable to placebo, reflecting minimal D2R/D3R-mediated effects. Preclinical primate studies have demonstrated levodopa-like motor rescue with markedly less dyskinesia, a pattern mirrored in clinical add-on trials. Collectively, evidence indicates that Tavapadon can match levodopa-mediated symptomatic efficacy, lower dyskinesia liability compared with levodopa or earlier full D1 receptor (D1R) agonists, and offer the convenience of once-daily dosing characteristics, which may bridge the therapeutic gap between levodopa and the current D2R/D3R agonists in PD management. In the present investigation, the emerging clinical role for Tavapadon is described, along with the mechanism of action, clinical efficacy, safety, and future directions. Full article

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms, including autonomic dysfunction. Structural alterations in the vagus nerve (VN) may contribute to PD pathophysiology, though existing data remain inconsistent. Objective: This study aimed to evaluate morphological changes in the VN using high-resolution ultrasound (USVN) and to investigate associations with autonomic symptoms, heart rate variability (HRV), and clinical characteristics in PD patients. Methods: A cross-sectional study was conducted involving 60 PD patients and 60 age- and sex-matched healthy controls. USVN was performed to assess VN cross-sectional area (CSA), echogenicity, and homogeneity bilaterally. Autonomic symptoms were measured using the Composite Autonomic Symptom Scale 31 (COMPASS-31). HRV parameters—SDNN, RMSSD, and pNN50—were obtained via 24 h Holter monitoring. Additional clinical data included Unified Parkinson’s Disease Rating Scale (UPDRS) scores, transcranial sonography findings, and third ventricle width. Results: PD patients showed significantly reduced VN CSA compared to controls (right: 1.90 ± 0.19 mm² vs. 2.07 ± 0.18 mm²; left: 1.74 ± 0.21 mm² vs. 1.87 ± 0.22 mm²; p < 0.001 and p < 0.02). Altered echogenicity and decreased homogeneity were also observed. Right VN CSA correlated with body weight, third ventricle size, and COMPASS-31 scores. Left VN CSA was associated with body size parameters and negatively correlated with RMSSD (p = 0.025, r = −0.21), indicating reduced vagal tone. Conclusions: USVN detects structural VN changes in PD, correlating with autonomic dysfunction. These findings support its potential as a non-invasive biomarker for early autonomic involvement in PD. Full article