Real-World Evidence for a Smartwatch-Based Parkinson’s Motor Assessment App for Patients Undergoing Therapy Changes

To determine the utility of an electronic diary for registering motor fluctuations and dyskinesia in Parkinson disease (PD). Free, open-access touch screen software suitable for Android 4.4 or higher, with medication alarms, adjustable intervals, and medication dose settings was developed to evaluate ON-OFF periods and dyskinesia. Prospective evaluation included a first phase conducted to make adjustments concerning motor limitations when using the tablet, as well as for proper motor complication identification, and a second phase of 3 days of use at home with a prior diary training session comparing a modified paper version of Core Assessment Program for Surgical Interventional Therapies in PD and the electronic diary. All patients correctly identified ON-OFF periods and dyskinesia. Rater/patient matching ON-OFF fluctuations ranged between 94% and 100% for evaluations of different motor states. Dyskinesia matching percentage was 100% for patients with dyskinesia interfering with activities of daily living and 88% for those who reported no-interference. No significant differences between paper and electronic diaries were identified when reporting ON-OFF motor states or in the number of errors when filling the diaries. This electronic motor diary proved to be reliable for ON-OFF state and dyskinesia identification and classification. However, no advantage to paper diary has been observed in terms of number of erroneous entries. Based on these results, to improve home motor fluctuations, detection efforts should be directed toward the development of automatic wearable devices rather than digital versions of current available ON-OFF diaries.

Will Artificial Intelligence Outperform the Clinical Neurologist in the Near Future? No.

Inflammation-associated peripheral blood cells and serum lipid levels are associated with Parkinson's disease.

Levodopa (L-dopa) is the gold-standard medication and the most commonly used substance in the treatment of motor complications in Parkinson's disease (PD) patients. The “Wearing-off” phenomenon is the most frequent complication developed by long-term L-dopa therapy, which results in the reemergence of PD symptoms and lower quality of life in patients. Detecting and monitoring the onset and the duration of wearing-off alongside the persistence of the symptoms, known as “delayed-on”, would enable the patients to receive the medication changes in the required time while preventing them from extravagant use of L-dopa. Home monitoring systems using inertial measurement units have enabled us to measure gait parameters in unsupervised environments. By using patients' medication diaries and their gait parameters obtained from continuous real-world data in the course of two weeks, we developed a system to identify the distorted gait spans during L-dopa therapy utilizing personalized machine learning. Our algorithm differentiates between the two states of medication in effect and the distorted gait states with the mean accuracy of 77% ± 3.37. Furthermore, through each model's feature importance, we found that maximum sensor lift was the most prominent feature affected in the distorted gait sequences. We contribute to a better understanding of the repercussions of wearing-off episodes on gait parameters during L-dopa therapy. Moreover, our proposed system facilitates clinicians in monitoring the severity of these episodes more efficiently.

This paper presents an automated real-time atrial fibrillation (AF) detection approach that relies on the observation of two characteristic irregularities of AF episodes in the electrocardiogram (ECG) signal. The results generated after the analysis of these irregularities are subsequently analyzed in real-time using a new fuzzy classifier. We have optimized this novel AF classification framework to require very limited processing, memory storage and energy resources, which makes it able to operate in real-time on a wearable wireless sensor platform. Moreover, our experimental results indicate that the proposed on-line approach shows a similar accuracy to state-of-the-art off-line AF detectors, achieving up to 96% sensitivity and 93% specificity. Finally, we present a detailed energy study of each component of the target wearable wireless sensor platform, while executing the automated AF detection approach in a real operating scenario, in order to evaluate the lifetime of the overall system. This study indicates that the lifetime of the platform is increased by using the proposed method to detect AF in real-time and diagnose the patient with respect to a streaming application that sends the raw signal to a central coordinator (e.g., smartphone or laptop) for its ulterior processing.

BackgroundBradykinesia in Parkinson's disease (PD) involves reduced movement speed, amplitude, and rhythmicity. While the MDS-UPDRS Part III is the standard clinical tool for motor assessment, it has limited sensitivity to specific kinematic features. Levodopa and subthalamic nucleus deep brain stimulation (STN-DBS) are common treatments for PD, yet their differential effects across motor domains are not fully characterized. This study applies AI-based video analysis to evaluate the effects of levodopa and STN-DBS on limb bradykinesia.MethodsThis retrospective study assessed fifty-three patients with Parkinson's disease undergoing STN-DBS. Motor performance was video-recorded during Levodopa-off and Levodopa-on states (levodopa challenge test performed prior to surgery), as well as after DBS activation (OFFMED/OFFSTIM, OFFMED/ONSTIM, ONMED/ONSTIM). Both clinical assessments and subsequent video-based analyses focused on the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part III, specifically evaluating items 3.4 Finger Tapping, 3.5 Fist-clenching test, 3.7 Toe Tapping, and 3.8 Leg Agility. Motor function was first evaluated using conventional UPDRS-III item scores rated by two experienced specialists, with the primary clinical comparison defined between the levodopa-on and OFFMED/ONSTIM states, to explore the differential therapeutic emphases of medication and DBS. Subsequently, AI-based video analysis was applied to quantify kinematic parameters, including amplitude, frequency, and coefficients of variation, using AI algorithms (NERVTEX Co. Ltd.). Comparisons were made for levodopa effects (Levodopa-off vs. Levodopa-on), DBS effects (OFFMED/OFFSTIM vs. OFFMED/ONSTIM), and therapy-specific differences (Levodopa-on vs. OFFMED/ONSTIM).ResultsConventional UPDRS-III item scores suggested that levodopa was more effective than DBS in improving upper-limb tasks (items 3.4 Finger Tapping and 3.5 Fist-clenching test), while lower-limb tasks (items 3.7 Toe Tapping and 3.8 Leg Agility) showed no significant changes. In contrast, AI-based kinematic analysis revealed more differentiated treatment effects. Levodopa was associated with improvements in movement speed, amplitude, and stability in the upper limbs, as well as a significant impact on lower-limb amplitude, both in toe tapping (item 3.7) and leg agility (item 3.8). DBS, by comparison, enhanced upper-limb motor output but had limited effects on the lower limbs, with improvements in speed and amplitude observed only in the toe tapping (item 3.7) task. Additionally, levodopa demonstrated superior improvements in lower-limb amplitude, both in toe tapping (item 3.7) and leg agility (item 3.8), compared to DBS.ConclusionThis study demonstrates that AI-based kinematic analysis enables a nuanced and individualized characterization of motor responses to medication and STN-DBS in Parkinson's disease, complementing conventional clinical scoring. Although both therapies improve bradykinesia, they appear to preferentially modulate distinct motor domains across individuals, underscoring their complementary roles in treatment. These findings highlight the potential of AI-based motor assessment to support personalized symptom profiling and more individualized therapeutic decision-making in Parkinson's disease.

Twenty years ago, we published a paper examining which of the clinical features of Parkinson’s disease (PD) were most closely associated with patients’ self-reported health-related quality of life (HR-QoL).1 In...

Bilateral subthalamic nucleus deep brain stimulation (DBS STN) is a very effective surgical method of treating motor symptoms in Parkinson's disease (PD) patients. The long-term cognitive outcome after the surgery is still discussed. This study compared the impact of DBS STN to best medical treatment (BMT) in patients with PD on cognitive function and mood over a 36-month observation period. The study included PD patients divided into two groups: the BMT group (n = 17), receiving pharmacotherapy alone throughout the entire 36-month observation period, and the DBS group (n = 20), which underwent DBS STN after the baseline visit, and was subsequently observed for the next 36 months. Both groups were examined at Baseline, 9 months, 18 months and 36 months using neuropsychological assessment and the Unified Parkinson's Disease Rating Scale (UPDRS) motor examination. At 36 months, neither group demonstrated a significant decline in visuospatial abilities, executive functions, or memory. Both groups showed longitudinal deterioration in attention/working memory measures; however, these changes were not associated with significant between-group differences. Language performance [Wechsler Adult Intelligence Scale - Revised (WAIS-R similarities)] improved over follow-up in the DBS group relative to BMT, and DBS was associated with a marked reduction in medication across all follow-up timepoints (p < 0.05). The study suggests that DBS STN does not have a significant additional impact on cognition performance in PD patients. Our results also suggest that while active DBS STN continues to improve motor symptoms, it did not prevent the longitudinal worsening of OFF-motor severity (UPDRS III OFF), which progressed similarly in both groups.

Correlation between frontal-executive function and motor functions, such as gait and postural control, has attracted attention in Parkinson's disease (PD). However, correlations between other cognitive functional domains and motor functions have not been examined. Thus, we examined the correlation between different domains of cognitive function and motor functions. Sixty-five PD patients were recruited for the present study. Cognitive functions were assessed by the 10 subtests of the Neurobehavioral Cognitive Status Examination (COGNISTAT). Motor functions were assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) as partIII for general motor function and sum of related items for tremor, rigidity, bradykinesia, and postural instability. Spearman's correlation coefficients between each cognitive and motor assessment were compared. Among the 10 subtests of the COGNISTAT, constructions showed significant correlation with UPDRS partIII (p<0.01), bradykinesia (p<0.01), and postural instability (p<0.001). The latter correlation was stronger than those between all motor assessments and both all patients backgrounds and other COGNISTAT subtests. In PD patients, postural instability correlates with not only frontal executive dysfunctions but also parietal dysfunctions, such as visuospatial and constructive impairments. The postural maintenance system is suggested to share common physiology with not only frontal-executive function but also parietal functions.

Does neurotrophic factor benefit to PD therapy via co-function with ubiquitin–proteasome system?

Background Studies attempting to elucidate an association between homocysteine and symptom progression in Parkinson's disease (PD) have had largely discrepant findings. This study aimed to investigate elevated serum homocysteine levels and symptom progression in a cohort of PD patients. Methods Serum homocysteine, folate, and vitamin B12 levels were measured in 205 people with PD and 78 age-matched healthy controls. People with Parkinson's disease underwent a battery of clinical assessments to evaluate symptom severity, including motor (MDS-UPDRS) and cognitive (ACE-R) assessments. Multivariate generalised linear models were created, controlling for confounding variables, and were used to determine whether serum markers are associated with various symptom outcome measures. Results People with Parkinson's disease displayed significantly elevated homocysteine levels (p < 0.001), but not folate or vitamin B12 levels, when compared to healthy controls. A significant positive correlation between homocysteine and MDS-UPDRS III score was identified in males with Parkinson's disease (rs = 0.319, p < 0.001), but not in females, whereas a significant negative correlation between homocysteine levels and total ACE-R score was observed in females with Parkinson's disease (rs = −0.449, p < 0.001), but not in males. Multivariate general linear models confirmed that homocysteine was significantly predictive of MDS-UPDRS III score in male patients (p=0.004) and predictive of total ACE-R score in female patients (p=0.021). Conclusion Elevated serum homocysteine levels are associated with a greater motor impairment in males with Parkinson's disease and poorer cognitive performance in females with Parkinson's disease. Our gender-specific findings may help to explain previous discrepancies in the literature surrounding the utility of homocysteine as a biomarker in PD.

The incidence of overactive bladder (OAB) increases with age, especially in patients with central nervous system (CNS) disorders such as cerebrovascular accident (CVA) and Parkinson's disease (PD). Mirabegron is a novel medication for the treatment of OAB. The present study investigated the therapeutic effect of mirabegron on OAB patients with CNS diseases. Patients with CVA, PD, dementia, and OAB symptoms were consecutively enrolled in the study group, and mirabegron 25 mg q.d. was prescribed. Clinical effects, evaluated using the Overactive Bladder Symptom Score (OABSS), Urinary Sensation Scale (USS), International Prostate Symptom Score (IPSS), and Patient Perception of Bladder Condition (PPBC), as well as urodynamic parameters and adverse events were assessed at baseline and 4 and 12 weeks after treatment. In all, 44 patients (mean [± SD] age 77.7 ± 9.49 years) with OAB due to CVA (n = 27), PD (n = 6), and dementia (n = 11) were included in the present prospective study. Mirabegron resulted in significant improvements in symptom scores on the OABSS (P = .02), USS (P = .009), total IPSS (P = .002), Storage and Voiding domains of the IPSS (P = .001 and .017, respectively), and PPBC (P = .001). No significant changes were noted in post-void residual, maximum flow rate, and voided volume after treatment. Only 5 patients dropped out due to poor therapeutic efficacy and shifted to antimuscarinics. Three patients complained of adverse effects, including dizziness and dysuria. No patient complained of urine retention or constipation. Mirabegron 25 mg once daily effectively decreased urgency symptoms in elderly OAB patients with CNS lesions after the 12-week treatment period. The adverse events were mild and only noted in a few cases.

To study the effects of deep brain stimulation (DBS) of bilateral subthalamic nucleus (STN) on the motor and non-motor symptoms in moderate or advanced Parkinson's disease (PD) patients. From August 2006 to January 2010, 21 consecutive PD patients with refractory motor fluctuations or dyskinesia underwent operations at our hospital. All patients were evaluated by unified Parkinson's disease rating scale (UPDRS), Hoehn & Yahr (H&Y) stage, Parkinson's disease questionnaire (PDQ-39), mini mental state examination (MMSE), Parkinson's disease sleep scale-Chinese vision (PDSS-CV), Pittsburgh sleep quality index (PSQI), Hamilton depression rating scale (HAMD) and Hamilton anxiety rating scale (HAMA). And the daily dosage of dopaminergic agents was recorded at 1 week pre-operation and 3, 6 and 12 months post-operation. Ten patients finished a 12-month follow-up. Their motor functions showed significant improvement. And the scores of UPDRS-motor, tremor, rigidity, bradykinesia and axial symptoms reduced significantly in the on-stimulation-off-medication condition and the on-stimulation-on-medication condition vs the on-medication condition pre-operation. And the improvement of tremor was the most pronounced (52.1% and 77.7% respectively). The H&Y stage decreased significantly from 3.2 ± 0.7 to 2.5 ± 0.4 post-operation. The activities of daily living improved while PDQ-39 declined significantly from 56 ± 9 pre-operation to 32 ± 13 at 12 months follow-up. The score changes of MMSE, PDSS-CV, PSQI, HAMA and HAMD were statistically insignificant. The levo-dopa equivalent dose of 1-year post-operation decreased significantly by 49.2% versus that of pre-operation (P < 0.05). Bilateral STN-DBS can significant ameliorate the motor symptoms of moderate or advanced PD patients, reduce the dosage of anti-PD medications and improve the quality of life. This procedure has the advantages of a greater safety, minor side effects and an easy controllability.

Concurrent TMS-EEG to characterize cortical responses in the motor and prefrontal cortices in Parkinson's disease

Redefining Bradykinesia.