The validation of a Japanese version of the New Freezing of Gait Questionnaire (NFOG-Q).

OBJECTIVE: This study aimed to develop a Japanese version of the New Freezing of Gait Questionnaire (NFOG-Q) and investigate its validity and reliability. METHODS: After translating the NFOG-Q according to a standardised protocol, 56 patients with Parkinson's disease (PD) were administered it. Additionally, the MDS-UPDRS parts II and III, Hoehn and Yahr (H&Y) stage, and number of falls over 1 month were evaluated. Spearman's correlation coefficients (rho) were used to determine construct validity, and Cronbach's alpha (α) was used to examine reliability. RESULTS: The interquartile range of the NFOG-Q scores was 10.0-25.3 (range 0-29). The NFOG-Q scores were strongly correlated with the MDS-UPDRS part II, items 2.12 (walking and balance), 2.13 (freezing), 3.11 (freezing of gait), and 3.12 (postural stability) and the postural instability and gait difficulty score (rho = 0.515-0.669), but only moderately related to the MDS-UPDRS item 3.10 (gait), number of falls, disease duration, H&Y stage, and time of the Timed Up-and-Go test (rho = 0.319-0.434). No significant correlations were observed between age and the time of the 10-m walk test. The internal consistency was excellent (α = 0.96). CONCLUSIONS: The Japanese version of the NFOG-Q is a valid and reliable tool for assessing the severity of freezing in patients with PD.

Decreased hepatic enzymes reflect the decreased vitamin B6 levels in Parkinson's disease patients.

The study aims to investigate the vitamin B6 levels in Parkinson's disease (PD) patients and their association with liver enzymes and evaluate how much dysregulation is associated with levodopa dose. Furthermore, to evaluate the effect of Opicapone, a catechol-o-methyl-transferase inhibitor, on vitamin B6 levels by monitoring the AST and ALT levels in patients treated with Levodopa-Carbidopa Intestinal Gel Infusion (LCIG). For these aims, serum vitamin B6 levels were measured (PD, n = 72 and controls, n = 31). The vitamin B6 level was compared with the total levodopa dose, clinical parameters, and blood homocysteine, albumin, and hemoglobin levels in PD patients. Correlations between vitamin B6 levels and AST and ALT levels, as well as the ratio ALT/AST, were analyzed. Changes in the AST and ALT levels and ALT/AST were analyzed in the patients treated with LCIG before and after the therapy (n = 24) and in the patients treated with LCIG + Opicapone before and after Opicapone treatment (n = 12). We found vitamin B6 levels were significantly lower in PD patients. Total levodopa dose and albumin levels were independently associated with vitamin B6 levels. Decreased vitamin B6 levels appeared as lower AST and ALT levels and ALT/AS. Treatment with LCIG decreased the AST and ALT levels and ALT/AST. Adjunctive therapy with Opicapone to LCIG ameliorated the decreased ALT and ALT/AST. We conclude that the ALT and ALT/AST can be useful parameters for monitoring vitamin B6 levels and Opicapone can ameliorate the dysregulated vitamin B6 in PD patients.

Measurement instruments to assess basic functional mobility in Parkinson's Disease: A systematic review of clinimetric properties and feasibility for use in clinical practice.

Taniguchi S, Yamamoto A. Measurement instruments to assess basic functional mobility in Parkinson's Disease: A systematic review of clinimetric properties and feasibility for use in clinical practice. Jpn J Compr Rehabil Sci 2023; 14: 16-25. Objective: To systematically review the evaluation of clinimetric properties and feasibility of the "Modified Parkinson Activity Scale (M-PAS)" and the "Lindop Parkinson's Disease Mobility Assessment (LPA)," which are Parkinson's Disease (PD)-specific measurement instruments to assess basic functional mobility, and to discuss their considerations for use in clinical practice. Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A risk of bias assessment was also performed. Results: Eleven studies were included: five studies used M-PAS (45%), five studies used LPA (45%), and one study used M-PAS and LPA (13%). The risk of bias was low for all evaluated studies. Conclusion: M-PAS and LPA showed adequate reliability, validity, and responsiveness in detecting intervention changes. M-PAS has more detailed qualitative scoring options, a lack of ceiling effect, and can be used by a non-expert in PD.In contrast, the drawback of M-PAS is that it is time-consuming to apply in everyday clinical practice. On the other hand, LPA with greater simplicity may lead to lower burdens for both patients and raters in situations with strict time limitations. Further research is required to identify new resources.

Cooperation and competition between the default mode network and frontal parietal network in the elderly.

Recent research has shown that the Default Mode Network (DMN) typically exhibits increased activation during processing of social and personal information but shows deactivation during working memory (WM) tasks. Previously, we reported the Frontal Parietal Network (FPN) and DMN showed coactivation during task preparation whereas the DMN exhibited deactivation during task execution in working memory tasks. Aging research has shown that older adults exhibited decreased functional connectivity in the DMN relative to younger adults. Here, we investigated whether age-related cognitive decline is related to a reduced relationship between the FPN and DMN using a working memory task during the execution period. First, we replicated our previous finding that the FPN and DMN showed coactivation during the preparation period, whereas the DMN showed deactivation during the execution period. The older adults showed reduced DMN activity during task preparation and reduced deactivation during task execution; however, they exhibited a higher magnitude of activation in the FPN than the young individuals during task execution. Functional connectivity analyses showed that the elderly group, compared to the young group, showed weaker correlations within the FPN and the DMN, weaker positive correlations between the FPN and DMN during task preparation, and weaker negative correlations between the FPN and DMN during execution. The results suggest that cognitive decline in the older adults might be related to reduced connectivity within the DMN as well as between the FPN and DMN.

Decreased cerebrospinal fluid orexin levels not associated with clinical sleep disturbance in Parkinson's disease: A retrospective study.

Patients with Parkinson's disease (PD) often suffer from sleep disturbances, including excessive daytime sleepiness (EDS) and rapid eye movement sleep behavior disorder (RBD). These symptoms are also experienced by patients with narcolepsy, which is characterized by orexin neuronal loss. In PD, a decrease in orexin neurons is observed pathologically, but the association between sleep disturbance in PD and cerebrospinal fluid (CSF) orexin levels is still unclear. This study aimed to clarify the role of orexin as a biomarker in patients with PD. CSF samples were obtained from a previous cohort study conducted between 2015 and 2020. We cross-sectionally and longitudinally examined the association between CSF orexin levels, sleep, and clinical characteristics. We analyzed 78 CSF samples from 58 patients with PD and 21 samples from controls. CSF orexin levels in patients with PD (median = 272.0 [interquartile range = 221.7-334.5] pg/mL) were lower than those in controls (352.2 [296.2-399.5] pg/mL, p = 0.007). There were no significant differences in CSF orexin levels according to EDS, RBD, or the use of dopamine agonists. Moreover, no significant correlation was observed between CSF orexin levels and clinical characteristics by multiple linear regression analysis. Furthermore, the longitudinal changes in orexin levels were also not correlated with clinical characteristics. This study showed decreased CSF orexin levels in patients with PD, but these levels did not show any correlation with any clinical characteristics. Our results suggest the limited efficacy of CSF orexin levels as a biomarker for PD, and that sleep disturbances may also be affected by dysfunction of the nervous system other than orexin, or by dopaminergic treatments in PD. Understanding the reciprocal role of orexin among other neurotransmitters may provide a better treatment strategy for sleep disturbance in patients with PD.

Determinants of impaired bed mobility in Parkinson's disease: Impact of hip muscle strength and motor symptoms.

BACKGROUND: Although most patients with Parkinson's disease (PD) present difficulties of bed mobility, the contributing factors to impaired bed mobility in PD are unknown. OBJECTIVE: To compare bed mobility and muscle strength between PD patients and healthy controls, and investigate the determinants of bed mobility in PD. METHODS: Sixteen patients with PD and ten age- and sex-matched healthy controls (HC) were enrolled. Time and pattern to get out of bed to their preferred side at usual speed, muscle torque in lower extremities and motor symptom burden were also measured. RESULTS: PD exhibited significantly slower speed in bed mobility and lower torque in the hip adductor/abductor/flexor muscle than HC. Slower movement time in PD was correlated with weaker hip adductor torque on the more affected side (Rs = -0.56, p < 0.05) and with higher score in arm rigidity both sides (Rs≥0.79, p < 0.01). There were no significant differences between the categorised movement patterns and movement time in PD (p = 0.31). CONCLUSIONS: Reduced hip adductors torque and severe arm rigidity are associated with slowness of getting out of bed, implying that these components could be used as targets for rehabilitation practice to improve bed mobility in PD.

Functional Connectivity and Networks Underlying Complex Tool-Use Movement in Assembly Workers: An fMRI Study.

The aim of this study was to identify the functional connectivity and networks utilized during tool-use in real assembly workers. These brain networks have not been elucidated because the use of tools in real-life settings is more complex than that in experimental environments. We evaluated task-related functional magnetic resonance imaging in 13 assembly workers (trained workers, TW) and 27 age-matched volunteers (untrained workers, UTW) during a tool-use pantomiming task, and resting-state functional connectivity was also analyzed. Two-way repeated-measures analysis of covariance was conducted with the group as a between-subject factor (TW > UTW) and condition (task > resting) as a repeated measure, controlling for assembly time and accuracy as covariates. We identified two patterns of functional connectivity in the whole brain within three networks that distinguished TW from UTW. TW had higher connectivity than UTW between the left middle temporal gyrus and right cerebellum Crus II (false discovery rate corrected p-value, p-FDR = 0.002) as well as between the left supplementary motor area and the pars triangularis of the right inferior frontal gyrus (p-FDR = 0.010). These network integrities may allow for TW to perform rapid tool-use. In contrast, UTW showed a stronger integrity compared to TW between the left paracentral lobule and right angular gyrus (p-FDR = 0.004), which may reflect a greater reliance on sensorimotor input to acquire complex tool-use ability than that of TW. Additionally, the fronto-parietal network was identified as a common network between groups. These findings support our hypothesis that assembly workers have stronger connectivity in tool-specific motor regions and the cerebellum, whereas UTW have greater involvement of sensorimotor networks during a tool-use task.

Validation and Reliability of the Japanese Version of the Modified Parkinson Activity Scale (M-PAS).

OBJECTIVE: The Modified Parkinson Activity Scale (M-PAS) is used to identify the most important activity limitations in patients with Parkinson's disease. We developed a Japanese version of the M-PAS and evaluated its reliability and validity. METHODS: Twenty-five patients with Parkinson's disease (median age 71 years old, range 58-83) were enrolled, and two raters used the Japanese version of M-PAS to assess the subjects. The inter-rater reliability was evaluated using Cohen's weighted kappa coefficient for the total score and three domain scores; systematic error was investigated using Bland-Altman analysis. Concurrent validity of the Japanese M-PAS was measured using Spearman's rank correlation coefficients. RESULTS: Cohen's kappa coefficients for the total score and the three domain scores were in the range 0.81-0.98, and 95% confidence intervals included zero for each item, suggesting excellent agreement and no systematic errors. The scores of the Japanese version of M-PAS were significantly correlated with the scores of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part II (Spearman's rho=-0.56, P <0.01) and Part III (Spearman's rho=-0.32, P <0.01). The percentage of patients with the highest and the lowest scores in the Japanese version of M-PAS suggested no ceiling or floor effects. CONCLUSION: The Japanese version of M-PAS showed excellent inter-rater reliability and good concurrent validity without ceiling or floor effects.

Assessment of leg muscle activity using toe tapping in patients with Parkinson's disease: comparison of two types of toe tapping.

[Purpose] This study investigates two types of toe tapping, i.e., "closed," with both feet on the floor, and "open," in which the foot does not touch the ground, and evaluates their usefulness in combination with monitoring of muscle activity during toe tapping. [Subjects and Methods] The study enrolled 11 patients with Parkinson's disease (PD) and 9 controls (Controls). The tibialis anterior (TA) and gastrocnemius (GS) muscle activity during toe tapping was measured using surface electromyography. [Results] In closed tapping, the minima in GS activation with the first tap was significantly higher in patients with PD than in Controls. In open tapping, the coefficient of variation (CV) of local maxima in TA activation was significantly higher in patients with PD than in Controls. In both types of tapping, the CV of extrema in GS activities increased with disease duration, but this may be due to the long-term administration of Levodopa, which itself tends to cause excessive GS activities. [Conclusion] Closed tapping is suitable for the assessment of GS activity and can detect excessive activities, which is observed as visible movement. Open tapping, on the other hand, is suitable for assessment of TA activity.