Japanese Parkinson's Disease Patients Research Articles

Risk factors for developing dyskinesia among Parkinson's disease patients with wearing-off: J-FIRST

BackgroundDyskinesia frequently occurs during long-term treatment with levodopa in patients with Parkinson's disease (PD) and impacts quality of life. Few studies have examined risk factors for developing dyskinesia in PD patients exhibiting wearing-off. Therefore, we investigated the risk factors and impact of dyskinesia in PD patients exhibiting wearing-off. MethodsWe investigated the risk factors and impact of dyskinesia in a 1-year observational study of Japanese PD patients exhibiting wearing-off (J-FIRST). Risk factors were assessed by logistic regression analyses in patients without dyskinesia at study entry. Mixed-effect models were used to evaluate the impact of dyskinesia on changes in Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) Part I and PD Questionnaire (PDQ)-8 scores from one timepoint before dyskinesia was observed. ResultsOf 996 patients analyzed, 450 had dyskinesia at baseline, 133 developed dyskinesia within 1 year, and 413 did not develop dyskinesia. Female sex (odds ratio [95% confidence interval]: 2.636 [1.645–4.223]) and administration of a dopamine agonist (1.840 [1.083–3.126]), a catechol-O-methyltransferase inhibitor (2.044 [1.285–3.250]), or zonisamide (1.869 [1.184–2.950]) were independent risk factors for dyskinesia onset. MDS-UPDRS Part I and PDQ-8 scores increased significantly after the onset of dyskinesia (least-squares mean change [standard error] at 52 weeks: 1.11 [0.52], P = 0.0336; 1.53 [0.48], P = 0.0014; respectively). ConclusionFemale sex and administration of a dopamine agonist, a catechol-O-methyltransferase inhibitor, or zonisamide were risk factors for dyskinesia onset within 1 year in PD patients exhibiting wearing-off. Nonmotor symptoms and quality of life deteriorated after dyskinesia onset.

Long-term safety and efficacy of safinamide as add-on therapy in levodopa-treated Japanese patients with Parkinson's disease with wearing-off: Results of an open-label study

IntroductionSafinamide, a selective, reversible monoamine oxidase B inhibitor with a sodium channel inhibitory effect, improves symptoms in advanced Parkinson's disease (PD). This study aimed to confirm the long-term safety and efficacy of safinamide in Japanese PD patients with wearing-off. MethodsJapanese PD patients aged ≥30 years with wearing-off were eligible. The primary efficacy endpoint was change from baseline in the mean daily ON-time without troublesome dyskinesias at 52 weeks of treatment. Other efficacy endpoints included changes from baseline in mean daily OFF-time and unified Parkinson's disease rating scale (UPDRS) and PDQ-39 scores. ResultsIn total, 203 patients entered the study, and 142 completed the 52-week treatment. Adverse events (AEs) occurred in 78.3% of patients, with nasopharyngitis (20.7%) and dyskinesias (17.7%) as the most common; serious AEs occurred in 17.2%, causing discontinuation in 10.8%. At Week 52, the mean daily ON-time without troublesome dyskinesias increased from baseline by 1.42 h. Change from baseline in mean daily OFF-time was −1.40 h, and that in the UPDRS Part III score in the ON-phase was −6.20. ConclusionsAs adjunctive treatment with levodopa, safinamide was safe, well tolerated, and effective in improving ON-time and other PD symptoms at 52 weeks.

Efficacy and safety of safinamide as an add-on therapy to L-DOPA for patients with Parkinson's disease: A randomized, double-blind, placebo-controlled, phase II/III study

IntroductionSafinamide is a reversible and selective monoamine oxidase-B (MAO-B) and sodium channel inhibitor with demonstrated efficacy in mid-to late-stage Parkinson's disease (PD) as an adjunct to l-DOPA. This study aimed to confirm the efficacy and safety of safinamide in PD patients with wearing-off. MethodsThis 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study included Japanese PD patients with wearing-off on l-DOPA treatment. Patients were randomized to receive placebo (P), safinamide 50 mg/day (S50), or safinamide 100 mg/day (S100). The primary endpoint was the change from baseline in mean daily ON-time without troublesome dyskinesias (ON-time). Other measures included the changes in mean daily OFF-time, the unified Parkinson's disease rating scale (UPDRS) score, and the PDQ-39 summary index. ResultsA total of 406 subjects were randomized, of whom 349 completed the study. Baseline characteristics were balanced. Differences in the change of mean daily ON-time at Week 24 compared with the P group were 1.39 h (p = 0.0002) in the S50 group and 1.66 h (p < 0.0001) in the S100 group. Changes from baseline in mean daily OFF-time, UPDRS Part II total score (OFF phase), UPDRS Part III total score (ON phase), and UPDRS Part I also showed significant improvements. Adverse events occurred in 58.9%, 60.2%, and 61.4% of the P, S50, and S100 groups, respectively. The most common adverse drug reactions were dyskinesias (2.1%, 8.3%, and 10.6%) and visual hallucinations (1.4%, 3.0%, and 4.5%). ConclusionAs an adjunct to l-DOPA, safinamide safely increased ON-time and improved PD symptoms/signs in PD patients with wearing-off.

Real-World Nonmotor Changes in Patients with Parkinson's Disease and Motor Fluctuations: J-FIRST.

ABSTRACTBackgroundNonmotor symptoms (NMSs) of Parkinson's disease (PD) impair health‐related quality of life.ObjectivesTo identify changes in NMSs during 52 weeks in Japanese PD patients exhibiting motor fluctuations.MethodsIn PD patients with ≥1 NMS and wearing‐off, changes in total/subscore of the Movement Disorder Society Unified PD Rating Scale (MDS‐UPDRS) Part I and 8‐item PD Questionnaire were assessed. Group‐based trajectory models were used to characterize longitudinal patterns of MDS‐UPDRS Part I.ResultsData from 996 patients were analyzed. MDS‐UPDRS Part I subscores for cognitive function decreased linearly over time. Total and subscores for apathy and lightheadedness on standing significantly deteriorated with fluctuations, whereas other subscores fluctuated without significant deterioration. Changes in the MDS‐UPDRS Part I total score correlated with changes in the 8‐item PD Questionnaire total score. Based on group‐based trajectory models, longitudinal pattern analysis of MDS‐UPDRS Part I scores yielded the following 3 separate groups: unchanged (63.8%), deteriorated (20.1%), and improved (16.2%). The improved group had significantly more NMSs at baseline, significantly higher MDS‐UPDRS Part I/8‐item PD Questionnaire total scores, and modified Hoehn and Yahr scores, and had received treatment for NMSs. The multivariate analysis revealed significant associations between severe motor disability and receiving any treatment for NMSs at baseline and improvement of MDS‐UPDRS Part I total scores.ConclusionsChanges in MDS‐UPDRS Part I scores were variable and related to changes in health‐related quality of life in PD patients with motor fluctuations.

Efficacy and safety of adjunctive rasagiline in Japanese Parkinson's disease patients with wearing-off phenomena: A phase 2/3, randomized, double-blind, placebo-controlled, multicenter study

IntroductionRasagiline, a selective, irreversible monoamine oxidase-B inhibitor, is in development in Japan as adjunctive therapy to levodopa. This Phase 2/3 trial evaluated the efficacy and safety of adjunctive rasagiline in Japanese patients with Parkinson's disease (PD) and wearing-off phenomena. MethodsPatients aged 30–79 years with diagnosed PD and stable levodopa use were randomized 1:1:1 to rasagiline (0.5/1 mg/day) or placebo for 26 weeks. The primary endpoint was change from baseline in mean daily OFF-time during the treatment period. ResultsIn total, 141, 134, and 129 patients were randomized to placebo, rasagiline 0.5 mg, or rasagiline 1 mg, respectively. Baseline characteristics were well balanced. Least squares (LS) mean differences vs. placebo for change from baseline in mean daily OFF-time were −0.84 h (rasagiline 1 mg/day) and −0.60 h (rasagiline 0.5 mg/day); both differences were statistically significant. LS mean differences vs. placebo for change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II and Part III total scores (in ON-state) and Parkinson's Disease Questionnaire-39 Summary Index Score were: −1.27, −1.74, and −2.51 (0.5 mg/day) and −1.27, −2.14, and −3.84 (1 mg/day); all statistically significant. Treatment-emergent adverse events (TEAEs) occurred in 50.4/69.9/73.6% of the placebo, 0.5 mg/day, and 1 mg/day groups, respectively (most common TEAEs were nasopharyngitis [9.2/18.0/14.7%] and dyskinesia [7.1/8.3/16.3%]). ConclusionsAs an adjunct to levodopa, rasagiline reduced OFF-time and improved PD symptoms/signs (MDS-UPDRS scores) and quality of life in Japanese patients with PD and wearing-off phenomena. No important safety concerns were raised.

Egogram characteristics in Japanese patients with Parkinson's disease

AbstractBackgroundPersonality has been investigated as a possible onset risk factor for Parkinson's disease (PD). Recently, personality has attracted increasing attention because certain non‐motor aspects may be associated with patients’ personality and deterioration of their quality of life. The Tokyo University Egogram version II (TEGII) is a reliable questionnaire for assessing personality in Japanese people, but few studies have reported personality assessments in Japanese PD patients.AimTo clarify the clinical utility of the TEGII for evaluating personality in Japanese PD.MethodsPatients were consecutively enrolled in four medical centers throughout Japan, and their personality was evaluated using the TEGII. Personality is described in terms of five ego‐states: critical parent (CP), nurturing parent (NP), adult (A), free child (FC), and adapted child (AP). The scores for each ego‐state and the egogram patterns describe personality characteristics. We statistically analyzed our data and compared the results with standardized data from a Japanese cohort.ResultsWe enrolled 133 PD patients. The mean scores ± SDs of the five ego‐states were CP: 11.4 ± 4.5, NP: 14.5 ± 4.2, A: 10.5 ± 4.8, FC: 11.1 ± 4.7, and AC: 9.5 ± 5.2. NP scores were significantly higher than the others (P &lt; 0.001), and the NP dominant pattern (15.8%) was most frequent.ConclusionThe NP dominant pattern, which illustrates a thoughtful, obliging and kind personality, is characteristic of Japanese PD patients. The TEGII is a simple clinical tool for evaluating personality in PD and can be used to evaluate changes in patients over time.

Clinical manifestations of nonmotor symptoms in 1021 Japanese Parkinson's disease patients from 35 medical centers

IntroductionWe aimed to investigate the prevalence and severity of nonmotor symptoms (NMSs) and to identify factors affecting NMSs and the health-related quality of life of Japanese patients with Parkinson's disease (PD). MethodsA total of 1021 patients with PD who had one or more NMS and showed wearing-off under anti-parkinsonian treatment were enrolled from 35 medical centers in Japan for this observational study. The primary measurements were the Movement Disorder Society unified Parkinson's disease rating scale (MDS-UPDRS) part I and the Parkinson's Disease Questionnaire (PDQ-8). The relationships of MDS-UPDRS and PDQ-8 with the patient's clinical background and undertaken medical interventions were determined. Here, we report baseline data of our 52-week ongoing study. ResultsThe mean MDS-UPDRS part I and PDQ-8 scores were 10.9 and 7.3, respectively. The most common NMSs were constipation problems (85.4%), sleep problems (73.7%), pain and other sensations (72.7%) and daytime sleepiness (72.0%). Fatigue was an NMS that affected 79.6% of females but only 72.6% of males, whereas features of dopamine dysregulation syndrome affected only 5.6% of females and 10.8% of males. Positive correlations were found between the MDS-UPDRS part I and the PDQ-8 (p < 0.0001, r = 0.56) and between the number of NMSs and the PDQ-8 score (p < 0.0001, r = 0.47). ConclusionsThis study revealed distinctive patterns of NMSs in Japanese patients with PD and suggested that the prevalence and severity of NMSs vary between sexes, and that the NMSs are important factors affecting the long-term quality of life of PD patients.

The Risk Factors for the Wearing-off Phenomenon in Parkinson's Disease in Japan: A Cross-sectional, Multicenter Study.

Objective Parkinson's disease (PD) is a common, progressive, neurodegenerative disorder. With progression of PD, the wearing-off phenomenon occurs more frequently as a motor complication, decreasing the patient's quality of life. The aim of this study was to investigate the risk factors for the wearing-off phenomenon in Japanese PD patients. Methods All of the study participants were clinically diagnosed as having PD. Each patient was assessed for the wearing-off phenomenon based on the findings of clinical assessments and interviews that were conducted during a single visit. The risk factors for wearing-off were analyzed by univariate and multivariate logistic regression analyses. Results Wearing-off was observed in 101 of the 180 (56.1%) patients who were enrolled in this study. The multivariate logistic regression analysis revealed that the onset of PD at ≥69 years of age (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.05-0.88; p=0.032), female sex (OR, 6.49; 95% CI, 2.34-17.99; p<0.001), catechol-O-methyltransferase (COMT) inhibitor treatment (OR, 19.59; 95% CI, 3.55-108.11; p<0.001) and a high daily levodopa dosage (≥600 mg/day) (OR, 7.69; 95% CI, 1.41-41.84; p=0.018) were independent predictive factors for wearing-off in Japanese PD patients. Conclusion Age at the symptomatic disease onset, female sex, COMT inhibitor treatment, and a high daily levodopa dose were associated with the occurrence of wearing-off in Japanese PD patients. Physicians need to consider the risk factors and carefully choose medications for PD patients to postpone the occurrence of this phenomenon for as long as possible.

Cognitive behavioral therapy for depression in Japanese Parkinson's disease patients: a pilot study.

ObjectivesThis study evaluated the feasibility of cognitive behavioral therapy (CBT) for Japanese Parkinson’s disease (PD) patients with depression. To increase cultural acceptability, we developed the CBT program using manga, a type of Japanese comic novel.MethodsParticipants included 19 non-demented PD patients who had depressive symptoms (GRID-Hamilton Rating Scale for Depression score ≥8). A CBT program comprising six sessions was individually administered. We evaluated the feasibility and safety of the CBT program in terms of the dropout rate and occurrence of adverse events. The primary outcome was depressive symptom reduction in the GRID-Hamilton Rating Scale for Depression upon completion of CBT. Secondary outcomes included changes in the self-report measures of depression (Beck Depression Inventory-II, Hospital Anxiety and Depression Scale-Depression), anxiety (Hospital Anxiety and Depression Scale-Anxiety, State and Trait Anxiety Inventory, Overall Anxiety Severity and Impairment Scale), functional impairment, and quality of life (Medical Outcomes Study 36-Item Short-Form Health Survey).ResultsOf the 19 participants (mean age =63.8 years, standard deviation [SD] =9.9 years; mean Hohen–Yahr score =1.7, SD =0.8), one patient (5%) withdrew. No severe adverse event was observed. The patients reported significant improvements in depression (Hedges’ g =−1.02, 95% confidence interval =−1.62 to −0.39). The effects were maintained over a 3-month follow-up period. Most of the secondary outcome measurements showed a small-to-moderate but nonsignificant effect size from baseline to post-intervention.ConclusionThis study provides preliminary evidence that CBT is feasible among Japanese PD patients with depression. Similar approaches may be effective for people with PD from other cultural backgrounds. The results warrant replication in a randomized controlled trial.

An Aerodynamic Study of Phonations in Patients With Parkinson Disease (PD)

The precise comparison of the voice characteristics of Parkinson disease (PD) patients with age-matched normal subjects is still one of the important research projects. The present study aimed at comparing the voice characteristics in sustained phonations of PD patients with an age-matched control group. The subjects were 30 Japanese PD patients (15 males and 15 females). The control group consisted of 30 age-matched normal Japanese subjects (15 males and 15 females). Each subject was required to phonate into a mouthpiece attached to Vocal Function Analyzer (PS-77E; Nagashima Medical Instrumental Corporation, Tokyo, Japan) with the airway interruption system, and expiratory lung pressure, mean flow rate, fundamental frequency and intensity of voice, and pitch range were measured. Maximum phonation time was also assessed. The highest pitch level was significantly lower in the PD group than that of the control group in both sexes, whereas the lowest pitch level was significantly higher in the PD group only in males. In both sexes, the pitch range was significantly narrower in the PD group than in the control group. There was no significant difference in intensity, mean flow rate, expiratory pressure, or maximum phonation time between the two groups, for both males and females. Only remarkable difference in the voice characteristics between PD patients and age-matched normal elderlies was limited to the narrowing of the pitch range in PD patients. The restriction in pitch regulation in PD patients was considered to be because of difficulty in reciprocal control of the laryngeal muscles secondary to latent rigidity.

Comparing the Montreal Cognitive Assessment with Mini‐Mental State Examination in Japanese Parkinson's disease patients

AbstractBackground and AimThe Montreal Cognitive Assessment (MoCA) is the most suitable measure for screening cognitive impairment in Parkinson's disease (PD). However, the utility of the MoCA has not been documented sufficiently, especially in Asian populations. The present multicenter study included a large number of Japanese patients, and compared Mini‐Mental State Examination (MMSE) and MoCA scores in PD patients.MethodsWe carried out a cross‐sectional study. Idiopathic PD patients (n = 304; age 70.6 ± 8.3 years (mean ± SD); disease duration 6.6 ± 5.1 years; Hoehn and Yahr stage 2.7 ± 0.7) were registered at 13 participating hospitals, and their clinical/neurological/cognitive features were examined using Japanese versions of the MMSE and MoCA.ResultsThe MMSE and MoCA scores were 26.3 ± 3.6 (range 12–30) and 20.9 ± 5.0 (range 5–30), respectively, and showed a strong correlation (R2 = 0.74, P &lt; 0.001) with each other. A MMSE score of &lt;26 was observed in 35% of the participants. A MoCA score of &lt;21 had 89% sensitivity and 83% specificity, comparable with a MMSE score of &lt;26. The two scores were correlated with age (R2 = 0.12 and 0.20, respectively; P &lt; 0.0001), but not with Hoehn and Yahr stage or disease duration.ConclusionsOne‐third of the patients had a MMSE score of &lt;26, a diagnostic criterion of PD with dementia. A MoCA score of &lt;21 seemed comparable with a MMSE score of &lt;26. The two scores were correlated with age, rather than severity of motor symptoms, suggesting that cognitive decline might be independent of motor decline in PD.

Serum uric acid concentration is linked to wearing-off fluctuation in Japanese Parkinson's disease patients.

Serum uric acid (UA) concentration is linked to the risk of progression of Parkinson's disease (PD). The aim of this study was to examine the association between serum UA concentration and the occurrence of wearing-off fluctuation (WOF) in Japanese PD patients. A total of 123 Japanese patients with PD were enrolled in this study. We collected data on demographics, clinical features, medications, and laboratory findings including serum UA concentration, and examined the presence of WOF. The association between serum UA concentration and WOF was assessed using multivariate logistic regression analysis. After adjusting for possible confounders, it was found that the odds ratio (OR) for WOF decreased with increasing quartile of UA (highest quartile vs. lowest quartile, adjusted OR 0.218, 95% confidence interval [CI] 0.053-0.891). This association was significant only in male PD patients, regardless of the use of sex-specific quartiles of UA. Additionally, disease duration (OR 7.80, 95% CI 2.62-23.17) and daily levodopa dosage (OR 4.06, 95% CI 1.45-11.38) were associated with the occurrence of WOF. Our results showed that serum UA concentration was associated with the occurrence of WOF. Serum UA concentration may be a predictive factor for WOF.

Impulsive compulsive behaviors in Japanese Parkinson's disease patients and utility of the Japanese version of the Questionnaire for Impulsive–/INS;Compulsive Disorders

Impulsive compulsive behaviors in Japanese Parkinson's disease patients and utility of the Japanese version of the Questionnaire for Impulsive–/INS;Compulsive Disorders

Impulsive compulsive behaviors in Japanese Parkinson's disease patients and utility of the Japanese version of the Questionnaire for Impulsive–Compulsive Disorders in Parkinson's disease

BackgroundIn order to evaluate impulsive compulsive behaviors (ICBs), such as pathological gambling, compulsive sexual behavior, compulsive buying, compulsive eating, punding, and dopamine dysregulation syndrome (DDS) in Japanese Parkinson's disease (PD) patients, we constructed a Japanese version of the Questionnaire for Impulsive–Compulsive Disorders in Parkinson's disease (J-QUIP) and evaluated the utility of the J-QUIP in Japanese PD patients. MethodsJ-QUIP was administered to 121 PD patients. Diagnoses of ICBs were made via interview of patients or their caregivers. Subsequently, in order to evaluate risk factors related to these conditions, we evaluated demographic and clinical characteristics, clinical features, and medications utilized. ResultsWe were able to administer the J-QUIP to 118 of 121 PD patients (97.5%). Sensitivity and specificity of J-QUIP were similar to that reported for the original version of QUIP. In our study, the actual prevalence of each disorder diagnosed via interview was as follows: pathological gambling (6.5%), compulsive sexual behavior (3.2%), compulsive buying (3.2%), compulsive eating (3.2%), punding (6.5%), and DDS (2.2%). Significantly risk factors for these conditions were younger age (p=0.047), earlier age of disease onset (p=0.015), longer PD duration (p=0.001), total levodopa equivalent dose (p=0.006), and dosage of levodopa (p=0.019). ConclusionsWe evaluated the prevalence of ICBs in Japanese PD patients along with factors associated with these behaviors via J-QUIP.

Focal myopathy in the neck extensor muscles in Japanese Parkinson's disease patients with dropped head syndrome

AbstractAimThe underlying etiology of dropped head syndrome (DHS) in Parkinson's disease (PD) patients seems to be heterogeneous, that is neck dystonia, a drug‐induced etiology or focal myopathy of the neck extensor muscles. Focal myopathy might be primary myositis or a stretched muscle injury. In Japan, several reports have argued that neck dystonia is the cause of DHS. There have been no reports to date that documented a focal myopathy of the neck extensor muscles. The aim of the present study was to investigate myopathic changes in the neck extensor muscles of PD patients with DHS by needle electromyography (EMG), and to evaluate the effect of steroid therapy.MethodsWe carried out needle EMG on 15 consecutive PD patients with DHS who visited our hospital between July 2009 and November 2011. The effects of prednisolone for the treatment of DHS were evaluated clinically and electrophysiologically.ResultsNeedle EMG of the neck extensor muscles in 15 PD patients with DHS revealed fibrillation potentials, positive sharp waves and small amplitude, short duration motor unit potentials in 14 patients. EMG findings were indicative of focal myopathy in five patients, and were compatible with focal myopathy in nine patients. DHS improved in eight out of 11 patients given prednisolone 20 mg/day. Follow‐up needle EMG after steroid therapy in four patients showed improvements in the myopathic changes.ConclusionWe report that focal myopathy of the neck extensor muscles is common in Japanese PD patients with DHS. Our findings suggest that steroid therapy might improve DHS in some PD patients.

REM sleep behavior disorder in Japanese patients with Parkinson’s disease: a multicenter study using the REM sleep behavior disorder screening questionnaire

REM sleep behavior disorder (RBD) is known to be observed more frequently in patients with an α-synucleinopathy such as Parkinson's disease (PD) than in the general population. The precise prevalence of RBD in Japanese PD patients is not known. Therefore, we investigated the prevalence and the clinical characteristics of patients with RBD in a large population of Japanese patients with PD. We investigated various clinical features and employed the Japanese version of the RBD screening questionnaire on 469 non-demented Japanese PD patients in this multicenter study. Probable or possible RBD was detected in 146 patients (31.1%) and was significantly associated with longer PD duration, higher Hoehn and Yahr stage, higher Unified Parkinson's Disease Rating Scale part III subscale (7 items), more motor fluctuations, and a higher levodopa-equivalent daily dose (p < 0.01). As to the major autonomic dysfunctions, severe constipation was significantly more frequent in PD patients with RBD than in those without it (p < 0.01). The RBD symptoms of 53 patients (39.0%) preceded the onset of PD motor symptoms. The median interval from the onset of RBD symptoms to PD motor symptoms was 17.5 years, and 3 patients had intervals of over 50 years. This large-scale multicenter study revealed that RBD is a frequent non-motor symptom in Japanese patients with PD, which may precede the onset of motor symptoms. Moreover, RBD that increases with the duration and severity of PD may be associated with autonomic dysfunction.

Validation of the Japanese translation of the Swallowing Disturbance Questionnaire in Parkinson’s disease patients

The Swallowing Disturbance Questionnaire (SDQ) was developed as a self-rated screening tool for dysphagia in patients with Parkinson's disease (PD). We developed the Japanese version of this questionnaire (SDQ-J), according to the cross-cultural adaptation guidelines, and examined its reliability. Subjects were 61 Japanese patients with PD (mean age, 67.0 ± 9.2 years) who answered the SDQ-J before undergoing videofluoroscopic examination of swallowing (VF). We compared the findings of the questionnaire with the patients' aspiration status during VF. Cronbach's alpha coefficient for the 15 questions of the SDQ-J was 0.84. According to the SDQ-J, 15 patients (24.6%) were diagnosed with dysphagia, while 9 patients (14.8%) aspirated liquid during VF. The sensitivity and specificity of the SDQ-J in predicting aspiration were 77.8 and 84.6%, respectively; therefore, the SDQ-J significantly predicted aspiration during VF (P < 0.01). The positive predictive value (PPV) and negative predictive value (NPV) for the SDQ-J were 0.46 and 0.96, respectively. The SDQ-J appears to be a reliable and useful screening tool for Japanese PD patients with aspiration. As the NPV was higher than the PPV in the SDQ-J, this questionnaire could potentially be used for early identification of severe dysphagia in patients with PD.

Rapid screening of ATP13A2 variant with high‐resolution melting analysis

Several genetic and environmental factors are involved in the pathogenesis of Parkinson's disease (PD). Recently, a novel variant of ATP13A2 (p.A746T) responsible for PARK9 was reported as a risk factor for PD in the Han-Chinese population. To investigate the role of this variant in Japanese PD patients, we examined 917 Japanese PD patients (871 index cases) and 190 controls by high-resolution melting curve analysis. We detected heterozygous p.A746T variant in a single patient with sporadic PD and a single control subject. These results suggest that ATP13A2 p.A746T variant is unlikely to play a role as a common risk factor or a pathogenic mutation for PD at least in Japanese. Our data on Japanese differ from those reported recently on Han-Chinese. Further studies are needed to confirm conclusions on roles of ATP13A2 variant in Asians or other populations.

Dopamine agonist‐induced antecollis in Parkinson's disease

Few cases of dopamine agonist-induced antecollis in Parkinson's disease (PD) have been reported. Literature review of 16 PD patients including our 3 cases with dopamine agonist-induced antecollis showed predominance of (1) Japanese, (2) women, and (3) Hoehn-Yahr stage of >or=3. We experienced three Japanese PD patients who subacutely exhibited antecollis following increased dopamine agonist dose that improved just after withdrawal of the agonist. One patient developed antecollis during increasing pramipexole dose in combination with cabergoline. Antecollis in another patient appeared during increasing pramipexole dose; it worsened after substituting pergolide for pramipexole, but improved after withdrawal of pergolide. Our cases indicate that there is no specific dopamine agonist causing antecollis, and it is possibly caused by a number of single dopamine agonists or a combination of them. Dopamine agonist-induced antecollis should be considered when encountering antecollis in PD patients being treated with dopamine agonists and withdrawal of the agonist can improve symptoms.

Fatigue in Japanese patients with Parkinson's disease: A study using Parkinson fatigue scale

The objective of this multicenter cross-sectional study was to determine the prevalence of fatigue and factors contributing to it in a large sample of Japanese patients with Parkinson's disease (PD). We used the 16-item Parkinson Fatigue Scale (PFS-16), which was designed to assess fatigue exclusively associated with PD. We carried out this study using PFS-16, the Unified Parkinson's Disease Rating Scale, Zung's Self-Rating Depression Scale, Parkinson's Disease Sleep Scale (PDSS), and the PD quality of life (QOL) scale (PDQ-39) by interview using questionnaires and physical examination by neurologists in 361 nondemented PD patients. Fatigue (an average PFS score of 3.3 or greater) was revealed in 151 patients (41.8%). Multiple logistic regression analysis indicated that the significant independent variables related to the presence of fatigue were the scores of PDSS and PDQ-39. Depression score was not a significant contributing factor. Our study revealed that the prevalence of fatigue in Japanese PD patients is as high as that in Western countries, and that fatigue is a relatively independent symptom, although sleep disturbance may be associated with fatigue. Since fatigue is significantly related to QOL reduction, therapeutic interventions including treatment of sleep disturbance are important.