[Embolic stroke due to ascending aortic thrombus in a patient with treatment-resistant ulcerative colitis].

The patient was a 49-year-old man presenting with recurrent melena due to progressive ulcerative colitis. One day, he developed left lower facial weakness and dysarthria, and the next day, he was transferred to our hospital because of muscle weakness in his left upper and lower extremities. On admission, neurological findings revealed left hemiplegia, including left facial palsy, dysarthria, and left hemispatial neglect. Brain MRI with diffusion-weighted image showed a fresh infarction in the right anterior and middle cerebral artery territory. Contrast-enhanced CT showed thrombus in the ascending aorta in addition to occlusion of the right internal carotid artery, suggesting the diagnosis of cerebral infarction with an embolic source in the aortic lesion. The intra-aortic thrombus disappeared after 48th day of antithrombotic therapy. Laboratory findings revealed elevated blood viscosity, proteinase-3-anti-neutrophil cytoplasmic antibody (PR3-ANCA), and ß2GP1-IgG antibodies, suggesting that the cause of the aortic thrombus may be due to elevated blood viscosity and autoantibodies, as well as highly active ulcerative colitis.

Perry Disease: Bench to Bedside Circulation and a Team Approach.

With technological applications, especially in genetic testing, new diseases have been discovered and new disease concepts have been proposed in recent years; however, the pathogenesis and treatment of these rare diseases are not as well established as those of common diseases. To demonstrate the importance of rare disease research, in this paper we focus on our research topic, Perry disease (Perry syndrome). Perry disease is a rare autosomal dominant neurodegenerative disorder clinically characterized by parkinsonism, depression/apathy, weight loss, and respiratory symptoms including central hypoventilation and central sleep apnea. The pathological classification of Perry disease falls under TAR DNA-binding protein 43 (TDP-43) proteinopathies. Patients with Perry disease exhibit DCTN1 mutations, which is the causative gene for the disease; they also show relatively uniform pathological and clinical features. This review summarizes recent findings regarding Perry disease from both basic and clinical perspectives. In addition, we describe technological innovations and outline future challenges and treatment prospects. We discuss the expansion of research from rare diseases to common diseases and the importance of collaboration between clinicians and researchers. Here, we highlight the importance of researching rare diseases as it contributes to a deeper understanding of more common diseases, thereby opening up new avenues for scientific exploration.

Association between physical activity and health literacy in patients with Parkinson's disease: an online web survey.

BACKGROUND: For patients with Parkinson's disease (PwPD), promotion of habitual physical activity (PA) assists in the prevention of disease progression. Patients' health literacy (HL) is integral for meeting PA standards and turning it into a habit. This study evaluated the association between PA level and each HL domain in PwPD. METHODS: Online web-based assessment instruments and self-administered questionnaires, including the PA Questionnaire (IPAQ) Short Form and the Functional, Communicative, and Critical Health Literacy (FCCHL) scale, were used to assess PA levels and health literacy domains of PwPD. RESULTS: The mean age of PwPD (n = 114) was 65.9 (SD = 11.6) years; 59.6% female, and the mean duration of disease was 6.4 (SD = 5.1) years. Of participants, 47.4% met the recommended criteria for PA. When comparing each HL domain by PA level, participants with lower PA had significantly lower critical HL (p = 0.03). Logistic regression analysis revealed that PA level correlated with critical HL (OR = 2.46; 95% CI = 1.16-5.19; p = 0.02). CONCLUSIONS: Adherence to recommended PA standards was associated with critical HL, but not other HL domains. Proactive attitudes to critically evaluate and utilize as well as understand health information may positively influence the promotion of PA.

Siblings with Cockayne Syndrome B Type III Presenting with Slowly Progressive Cerebellar Ataxia.

Two patients, 48- and 50-year-old sisters, presented with a characteristic facial appearance with slowly progressive deafness and cerebellar ataxia starting in their 30s. Genetic testing identified compound heterozygous pathogenic variants in the ERCC6 gene: c.1583G>A (p.G528E) and c.1873T>G (p.Y625D). A diagnosis of Cockayne syndrome (CS) B type III was made. CS is usually diagnosed in childhood with well-defined facial characteristics and photosensitivity. This case report describes rare cases of adulthood CS with a primary presentation of slowly progressing deafness and cerebellar ataxia. CS should be considered in adults with characteristic facial and skin findings, deafness, and cerebellar ataxia.

Impact of non-motor fluctuations on QOL in patients with Parkinson's disease.

Introduction: Long-term levodopa treatment in patients with Parkinson's disease (PwPD) often causes motor fluctuations, which are known to affect their quality of life (QOL). These motor fluctuations may be accompanied by fluctuations in non-motor symptoms. There is no consensus on how non-motor fluctuations affect QOL. Methods: This was a single-center, retrospective study and included 375 patients with Parkinson's disease (PwPD) who visited the neurology outpatient department of Fukuoka University Hospital between July 2015 and June 2018. All patients were evaluated for age, sex, disease duration, body weight, and motor symptoms by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, depression scale by the Zung self-rating depression scale, apathy scale, and cognitive function by the Japanese version of The Montreal Cognitive Assessment. A nine-item wearing-off questionnaire (WOQ-9) was used to assess the motor and non-motor fluctuations. QOL in PwPD was investigated using the eight-item Parkinson's Disease Questionnaire (PDQ-8). Results: In total, 375 PwPD were enrolled and classified into three groups according to the presence or absence of motor and non-motor fluctuations. The first group included 98 (26.1%) patients with non-motor fluctuations (NFL group), the second group included 128 (34.1%) patients who presented with only motor fluctuations (MFL group), and the third group included 149 (39.7%) patients without fluctuations in motor or non-motor symptoms (NoFL group). Among them, the PDQ-8 SUM and SI were significantly higher in the NFL group than in the other groups (p < 0.005), implying that the NFL group had the poorest QOL among groups. Next, multivariable analysis showed that even one non-motor fluctuation was an independent factor that worsened QOL (p < 0.001). Conclusion: This study showed that PwPD with non-motor fluctuation had a lower QOL than those with no or only motor fluctuation. Moreover, the data showed that PDQ-8 scores were significantly reduced even with only one non-motor fluctuation.

Evaluation of perception threshold and pain in patients with Parkinson's disease using PainVision®.

Introduction: Pain is one of the most frequent non-motor symptoms occurring in patients with Parkinson's disease (PD). Traditionally, the Visual Analog Pain Scale (VAS), Numerical Rating Scale (NRS), and Wong-Baker Faces Pain Rating Scale (FRS) have been used for clinical pain assessment, but these assessments are subjective at best. In contrast, PainVision® is a perceptual/pain analyzer that can quantitatively evaluate pain as "pain intensity" based on "current perception threshold" and "pain equivalent current." We evaluated the current perception threshold in all PD patients and pain intensity in PD patients with pain using PainVision®. Methods: We recruited 48 patients with PD (PwPD) with pain and 52 PwPD without pain. For patients with pain, we measured current perception threshold, pain equivalent current, and pain intensity using PainVision®, in addition to evaluation by VAS, NRS, and FRS. For patients without pain, only current perception threshold was measured. Results: There was no correlation with either VAS or FRS, whereas only weak correlation was identified for NRS (γ = -0.376) with pain intensity. Current perception threshold was positively correlated with duration of the disease (γ = 0.347) and the Hoehn and Yahr stage (γ = 0.259). As a quantitative evaluation of pain, pain intensity by PainVision® does not correlate with conventional subjective pain assessments. Discussion: This new quantitative evaluation method of pain may be suitable as an evaluation tool for future intervention research. Current perception threshold in PwPD was related to the duration and severity of the disease and may be involved in peripheral neuropathy associated with PD.

Impact of Parkinson's Disease on Caregiver Quality of Life in Japan.

Background: Parkinson's disease (PD) adversely affects the quality of life (QoL) of not only patients but also their caregivers. Objective: To determine the factors that most impact the QoL of family caregivers of patients with PD in a large Japanese population using data from the Japanese Quality-of-Life Survey of Parkinson's Disease (JAQPAD) study. Methods: Questionnaires, including the Parkinson's Disease Questionnaire-Carer (PDQ-Carer), were distributed to patients and their caregivers. Univariate and multivariate regression analyses were performed with the PDQ-Carer Summary Index (SI) score as the dependent variable to determine the factors that impact caregiver QoL. Results: Overall, 1,346 caregivers were included in the analysis. Female sex, unemployment, caring for a patient with a high-level need for nursing care, and a high Nonmotor Symptoms Questionnaire score were factors with a significant negative impact on caregiver QoL. Conclusion: Results from this study identified several factors that affect caregiver QoL in Japan.

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

BACKGROUND: Dyskinesia 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. METHODS: We 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. RESULTS: Of 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). CONCLUSION: Female 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.

HTLV-1-associated demyelinating neuropathy: A case report and review of the literature.

A 78-year-old man developed paresthesias in the extremities. He was referred to our hospital because of positive anti-human T-cell leukemia virus type 1 (HTLV-1) antibodies in the serum and the presence of abnormal lymphocytes. He was diagnosed as chronic-type adult T-cell leukemia/lymphoma. Neurological examination revealed sensory impairment in the distal parts of the extremities with loss of deep tendon reflexes. Nerve conduction study showed motor and sensory demyelinating polyneuropathy, indicating a diagnosis of HTLV-1-associated demyelinating neuropathy. Corticosteroid therapy followed by intravenous immunoglobulin therapy improved his symptoms. Since demyelinating neuropathy associated with HTLV-1 infection is not well recognized, we here report its characteristics and clinical course through our case report and literature review.

Neurologists' preferences for device-aided therapy for advanced Parkinson's disease in Japan.

OBJECTIVE: This study measures the relative preference for attributes of device-aided therapies (DATs) for advanced Parkinson's Disease (PD) from the perspective of Japanese neurologists. METHODS: Attributes and levels were elicited based on literature and interviews with certified neurologists experienced with DATs. An online survey including a discrete choice experiment (DCE) was developed, pilot tested, and distributed through an online panel to neurologists treating advanced PD patients. Participants were asked to choose treatments among several choice sets of two hypothetical DATs described only by the attributes, or no DAT (continuing oral treatment). A conditional logit model using the Bayesian framework was developed to estimate the marginal utilities of attributes' levels, and the relative utility of treatments available to Japanese advanced PD patients or being developed in Japan was assessed. RESULTS: The DCE survey completed by 308 neurologists showed that the attributes with the greatest influence on DAT selection were surgery requirement (relative importance of 28%), average increase in the duration of daily "on" time without dyskinesia which affects daily activities (15%), average change in cognitive function related to treatment introduction (15%), device management frequency (14%), average number of pills of oral PD medication after treatment introduction (13%), average influence of treatment on symptoms of depression (12%), and type of device (large/small) (3%). All attributes significantly influenced respondents' choices, except for external device type. Experience with DATs did not influence the directions of preferences. Out of treatment profiles representing DATs, continuous subcutaneous infusion of levodopa-carbidopa had a higher preference score than levodopa-carbidopa intestinal gel infusion and deep brain stimulation. CONCLUSIONS: Our findings suggest that Japanese neurologists would prefer a DAT without surgery requirement. Other factors related to efficacy, safety, and administration mode have a significant, but a smaller influence on prescription choices.

Impact of weight loss for depressive symptom in mid-stage patients with Parkinson's disease: a 4-year follow-up study.

Introduction: Weight loss is one of the non-motor symptoms frequently seen in patients with Parkinson's disease (PwPD). Weight loss in PwPD is known to be negatively associated with motor and other non-motor symptoms and has been shown to influence the prognosis of PD. In this study, we followed weight change over a 4-year period in PwPD at a single institution and investigated the relationship between weight change and patients' motor and non-motor symptoms. Methods: PwPD who visited our hospital from January 2018 to December 2022 were enrolled. Body weights were measured at two points in 2018 (at the start of observation, 'baseline') and 2022 (at the end of observation, 'end date'). In addition, motor symptoms, disease severity, cognitive function, and psychiatric symptoms were evaluated during the same period, and the relationship with weight loss was examined. Results: Data of 96 PwPD were available for a 4-year follow-up. At baseline, the mean age was 65.7 ± 10.0 years, the mean disease duration was 6.8 ± 4.0 years, and the mean Hoehn and Yahr stage was 2.4 ± 0.7. Among them, 48 patients (50.0%) had a weight loss of ≥5% from baseline (weight loss group; mean loss was 6.6 ± 2.9 kg). The weight loss group was older (p = 0.031), had a lower Mini-Mental State Examination (MMSE) at baseline (p = 0.019), a significantly lower body mass index (p < 0.001), and a higher Zung Self-Rating Depression Scale (SDS) (p = 0.017) at the end date. There was a negative correlation (γ = -0.349, p < 0.001) between weight change and age, a positive correlation (γ = 0.308, p = 0.002) between weight change and MMSE at baseline, and a negative correlation (γ = -0.353, p < 0.001) between weight change and SDS at the end date. Age-adjusted correlations showed a final negative correlation (γ = -0.331, p = 0.001) between weight change and SDS. MMSE and age-adjusted correlations showed a low negative correlation (γ = -0.333, p = 0.001) between weight change and SDS at the end date. Conclusion: Weight loss in PwPD in mid-stage was more likely with increasing age, and ≥ 5% weight loss was associated with worsening depression. Further research is needed regarding the significance of weight loss in PwPD.

Role of cytochrome P450 for vitamin D metabolisms in patients with neurodegenerative disorders.

Introduction: We previously reported lower serum 25-hydroxyvitamin D concentrations in patients with Alzheimer's disease (AD), Parkinson's disease (PD) and Multiple system atrophy (MSA) compared to healthy controls (HC), whereas 1,25-di-hydroxyvitamin D levels were solely lower in MSA patients. We investigate serum concentrations of P450 involved in Vitamin D(VD) hydroxylation to clarify the responsible hydroxylase for the low serum concentrations of VD metabolites. Methods: A total of 79 individuals were enrolled including 20 HC, 20 AD, 19 PD and 20 MSA patients. The serum concentrations of P450 involved in VD hydroxylation were assayed by ELISA. The data were analyzed by the nonparametric Kruskal-Wallis test between groups. Results: Though CYP2R1 and CYP27A1 mediate 25-hydroxylation for VD, CYP2R1 is the main hydroxylase, and CYP27A1 is also involved in VD synthesis. CYP2R1 concentrations showed no differences among groups, while lower CYP27A1 concentrations were found in PD (p < 0.05) and MSA (p < 0.005) compared to HC and differences between AD and MSA (p < 0.05), however no differences between PD and MSA. CYP27B1 is the main 1α-hydroxylase for 25-hydroxyvitamin D and showed differences between HC and PD (p < 0.05), between HC and MSA (p < 0.005) and between PD and MSA (p = 0.055). CYP24A1, which inactivate 1,25-di-hydroxyvitamin D, showed no differences among groups. Conclusions: CYP27A1 might affect VD synthesis and cause low 25-hydroxyvitamin D levels in AD, PD and MSA patients. Low 1,25-di-hydroxyvitamin D levels in MSA patients might be caused by impaired feedback mediated by CYP27B1.

Constipation Symptoms in Multiple System Atrophy Using Rome Criteria and Their Impact on Personalized Medicine.

Constipation is one of the most common non-motor symptoms in multiple system atrophy (MSA); however, it has not been evaluated according to the standard diagnostic criteria for constipation in patients with MSA. We evaluated the characteristics of constipation in patients with MSA by using Rome criteria (Rome III), which has been validated and the widely used for gastrointestinal disorders. Fifty-one patients with MSA (29 female) were enrolled in the study. Based on the Rome III criteria, constipation was diagnosed in 29 patients (56.9%); irritable bowel syndrome was not detected. Thirty-seven patients (72.5%) were aware of their constipation. The most common constipation symptom was the sensation of anorectal obstruction (68.6%). Patients' self-awareness of constipation was most strongly correlated to the sensation of incomplete evacuation (odds ratio: 7.377, 95% confidence interval: 1.402−38.817). The number of constipation-related symptoms was correlated with the total levodopa equivalent dose (p < 0.05). Rome criteria, which can detect various constipation symptoms, are useful for evaluating constipation in MSA, and these findings may greatly impact personalized medicine.

Unilateral GPi-DBS Improves Ipsilateral and Axial Motor Symptoms in Parkinson's Disease as Evidenced by a Brain Perfusion Single Photon Emission Computed Tomography Study.

Introduction: Deep brain stimulation (DBS) is an effective treatment for advanced Parkinson's disease (PD) with the targeting bilateral subthalamic nucleus or globus pallidus internus (STN or GPi-DBS). So far, detailed studies on the efficacy of unilateral STN-DBS for motor symptoms have been reported, but few studies have been conducted on unilateral GPi-DBS. Materials and Methods: Seventeen patients with Parkinson's disease (PwPD) who underwent unilateral GPi-DBS were selected. We conducted comparison analyses between scores obtained 6-42 months pre- and postoperatively using the following measurement tools: the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III, the Hoehn and Yahr stage, the presence/absence of dyskinesia, Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), Geriatric Depression Scale (GDS), levodopa equivalent dose (LED), and cerebral blood flow by single photon emission computed tomography (SPECT). Patient backgrounds were compared between four cohorts with favorable (good responders, ≥50% improvement) and unfavorable (poor responders, <50% improvement) postoperative outcome. Results: Significant improvement was observed postoperatively in the following: total MDS-UPDRS Part III scores during the off period, contralateral scores, ipsilateral scores, and axial scores. Similarly, the Hoehn and Yahr stages during the off period, and GDS also showed significant decrease. In contrast, LED, MMSE, and FAB remained unchanged while the number of patients who scored positive for dyskinesia decreased by 40%. Abnormal cerebral blood flow preoperatively seen in the cerebral cortex had normalized in the total score-based good responder cohort. In the ipsilateral score-based good responder cohort, cerebral blood flow increased in the contralateral frontal lobe including in the premotor cortex, contralateral to the DBS. Compared to the poor responders, postoperative good responders demonstrated significantly higher preoperative MMSE scores. Discussion: Unilateral GPi-DBS therapy was effective in improving contralateral, ipsilateral, and axial motor symptoms of patients with advanced PD; in particular, it was found to be especially beneficial in PwPD whose cognitive function was unimpaired; the treatment efficacy rivaled that of bilateral counterparts up till at least 6 months postoperatively. Finally, normalization of preoperative abnormalities in cerebral blood flow and increased cerebral blood flow in the contralateral frontal lobe indicated the beneficial potential of this therapy on ipsilateral motor symptoms.

Polymyalgia Rheumatica Following COVID-19 Vaccination.

We herein report a 71-year-old woman presented with a fever, arthralgia, general malaise and leg muscle stiffness following administration of the COVID-19 mRNA vaccine (Comirnaty, Pfizer-BioNTech). Laboratory findings showed an elevated C-reactive protein level and erythrocyte sedimentation rate. In addition, Gallium-67 scintigraphy demonstrated an increased uptake in multiple joints. Typing of human leukocyte antigen (HLA) revealed the presence of the DRB1*0404/*0803 allele. These findings met the diagnostic criteria for polymyalgia rheumatica (PMR), and when we started steroid treatment, her symptoms improved rapidly. This patient developed PMR after receiving a COVID-19 mRNA vaccine (Comirnaty, Pfizer-BioNTech). This case is considered to be valuable, as the HLA-DRB1 allele was also confirmed.

Efficacy and safety evaluation of safinamide as an add-on treatment to levodopa for parkinson's disease.

INTRODUCTION: While levodopa is still the most effective treatment for Parkinson's disease, concerns about long-term complications such as wearing-off and dyskinesia with levodopa usage remain. AREAS COVERED: Safinamide is a highly selective and reversible monoamine oxidase B inhibitor introduced in the European Union, Japan, and the United States as an adjunctive agent to levodopa in PD patients with motor fluctuation. This review outlines the pharmacological properties, therapeutic effects, and tolerability of safinamide as an adjunct to levodopa in patients with advanced PD. Efficacy and safety findings from double-blind and placebo-controlled clinical trials for safinamide as an adjunct therapy to levodopa for PD are summarized. EXPERT OPINION: Safinamide was well tolerated as a treatment for PD, and there was no significant difference in the frequency and severity of adverse events between the safinamide and placebo groups. It was also suggested that safinamide had a beneficial effect on the accompanying non-motor symptoms such as PD-related pain. Safinamide may exhibit neuroprotective effects through antioxidant and anti-glutamate effects, and research on the disease-modifying effect of PD is desired in the future.

[Japanese translation and linguistic validation of King's Parkinson's Disease Pain Scale (KPPS) and King's Parkinson's Disease Pain Questionnaire (KPPQ)].

Pain is one of the most frequent non-motor symptoms associated with Parkinson's disease (PD) and it has a great impact on patient's quality of life. Thus, its quantitative evaluation is critical in establishing therapeutic evidence. The King's Parkinson's Disease Pain Scale (KPPS) was introduced as a scale of pain specific to PD in 2015. As a follow-up to the evaluator-based KPPS, the patient-based questionnaire, the King's Parkinson's Disease Pain Questionnaire (KPPQ), was introduced in 2018. We developed a linguistically validated Japanese version of the KPPS and KPPQ, and the process of its construction is reported in this study.

Fluctuating pain in Parkinson's disease: Its prevalence and impact on quality of life.

Pain is a common non-motor symptom in Parkinson's disease (PD) patients, and the incidence of fluctuating pain may be improved by taking levodopa. There are only a few detailed reports regarding fluctuating pain. In this study, 331 PD patients were classified into three groups: no-pain group (67.4%), non-fluctuating pain group (22.1%), and fluctuating pain group (10.6%). We evaluated patients' background and its impact on the quality of life (QOL) of each group. The pain group exhibited higher levels of depression (p < 0.0001), had a higher frequency of visual hallucinations (p = 0.007), and lower QOL (p < 0.0001) compared with the no-pain group. The fluctuating pain group had a younger onset (p = 0.006), higher Hoehn & Yahr stage (p = 0.018), and higher frequency of wearing-off (p < 0.001) and dyskinesia (p = 0.007) than the other groups. We compared the Parkinson's Disease Questionnaire-8 summary index (PDQ-8 SI) in each pain group to the no-pain group using analysis of variance. As a result, PDQ-8 SI was significantly higher in both the non-fluctuating and fluctuating pain groups (p < 0.0001). Pain is regarded as a non-negligible symptom that affects the QOL of PD patients, and given the unique characteristics, fluctuating pain might be considered as an independent clinical subtype of PD.

Off Time Independently Affects Quality of Life in Advanced Parkinson's Disease (APD) Patients but Not in Non-APD Patients: Results from the Self-Reported Japanese Quality-of-Life Survey of Parkinson's Disease (JAQPAD) Study.

INTRODUCTION: Parkinson's disease (PD) is characterized by a triad of motor symptoms and several nonmotor symptoms (NMS). Identifying the most appropriate treatment is essential for improving patient quality of life (QoL). However, it is still not known which PD symptoms more commonly affect patients with advanced PD (APD) versus non-APD. This study examined the factors that most affected the QoL of patients with APD (defined using the 5-2-1 criteria: ≥5 oral levodopa doses a day, off time ≥2 hours a day, or troublesome dyskinesia ≥1 hour a day) versus non-APD in a large Japanese population using the Japanese Quality-of-Life Survey of Parkinson's Disease (JAQPAD) study. METHODS: Participants in this self-reported survey-based study included all members of the Japan Parkinson's Disease Association. Questionnaires assessing NMS and QoL (e.g., the 8-item PD Questionnaire [PDQ-8]) were included. Univariate and multivariate regression analyses were conducted to identify clinical factors impacting QoL using the PDQ-8 Summary Index (PDQ-8 SI). RESULTS: Of the 3022 eligible patients, 864 were classified as having non-APD and 1599 as having APD. QoL as assessed by the PDQ-8 SI was notably worse in patients with APD versus non-APD (39.2 vs. 26.9, p < 0.0001). Although off time affected QoL only in patients with APD, PD duration and the NMS Questionnaire score significantly contributed to the QoL in both patients with APD and non-APD. CONCLUSIONS: This study identified the factors more commonly associated with worse QoL in patients with APD versus non-APD. Our findings offer new insights for providing optimal treatment and improving treatment satisfaction in patients with PD.