The Interrelationship of Benefit Finding, Demoralization, and Stigma among Patients with Parkinson's Disease and Their Caregivers.

Parkinson's disease (PD) is a debilitating neurodegenerative disease with a relentlessly progressive course of illness. This study aimed to assess the dyadic dynamics of benefit finding (BF), demoralization, and stigma on the depression severity of PD patients and their caregivers. This study used a cross-sectional design with purposive sampling. In total, 120 PD patients and 120 caregivers were recruited from the neurological ward or neurological outpatient clinic of a medical center in Taiwan from October 2021 to September 2022. PD patients and their caregivers were enrolled and assessed using the Mini International Neuropsychiatric Interview, the Benefit Finding scale, Demoralization Scale, Stigma Subscale of the Explanatory Model Interview Catalogue, and Taiwanese Depression Questionnaire. Among the 120 patients and 120 caregivers that successfully completed the study, 41.7% (N = 50) and 60% (N = 72) were female, respectively. The most common psychiatric diagnoses of both the PD patients (17.5%) and their caregivers (13.3%) were depressive disorders. Using structural equation modeling, we found that the stigma, BF, and demoralization of PD patients might contribute to their depression severity. Demoralization and stigma of PD patients' caregivers might also contribute to the depression severity of PD patients. Caregivers' BF and demoralization were significantly linked with their depression severity. PD patients' BF degree and their caregivers' BF degree had significant interactive effects. Both patients' and their caregivers' stigma levels had significant interactive effects. Clinicians should be aware of and manage these contributing factors between PD patients and their caregivers in order to prevent them from exacerbating each other's depression.

Genetic analysis of IRF2BPL in a Taiwanese dystonia cohort: The genotype and phenotype correlation.

OBJECTIVE: IRF2BPL mutation has been associated with a rare neurodevelopmental disorder with abnormal movements, including dystonia. However, the role of IRF2BPL in dystonia remains elusive. We aimed to investigate IRF2BPL mutations in a Taiwanese dystonia cohort. METHODS: A total of 300 unrelated patients with molecularly unassigned isolated (n = 256) or combined dystonia (n = 44) were enrolled between January 2015 and July 2023. The IRF2BPL variants were analyzed based on whole exome sequencing. The in silico prediction of the identified potential pathogenic variant was performed to predict its pathogenicity. We also compared the clinical and genetic features to previous literature reports. RESULTS: We identified one adolescent patient carrying a de novo heterozygous pathogenic variant of IRF2BPL, c.379C>T (p.Gln127Ter), who presented with generalized dystonia, developmental regression, and epilepsy (0.33% of our dystonia cohort). This variant resides within the polyglutamine (poly Q) domain before the first PEST sequence block of the IRF2BPL protein, remarkably truncating the protein structure. Combined with other patients with IRF2BPL mutations in the literature (n = 60), patients with variants in the poly Q domain have a higher rate of nonsense mutations (p < 0.001) and epilepsy (p = 0.008) than patients with variants in other domains. Furthermore, as our index patient, carriers with substitutions before the first PEST sequence block have significantly older age of onset (p < 0.01) and higher non-epilepsy symptoms, including generalized dystonia (p = 0.003), and ataxia (p = 0.003). INTERPRETATION: IRF2BPL mutation is a rare cause of dystonia in our population. Mutations in different domains of IRF2BPL exhibit different phenotypes.

Blood neurofilament light chain as a surrogate marker for dystonia.

BACKGROUND AND PURPOSE: Dystonia is a heterogeneous movement disorder, and it remains unclear whether neurodegeneration is involved. Neurofilament light chain (NfL) is a biosignature of neurodegeneration. We aimed to investigate whether plasma NfL levels were elevated and associated with disease severity in patients with dystonia. METHOD: We enrolled 231 unrelated dystonia patients (isolated dystonia n = 203; combined dystonia n = 28) and 54 healthy controls from movement disorder clinics. Clinical severity was evaluated using the Fahn Marsden Dystonia Rating Scale, the Unified Dystonia Rating Scale, and the Global Dystonia Rating Scale. Blood NfL levels were measured by single-molecule array. RESULTS: Plasma NfL levels were significantly higher in those with generalized dystonia compared to those with focal dystonia (20.1 ± 8.8 vs. 11.7 ± 7.2 pg/mL; p = 0.01) or controls (p < 0.01), while the level was comparable between the focal dystonia group and controls (p = 0.08). Furthermore, the dystonia combined with parkinsonism group had higher NfL levels than the isolated dystonia group (17.4 ± 6.2 vs. 13.5 ± 7.5 pg/mL; p = 0.04). Notably, whole-exome sequencing was performed in 79 patients and two patients were identified as having likely pathogenic variants: one had a heterozygous c.122G>A (p.R41H) variant in THAP1 (DYT6) and the other carried a c.1825G>A (p.D609N) substitution in ATP1A3 (DYT12). No significant correlation was found between plasma NfL levels and dystonia rating scores. CONCLUSION: Plasma NfL levels are elevated in patients with generalized dystonia and dystonia combined with parkinsonism, suggesting that neurodegeneration is involved in the disease process of this subgroup of patients.

Higher prevalence of idiopathic normal pressure hydrocephalus-like MRI features in progressive supranuclear palsy: An imaging reminder of atypical parkinsonism.

OBJECTIVES: The classic triad of idiopathic normal pressure hydrocephalus (NPH) encompass gait disturbance, cognitive impairment, and urinary incontinence. These symptoms overlap with parkinsonism but with distinct treatment. Lacking applicable differentiation also hampers the prediction to therapeutic response. Here, we try to clarify this issue among different Parkinsonian syndromes and propose some innovative thinking while approaching a patient with parkinsonism and hydrocephalus concomitantly. METHODS: Twenty-four patients with clinical probable multiple system atrophy (MSA), 34 with probable progressive supranuclear palsy (PSP), and 58 with sex- and age-matched Parkinson's disease (PD) were enrolled. Evans' index (EI), callosal angle (CA), antero-posterior (AP) diameter of the midbrain, length of the midbrain tegmentum diameter (MBTegm ), and disproportionately enlarged subarachnoid space hydrocephalus (DESH) were evaluated using the conventional MRI. Logistic regression was applied to identify the independent variables in hydrocephalus. RESULTS: Patients with PSP had higher mean EI than those with MSA and PD. Around 38.2% of patients with PSP had accompanied hydrocephalus (EI > 0.3). Parkinsonism subtypes (PD, MSA, or PSP), AP diameter of the midbrain, and MBTegm were significantly different among patients with and without hydrocephalus. After regression analysis, parkinsonism subtype stood out to be the most key risk factor of hydrocephalus. The comparison between patients with PSP with and without hydrocephalus did not disclose specific clinical characteristics or risk factors. CONCLUSIONS: This study demonstrates that the presence of NPH-like MRI features is much higher in PSP patients, and this tendency is decided upon the determination of parkinsonism subtype. Sharing pathophysiological characteristics in these two diseases is implied. More diagnostic tools are needed to better differentiate the two diseases and decide the treatment. To closely observe hydrocephalic parkinsonism patients and well inform the possible limited shunting benefits if PSP core features appear, will be more pivotal and practical at present clinical practice.

Genetic analysis of IMPDH2 gene in Taiwanese patients with isolated or combined dystonia.

The inosine monophosphate dehydrogenase gene (IMPDH2) was recently reported as a novel gene associated with autosomal dominantly inherited dystonia. We investigated 245 Taiwanese patients with molecularly unassigned isolated or combined dystonia without features of neurodevelopmental disorders and found none had pathogenic variants. Our findings suggest that IMPDH2 may not play a major role in dystonia.

Clinical and genetic characterization of a Taiwanese cohort with spastic paraparesis combined with cerebellar involvement.

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders clinically characterized by progressive lower-limb spasticity. Cerebellar ataxia commonly co-occurs with complicated HSPs. HSP with concurrent cerebellar ataxia has significant clinical and genetic overlaps with hereditary cerebellar ataxia (HCA) and other inherited neurological diseases, adding to the challenge of planning genetic testing for the disease. In this study, we characterized clinical features of a cohort of 24 patients (male/female: 15/9) from 22 families who presented spastic paraparesis combined with cerebellar involvement, with a median disease onset age 20.5 (range 5-53) years. Aside from the core phenotype, 18 (75%) patients had additional neuropsychiatric and systemic manifestations. A stepwise genetic testing strategy stratified by mode of inheritance, distinct neuroimaging features (e.g., thin corpus callosum), population-specific prevalence and whole-exome sequencing was utilized to investigate the genetic etiology. Causative mutations in up to 10 genes traditionally related to HSP, HCA and other neurogenetic diseases (autosomal recessive spastic ataxia of Charlevoix-Saguenay, neurodegeneration with brain iron accumulation, and progressive encephalopathy with brain atrophy and thin corpus callosum) were detected in 16 (73%) of the 22 pedigrees. Our study revealed the genetic complexity of HSP combined with cerebellar involvement. In contrast to the marked genetic diversity, the functions of the causative genes are restricted to a limited number of physiological themes. The functional overlap might reflect common underlying pathogenic mechanisms, to which the corticospinal tract and cerebellar neuron circuits may be especially vulnerable.

Prevalence and Risk Factors of Depression between Patients with Parkinson's Disease and Their Caregivers: A One-Year Prospective Study.

Depression is a common comorbidity in patients with Parkinson's disease (PD) and in their caregivers. This study aimed to compare the prevalence and risk factors of depression between patients with PD and their caregivers. In total, 113 patients with PD and 101 caregivers were enrolled. Patients with PD were assessed using the Mini International Neuropsychiatric Interview, Unified Parkinson's Disease Rating Scale (UPDRS), Activities of Daily Living (ADL), Hospital Anxiety and Depression Scale, Beck Hopelessness Scale, Brief Fatigue Inventory, Connor-Davidson Resilience Scale, and Big Five Inventory-10. Caregivers of patients with PD were also assessed using the above-mentioned instruments, with the exception of the UPDRS and ADL. During a 12-month follow-up period, depressive disorders were the most common psychiatric diagnosis of PD patients (27.4%) and their caregivers (17.8%). Depressive disorders were more prevalent in PD patients than in caregivers of PD patients throughout the entire follow-up phase. The severity of fatigue and severity of suicide risk were significantly associated with depression among patients with PD. The severity of pain and severity of anxiety were predictors of depression in caregivers of PD patients. The findings in this study provide references for early detection and treatment of depressive disorders in PD patients and their caregivers.

Morbidity and Associated Factors of Depressive Disorder in Patients With Parkinson's Disease.

ABSTRACT: Parkinson's disease (PD) is a progressive, neurodegenerative disorder and is commonly comorbid with depression. The aim of this cross-sectional study was to assess morbidity and associated factors of depression in patients with PD. In total, 181 patients with PD were enrolled and assessed using the Mini-International Neuropsychiatric Interview. Of the sample, 51% had at least one psychiatric diagnosis. The most prevalent psychiatric disorder was depressive disorder (27.6%), followed by rapid eye movement sleep behavior disorder (9.9%), insomnia disorder (8.8%), and adjustment disorder (2.8%). Severity of anxiety, suicide risk, and anxiolytics/hypnotics use were factors associated with depressive disorder in PD patients. Furthermore, severity of anxiety was significantly linked with suicide risk. We suggest that use of a standardized structured interview for early detection of depression in PD patients is crucial. Anxiety, anxiolytics/hypnotics use, depression, and suicide risks are interrelated and warrant clinical concerns regarding PD patients.

A Clinical and Integrated Genetic Study of Isolated and Combined Dystonia in Taiwan.

Dystonia is a clinically and genetically heterogeneous movement disorder. However, genetic causes of dystonia remain largely unknown in Asian subjects. To address this, we applied an integrated two-step approach that included gene dosage analysis and a next-generation sequencing panel containing 72 known genes causative for dystonia and related movement disorders to 318 Taiwanese patients with isolated or combined dystonia. Whole-genome sequencing was performed for one multiplex family with no known causative variant. The panel confirmed the genetic diagnosis in 40 probands (12.6%). A genetic diagnosis was more likely with juvenile onset compared with adult onset (24.2% vs 10.8%; P = 0.03) and those with combined features, especially with myoclonus, compared with isolated dystonia (35.3% vs 10.5%; P = 0.004). The most common causative genes were SGCE followed by GCH1, TH, CACNA1B, PRRT2, MR1, CIZ1, PLA2G6, and PRKN. Genetic causes were identified from single cases in TOR1A, TUBB4A, THAP1, ATP1A3, ANO3, GNAL, KMT2B, SLC6A3, ADCY5, CYP27A1, PANK2, C19orf12, and SPG11. The whole-genome sequencing analysis identified a novel intragenic deletion in OPHN1 in a multiplex family with X-linked dystonia and intellectual delay. Our findings delineate the genetic architecture and clinical spectrum of dystonia-causing pathogenic variants in an Asian population.

Investigating DYT1 in a Taiwanese dystonia cohort.

BACKGROUND/PURPOSE: A heterozygous three-nucleotide (GAG) in-frame deletion in the TOR1A gene causes the rare disease, dystonia (DYT1), which typically presents as focal limb dystonia during adolescence, then spreads to other limbs. This study investigated the frequency and clinical features of DYT1 in a Taiwanese dystonia cohort. METHODS: We performed targeted next generation sequencing in 318 patients with primary dystonia. We identified one DYT1 family with various types of dystonia, and we described the clinical presentations observed in this family during a 30-year follow-up. We compared the clinical characteristics to those reported in previous studies on DYT1 from 2000 to 2020. RESULTS: Among 318 patients, we identified only one DYT1 patient (0.3%) with an autosomal dominant family history of dystonia. The proband was a 43-year-old man that experienced progressive onset of focal lower limb dystonia from age 11 years. The disease spread caudal-rostrally to the upper limbs and cervical muscles. Prominent cervical dystonia was noted during follow-up, which was an atypical presentation of DYT1. Clinical assessments of other family members showed intrafamily variability. The proband's father and an affected sibling demonstrated only mild right-hand writer's cramp. A systematic review of previously reported DTY1 cases showed that Asian patients had a higher frequency of cervical dystonia (44.8%) than groups of Ashkenazi Jews (35%) and Non-Jewish Caucasians (30.5%) (P = 0.04). CONCLUSION: Our findings revealed that DYT1 is rare in a Taiwanese dystonia cohort. The presentation of marked cervical dystonia could be the main feature of Asian patients with DYT1.

Effect of Intraoperative Computed Tomography in Microelectrode Recording during Frameless Stereotactic Deep Brain Stimulation for Parkinson Disease.

BACKGROUND: Microelectrode recording (MER)-guided deep brain stimulation (DBS) remains the standard electrophysiological procedure to place the DBS lead at the optimal target. When single-track MER or test stimulation yields suboptimal results, trajectory adjustments are needed. Intraoperative computed tomography (iCT) can be useful to visualize the microelectrode and verify possible adjustments. The aim of this study was to evaluate the effect of iCT in MER during frameless stereotactic DBS for Parkinson disease (PD). METHODS: We retrospectively collected 28 PD patients, of whom 19 received iCT and 9 did not, and measured intracranial volume, cerebral volume, cerebrospinal fluid volume, and pneumocephalus volume. Euclidean distance was assessed according to merged preoperative brain CT and magnetic resonance imaging and postoperative brain CT. RESULTS: Fifty-six hemispheres in the 28 patients were analyzed for MER tracks. The patients who received iCT had a significantly lower mean number of MER tracks (1.6 vs. 2.6, P = 0.013) and lower mean Euclidean distance (2.2 mm vs. 2.7 mm, P = 0.033) compared with those who did not receive iCT. Although there was a trend of a decrease in pneumocephalus using intraoperative imaging, there was no significant difference in surgical time. CONCLUSIONS: iCT can reduce the number of MER tracks and increase surgical accuracy. Further studies are warranted to investigate whether iCT can reduce surgical complications and improve surgical outcomes.

A dyadic study of psychological well-being of individuals with Parkinson's disease and their caregivers.

Parkinson's disease (PD) is an incapacitating neurodegenerative disease. Patients with PD and their caregivers may have interactive effects on each other's psychological well-being. This study aimed to assess the dyadic dynamics of resilience, fatigue, and suicidal ideation on the depression severity of PD patients and their caregivers. In total, 175 PD patients and 175 caregivers were recruited at a medical center from August 2018 to May 2020. Structural equation modeling (SEM) was used to examine the actor/partner effects on the psychological well-being of both the PD patients and their caregivers. The most common psychiatric diagnoses of both the PD patients (28.6%) and their caregivers (11.4%) were depressive disorders. The PD patients' and their caregivers' fatigue, suicidal ideation, and lack of resilience were significantly associated with the severity of their depression, respectively. Interactive effects existed between psychological well-being of individuals with PD and their caregivers. Clinicians must be aware of, and manage, these contributing factors between PD patients and their caregivers in order to prevent them from worsening each other's depression.

Prevalence and Associated Factors of Depressive Disorder in Caregivers of Individuals With Parkinson Disease.

OBJECTIVE: Parkinson disease (PD) is a debilitating neurodegenerative disease. Caring for an individual with PD can have a variety of negative physical and psychological effects on caregivers which may challenge their ability to continue in their caretaking role. The aim of this study was to assess the prevalence and associated factors of depressive disorders in caregivers of individuals with PD using standardized instruments. METHODS: This study used a cross-sectional design with consecutive sampling. Study participants were recruited from the neurological ward or neurological outpatient clinic of a medical center from August 2018 to July 2019. Caregivers of persons with PD were enrolled and assessed using the Mini International Neuropsychiatric Interview, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Beck Hopelessness Scale, Brief Fatigue Inventory, Connor-Davidson Resilience Scale, and Big Five Inventory-10. RESULTS: Of the 162 caregivers that completed the study, 67.3% (n = 109) were females. The most common psychiatric diagnosis was depressive disorder (11.1%), followed by insomnia disorder (7.4%) and anxiety disorder not otherwise specified (4.3%); 28% of the caregivers had a psychiatric diagnosis. Using logistic regression analysis, it was found that duration of caregiving (odds ratio [OR] = 1.28; 95% CI, 1.05-1.58), severity of anxiety (OR = 1.86; 95% CI, 1.36-2.53), and severity of fatigue (OR = 1.08; 95% CI, 1.01-1.16) were 3 significant associated factors for the development of depression. CONCLUSION: Depression was the most prevalent psychiatric diagnosis in caregivers of people with PD. Early diagnosis of these caregivers is crucial to the offering of suitable support and treatment and might improve caregivers' quality of life.

Nutritional Status Associated with Molecular Biomarkers, Physiological Indices, and Clinical Severity in Parkinson's Disease Patients.

This study is intended to explore the associations between nutritional status and molecular biomarkers and the clinical severity of Parkinson's disease (PD), as well as to examine the differences in related factors between PD patients with normal nutrition and those with at risk for malnutrition. A cross-sectional assessment of 82 consecutive outpatients with PD was conducted using the mini nutritional assessment (MNA), Unified Parkinson's Disease Rating Scale (UPDRS), and the Hoehn and Yahr scale to determine the nutritional status, the clinical severity of PD, and the stage of the disease. Recordings of blood samples collected after 12 h of overnight fasting were also assessed in terms of serum levels of glycated hemoglobin (HbA1c), blood urea nitrogen (BUN), creatinine, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), hemoglobin (Hgb), folate, and vitamin B12. All participants were divided into normal nutrition and malnutrition risk groups via the MNA scores to compare the above-mentioned parameters. The results showed that the total MNA score was significantly correlated with some parts of the UPDRS scale (e.g., Sections 1 and 2) and the levels of HbAlc in PD patients and those with risk for malnutrition, with significantly lower weight and body mass index (BMI), and with lower levels of Hgb and HDL. Higher levels of cholesterol were observed in the malnutrition risk group as compared with the normal nutrition group. The findings suggest that the clinical severity of PD is associated with nutritional status. Body weight, BMI, and the levels of Hgb, cholesterol, and HDL could be, at least partially, important biological markers to monitor malnutrition and the progression of the disease.

TP3, an antimicrobial peptide, inhibits infiltration and motility of glioblastoma cells via modulating the tumor microenvironment.

Glioblastoma multiforme (GBM) is a cancer of the central nervous system with limited therapeutic outcomes. Infiltrating cancer cells are the contributing factor to high GBM malignancy. The intracranial brain cancer cell infiltration is a complex cascade involving adhesion, migration, and invasion. An arsenal of natural products has been under exploration to overcome GBM malignancy. This study applied the antimicrobial peptide tilapia piscidin 3 (TP3) to GBM8401, U87MG, and T98G cells. The cellular assays and microscopic observations showed that TP3 significantly attenuated cell adhesion, migration, and invasion. A live-cell video clip showed the inhibition of filopodia protrusions and cell attachment. Probing at the molecular levels showed that the proteolytic activities (from secretion), the mRNA and protein expression levels of matrix metalloproteinases-2 and -9 were attenuated. This result strongly evidenced that both invasion and metastasis were inhibited, although metastatic GBM is rare. Furthermore, the protein expression levels of cell-mobilization regulators focal adhesion kinase and paxillin were decreased. Similar effects were observed in small GTPase (RAS), phosphorylated protein kinase B (AKT) and MAP kinases such as extracellular signal-regulated kinases (ERK), JNK, and p38. Overall, TP3 showed promising activities to prevent cell infiltration and metastasis through modulating the tumor microenvironment balance, suggesting that TP3 merits further development for use in GBM treatments.

Spastic paraparesis as the first manifestation of Machado-Joseph disease: A case report and review of the literature.

Machado-Joseph disease (MJD), or spinocerebellar ataxia type 3, is characterized by remarkable clinical heterogeneity. We present a MJD family in which variable phenotypes were noted in affected members, including one presenting predominantly with spastic paraparesis. A review of the literature revealed that MJD with the initial presentation of spastic paraparesis is more frequently observed in cases of eastern Asian origin who carry a greater CAG expansions in the ATXN3 gene. A greatly expanded allele in ATXN3 combined with an eastern Asian genetic background is associated with a phenotype of spastic paraparesis in MJD.

Identification of VPS35 p.D620N mutation-related Parkinson's disease in a Taiwanese family with successful bilateral subthalamic nucleus deep brain stimulation: a case report and literature review.

BACKGROUND: Vacuolar protein sorting 35 (VPS35) was recently reported to be a genetic cause for late-onset autosomal dominant Parkinson's disease (PD). However, VPS35 mutations are rarely reported in Asian populations. Herein, we report the first Taiwanese family with the pathogenic VPS35 p.D620N mutation, including one patient treated successfully with subthalamic nucleus deep brain stimulation (STN-DBS). CASE PRESENTATION: A 61-year-old woman presented with progressive left hand resting tremor at the age of 42. Neurological examinations revealed mask face and akinetic-rigidity over left extremities. She showed a good response to levodopa treatment, and her unified Parkinson's disease rating scale (UPDRS) motor scores improved from 42 to 15 under the levodopa equivalent dose of 1435 mg/day. She developed peak-dose dyskinesia and motor fluctuation seven years after the onset of symptoms, and received bilateral STN-DBS at the age of 55. Stimulation led to a marked improvement in her motor symptoms with a 37% improvement in the UPDRS motor score during the OFF period five years after surgery. The patient's mother and three siblings were also diagnosed with PD in their forties, following an autosomal-dominant inheritance pattern. We performed genetic analysis of the proband using a targeted next generation sequencing (NGS) panel covering 17 known PD-causative genes. We identified a pathogenic missense mutation in VPS35 gene, c.1858G > A (p.D620N), in this patient. CONCLUSIONS: This is the first report of the VPS35 p.D620N mutation in a Taiwanese family. Additionally, our report contributes to the current understanding of genetically defined PD patients treated successfully with STN-DBS.

The relationship of leukoaraiosis and the clinical severity of vascular Parkinsonism.

Vascular Parkinsonism (VP) is referred to as secondary Parkinsonian syndrome. It occurs with lacunar state or sub-cortical white matter micro-angiopathy and is highly associated with vascular risk factors and leukoaraiosis, also known as cerebral white matter lesions (WML). This study aimed to assess the prevalence of different vascular risk factors and WML in patients with VP, and their impact on clinical features. Sixty-two consecutive VP patients (70.2 ± 9.2 years) were evaluated for clinical severity using the Unified Parkinson's Disease Rating Scale (UPDRS). WML was assessed and scored on fluid-attenuated inversion recovery T2-weighted (FLAIR) magnetic resonance imaging (MRI). Cerebro-vascular risk factors, WML severity, and the UPDRS for clinical disability were analyzed statistically. There were no associations between WML score and age, sex, hypertension, diabetes, previous stroke, cardiac disease, cigarette smoking, or serum levels of cholesterol and triglyceride. The WML score positively correlated with UPDRS part I (p = 0.035) and part III (p = 0.041) scores. After adjustments for age, gender, stroke history, and use of levodopa, the WML score was associated with the UPDRS total (p = 0.020), part I (p = 0.012), part II (p = 0.039), and part III (p = 0.019) scores. The severity of WML is not associated with conventional vascular risk factors in VP patients but is significantly correlated with the UPDRS total and all sub-scores, which suggests that disruption of the cortico-sub-cortical circuits may lead to impaired mentation, behavior and mood, activities of daily living, and motor performance in these patients.