Influence of istradefylline on non-motor symptoms of Parkinson's disease: A subanalysis of a 1-year observational study in Japan (J-FIRST)

IntroductionThe non-motor symptoms (NMSs) of Parkinson's disease (PD) significantly impact the patient's health-related quality of life. This subanalysis of the J-FIRST study evaluated the effect of istradefylline, a selective adenosine A_2A receptor antagonist, on NMSs in istradefylline-naïve Japanese patients with PD.MethodsPatients with PD and ≥1 NMS and ‘wearing-off’ with their current antiparkinsonian treatment were observed for up to 52 weeks. The effect of istradefylline on NMSs was measured in terms of changes in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 1 total, individual sub-items scores and the 8 item PD questionnaire (PDQ-8) estimated by the marginal structural model.ResultsOverall, 732 patients were istradefylline-naïve prior to the study, of whom 171 were treated with istradefylline for ≥8 weeks during the observation period (istradefylline-treated patients). At baseline, istradefylline-treated patients were more likely to have a dyskinesia (49.7% vs 40.8%) and received a significantly higher daily dose of levodopa (462.8 mg vs 413.0 mg) than those who did not receive istradefylline (n = 561). MDS-UPDRS Part 1 total score at the end of the 52-week observational period slightly increased in patients who received istradefylline and those who did not (0.49 ± 0.41 vs 0.07 ± 0.20; P = 0.36). There were no statistically significant differences between the two groups of patients in terms of changes in the MDS-UPDRS Part 1 total score or any sub-items, or in the PDQ-8 total score.ConclusionNMSs remained generally controlled in istradefylline-treated Japanese patients with PD who exhibited wearing-off with their current antiparkinsonian treatment. Istradefylline could be a feasible treatment option for patients with advanced PD, without worsening existing NMSs.     

Levodopa/carbidopa intestinal gel can improve both motor and non-motor experiences of daily living in Parkinson’s disease: An open-label study

BackgroundLevodopa/carbidopa intestinal gel therapy (LCIG) can efficiently improve several motor and non-motor symptoms of advanced Parkinson's disease (PD). The recently developed Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) improved the original UPDRS making it a more robust tool to evaluate therapeutic changes. However, previous studies have not used the MDS-UPDRS and the Unified Dyskinesia Rating Scale (UDysRS) to assess the efficacy of LCIG.ObjectivesOur aim was to determine if the MDS-UPDRS and UDysRS could detect improvement in the experiences of daily living following 1-year LCIG treatment.MethodsIn this prospective, multicenter, open-label study, 34 consecutive patients undergoing LCIG treatment were enrolled. Patients were examined twice: prior to LCIG initiation and 12 months later. Impact of PD-related symptoms and dyskinesia was assessed by the MDS-UPDRS and UDysRS.ResultsNon-motor Experiences of Daily Living part of MDS-UPDRS improved from 20 (median, interquartile-range, IQR:14–23) to 16 points (median, IQR:12–20, p = 0.044) and the Motor Experiences of Daily Living ameliorated from 24 (median, IQR:20–29) to 18 points (median, IQR:13–25, p = 0.025). Health-related quality of life, measured by PDQ-39, also improved from 35.4 (median, IQR:26.9–50.3) to 27.0 (median, IQR:21.3–31.4) points (p = 0.003). The total score of UDysRS decreased from 47 (median, IQR:36–54) to 34 (median, IQR:21–45) points (p = 0.003).ConclusionsAs far as the authors are aware of, our paper is the first to evaluate the impact of LCIG on dyskinesia by the means of UDysRS. Changes in MDS-UPDRS and UDysRS confirm that LCIG treatment can efficiently improve experiences of daily living in advanced PD.     

Nonmotor symptoms more closely related to Parkinson's disease: Comparison with normal elderly

Nonmotor symptoms (NMSs) commonly occur in Parkinson's disease (PD). This study sought to explore the domains of NMSs that are more closely related to PD using nonmotor symptoms scale (NMSS), through a quantitative comparison of NMSs' prevalence and NMSS scores of PD patients with normal controls, and clinical implications. We performed a prospective case–control study on PD patients (n = 131) and age- and gender-matched normal controls (n = 129). We compared NMSs' prevalence and NMSS scores of the PD patients with those of normal controls, and obtained the ratio to identify the domains that were more closely related to PD than normal aging using the NMSS. NMSs are very common among normal elderly as well as PD patients. The domains with the highest ratio of NMSs' prevalence and NMSS scores between the patient and control groups were the miscellaneous, perceptual problems/hallucinations, and sexual function. These three domains were found to be most closely related to PD. NMSs with higher prevalence in PD patients do not always relate more to PD. As NMSs in PD can also commonly occur among the normal elderly, the NMS prevalence should be interpreted with extreme caution. To properly manage the NMSs in PD, it should be kept in mind that avoiding the overestimation of NMSs as part of PD is as important as their early recognition in PD.     

Malnutrition and associated factors in Chinese patients with Parkinson's disease: Results from a pilot investigation

ObjectiveThis study was conducted to evaluate the prevalence of malnutrition among patients with Parkinson's disease (PD) and determine the associations between malnutrition and non-motor symptoms (NMS).MethodsWe conducted a cross-sectional assessment of 117 consecutive outpatients with PD and their respective caregivers. The participants were interviewed and assessed using various scales, including the Mini Nutritional Assessment (MNA), Non-Motor Symptoms questionnaire for Parkinson's disease (NMS quest), Mini-mental State Examination (MMSE), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Geriatric Depression Scale (GDS), and Hamilton Anxiety Scale (HAMA). We also investigated the socio-demographic characteristics of the subjects.ResultsThe prevalence of malnutrition (MNA score < 17) was 1.71%, and 19.66% patients were at risk of malnutrition (17 ≤ MNA score ≤ 23.5). Poor nutrition (malnutrition and at risk of malnutrition) was associated with some of the NMS including the constipation, vomiting, loss of interest, inability to concentrate and sadness, and high scores in PSQI, GDS, and HAMA. Constipation (OR, 6.646; 95% CI, 1.561–28,300; P = 0.010) and GDS scores (OR, 1.166; 95% CI, 1.042–1.304; P = 0.007) were considered to be the 2 most important predictors of nutritional impairment.ConclusionsNearly 22% of PD patients were malnourished or at the risk of malnutrition and the negative association between NMSs and nutritional care needs to be determined by further studies.     

Impact of deep brain stimulation on quality of life and motor symptoms in Parkinson's disease and X-linked dystonia parkinsonism: The Philippine experience

Background and objectivesDeep brain stimulation (DBS) is indisputable in improving motor symptoms of Parkinson's Disease (PD) and X-Linked Dystonia Parkinsonism (XDP)(4,9,22,23,26). However, a discrepancy between this improvement and the perceived quality of life (QoL) has been observed. This study aims to investigate changes and correlation between quality of life, motor symptoms and medication dosing.MethodologyThis prospective observational study enrolled 13 patients (6 PD, 7 XDP) who underwent DBS from 2017 to 2018. Quality of life changes were determined by Parkinson's Disease - 39 (PDQ-39 English and Filipino versions) at baseline, 6 months and 12 month after DBS. Motor symptoms and medication dosing were also evaluated within the same period and correlated with QoL changes.Results and discussionThere is a significant reduction of PDQ-39 mean scores[F(1.06,11.64) = 18.235; p = 0.001; ηp2 = 0.624] between baseline and 6 months among XDP patients (p = 0.018) and baseline and 12 months among PD patients (p = 0.027) and XDP patients (p < 0.001). Specific domains with significant improvement were stigma, cognition, mobility, ADLs, communication and bodily discomfort. Correlating these with changes in motor symptoms, only mobility for PD and ADLs for XDP were positively related.ConclusionThis study has shown the positive impact of DBS in improving QoL among PD and XDP patients over a 12-month period.     

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.     

Quantitative mobility measures complement the MDS-UPDRS for characterization of Parkinson's disease heterogeneity

IntroductionEmerging technologies show promise for enhanced characterization of Parkinson's Disease (PD) motor manifestations. We evaluated quantitative mobility measures from a wearable device compared to the conventional motor assessment, the Movement Disorders Society-Unified PD Rating Scale part III (motor MDS-UPDRS).MethodsWe evaluated 176 PD subjects (mean age 65, 65% male, 66% H&Y stage 2) during routine clinic visits using the motor MDS-UPDRS and a 10-min motor protocol with a body-fixed sensor (DynaPort MT, McRoberts BV), including the 32-ft walk, Timed Up and Go (TUG), and standing posture with eyes closed. Regression models examined 12 quantitative mobility measures for associations with (i) motor MDS-UPDRS, (ii) motor subtype (tremor dominant vs. postural instability/gait difficulty), (iii) Montreal Cognitive Assessment (MoCA), and (iv) physical functioning disability (PROMIS-29). All analyses included age, gender, and disease duration as covariates. Models iii-iv were secondarily adjusted for motor MDS-UPDRS.ResultsQuantitative mobility measures from gait, TUG transitions, turning, and posture were significantly associated with motor MDS-UPDRS (7 of 12 measures, p < 0.05) and motor subtype (6 of 12 measures, p < 0.05). Compared with motor MDS-UPDRS, several quantitative mobility measures accounted for a 1.5- or 1.9-fold increased variance in either cognition or physical functioning disability, respectively. Among minimally-impaired subjects in the bottom quartile of motor MDS-UPDRS, including subjects with normal gait exam, the measures captured substantial residual motor heterogeneity.ConclusionClinic-based quantitative mobility assessments using a wearable sensor captured features of motor performance beyond those obtained with the motor MDS-UPDRS and may offer enhanced characterization of disease heterogeneity.     

Apathy: An underestimated feature in GBA and LRRK2 non-manifesting mutation carriers

IntroductionHigher prevalence of motor and non-motor features has been observed in non-manifesting mutation carriers of Parkinson's Disease (PD) compared to Healthy Controls (HC). The aim was to detect the differences between GBA and LRRK2 mutation carriers without PD and HC on neuropsychiatric symptoms.MethodsThis is a cross-sectional retrospective study of non-manifesting GBA and LRRK2 mutation carriers and HC enrolled into Parkinson's Progression Markers Initiative (PPMI). Data extracted from the PPMI database contained: demographics and performance in MoCA scale and MDS-UPDRS scale part 1A (neuropsychiatric symptoms). All six features were treated as both continuous (MDS-UPDRS individual scores) and categorical variables (MDS-UPDRS individual score>0 and MDS-UPDRS individual score = 0). Logistic regression analyses were applied to evaluate the association between mutation carrying status and neuropsychiatric symptoms.ResultsIn this study, the neuropsychiatric evaluation was performed in 285 GBA non-manifesting carriers, 369 LRRK2 non-manifesting carriers and 195 HC. We found that GBA non-manifesting mutation carriers were 2.6 times more likely to present apathy compared to HC, even after adjustment for covariates (adjusted OR = 2.6, 95% CI = 1.1–6.3, p = 0.031). The higher percentage of apathy for LRRK2 carriers compared to HC was marginally non-significant. GBA carriers were 1.5 times more likely to develop features of anxiety compared to LRRK2 carriers (adjusted OR = 1.5, 95% CI = 1.1–2.2, p = 0.015). Other neuropsychiatric symptoms, such as psychotic or depressive manifestations, did not differ between groups.ConclusionSymptoms of apathy could be present in the prediagnostic period of non-manifesting mutation carriers, especially, GBA. Longitudinal data, including detailed neuropsychiatric evaluation and neuroimaging, would be essential to further investigate the pathophysiological basis of this finding.     

Validation of the Italian version of the Non Motor Symptoms Scale for Parkinson's disease

ObjectiveTo validate the adapted Italian version of the Non-Motor Symptoms Scale (NMSS), a tool to assess non-motor symptoms (NMS) in Parkinson's disease (PD).MethodsA cross cultural adaptation of the NMSS into Italian and a psychometric analysis of the translated version of the NMSS was carried out in patients with PD from two university centres–affiliated hospitals. The quality of data and the acceptability, reliability and construct validity of NMSS were analyzed. The following standard scales were also applied: Hoehn and Yahr staging, Unified Parkinson's Disease Rating Scale (UPDRS) part III, Montreal Cognitive Assessment, Beck Depression Inventory, Neuropsychiatric Inventory, Epworth Sleepiness Scale, Autonomic Scale for Outcomes in Parkinson's disease-Motor, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part I and Modified Cumulative Illness Rating Scale (CIRS). Levodopa equivalent daily dose (LEDD) was calculated.ResultsSeventy-one patients with PD were assessed (mean age years 69.8 ± 9.6 SD; 31% women; mean length of disease 6.3 ± 4.6 years; H&Y median: 2). Mean NMSS was 39.76 (SD 31.9; skewness 0.95). The total score of NMSS was free of floor or ceiling effects and showed a satisfactory reliability (Cronbach's alpha coefficient on total score was 0.72 [range for domains: 0.64–0.73], SEM value was 3.88 [½ SD = 31.90]). Significant positive correlations were found among total NMSS and other NMS standard tests, but no significant correlation appeared with UPDRS part III, CIRS and LEDD.ConclusionsThe Italian NMSS is a comprehensive and helpful measure for NMS in native Italian patients with PD.     

Prolonged-release melatonin in Parkinson's disease patients with a poor sleep quality: A randomized trial

BackgroundThe present study was a randomized, double-blind, placebo-controlled, multi-center trial to evaluate the efficacy and safety of prolonged-release melatonin (PRM) in Parkinson's disease (PD) patients with poor sleep quality.MethodsPD patients with a global Pittsburgh Sleep Quality Index (PSQI) score > 5 were included. Patients were assessed using the PSQI, a rapid eye movement sleep behavior disorder screening questionnaire, the Epworth Sleepiness Scale, Non-Motor Symptoms Scale (NMSS), Parkinson's Disease Quality of Life-39 (PDQ-39), and Unified Parkinson's Disease Rating Scale (UPDRS)-III at the beginning of the study and after 4 weeks of treatment with 2 mg of PRM. Partial correlation analysis was performed to investigate the relationship between PSQI score and the other scales.ResultsThirty-four PD patients with poor sleep quality were enrolled and divided into 2 groups based on medication; PRM (n = 16) and placebo (n = 18). Regarding efficacy, PSQI was significantly improved in the PRM group compared to the control group. Improvement in the NMSS and PDQ-39 summary index were observed in the PRM but not in the placebo group; UPDRS-III score was not significantly changed in either group. PSQI improvement correlated with improvement in NMSS score and PDQ-39 summary index. Regarding safety, all enrolled subjects did not complain of side effects due to PRM.ConclusionPRM is an effective and safe treatment option for subjective sleep quality in PD patients and beneficial effects on sleep quality are associated with improved non-motor symptoms and quality of life in PD patients.     

Early DEtection of wEaring off in Parkinson disease: The DEEP study

ObjectiveAssessing the frequency of Wearing-Off (WO) in Parkinson's disease (PD) patients, and its impact on Quality of Life (QoL).MethodsConsecutive ambulatory patients, who were on dopaminergic treatment for ≥1 year, were included in this multicentre, observational cross-sectional study. In a single visit, WO was diagnosed based on neurologist assessment as well as using the validated Italian version of a patient self-rated 19-question Wearing-Off Questionnaire (WOQ-19); WO was defined for scores ≥ 2. QoL was evaluated by the 8-item Parkinson's Disease Questionnaire (PDQ-8).Results617 subjects were included, with a mean anti-Parkinson treatment duration of 6.6 ± 4.6 years, 87.2% were on levodopa treatment. Neurologists identified presence of WO in 351 subjects (56.9%), whereas 415 subjects (67.3%) were identified by the self-administered WOQ-19. In patients with a <2.5 years disease duration, WO was diagnosed in 12 subjects (21.8%) by neurologists and in 23 subjects (41.8%) by the WOQ-19. The most frequent WO symptoms, as identified by WOQ-19, were “slowness of movements” (55.8%) and “reduced dexterity” (48.8%). Younger age, female gender, Unified Parkinson's Disease Rating Scale (UPDRS) part II score and duration of anti-Parkinson treatment were found significantly associated with WO. The number of motor (p < 0.0001) and non-motor (p < 0.0001) WO symptoms correlated with PDQ-8 total score.ConclusionsWO is common already at the early stages of PD and is underestimated by routine neurological clinical evaluation. The number of WO symptoms, both motor and non motor, increases along with disease duration and has a negative impact on patients QoL.     

Timing matters: Otological symptoms and Parkinson's disease

IntroductionOtological symptoms contribute to the disability of established Parkinson's disease (PD). We sought to evaluate whether prodromal onset may affect PD progression.MethodsA retrospective cohort design was used to compare time to advanced disease, defined as a Hoehn & Yahr stage ≥3 in consecutive PD patients with history of auditory and/or vestibular symptoms appearing before versus after PD onset. Time from PD onset to H&Y ≥ 3 was determined using Cox proportional hazards, with adjusted results summarized as hazards ratio (HR).ResultsAfter adjusting for age at PD onset, there was a lower risk of progression to advanced disease in patients with prodromal otological symptoms compared to those with otological symptoms after PD onset (HR = 0.34; 95%CI: 0.15–0.75, p = 0.008). This association remained significant after adjusting for age at PD onset and MDS-UPDRS III (HR = 0.25; 95% CI: 0.10–0.63, p = 0.003) and propensity score-adjusted analysis (HR = 0.46; 95% CI: 0.24–0.91, p = 0.025).ConclusionProdromal otological symptoms might be associated with a reduced risk of motor progression in PD.     

Comparative study of the substantia nigra echogenicity and 123I-Ioflupane SPECT in patients with synucleinopathies with and without REM sleep behavior disorder

ObjectivesHyperechogenicity of the substantia nigra (SN) and abnormal dopamine transporter-single-photon emission computed tomography (DAT-SPECT) are biomarkers commonly used in the assessment of prodromal synucleinopathy. Our goals were as follows: (1) to compare echogenicity of SN in idiopathic rapid eye movement (REM) behavior disorder (iRBD), Parkinson's disease (PD) without RBD (PD-noRBD), PD with RBD (PD + RBD), and control subjects; and (2) to examine association between SN degeneration assessed by DAT-SPECT and SN echogenicity.Patients/methodsA total of 61 subjects with confirmed iRBD were examined using Movement Disorders Society-unified PD rating scale (MDS-UPDRS), TCS (transcranial sonography) and DAT-SPECT. The results were compared with 44 patients with PD (25% PD + RBD) and with 120 age-matched healthy subjects.Results and conclusionThe abnormal SN area was found in 75.5% PD, 23% iRBD and 7.3% controls. Median SN echogenicity area in PD (0.27 ± 0.22 cm²) was higher compared to iRBD (0.07 ± 0.07 cm²; p < 0.0001) and controls (0.05 ± 0.03 cm²; p < 0.0001). SN echogenicity in PD + RBD was not significantly different from PD-noRBD (0.30 vs. 0.22, p = 0.15).Abnormal DAT-SPECT was found in 16 iRBD (25.4%) and 44 PD subjects (100%). No correlation between the larger SN area and corresponding putaminal binding index was found in iRBD (r = −0.13, p = 0.29), nor in PD (r = −0.19, p = 0.22).The results of our study showed that: (1) SN echogenicity area in iRBD was higher compared to controls, but the hyperechogenicity was present only in a minority of iRBD patients; (2) SN echogenicity and DAT-SPECT binding index did not correlate in either group; and (3) SN echogenicity does not differ between PD with/without RBD.     

Attentional dysfunction and the punding spectrum in Parkinson's disease

BackgroundPunding is a complication of Parkinson's disease (PD) treatment and stimulant abuse that features excessive preoccupation with repetitive and/or aimless behaviors. We hypothesized that cognitive impairment and functional limitations influence how punding behaviors manifest in PD.MethodsWe extracted data on punding, hobbyism, and cognition from the Parkinson's Progression Marker Initiative (PPMI). Punding and hobbyism were measured with the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP) scale. We determined how cognition predicted punding and hobbyism behaviors—adjusting for levodopa dose, Hoehn & Yahr stage, disease duration, and age—using generalized estimating equation (GEE) logistic regression. Activities of daily living (ADL) and motor impairment were measured with the MDS-UPDRS scale.ResultsIn GEE logistic regression models, punding was selectively associated with lower scores on the Letter Number Sequencing test (LNS), the primary attention test in PPMI (Odds ratio: 0.87 (95% CI: 0.79–0.96); p = 0.022). This was corroborated by a subscale-analysis of Montreal Cognitive Assessment (MoCA) scores, as only the attention subscale was significantly associated with punding (OR: 0.59 (0.45–0.77); p < 0.001). Baseline impairment in LNS (Hazard ratio: 2.52 (1.22–5.20); p = 0.012) and MoCA attention (HR: 2.68 (1.32–5.42); p = 0.006) predicted earlier punding in Cox regression. In turn, ADL dysfunction predicted punding (OR: 1.55 (1.20–2.00); p < 0.001), but not hobbyism.ConclusionAttentional dysfunction is a domain-specific cognitive biomarker of punding risk in PD. Further, attentional capacity and functional impairment may determine the complexity of perseverative behaviors on the continuum from rudimentary punding to semi-purposeful hobbyism.     

Characteristics,correlates, and assessment of psychosis in Parkinson disease without dementia

IntroductionConsidering that psychosis in Parkinson disease (PD) is associated with worse outcomes, including dementia, we aimed to study the characteristics, correlates, and assessment of PD psychosis in those without dementia.Methods101 PD subjects without dementia (Montreal Cognitive Assessment ≥21/30) were recruited to participate in a study of neuropsychiatric symptoms in PD. This study included a baseline standard neurological exam and common PD symptom assessments. Using the Scale for the Assessment of Positive Symptoms (SAPS) and separate assessment of visual illusions and sense of presence, NINDS-NIMH criteria for PD psychosis were applied.ResultsOf the 33 (32.7%) PD subjects who met diagnostic criteria for psychosis in PD, visual illusions were most common (72.7%), followed by visual hallucinations (39.4%). Adjusted for presence of REM sleep behavior disorder (RBD) (p = 0.097), use of dopamine agonists (OR = 3.7, p = 0.012) and greater autonomic symptom burden (OR = 1.1 (per 1-unit change in score on SCOPA-AUT), p = 0.012) were associated with greater risk of psychosis. Use of dopamine agonists (OR = 5.0, p = 0.007), higher MDS-UPDRS Part II score (OR = 1.1, p = 0.010), and presence of RBD (OR = 4.8, p = 0.012) were independent predictors of visual hallucinations and visual illusions. MDS-UPDRS item 1.2 score ≥1 had highly correlated with the SAPS score (r = 0.65, p < 0.0001), but was 42% sensitive and 96% specific for identifying psychosis.ConclusionThis study confirms the association between dopamine agonists and psychosis in PD patients without dementia. The association of RBD, autonomic symptoms, and MDS-UPDRS Part II scores with psychosis underscore its link to brainstem dysfunction and greater PD motor symptom severity.     

Non-motor symptoms and the quality of life in multiple system atrophy with different subtypes

BackgroundThe differences in non-motor symptoms (NMS) and quality of life (QOL) between MSA patients with different subtypes remain unknown, so do the determinants of poor QOL in both subtypes.MethodsA total of 172 MSA patients were enrolled in the study. NMS of patients with MSA were assessed using the non-motor symptoms scale (NMSS) and Parkinson's Disease Questionnaire-39 item version (PDQ-39) was used to evaluate the QOL of patients with MSA.ResultsThe most prevalent NMS domain was urinary (91.3%) in both subtypes. The mood/apathy domain was more severe in MSA-P than MSA-C patients (P < 0.05). Drooling, constipation, and pain symptoms were more prevalent and severe in the MSA-P patients compared to the MSA-C patients (P < 0.05). We found that the MSA-C patients had a higher score of mobility than the MSA-P patients (P = 0.002); However, the MSA-P patients had a higher score of bodily discomfort than the MSA-C patients (P = 0.036). There were close correlations between NMS and PDQ-39 in both subtypes. Disease severity, cardiovascular symptoms, sleep/fatigue symptoms and gastrointestinal symptoms were determinants of poor QOL in MSA-P patients. While in MSA-C patients, longer disease duration, disease severity and mood/apathy symptoms were determinants of poor QOL.ConclusionNMS are more severe and prevalent in MSA-P patients, especially for mood/apathy and gastrointestinal symptoms. There is a close relationship between NMS and QOL in both MSA subtypes. Disease severity, longer disease duration and severe NMS are determinants of poor QOL in MSA.     

Anxiety is associated with cognitive impairment in newly-diagnosed Parkinson's disease

IntroductionAnxiety and mild cognitive impairment (MCI) are prevalent non-motor manifestations of Parkinson's disease (PD). While few studies have demonstrated a possible link between cognitive dysfunction and anxiety in PD, to our knowledge, no studies have directly examined the association between them. This study investigated the association between anxiety and cognitive deficits in newly diagnosed PD patients.MethodsPatients with newly diagnosed PD (N = 185) were recruited from community and outpatient clinics. Anxiety was assessed using the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) clinician rated anxiety item, which has previously been validated against a standardized criteria for the diagnosis of anxiety disorders in PD. Participants scoring ≥2 were classified as anxious. A threshold of 1 SD below normative values (obtained from controls) was used to define cognitive impairment. Impairments in specific cognitive domains were identified as being >1 SD below controls in ≥1 test per domain.ResultsAfter controlling for age, education and motor severity, patients with anxiety were three times more likely to have cognitive impairment compared to those without anxiety (OR = 3.0, 95% CI = 1.2–7.3, p < 0.05). Patients with anxiety were more than twice as likely to be classified as having cognitive impairment due to impairment in the memory domain compared with PD without anxiety (OR = 2.3, 95% CI = 1.0–5.1, p < 0.05), whilst no associations were found between anxiety and performance on other cognitive domains.ConclusionThis study shows an association between anxiety and cognitive impairment (specifically memory impairment). Examining the neural basis of this association warrants future research in this developing field.     

Orthostatic hypotension in Parkinson's disease: Does it matter if asymptomatic?

IntroductionOrthostatic hypotension (OH) may frequently be asymptomatic in patients with Parkinson's disease (PD). However, the relationship between symptomatic/asymptomatic status and functional disability remains unclear.MethodsUsing orthostatic blood pressure (BP) measurements and the Orthostatic Hypotension Symptom Assessment (OHSA) questionnaire, 121 consecutive PD patients without history of chronic hypertension and not taking alpha-adrenergic antagonists for bladder disorders were classified according to (1) OH symptomatic status, based on presence/absence of orthostatic symptoms (symptomatic OH: OHSA item 1 ≥ 1), and (2) OH severity, based on the magnitude of BP fall on the lying-to-standing test: OH- (<20/10 mmHg); moderate OH+ (≥20/10 mmHg but < 30/15 mmHg); and severe OH+ (≥30/15 mmHg). The primary endpoints were the activities of daily living/instrumental activities of daily living (ADL/iADL) and the Ambulatory Capacity Measure (ACM). Secondary endpoints included PD quality of life (PDQ-8) and prevalence of falls.ResultsThe overall prevalence of OH+ was 30.6% (37/121 patients), with 62.2% symptomatic (23/37) and 37.8% asymptomatic (14/37). Symptomatic and asymptomatic OH + patients had similar impairments in ADL/iADL and ACM, significantly worse than OH- (p ≤ 0.035). There was a trend for worse ADL/iADL and ACM scores in severe OH + compared to moderate OH+, but both were worse than OH- (p ≤ 0.048). Symptomatic and asymptomatic OH + showed similar impairment in PDQ-8 and higher prevalence of falls compared to OH-.ConclusionsAsymptomatic OH+ was associated with similar impairments in ADL/iADL and ACM than symptomatic OH+. These findings support screening for OH in PD patients regardless of postural lightheadedness.     

Patients with REM sleep behavior disorder have higher serum levels of allantoin

IntroductionRapid eye movement (REM) sleep behavior disorder (RBD) is associated with an increased risk of developing Parkinson's disease (PD). Low uric acid (UA) levels are associated with the risk of development and progression of PD. Allantoin is the major oxidation product of UA and is considered as a biomarker of oxidative stress. We aimed to compare serum levels of UA, allantoin, and allantoin/UA ratio in RBD patients with those in healthy controls, and to examine their associations with clinical severity.MethodsWe evaluated serum levels of UA, allantoin, and allantoin/UA ratio in 38 RBD patients (one female, mean age 66.8 (SD 6.3) years) and in 47 controls (four females, 66.8 (7.6) years). All RBD patients were assessed according to an examination protocol, which included structured interview, Montreal Cognitive Assessment (MoCA), Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), and dopamine transporter single-photon emission computed tomography (DAT-SPECT). The lower putaminal binding ratio from both hemispheres was used for analysis.ResultsMean serum allantoin concentration and allantoin/UA ratio were significantly increased in the RBD group compared to controls (2.6 (1.8) vs. 1.4 (0.7) μmol/l, p = 0.0004, and 0.008 (0.004) vs. 0.004 (0.002), p < 0.0001, respectively). There were no significant differences in UA levels between the two groups. No significant associations between any biochemical parameter and RBD duration, putaminal binding ratio on DAT-SPECT, MDS-UPDRS, or MoCA score were found.ConclusionSerum allantoin and allantoin/UA ratio are increased in RBD patients in comparison to controls, which may reflect increased systemic oxidative stress in prodromal synucleinopathy.