Scales For Outcomes In Parkinson's Disease-Autonomic Research Articles

Validation of the Non-Motor Symptoms Scale for Parkinson's Disease of Persian Version.

We aimed to assess the validity and reliability of the Persian version of the NonMotor Symptoms Scale (NMSS) in Iranian patients with PD. This cross-sectional study was conducted in patients with PD. After the cross-cultural adaptation of the NMSS, the acceptability, reliability, precision, and validity of the Persian NMSS were evaluated. For this purpose, in addition to NMSS, we used the following measures: Scales for Outcomes in Parkinson's Disease (SCOPA)-Autonomic (SCOPA-AUT), SCOPA-Sleep, Beck's Depression Inventory (BDI) questionnaire, Parkinson's Disease Questionnaire-8 questions (PDQ-8), SCOPA-Motor, SCOPA-Psychiatric Complications (SCOPA-PC), SCOPA-Cognition (SCOPA-COG), Mini-Mental State Examination (MMSE), Hoehn and Yahr Staging (H and Y), and Unified Parkinson Disease Rating Scale (UPDRS). 186 patients were enrolled (mean age 64.46 ± 9.9 years; disease duration 5.59 ± 3.99 years; 118 (63.4%) male; mean NMSS score 52.01 ± 38.54). Neither the floor effect (2.7%) nor the ceiling effect (0.5%) was seen in NMSS total score. Cronbach's alpha of total NMSS was 0.84. The test-retest reliability was 0.93 for the NMSS total and 0.81-0.96 for domains. The standard error of measurement (SEM) was lower than half of the standard deviation for NMSS total and all domains. NMSS total showed a high correlation with UPDRS I (rs = 0.84), UPDRS II (rs = 0.58), PDQ-8 (rs = 0.61), BDI (rs = 0.71), SCOPA-sleep (rs = 0.60), and SCOPA AUT (rs = 0.66). NMSS has an acceptable discriminative validity based on disease duration and severity of disease according to H and Y staging. The Persian NMSS is a valid and reliable measure for evaluating the burden of nonmotor symptoms in Iranian patients with PD.

Serum but not cerebrospinal fluid levels of allantoin are increased in de novo Parkinson’s disease

Oxidative stress supposedly plays a role in the pathogenesis of Parkinson’s disease (PD). Uric acid (UA), a powerful antioxidant, is lowered in PD while allantoin, the oxidation product of UA and known biomarker of oxidative stress, was not systematically studied in PD. We aim to compare serum and cerebrospinal fluid (CSF) levels of UA, allantoin, and allantoin/UA ratio in de novo PD patients and controls, and evaluate their associations with clinical severity and the degree of substantia nigra degeneration in PD. We measured serum and CSF levels of UA, allantoin, and allantoin/UA ratio in 86 PD patients (33 females, mean age 57.9 (SD 12.6) years; CSF levels were assessed in 51 patients) and in 40 controls (19 females, 56.7 (14.1) years). PD patients were examined using Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment (MoCA), Scales for Outcomes in Parkinson Disease-Autonomic (SCOPA-AUT), the University of Pennsylvania Smell Identification Test (UPSIT), one-night video-polysomnography, and dopamine transporter single-photon emission computed tomography (DAT-SPECT). Serum allantoin and allantoin/UA ratio were significantly increased in the PD group compared to controls (p < 0.001 and p = 0.002, respectively). Allantoin/UA ratios in serum and CSF were positively associated with the SCOPA-AUT score (p = 0.005 and 0.031, respectively) and RBD presence (p = 0.044 and 0.028, respectively). In conclusion, serum allantoin and allantoin/UA ratio are elevated in patients with de novo PD. Allantoin/UA ratio in serum and CSF is associated with autonomic dysfunction and RBD presence, indicating that higher systemic oxidative stress occurs in PD patients with more diffuse neurodegenerative changes.

Selected autonomic signs and symptoms as risk markers for phenoconversion and functional dependence in prodromal Parkinson's disease.

To determine whether dysautonomia can stratify individuals with other prodromal markers of Parkinson's disease (PD) for risk of phenoconversion and functional decline, which may help identify subpopulations appropriate for experimental studies. Data were obtained from Parkinson's Progression Markers Initiative. Cohorts without PD but with at-risk features were included (hyposmia and/or rapid-eye-movement-sleep behavior disorder, LRRK2 gene mutation, GBA gene mutation). Dysautonomia measures included Scales-for-Outcomes-in-Parkinson's-Disease Autonomic (SCOPA-AUT), seven SCOPA-AUT subscales, and cardiovascular dysfunction (supine hypertension, low pulse pressure, neurogenic orthostatic hypotension). Outcome measures were phenoconversion and Schwab-and-England Activities-of-Daily-Living (SE-ADL) ≤ 70, which indicates functional dependence. Cox proportional-hazards regression was used to evaluate survival to phenoconversion/SE-ADL ≤ 70 for each dysautonomia measure. If a significant association was identified, a likelihood-ratio test was employed to evaluate whether a significant interaction existed between the measure and cohort. If so, regression analysis was repeated stratified by cohort. Median follow-up was 30months. On multivariable analysis, gastrointestinal and female sexual dysfunction subscales were associated with increased risk of phenoconversion, while the cardiovascular subscale and neurogenic orthostatic hypotension were associated with increased risk of SE-ADL ≤ 70; respective hazard ratios (95% confidence intervals) were 1.13 (1.01-1.27), 3.26 (1.39-7.61), 1.87 (1.16-2.99), 5.45 (1.40-21.25). Only the association between the cardiovascular subscale and SE-ADL ≤ 70 was modified by cohort. Symptoms of gastrointestinal and female sexual dysfunction predict phenoconversion in individuals with other risk markers for PD, while signs and symptoms of cardiovascular dysfunction may be associated with functional decline.

Screening autonomic functions in patients with restless legs syndrome: A case-control study in a tertiary care hospital.

The clinical importance of autonomic involvement in patients with restless legs syndrome (RLS) remains unclear. To our knowledge, no study has explored the relationship between autonomic dysfunction and disease-related variables in patients with RLS. Therefore, this study aimed 1) to determine the presence of autonomic symptoms in drug-naïve patients with RLS in comparison with healthy controls using Scales for Outcomes in Parkinson's disease-Autonomic (SCOPA-AUT) questionnaire and 2) to evaluate the possible associations of autonomic dysfunction with clinical factors in RLS. A total of 70 drug-naïve patients with RLS and 85 healthy volunteers were enrolled. The SCOPA-AUT questionnaire and Epworth Sleepiness Scale (ESS) scores were used to determine autonomic functions and sleep propensity, respectively. Moreover, the International Restless Legs Syndrome Study Group rating scale was used to evaluate disease severity in the patient group. Compared with the control group, the RLS group had significantly higher subscale scores (gastrointestinal, urinary, cardiovascular, thermoregulatory, pupillomotor, and sexual [women]) and total scores of the SCOPA-AUT questionnaire (p<0.05). In the patient group, there was a significant correlation between the total scores and subscale scores (gastrointestinal, cardiovascular, and thermoregulatory subscales) of the SCOPA-AUT questionnaire and disease severity. Moreover, ESS was positively correlated with the total scores and subscale scores (urinary, cardiovascular, and pupillomotor) of the SCOPA-AUT questionnaire. Disease severity and daytime sleepiness may be related to autonomic dysfunction in RLS. Further studies focusing on autonomic functions in RLS are required to improve management strategies and clinical outcomes. ClinicalTrials.gov. NCT04906486; May 28, 2021.

Autonomic symptoms are predictive of dementia with Lewy bodies

IntroductionAutonomic symptoms are common in patients with dementia with Lewy bodies (DLB). Although autonomic dysfunction is considered as one of the primary early markers in patients with DLB, there are few studies that examine the timing of the onset of autonomic symptoms in these patients. The purpose of the current study was to evaluate the time of onset of autonomic symptoms in patients with DLB using a questionnaire. MethodsAutonomic symptoms were evaluated in patients with DLB using the Scales for Outcomes in Parkinson's disease - autonomic (SCOPA-Aut) questionnaire. Time of the onset of autonomic symptoms of patients with DLB was also assessed relative to that of memory loss. ResultsA total of 106 patients with DLB were included. The most frequent symptom of dysautonomia in patients with DLB was constipation (60.4%), followed by orthostatic dizziness (33%), urinary frequency (30.2%), and daytime hyperhidrosis (22.6%). The gastrointestinal system was the most prominent system of autonomic dysfunction in patients with DLB. Orthostatic dizziness, daytime hyperhidrosis, and constipation all preceded the onset of memory loss by 0.2 ± 4.9, 3.3 ± 8.6, and 3.7 ± 9.2 years, respectively, while urinary incontinence occurred 1.7 ± 1.5 years following the onset of memory loss. ConclusionMany autonomic symptoms precede the onset of memory loss in patients with DLB, especially constipation and daytime hyperhidrosis. These symptoms can facilitate an early diagnosis of patients with DLB.

Activities of daily living as a longitudinal moderator of the effect of autonomic dysfunction on anxiety and depression of Parkinson's patients.

BackgroundThere is no clear time point for the onset of depression and anxiety in Parkinson's disease (PD), and their atypical physical symptoms often overlap with other nonmotor symptoms. Autonomic dysfunction usually appears earlier than motor symptoms, seriously impairing activities of daily living (ADL), even quality of life. Whether autonomic dysfunction can affect depression and anxiety in PD patients through ADL is still unclear.MethodsWe conducted three progressive autoregressive mediation models to evaluate whether ADL may mediate the association between autonomic symptom burden, where the mediation chain with autonomic function as an independent variable, ADL as a mediating variable, and anxiety and depression as dependent variables. The ADL of PD patients were measured by the Scales for Outcomes in Parkinson's disease‐Autonomic (SCOPA‐AUT) and Modified Schwab and England ADL scale, respectively, and the status of depression and anxiety were measured by the Geriatric Depression Scale (GDS) and State‐Trait Anxiety Inventory (STAI).ResultsThere were 338 PD patients, including 220 males and 118 females. Demographic information, including age, gender, and education level, were not correlated with the depression and anxiety. Model III had the smallest AIC (AIC = 12,669.89), and the cross‐lagged relations were not statistically significant, so we selected Model II as the optimal model. In Model II, longitudinal autoregressive mediated effect and longitudinal mediated effect of autonomic dysfunction affecting anxiety and depression through ADL were not statistically significant, suggesting longitudinal changes of autonomic dysfunction were independent of anxiety and depression through ADL. Contemporaneous mediated effects of autonomic dysfunction affecting anxiety and depression through ADL were statistically significant, suggesting contemporaneous autonomic dysfunction may contribute to anxiety and depression through ADL.ConclusionsTargeted prevention and intervention measures for autonomic dysfunction and ADL should be taken to preserve and improve self‐perceived life satisfaction in the clinical practice and preventive health care of PD.

Association of autonomic symptoms with cerebrospinal fluid biomarkers in Parkinson disease and scans without evidence of dopaminergic deficit.

Dysautonomia is common in patients with Parkinson disease (PD) since disease early phase. Scales for Outcomes in Parkinson's disease – Autonomic (SCOPA-AUT) is a well-designed scale assessing the autonomic dysfunctions of PD patients. Our objectives were to examine the autonomic dysfunction in PD and scan without evidence of dopaminergic deficit (SWEDD) patients and to assess the correlation of autonomic dysfunctions with cerebrospinal fluid (CSF) biomarkers.An analysis of the Parkinson's Progression Markers Initiative (PPMI) data including 414 PD patients, 60 SWEDD patients, and 170 healthy controls (HCs) with baseline CSF biomarker measurements and SCOPA-AUT assessments was presented. Autonomic symptoms including gastrointestinal, urinary, cardiovascular, pupillomotor, thermoregulatory and sexual dysfunctions were assessed by SCOPA-AUT scales. Spearman correlation test was used to examine the correlations between CSF measurements and each section of SCOPA-AUT scales in HCs and subjects with PD or SWEDD.More severe autonomic dysfunctions were observed in patients with SWEDD than those with PD (P < .001). Specifically, patients with PD have lower scores on the urinary scale [4 (0–17) vs 5 (1–18)], pupillomotor scale [0 (0–3) vs 0 (0–3)], thermoregulatory scale [0 (0–4) vs 1.5 (0–10)] and sexual scale [1 (0–6) vs 2 (0–6)] compared with SWEDD patients. Thermoregulatory dysfunction scores were found correlated with CSF α-syn levels in SWEDD group, and gastrointestinal dysfunction scores were correlated with CSF Abeta1–42 in PD group. Additionally, urinary dysfunction scores were correlated with CSF total tau and tau phosphorylated at threonine 181(p-tau181) levels in both HCs and PD patients.

Gastrointestinal symptoms are predictive of trajectories of cognitive functioning in de novo Parkinson's disease

IntroductionNon-motor symptoms such as cognitive and gastrointestinal (GI) symptoms are common in Parkinson's disease (PD). In PD, GI-symptoms often present prior to motor symptoms. It is hypothesized that GI-symptoms reflect disruptions of the microbiome-gut-brain axis, which leads to altered immune functioning, chronic neuroinflammation, and subsequent neurodegeneration. Initial evidence links gut-dysbiosis to PD pathology and motor symptom severity. The present study examines the longitudinal relationship between severity of GI-symptoms and cognitive impairment in newly diagnosed PD patients. MethodsA secondary data analysis of the Parkinson's Progression Markers Initiative (PPMI) included 423 newly diagnosed PD patients who were followed for up to 5 years. Participants underwent neuropsychological tests of processing speed, attention, visuospatial functioning, verbal learning and verbal delayed recall. Participant were classified as cognitive intact, mild cognitive impairment or Parkinson's disease dementia. Frequency of GI-symptoms were assessed with the Scales for Outcomes in Parkinson's Disease Autonomic (SCOPA-AUT). Multi-level models (MLM) examined the longitudinal relationship between GI symptoms and cognitive impairment. ResultsAll cognitive outcomes were predicted by the main effect of GI symptoms, or the GI-symptom X Occasion interaction term. Specifically, more severe GI-symptoms were predictive of a less favorable trajectory of performance on tests of letter fluency, visuospatial, learning and memory. Cognitive performance was uniquely associated with GI-symptoms and unrelated to non-GI autonomic symptoms. ConclusionsThe presence of GI symptoms may serve as an early marker of cognitive impairment in PD. Future studies should examine specific mechanisms underlying the relationship between gut-dysbiosis and cognitive impairment.

Patients with primary restless legs syndrome have higher prevalence of autonomic dysfunction and irritable bowel syndrome

Given the limited data on autonomic dysfunction in patients with primary restless legs syndrome (pRLS), we compared autonomic dysfunction and presence of irritable bowel syndrome (IBS) between patients with pRLS and control patients. Consecutive adult drug-naïve patients with pRLS, and age- and gender-matched healthy control patients were enrolled in this study. Diagnoses, based on validated self-reported questionnaires, were made using the following guidelines: Rome III classification system for functional gastrointestinal disorders for IBS; Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) for the presence of anxiety and depression, respectively; Pittsburgh Sleep Quality Index (PSQI) for severity of sleep disturbances; and Scales for Outcomes in Parkinson's disease-Autonomic (SCOPA-AUT) for autonomic dysfunction. There were 88 patients with pRLS (18 male, 70 female) and 128 control patients (40 men, 88 women). The mean age of the pRLS patients and control patients was 50.3 ± 9.3 years and 49.7 ± 8.2 years, respectively. Overall, 41 (46.6%) of the patients with pRLS and 16 (12.5%) of the control patients had IBS. Among patients with pRLS, IBS was significantly more common and the total autonomic SCOPA-AUT scores were higher than those found among control patients. Among pRLS patients with IBS, total autonomic SCOPA-AUT, PSQI, BAI and BDI scores were significantly higher than among pRLS patients without IBS. The presence of IBS did not affect the severity of restless legs syndrome. The presence of autonomic nervous system impairment in patients with pRLS and the strong link between IBS and pRLS merit further, more extensive investigation.

Probable REM-Sleep Behavior Disorder and Dysautonomic Symptoms in Essential Tremor.

BackgroundNon-motor symptoms can be present in essential tremor (ET). We intend to assess the frequency of rapid eye movement (REM) sleep behavior disorder (RBD) and dysautonomic symptoms in ET patients and evaluate the differences between patients with ET and RBD (ET-RBD and ET without RBD [ET-nonRBD]).MethodsAll ET patients were contacted by telephone. Autonomic symptoms were assessed using the Scales for Outcomes in Parkinson’s Disease-Autonomic (SCOPA-AUT) questionnaire, and RBD symptoms with the RBD screening questionnaire (RBDSQ) using ≥5 as a cut-off for probable RBD (pRBD).ResultsFrom 92 ET patients contacted, 53 (55% female) were included. The mean age at assessment was 73.6±19 years, and the average disease duration was 19.9±17.3 years. Fourteen patients (26.4%) had pRBD and 52 (98.1%) reported at least one autonomic symptom, the most prevalent being urinary symptoms (96%). The ET-RBD group had higher SCOPA-total and thermoregulatory scores than ET-nonRBD patients (13.9±9.6 vs. 7.7±5.1, p=0.017 and 2.5±2.0 vs. 0.9±1.6, p=0.001). There were no other differences between groups.DiscussionOur results suggest that pRBD is common in ET, and its presence is associated with dysautonomic symptoms. As these symptoms are known to be prodromal symptoms of Parkinson’s disease (PD), we question if this patient subgroup has a higher risk of developing a synucleinopathy.

Clinical features of Parkinson disease with constipation

Objective To investigate the clinical features of Parkinson disease(PD)with constipation. Methods From October 2013 to August 2015, a total of 204 PD patients were consecutively recruited from the Departments of Geriatrics and Neurology, Beijing Tiantan Hospital, Capital Medical University, and were evaluated by Rome Ⅲ diagnostic criteria for functional constipation and other related scales of motor symptoms(MS)and non-motor symptoms(NMS), the activity of daily living(ADL)and quality of life. Results Overall, 131 of 204(64.2%)PD patients with constipation were assigned to the PD-C group and 73 of 204(35.8%)PD patients without constipation were assigned to the PD-NC group.In the PD-C group, 38 of 131(29%)PD patients had constipation before motor symptoms occurred.The mean age and age of onset in the PD-C group were significantly older than those in the PD-NC group(64.13±9.67 vs.58.35±11.37; 60.07±10.46 vs.55.10±12.97; F=2.287, 4.948; t=-3.827, -2.788; P<0.01 for both). Meanwhile, compared with the PD-NC group, the PD-C group was associated with dramatically longer disease duration(2.25, range: 1.00-5.00 vs.2.00, range: 1.00-3.13; Z=-2.254; P<0.05), increased scores of the Unified Parkinson Disease Rating Scale(UPDRS)Ⅲ(26.00 scores, range: 18.00-37.50 vs.19.00, range: 12.50-31.00; Z=-2.349, P<0.05), more advanced stages on the Hoehn-Yahr(H-Y)scale(2.00 stage, range: 1.50-2.50 vs.1.50, range: 1.00-2.50; Z=-2.334, P<0.05), higher total numbers of NMS(11.00, range: 6.00-15.00 vs.6.00, range: 3.00-11.00; Z=-3.715, P<0.05), and higher numbers of NMS occurring before and after MS(before, 2.00, range: 0.00-4.00 vs.1.00, range: 0.00-2.00; after, 8.00, range: 3.00-14.00 vs.5.00, range: 2.00-9.50; Z=-2.612, -2.630, respectively; P<0.05 for both). Additionally, there were significant differences between the groups in the scores of the Hamilton depression scale(HAMD), the Hamilton anxiety scale(HAMA), the Pittsburgh sleep quality index(PSQI), the scales for outcomes in Parkinson disease-autonomic(SCOPA-AUT), the Fatigue severity scale(FSS), the Apathy scale, the Montreal Cognitive Assessment(MoCA)scale, the UPDRSⅡ and ADL Scale, and the PDQL-39(all P<0.05). Binary Logistic regression analysis showed that age, SCOPA-AUT, HAMA and HAMD were risk factors for PD-C(OR=1.091, 1.107, 1.10 and 1.080; P<0.05 for all). Conclusions PD patients have a high incidence of constipation, and more than a quarter of patients have constipation before MS occurs.Meanwhile, PD patients with constipation are usually associated with old age and late age of onset, long disease duration, severe MS, frequent and severe NMS, bad cognition, emotional state and sleep, severe fatigue, and apathy.Moreover, advanced age, autonomic dysfunction, anxiety and depression increase the risk of PD with constipation.Constipation has a serious negative impact on the activity of daily living and quality of life in PD patients. Key words: Parkinson disease; Constipation

Reliability of the Japanese version of the scales for outcomes in Parkinson's disease-autonomic questionnaire

ObjectiveThe Scales for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT) questionnaire was used to assess autonomic dysfunction in patients with neurological disorders. The aim of this study was to evaluate the reliability of the Japanese version of the SCOPA-AUT. MethodsWe translated the SCOPA-AUT from English to Japanese. Thirty-one patients with diseases involving autonomic symptoms completed the form twice. The reliability was assessed by Cronbach's coefficient alphas and intraclass correlation coefficients (ICCs). ResultsThe average (standard deviation, SD) total scores of the first and second assessments of the SCOPA-AUT were 15.7 (SD, 7.1) and 13.6 (SD, 6.5), respectively. The Cronbach's coefficient alphas were globally high, but the ICCs were moderately high. The valid response rates for the questions about sexual dysfunction were 36.7% in men and 26.6% in women. ConclusionsThe Japanese version of the SCOPA-AUT had high internal consistency. However, the questions about sexual dysfunction showed less valid response rates.

Markers of Disease Severity Are Associated with Malnutrition in Parkinson's Disease

ObjectiveIn Parkinson's disease (PD), commonly reported risk factors for malnutrition in other populations commonly occur. Few studies have explored which of these factors are of particular importance in malnutrition in PD. The aim was to identify the determinants of nutritional status in people with Parkinson's disease (PWP).MethodsCommunity-dwelling PWP (>18 years) were recruited (n = 125; 73M/52F; Mdn 70 years). Self-report assessments included Beck's Depression Inventory (BDI), Spielberger Trait Anxiety Inventory (STAI), Scales for Outcomes in Parkinson's disease – Autonomic (SCOPA-AUT), Modified Constipation Assessment Scale (MCAS) and Freezing of Gait Questionnaire (FOG-Q). Information about age, PD duration, medications, co-morbid conditions and living situation was obtained. Addenbrooke's Cognitive Examination (ACE-R), Unified Parkinson's Disease Rating Scale (UPDRS) II and UPDRS III were performed. Nutritional status was assessed using the Subjective Global Assessment (SGA) as part of the scored Patient-Generated Subjective Global Assessment (PG-SGA).ResultsNineteen (15%) were malnourished (SGA-B). Median PG-SGA score was 3. More of the malnourished were elderly (84% vs. 71%) and had more severe disease (H&Y: 21% vs. 5%). UPDRS II and UPDRS III scores and levodopa equivalent daily dose (LEDD)/body weight(mg/kg) were significantly higher in the malnourished (Mdn 18 vs. 15; 20 vs. 15; 10.1 vs. 7.6 respectively). Regression analyses revealed older age at diagnosis, higher LEDD/body weight (mg/kg), greater UPDRS III score, lower STAI score and higher BDI score as significant predictors of malnutrition (SGA-B). Living alone and higher BDI and UPDRS III scores were significant predictors of a higher log-adjusted PG-SGA score.ConclusionsIn this sample of PWP, the rate of malnutrition was higher than that previously reported in the general community. Nutrition screening should occur regularly in those with more severe disease and depression. Community support should be provided to PWP living alone. Dopaminergic medication should be reviewed with body weight changes.