Comparison of sleep and other non-motor symptoms between SWEDDs patients and de novo Parkinson's disease patients

BackgroundSWEDDs (Scans Without Evidence of Dopaminergic Deficits) was defined from a series of pharmaceutical trials on Parkinson's disease (PD). Non-motor features including sleep-related problems are common even in early-stage PD patients; however, little is known about the burden of the non-motor symptoms in SWEDDs patients.MethodsThe Non-motor Symptoms Assessment Scale (NMSS), revised version of the Parkinson's Disease Sleep Scale (PDSS-2), Epworth Sleepiness Scale (ESS), and EuroQol 5-Dimension (EQ-5D) were applied to evaluate 17 SWEDDs patients and 28 de novo PD patients. The presence of clinically probable rapid eye movement sleep behavior disorder (cpRBD) was assessed using the International Classification of Sleep Disorders-Revised (ICSD-R) criteria.ResultsThe total NMSS score for the SWEDDs group was significantly lower than for the de novo PD group (p = 0.032). The most distinct difference was in taste or smell change (p < 0.000). Prevalence of cpRBD was higher in de novo PD patients than in SWEDDs patients (p = 0.030), though no significant differences in the PDSS-2 total score (p = 0.496) or the ESS score (p = 0.517) were found. The SWEDDs patients did not significantly differ from the de novo PD patients with regard to quality of life, as measured by the EQ-5D index score (p = 0.177).ConclusionsThe patients with SWEDDs have less non-motor problems than newly diagnosed untreated PD patients. Given the difficulty distinguishing between SWEDDs and early PD, identifying some of non-motor symptoms, such as RBD or olfactory impairment, could aid clinicians in their work.     

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.     

Motor,behavioural, and cognitive correlates of fatigue in early,de novo Parkinson disease patients

IntroductionFatigue is one of the most common and disabling non-motor symptoms in Parkinson's disease (PD). The objective of this study was to determine prevalence and motor, behavioural, and cognitive correlates of distressing fatigue in early, de novo PD patients.MethodsEighty-one consecutive de novo PD patients (64% men; mean age 65.73 ± 8.26 years) underwent a comprehensive examination, including Parkinson's disease Fatigue Scale (PFS), Epworth Sleepiness Scale (ESS), Parkinson's Disease Sleep Scale (PDSS), Beck Depression Inventory (BDI), Parkinson's Anxiety Scale (PAS), and Apathy Evaluation Scale (AES). Moreover, all patients underwent a detailed neuropsychological evaluation exploring attention and working memory, executive functions, memory, visuospatial abilities and language. Score of patients with or without distressing fatigue (defined as a PFS score ≥ 8) were compared by Student's t-test or Pearson's chi-square test. Logistic regression analyses were performed to search for motor and non-motor features independently associated with presence of distressing fatigue.ResultsTwelve (15%) patients presented distressing fatigue. Logistic regression identified sleepiness (p = 0.04), “episodic anxiety” subscale of PAS (p = 0.005), and “cognitive apathy” subscale of AES (p = 0.017) as the main factors associated with distressing fatigue. No significant association was found between diagnosis of Mild Cognitive Impairment and distressing fatigue (p = 0.745).ConclusionIn a sample of consecutive de novo PD patients, distressing fatigue is associated with episodic anxiety, cognitive apathy and sleepiness, but not with cognitive impairment. Our findings suggest possible shared pathogenic mechanisms underlying these non-motor symptoms and foster development of early combined therapeutic approaches.     

Neural correlates of clinical symptoms and cognitive dysfunctions in obsessive-compulsive disorder

Although results from neuropsychological and neuroimaging studies have postulated the involvement of the frontal lobe and the subcortical brain regions in the pathophysiology of obsessive-compulsive disorder (OCD), neuroimaging studies have provided little evidence that cognitive abnormalities in patients with OCD are related to dysfunctions in these areas. This study was designed to determine whether the clinical features and cognitive deficits of OCD might be taken to reflect frontal-subcortical dysfunction. Fourteen patients with OCD and 14 case-matched normal subjects completed clinical and cognitive evaluation, including four sets of neuropsychological tests that assessed the executive functions and visual memory. Cerebral glucose metabolic rates were measured by using positron emission tomography (PET) with 18F-fluorodeoxyglucose. Behavioral and PET data were analyzed using statistical parametric mapping for group differences and behavioral-metabolic correlates. The right orbitofrontal cortex showed increased metabolic activity and the left parieto-occipital junction showed decreased metabolic activity in patients. Metabolism in the right hippocampus, the left putamen and the right parietal region was associated with the severity of obsessive-compulsive symptoms. Correlations between metabolic rates and neuropsychological test scores in the prefrontal cortex and the putamen occurred only in the patient group. These results suggest that patients with OCD have distinct features of brain metabolic activities for performing cognitive tasks as well as presenting obsessive-compulsive symptoms. In particular, the frontal-subcortical circuits might mediate not only symptomatic expression but also cognitive expression in patients with OCD.     

帕金森病患者血浆肿瘤坏死因子-α和白介素-6与非运动症状的相关性分析

目的探讨帕金森病(PD)患者血浆TNF-α和IL-6水平与非运动症状的相关性。方法采用ELISA法测定41例原发性PD患者(PD组)和37名健康对照者(正常对照组)血浆TNF-α和IL-6的水平。采用Hoehn-Yahr分期(H-Y分期)、统一PD评定量表第Ⅱ部分(UPDRSⅡ)、统一PD评定量表第Ⅲ部分(UPDRSⅢ)、非运动症状量表(NMSS)评价PD患者关期时的运动和非运动症状。结果与正常对照组比较,PD组TNF-α和IL-6水平显著降低(均P0.05)。PD组TNF-α水平与H-Y分期、UPDRSⅡ、UPDRSⅢ和NMSS评分无相关性(r=0.093,P=0.562;r=-0.024,P=0.882;r=0.131,P=0.415;r=-0.109,P=0.499)。PD组IL-6水平与H-Y分期、UPDRSⅡ、NMSS评分呈显著负相关(r=-0.411,P=0.008;r=-0.321,P=0.041;r=-0.324,P=0.039),与UPDRSⅢ评分无相关性(r=-0.126,P=0.431)。结论 PD患者可能存在免疫功能异常,且免疫炎症机制的异常可能参与PD非运动症状的致病过程。     

帕金森病患者血清脂联素水平与运动症状及非运动症状的相关性

目的 探讨帕金森病(PD)患者血清脂联素水平与运动症状以及非运动症状的相关性.方法 选取94例PD患者以及90名健康对照者,利用ELISA法检测PD患者及健康对照者血清脂联素水平,并记录PD患者的年龄、多巴丝肼片剂量,并对所有PD患者行帕金森病评价量表第三部分评分(UPDRSⅢ)、Hoehn-Yahr分期、ADL、Webster、疲劳严重度量表(FSS)、匹茨堡睡眠质量指数(PSQI)、自主神经功能量表(SCOPA-AUT)、汉密尔顿抑郁量表(HAMD)评估.结果 PD患者血清脂联素水平为(8.2士2.6)mg/L,明显低于健康对照组的(17.5±7.1)mg/L,且差异有统计学意义(t=-4.12,P＜0.01).脂联素水平与PD患者的UPDRSⅢ评分、H-Y分期、Webster评分、ADL评分及PSQI评分均呈负相关(r分别为-0.71,-0.82,-0.77,-0.64,-0.69;P＜ 0.05).结论 PD患者血清脂联素水平降低,且与PD患者的运动症状及非运动症状均有关.     

Relationship between sleep disorders and other non-motor symptoms in Parkinson's disease

BackgroundThe association between sleep disorders and other non-motor symptoms (NMS) in Parkinson's disease (PD) has been scarcely investigated.ObjectiveTo describe the prevalence of insomnia and hypersomnia in PD and analyze their relationship with other NMS.MethodsCross-sectional, multicenter study including 388 PD patients evaluated with Hoehn and Yahr, Clinical Impression of Severity Index for PD, Scales for Outcomes in Parkinson's Disease (SCOPA)-Sleep(S), SCOPA-Cognition, SCOPA-Psychiatric Complications, SCOPA-Autonomic, Hospital Anxiety and Depression Scale, and fatigue and pain visual analogue scales. Spearman correlation coefficients, Mann–Whitney test and multiple linear regression analysis were applied.ResultsMean age (54% male) was 65.9 ± 11.2 years old, with disease duration of 8.1 ± 6.0 years and median HY = 2 (range: 1–5). Mean SCOPA-S nocturnal sleep (NS) was 5.4 ± 4.0 (range: 0–15), daytime sleepiness (DS) was 3.76 ± 3.04 (range: 0–15). Most of the sample declared nocturnal or daytime sleep problems (87.4%). Weak-to-moderate correlations were found between sleep disturbances and other NMS (range: 0.14–0.37). SCOPA-S subscales showed higher scores with the presence of most other NMS such as psychiatric complications and autonomic dysfunctions (p < 0.05). Regression models showed that fatigue, depression, urinary, cardiovascular, and thermoregulatory dysfunctions were significant determinants of SCOPA-NS score (variance: 23%); cognitive impairment, urinary, cardiovascular, and pupillomotor disorders influenced SCOPA-DS score (variance: 14%).ConclusionsInsomnia and daytime sleepiness are extremely prevalent in PD. Depression, fatigue, cognitive impairment, cardiovascular, urinary and thermoregulatory dysfunctions may contribute to insomnia/hypersomnia. This is the first clinical study to relate cardiovascular and thermoregulatory dysfunctions with sleep in PD.     

The association between non-motor symptoms in Parkinson's disease and age at onset

Objective

Age at onset is likely to be related to a wide range of problems in Parkinson's disease (PD), including cardinal motor features, motor complications and non-motor symptoms (NMS). This study investigated the effect of the age at onset on NMS.

Methods

Two hundred and thirty patients were examined and classified into one of three groups based on age at onset: early onset PD (EOPD) group (<45 years), middle-age onset group (45–64 years) and old-age onset group (≥65 years). The trends relating to NMS were compared across the three groups. The EOPD and old-age onset groups were separately studied to determine their association to the appearance of non-motor features using logistic regression analysis.

Results

There were upward trends in the occurrence of dribbling (P = 0.009; all P values are stated for trend), impaired taste/smelling (P = 0.016), constipation (P = 0.006), urinary urgency (P = 0.002), nocturia (P = 0.018), hallucinations (P = 0.016) and acting out during dreams (P = 0.011) with the increase of age at onset. Older age at onset is an independent risk factor for dementia (OR = 8.42, CI 3.16–22.44), dribbling (OR = 4.14, CI 1.93–8.87), impaired taste/smelling (OR = 2.23, CI 1.20–4.13), constipation (OR = 3.42, CI 1.88–6.24), incomplete bowel emptying (OR = 2.23, CI 1.19–4.20), urinary urgency (OR = 2.58 CI 1.46–4.57), nocturia (OR = 2.65, CI 1.49–4.71), hallucinations (OR = 5.32, CI 1.78–15.97), dizziness (OR = 3.03, CI 1.59–5.79), falling (OR = 3.60, CI 1.67–7.77), insomnia (OR = 2.29, CI 1.28–4.11), intense vivid dreaming (OR = 2.10, CI 1.21–3.66) and acting out during dreams (OR = 2.23, CI 1.24–4.01).

Conclusions

PD patients with different ages at onset present clinically different symptoms in terms of NMS. Old-age onset PD is characterized by more olfactory and sensory symptoms, autonomic symptoms, sleep disorders, dementia and psychosis compared to EOPD.     

精神病临床高危综合征与首发精神分裂症患者的神经认知功能比较研究

目的 探讨精神病临床高危综合征人群和首发未服药精神分裂症（First-episode Drug-naive Schizophrenia,FES）患者的神经认知功能特征.方法 应用中文版精神病高危综合征定式访谈（SIPS）收集精神病高危综合征人群46例,采用Matrics成套认知功能测试（MCCB）中文版评估认知功能,并与20例FES患者和37例健康对照进行比较分析.结果 除情绪管理分测验外,MCCB的其他8项分测验结果在三组之间差异均有统计学意义,包括连线（F=5.76,P=0.00）、符号编码（F=19.82,P=0.00）、词语学习（F=10.20,P=0.00）、空间广度（F=5.30,P=0.01）、迷宫（Hc=16.97,P=0.00）、空间记忆（Hc=19.07,P=0.00）、语义流畅（F=9.99,P=0.00）以及持续操作（Hc=15.46,P=0.00）.两两比较发现：两组患者的成绩均显著差于健康对照组;精神病临床高危综合征人群与FES患者相比,词语学习测验分较高（LSD-t=2.60,P=0.01）.结论 精神病临床高危综合征的神经认知功能明显受损,其特征与首发精神分裂症相似.词语学习测验,对于区分精神病临床高危综合征和已经发病的精神分裂症患者,可能具有参考价值.     

Effects of antipsychotics on cognitive performance in drug-naive schizophrenic patients

It has been reported that antipsychotics may improve cognitive function in the treatment of schizophrenia. The present study examined the effect of haloperidol and risperidone on cognitive performance in schizophrenic patients. 95 healthy subjects and 68 schizophrenic patients were recruited for comparison of cognitive function. As 20 of the 68 schizophrenic patients were drug-naive, they were randomly divided into two groups and double-blinded for treatment with either haloperidol or risperidone for an 8-week period. Each subject received Wisconsin Card Sorting Test (WCST) and Maze paradigms for cognitive function performance. For schizophrenic patients, the Positive and Negative Syndrome Scale (PANSS) was used for evaluation of clinical symptoms. Results demonstrated that in both WCST and Maze paradigms the 68 schizophrenic patients had worse cognitive performance compared with healthy subjects. Of the 20 drug-naive schizophrenic patients from the 68 in-patients, both haloperidol and risperidone improved the clinical symptoms. Maze tasks performance was improved progressively after haloperidol and risperidone treatment, although improvement was greatest with risperidone. Both haloperidol and risperidone had no evident effect on WCST performance. Our findings suggest that Maze paradigms may be an ideal tool for evaluation of pharmacological treatment effects on cognitive function in schizophrenic patients. Furthermore, risperidone may have more treatment benefits than haloperidol on cognitive performance in drug-naive schizophrenic patients.     

Improvements in motor and non-motor symptoms in parkinson patients under ropinirole therapy

Ropinirole is a non-ergoline selective D2 dopamine agonist. Its efficacy and safety has been established in several controlled double-blind studies in patients with early and advanced Parkinson's disease. It is assumed that the improvement in the activities of daily living under ropinirole is not only due to the improved motor symptoms but also due to the improvement of non-motor symptoms like symptoms of mood and anxiety. The objective of this post marketing surveillance study was to show that under the conditions of the daily routine in the neurologic practice ropinirole may not only improve motor symptoms, the activity of daily living and complications of the treatment (dystonia, dyskinesia) but also alleviate symptoms of depression and anxiety. A total of 110 neurological practices enrolled 327 patients in early and advanced stages of the disease (139 females, 188-males; mean age: 67 years). They were treated with ropinirole as monotherapy and as adjunctive therapy with l-dopa over a period of 12 - 14 weeks. Selected symptoms of the Unified Parkinson's Disease Rating Scale (UPDRS) part II-IV and symptoms of depression and anxiety were rated by the clinicians. Mood and functional impairment in job, family and social life were rated by the patients using selected items of the Beck Depression Inventory and the Sheehan Disability Scale (SDS). The different subtypes, i. e. the akinetic-rigid, tremor-dominant and the mixed subtype, are described separately. The total UPDRS score at baseline was similar for all three subtypes and there was also a similar improvement in the three groups under ropinirole. Both according to self-rating and to clinician rating the symptoms of depression and anxiety at baseline were more severe in the akinetic-rigid and the mixed subtype compared to the tremor-dominant subtype. The symptoms considerably improved and were reduced by 48 % under therapy with ropinirole. Adverse events were reported by 7.7 % of the patients. The surveillance study has shown that ropinirole may improve not only motor symptoms, activities of daily living and complications of treatment but also symptoms of mood and anxiety.     

Effects of safinamide on non-motor,cognitive, and behavioral symptoms in fluctuating Parkinson’s disease patients: a prospective longitudinal study

Neurological Sciences - Parkinson’s disease (PD) patients in chronic levodopa treatment may experience motor and non-motor fluctuations, which may affect their quality of life. Safinamide is...     

首发未用药精神分裂症患者脑内神经生化代谢物与认知功能的相关性

目的 探讨首发未经治疗的精神分裂症患者用药前脑内神经生化代谢物质的特点及其与 认知功能之间的相关性。方法 纳入首发未治精神分裂症患者33例（男性19例、女性14例）作为研究组, 对照组为符合纳入标准的健康成人33人（男性14名、女性19名）。采用单体素氢质子磁共振波谱（1H-MRS） 检测左侧前额叶和丘脑N-乙酰基天门冬氨酸（NAA）、胆碱复合物（Cho）、肌酸复合物（Cr）与磷酸化肌酸 复合物（Cr2）的水平,并计算NAA/Cr 值、Cho/Cr 值、Cr2/Cr 值、NAA/Cho 值。选取剑桥神经心理自动化成 套测试（CANTAB）中的图形识别记忆（PRM）延迟再识别正确率评定其认知功能。结果 研究组左侧前 额叶Cr2/Cr 值（1.15±0.87）高于对照组（0.72±0.46）,差异有统计学意义（P ＜ 0.05）。左侧前额叶NAA/Cr 值、Cho/Cr 值、NAA/Cho 值以及丘脑NAA/Cr 值、Cho/Cr 值、Cr2/Cr 值、NAA/Cho 值与对照组比较差异均 无统计学意义（P ＞ 0.05）。CANTAB 认知测试中PRM 正确率,研究组为（82.81±15.44）% 低于对照组的 （95.20±6.26）%,差异有统计学意义（P ＜ 0.05）。Pearson 相关分析发现,研究组左侧前额叶Cho/Cr 值与 PRM 正确率呈负相关（r=-0.424,P ＜ 0.05）,NAA/Cho 值与PRM 正确率呈正相关（r=0.473,P ＜ 0.01）。研 究组左侧前额叶NAA/Cr 值、Cho/Cr 值与PANSS 总分呈正相关（r=0.538、0.450,P ＜ 0.01）。结论 首发 未治精神分裂症患者用药前存在认知功能缺陷,其左侧前额叶部分神经生化代谢物质神经元细胞膜磷 酸化水平在用药前就出现了异常。提示首发未治精神分裂症患者用药前的认知功能损害与前额叶神经 生化代谢功能异常存在一定的相关性。     

帕金森病非运动症状与血清铁代谢相关蛋白关系的研究

目的研究帕金森病(PD)非运动症状与血清铁代谢相关蛋白之间的关系。方法 (1)连续收集2016年9月-2019年5月就诊于大连市中心医院的60例PD患者,同时纳入60例健康对照组,采用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)、蒙特利尔认知评估量表(MoCA)、PD改良淡漠量表(MAES)、快动眼睡眠行为障碍筛查量表(RBDSQ)、国际不宁腿综合征评定量表(IRLSRS)、阿根廷嗅觉减退评定量表(AHRS)评估PD患者的非运动症状;(2)在停用治疗PD药物10～12 h后于空腹下采集采取4 ml静脉血;(3)采用酶联免疫吸附法检测PD患者及对照组血清铁、铁蛋白、转铁蛋白的水平;(4)对PD不同非运动症状患者血液中上述指标的结果进行对比分析。结果 PD组血清中转铁蛋白水平明显高于健康对照组(P <0. 05),PD组铁蛋白水平明显低于对照组(P <0. 05); PD-抑郁组铁蛋白水平明显低于PD-非抑郁组,PD-淡漠组铁蛋白水平明显低于PD-非淡漠组,PDRBD组的转铁蛋白水平明显高于PD-NRBD组(P <0. 05)。结论外周铁代谢紊乱可能参与了PD非运动症状中快动眼睡眠行为障碍、淡漠及抑郁的发生、发展,铁蛋白、转铁蛋白可能是帕金森病快动眼睡眠行为障碍、淡漠及抑郁发生的外周血指标。     

Synuclein deposition and non-motor symptoms in Parkinson disease

Parkinson disease (PD) is a multisystem neurodegenerative disorder clinically characterized by motor and non-motor (NM) symptoms. The causes of NM symptoms in PD, many of which antedating motor dysfunction, are multifocal and unlikely explained by single lesions. They include olfactory, autonomic, sensory, skin, sleep, visual, neuropsychiatric, and other manifestations. Most NM features in PD are related to α-synuclein pathology which, in addition to the dopaminergic striatonigral system, involves non-nigral brainstem nuclei, sympathetic, parasympathetic, enteric and pelvic plexuses, cardiac systems, submandibular gland, adrenal medulla, skin, retina, and other visceral organs. This suggests a topographical and chronological spread of lesions, particularly in the prodromal stages of the disease, which, however, awaits further confirmation. A few animal models are available that recapitulate NM symptoms in human PD, but their validity is under discussion. More studies are warranted to refine the exact correlations between presymptomatic and late-developing NM features of PD and α-synuclein pathology as a basis for more effective preventive and therapeutic options of this devastating disease.