Since the introduction of the first edition of International Classification of Sleep Disorders: Diagnostic and Coding Manual(ICSD-1)in 1990,national and international meetings were held to openly discuss the ongoing developments of sleep disorders and a new International Classification of Sleep Disorders: Diagnostic and Coding Manual(ICSD-2)was published in 2005.Compared with ICSD-1,the classification of ICSD-2 was developed in a manner compatible with new International Classification of Diseases(ICD-9 and ICD-10)and formed a coordinated system of International Classification of Diseases.The updated version was characterized by the significant improvements of its logicality and clinical practicability,and was more consistent with the International Classification of Disease.The contents of ICSD-2 were introduced in this article.

Brief introduction to second edition of International Classification of Sleep Disorders:Diagnostic and Coding Manual

Since the official and systematic inclusion of sex and gender in biomedical research, gender differences have been acknowledged as important determinants of both the susceptibility to develop neurodegenerative diseases in general population and the clinical and therapeutic management of neurodegenerative patients. In this review, we gathered the available evidence on gender differences in Parkinson’s disease (PD) regarding clinical phenotype (including motor and non-motor symptoms), biomarkers, genetics and therapeutic management (including pharmacological and surgical treatment). Finally, we will briefly discuss the role of estrogens in determining such differences. Several data demonstrate that PD in women starts with a more benign phenotype, likely due to the effect of estrogens. However, as the disease progresses, women are at higher risk of developing highly disabling treatment-related complications, such as motor and non-motor fluctuations as well as dyskinesia, compared with men. In addition, women have lower chances of receiving effective treatment for PD as deep brain stimulation. Taken together these findings challenge the definition of a more benign phenotype in women. Still, much work needs to be done to better understand the interaction between gender, genetics and environmental factors in determining the PD risk and clinical features. Improving our understanding in this field may result in implementation of strategies to identify prodromal PD and speed efforts to discern new directions for disease tailored treatment and management.

The relevance of gender in Parkinson’s disease: a review

Parkinson disease (PD) is a multisystem disorder associated with α-synuclein aggregates throughout the central, autonomic, and peripheral nervous system, clinically characterized by motor and non-motor (NM) symptoms. The NMS in PD, many of which antedating motor dysfunction and representing a preclinical phase spanning 20 or more years, are linked to widespread distribution of α-synuclein pathology not restricted to the dopaminergic nigrostriatal system that is responsible for core motor features of PD. The pathologic substrate of NM manifestations such as olfactory, autonomic (gastrointestinal, urogenital, cardia, respiratory), sensory, skin, sleep, visual, neuropsychiatric dysfunctions (cognitive, mood, dementia), and others are critically reviewed. In addition to non-nigral brainstem nuclei, α-synuclein pathology involves sympathetic and parasympathetic, enteric, cardiac and pelvic plexuses, and many other organs indicating a topographical and chronological spread, particularly in the prodromal stages of the disease. Few animal models recapitulate NMS in PD. The relationship between regional α-synuclein/Lewy pathology, neurodegeneration and the corresponding clinical deficits awaits further elucidation. Controlled clinicopathologic studies will refine the correlations between presymptomatic and late-developing NM features of PD and neuropathology, and new premotor biomarkers will facilitate early diagnosis of PD as a basis for more effective preventive and therapeutic options of this devastating disease.

Neuropathobiology of non-motor symptoms in Parkinson disease

[Clinical subtypes of Parkinson's disease].

Available data indicate that there are gender differences in many features of Parkinson's disease (PD). Precise identification of the gender differences is important to tailor treatment, predict outcomes, and meet other individual and social needs in women and men with PD. The aim of this study was to review the available clinical data on gender differences in PD. Original articles and meta-analyses published between 1990 and 2016 systematically exploring gender differences in PD were reviewed. There is slight male preponderance in incidence and prevalence of PD. PD starts earlier in men. Women tend to be more prone to develop tremor-dominant PD but are less rigid than men. Motor improvement after deep brain stimulation is equal in both sexes, but women tend to show better improvement in activities of daily living. Furthermore, women with PD show better results on tests for general cognitive abilities, outperform men in verbal cognitive tasks, show more pain symptoms, and score higher on depression scales. It seems, however, that the differences in cognition, mood, and pain perception are not disease specific as similar gender differences can be found in healthy subjects and in other neurological conditions. Despite PD being the most frequently studied movement disorder, studies investigating gender differences in PD are still scarce with most of the studies being cross-sectional. Good-quality, prospective, longitudinal studies analyzing gender differences in PD and comparing them to matched healthy controls are needed in order to properly address the issues of gender differences in PD.

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Gender differences in Parkinson's disease: A clinical perspective

The affect of gender differences on clinical presentation of Parkinson’s disease (PD) remains controversial. De novo PD subjects were recruited from a trial-based multicenter cohort in clinical sites of Chinese Parkinson Study Group. Demographic information, motor and non-motor symptom measurements were performed by face-to-face interview using specific scales. Scores and frequencies of symptoms were compared between male and female patients, and regression models were used to control the effects of age and disease duration. Totally 428 PD patients were enrolled in this study, and 60.3 % of them were male. Total UPDRS scores were not significantly different between male and female (25.02 ± 12.84 vs. 25.24 ± 13.22, adjusted p = 0.984). No significant gender differences were found on scores for four cardinal motor signs, neither on motor subtypes (PIGD 19.0 vs. 15.9 %, adjusted p = 0.303). Female patients more likely had depressive symptoms (38.8 vs. 27.5 %, adjusted p = 0.023; CES-D score 13.78 ± 10.91 vs. 11.23 ± 9.42, adjusted p = 0.015). Male patients had significantly higher scores for MMSE (28.26 ± 2.21 vs. 27.00 ± 3.38, adjusted p = 0.0001), and lower scores for identification (1.39 ± 1.63 vs. 2.01 ± 2.63, adjusted p = 0.002) in ADAS-cog. No significant differences were found for other non-motor symptoms including motivation problems (male 29.8 % vs. female 30.6 %, adjusted p = 0.760), fatigue (62.6 vs. 70.5 %, adjusted p = 0.140), constipation (37.2 vs. 30.1 %, adjusted p = 0.243), and sleep quality (57.6 vs. 61.3 %, adjusted p = 0.357; PSQI score: 5.62 ± 3.31 vs. 6.10 ± 3.53, adjusted p = 0.133). Female might be more depressed and have worse performance on cognition in early untreated PD patients, but gender differences are not apparent on motor and other non-motor symptoms.

Gender differences on motor and non-motor symptoms of de novo patients with early Parkinson's disease

Association of Catechol-O-Methyltransferase and monoamine oxidase B gene polymorphisms with motor complications in parkinson's disease in a Chinese population

Non-motor symptoms (NMS) are important preclinical features of Parkinson's disease (PD) and have become the leading cause of poor quality of life with disease progression. There are little data on how antiparkinsonian medications influence the NMS in PD at early stage. In this study, we explored the distribution of NMS in treated and untreated PD and investigated the association between NMS and antiparkinsonian medications in Chinese patients with early PD. Subjects were enrolled from a Chinese PD patient cohort based on 2 clinical trials. Face-to-face interviews and evaluations were performed for clinical information. NMS were compared in patients with or without antiparkinsonian treatment, and between subgroups of dopaminergic medications. Eight hundred and sixteen PD patients were enrolled in this study, of whom 428 were newly diagnosed PD. Only 5 in 646 patients who completed all these NMS measurements (0.6%) were free of NMS. PD patients with antiparkinsonian medications had a significantly higher frequency of poor sleep (p = 0.001), depression (p = 0.0001) and constipation (p = 0.0001) after adjusted gender, onset age, duration, and Hoehn & Yahr stage. Moreover, patients treated by levodopa plus dopamine agonist had a higher percentage of bad sleepers (adjusted p = 0.040), and correlation analysis revealed that Levodopa Equivalent Dose (LED) was associated with constipation (coefficient 0.146, p = 0.005). These findings suggest that although NMS exist in the prodromal stage of PD, antiparkinsonian treatment is associated with increased frequency of some NMS, which may challenge the management for PD.

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Non-motor symptoms in treated and untreated Chinese patients with early Parkinson's disease.

REM sleep behavior disorder (RBD) is one type of parasomnia characterized by nocturnal complex motor activity associated with dream mentation. Growing evidence has indicated that RBD is a preclinical stage of neurodegenerative diseases. Therefore screening RBD patient is becoming important. The RBD Questionnaire-Hong Kong (RBDQ-HK) is an effective questionnaire to screen RBD patients. However, it is hard to distinguish RBD with the questionnaire from severe OSAS patients, who could mimic some symptoms of RBD patients. Therefore, we made RBDQ-Beijing by adding two screening questions for OSAS into original RBDQ-HK, including habitual loud snoring and witnessed apnea during sleep. To validate and compare these two questionnaires, 224 subjects were enrolled and screened with these questionnaires, and consequently analyzed with video-polysomnography. Receiver-operator characteristics curve analysis was conducted to attain the best cut-off values of the RBDQ-HK and RBDQ-Beijing. For the RBDQ-HK, the sensitivity was 97.1% and the specificity was 83.2%. More than half of misclassified RBD patients were proved to be severe OSAS patients. For the RBDQ-Beijing, the sensitivity was 95.8% and specificity was 94.3%, indicating that our questionnaire is able to distinguish RBD from severe OSAS patients. In conclusion, RBDQ-Beijing is of help to improve the specificity in RBD screening without excluding the patients with RBD combined OSAS. Therefore the RBDQ-Beijing may be a better screening and preliminary diagnostic tool for RBD than the RBDQ-HK. Moreover, the RBDQ-Beijing would be important for early diagnosis of neurodegenerative diseases and for prevention of injuries to the patient or the patient's bed partner.

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Validation of the Beijing Version of the REM Sleep Behavior Disorder Questionnaire (RBDQ-Beijing) in a Mainland Chinese Cohort

Diabetes mellitus (DM) and Parkinson’s disease (PD) are both age-related diseases of global concern being among the most common chronic metabolic and neurodegenerative diseases, respectively. While both diseases can be genetically inherited, environmental factors play a vital role in their pathogenesis. Moreover, DM and PD have common underlying molecular mechanisms, such as misfolded protein aggregation, mitochondrial dysfunction, oxidative stress, chronic inflammation, and microbial dysbiosis. Recently, epidemiological and experimental studies have reported that DM affects the incidence and progression of PD. Moreover, certain antidiabetic drugs have been proven to decrease the risk of PD and delay its progression. In this review, we elucidate the epidemiological and pathophysiological association between DM and PD and summarize the antidiabetic drugs used in animal models and clinical trials of PD, which may provide reference for the clinical translation of antidiabetic drugs in PD treatment.

Jing An

Papers

Gender differences on motor and non-motor symptoms of de novo patients with early Parkinson's disease

Association of Catechol-O-Methyltransferase and monoamine oxidase B gene polymorphisms with motor complications in parkinson's disease in a Chinese population

Non-motor symptoms in treated and untreated Chinese patients with early Parkinson's disease.

Validation of the Beijing Version of the REM Sleep Behavior Disorder Questionnaire (RBDQ-Beijing) in a Mainland Chinese Cohort

Association between Parkinson’s Disease and Diabetes Mellitus: From Epidemiology, Pathophysiology and Prevention to Treatment