Parkinson's disease is the second most common neurodegenerative disease and its prevalence has been projected to double over the next 30 years. An accurate diagnosis of Parkinson's disease remains challenging and the characterisation of the earliest stages of the disease is ongoing. Recent developments over the past 5 years include the validation of clinical diagnostic criteria, the introduction and testing of research criteria for prodromal Parkinson's disease, and the identification of genetic subtypes and a growing number of genetic variants associated with risk of Parkinson's disease. Substantial progress has been made in the development of diagnostic biomarkers, and genetic and imaging tests are already part of routine protocols in clinical practice, while novel tissue and fluid markers are under investigation. Parkinson's disease is evolving from a clinical to a biomarker-supported diagnostic entity, for which earlier identification is possible, different subtypes with diverse prognosis are recognised, and novel disease-modifying treatments are in development.Copyright © 2021 Elsevier Ltd. All rights reserved.

Parkinson's disease is a recognisable clinical syndrome with a range of causes and clinical presentations. Parkinson's disease represents a fast-growing neurodegenerative condition; the rising prevalence worldwide resembles the many characteristics typically observed during a pandemic, except for an infectious cause. In most populations, 3-5% of Parkinson's disease is explained by genetic causes linked to known Parkinson's disease genes, thus representing monogenic Parkinson's disease, whereas 90 genetic risk variants collectively explain 16-36% of the heritable risk of non-monogenic Parkinson's disease. Additional causal associations include having a relative with Parkinson's disease or tremor, constipation, and being a non-smoker, each at least doubling the risk of Parkinson's disease. The diagnosis is clinically based; ancillary testing is reserved for people with an atypical presentation. Current criteria define Parkinson's disease as the presence of bradykinesia combined with either rest tremor, rigidity, or both. However, the clinical presentation is multifaceted and includes many non-motor symptoms. Prognostic counselling is guided by awareness of disease subtypes. Clinically manifest Parkinson's disease is preceded by a potentially long prodromal period. Presently, establishment of prodromal symptoms has no clinical implications other than symptom suppression, although recognition of prodromal parkinsonism will probably have consequences when disease-modifying treatments become available. Treatment goals vary from person to person, emphasising the need for personalised management. There is no reason to postpone symptomatic treatment in people developing disability due to Parkinson's disease. Levodopa is the most common medication used as first-line therapy. Optimal management should start at diagnosis and requires a multidisciplinary team approach, including a growing repertoire of non-pharmacological interventions. At present, no therapy can slow down or arrest the progression of Parkinson's disease, but informed by new insights in genetic causes and mechanisms of neuronal death, several promising strategies are being tested for disease-modifying potential. With the perspective of people with Parkinson's disease as a so-called red thread throughout this Seminar, we will show how personalised management of Parkinson's disease can be optimised.Copyright © 2021 Elsevier Ltd. All rights reserved.

目的 探究丁苯酞(DL-3-n-butylphthalide,NBP)软胶囊联合左旋多巴和多巴丝肼(levodopa and benserazide,LB)对老年帕金森病(Parkinson's disease,PD)患者运动功能及血清同型半胱氨酸(homocysteine,Hcy)、胰岛素样生长因子1(insulin-like growth factor-1,IGF-1)的影响。方法 将2021年3月至2023年3月浙江省金华市中医医院收治的100例老年中晚期PD患者纳入本次回顾性研究,根据治疗方法不同分成对照组(n=50)和观察组(n=50),对照组患者接受LB治疗,观察组患者接受LB+NBP软胶囊治疗,治疗持续1年。比较两组的临床疗效、治疗前后的统一帕金森病评定量表(unified Parkinson's disease rating scale,UPDRS)评分、Hoehn-Yahr 分期及UPDRS-Ⅲ评分及血清Hcy、IGF-1。结果 观察组的临床疗效显著优于对照组(P<0.05);两组治疗1年后的UPDRS评分、Hoehn-Yahr 分期、UPDRS-Ⅲ评分均较治疗前显著下降,且观察组治疗1年后的UPDRS评分、Hoehn-Yahr 分期、UPDRS-Ⅲ评分显著低于对照组(P<0.05);两组治疗1年后的血清Hcy较对照组显著降低,而血清IGF-1刚好相反,且观察组治疗1年后的血清Hcy显著低于对照组,而血清IGF-1显著高于对照组(P<0.05)。结论 在老年中晚期PD患者中,NBP软胶囊联合LB可显著降低血清Hcy,显著提高IGF-1,显著改善患者的运动功能。

To review the current evidence on the options available for initiating dopaminergic treatment of motor symptoms in early-stage Parkinson disease and provide recommendations to clinicians.A multidisciplinary panel developed practice recommendations, integrating findings from a systematic review and following an Institute of Medicine-compliant process to ensure transparency and patient engagement. Recommendations were supported by structured rationales, integrating evidence from the systematic review, related evidence, principles of care, and inferences from evidence.Initial treatment with levodopa provides superior motor benefit compared to treatment with dopamine agonists, whereas levodopa is more likely than dopamine agonists to cause dyskinesia. The comparison of different formulations of dopamine agonists yielded little evidence that any one formulation or method of administration is superior. Long-acting forms of levodopa and levodopa with entacapone do not appear to differ in efficacy from immediate-release levodopa for motor symptoms in early disease. There is a higher risk of impulse control disorders associated with the use of dopamine agonists than levodopa. Recommendations on initial therapy for motor symptoms are provided to assist the clinician and patient in choosing between treatment options and to guide counseling, prescribing, and monitoring of efficacy and safety.© 2021 American Academy of Neurology.

Parkinson's disease is a common, progressive neurodegenerative disorder, the prevalence of which is on the rise. The diagnosis and management of Parkinson's disease is therefore likely to become increasingly frequent in general practice.The aim of this article is to provide a practical overview for the general practitioner of the initial diagnosis and management of Parkinson's disease.Parkinson's disease is a multisystem disorder, and the way the diagnosis is delivered, as well as the early management, can have a lasting impact on the patient experience. In this article, the authors present their preferred approach to diagnosis and initial treatment, while highlighting common pitfalls and some useful simple strategies for communicating the diagnosis.

脂质代谢可能参与帕金森病的发生及进展，涉及α-突触核蛋白异常折叠及积聚、铁死亡、GBA1基因变异、线粒体功能障碍等多种病理生理学机制。本文综述帕金森病的脂质代谢异常以及可能的相关致病机制，为帕金森病的早期诊断与治疗探索新的思路。

The most effective pharmacologic intervention used to treat motor symptoms in Parkinson's disease is levodopa, which is available in various formulations, including newer continuous subcutaneous infusions. Dopamine agonists, monoamine oxidase-B enzyme inhibitors, catechol-O-methyltransferase enzyme inhibitors, amantadine, istradefylline, and anticholinergics can be used as adjuncts to levodopa. With disease progression, pharmacologic interventions alone may not suffice to manage motor symptoms, making it necessary to consider device-aided therapies (eg, levodopa-carbidopa intestinal gel infusion, continuous subcutaneous infusions of apomorphine, levodopa, or foslevodopa) or invasive surgical techniques (eg, deep brain stimulation or MRI-guided high-frequency focused ultrasound).Copyright © 2024 Elsevier Inc. All rights reserved.

Atremorine is a novel bioproduct obtained by nondenaturing biotechnological processes from a genetic species of Vicia faba. Atremorine is a potent dopamine (DA) enhancer with powerful effects on the neuronal dopaminergic system, acting as a neuroprotective agent in Parkinson's disease (PD). Over 97% of PD patients respond to a single dose of Atremorine (5 g, p.o.) 1 h after administration. This response is gender-, time-, dose-, and genotype-dependent, with optimal doses ranging from 5 to 20 g/day, depending upon disease severity and concomitant medication. Drug-free patients show an increase in DA levels from 12.14 ± 0.34 pg/ml to 6463.21 ± 1306.90 pg/ml; and patients chronically treated with anti-PD drugs show an increase in DA levels from 1321.53 ± 389.94 pg/ml to 16,028.54 ± 4783.98 pg/ml, indicating that Atremorine potentiates the dopaminergic effects of conventional anti-PD drugs. Atremorine also influences the levels of other neurotransmitters (adrenaline, noradrenaline) and hormones which are regulated by DA (e.g., prolactin, PRL), with no effect on serotonin or histamine. The variability in Atremorine-induced DA response is highly attributable to pharmacogenetic factors. Polymorphic variants in pathogenic (SNCA, NUCKS1, ITGA8, GPNMB, GCH1, BCKDK, APOE, LRRK2, ACMSD), mechanistic (DRD2), metabolic (CYP2D6, CYP2C9, CYP2C19, CYP3A4/5, NAT2), transporter (ABCB1, SLC6A2, SLC6A3, SLC6A4) and pleiotropic genes (APOE) influence the DA response to Atremorine and its psychomotor and brain effects. Atremorine enhances DNA methylation and displays epigenetic activity via modulation of the pharmacoepigenetic network. Atremorine is a novel neuroprotective agent for dopaminergic neurons with potential prophylactic and therapeutic activity in PD.© 2021 Wiley Periodicals LLC.