Rehabilitación Neurocognitiva en Enfermedades Neurodegenerativas. Un Enfoque para Ralentizar el Deterioro Neurológico en Demencias / Neurocognitive Rehabilitation in Neurodegenerative Diseases. An Approach to Slowing Neurological Impairment in Dementias

Resumen El incremento de la incidencia y prevalencia de las patologías Parkinson y Alzheimer generan una alarma en los sistemas de salud debido a sus consecuencias en los individuos, familia y sociedad. El desarrollo de tratamientos no farmacológicos dirigidos a la rehabilitación cognitiva abre nuevas posibilidades para el incremento de la calidad de vida de estos pacientes.

Abstract The increase in the incidence and prevalence of Parkinson's and Alzheimer's diseases is causing alarm in health systems due to their consequences on individuals, families, and society. The development of non-pharmacological treatments aimed at cognitive rehabilitation opens new possibilities for increasing the quality of life of these patients.

Levodopa Versus Levodopa Sparing in Early Parkinson´s Disease: Can we Meet Halfway?

ABSTRACT Monotherapy is the recommended initial treatment for early Parkinson´s disease. The pharmacological options for initial treatment include dopaminergic agonists, monoamine oxidase B inhibitors, and levodopa formulations. Several factors should be considered when selecting the optimal treatment, such as disease severity, disease duration, age, activity level, and the risk of developing motor and non-motor complications. Early evidence on the potential role of levodopa formulations in the risk of dyskinesia led to levodopa aversion in the late 1990s and early 2000s, favoring the use of levodopa-sparing options like dopamine agonists. This shift resulted in an increase in behavioral adverse effects, such as impulse control disorders, leading to a subsequent dopamine agonist aversion in the mid-2000s. This review aims to provide a comprehensive evaluation of the existing literature regarding the benefits and drawbacks of levodopa versus levodopa-sparing strategies in drug-naive early-stage Parkinson´s disease.

Immunomodulation as a Treatment for Parkinson´s Disease in Current Trials: A Systematic Review and Meta-Analysis

ABSTRACT Background: Immunomodulatory drugs and immunotherapies are being evaluated in clinical trials for the treatment of neuroinflammation, as the latter is an essential mechanism for the development and progression of Parkinson´s disease. Objective: The objective of the study is to review recent evidence on the evaluation of immunomodulators in randomized controlled clinical trials measuring improvement of motor symptoms. Methods: A meta-analysis of Movement Disorder Society-Unified Parkinson´s disease Rating Scale (MDS-UPDRS III) scores extracted from seven articles selected after an online search of PubMed, Cochrane Library, and Clarivate's Web of Science for randomized controlled clinical trials published between 2000 and July 2023 was performed. The selected articles reported clinical trials evaluating the effects of specific immunomodulators or treatments with known effects on the immune system and inflammation. MDS-UPDRS III scores were reported in these studies, and the results of the placebo groups were compared with those of the treatment groups. Results: A total of 590 patients treated with immunomodulators and 622 patients treated with placebo were included. A test for heterogeneity yielded an I2 value > 50%. The mean standard difference for change in MDS-UPDR III score was −0.46 (CI [95%] = −0.90 - −0.02, p < 0.01). No significant differences were found in the change in mean MDS-UPDR III score between the treatment and placebo groups; however, two studies showed a trend toward separation from the mean. Conclusion: The immunomodulatory treatments included in this study showed no efficacy in improving motor symptoms in Parkinson´s disease patients. Further clinical trials with larger patient populations are needed.

Deep brain stimulation of dorsal and ventral borders of the subthalamic nucleus in patients with parkinson's disease: a systematic review / Estimulação cerebral profunda das bordas dorsal e ventral do núcleo subtalâmico em pacientes com doença de parkinson: uma revisão sistemática

Parkinson's disease patients experience motor signs and non-motor symptoms caused by the disease. Deep brain stimulation of the Subthalamic Nucleus (STN) itself or its ventral or dorsal borders is one of the treatment options indicated to treat the refractory symptoms of this disease. However, it is still unknown which edge, when stimulated, generates more beneficial effects for these patients, which is the objective of this systematic review. To answer this question, electronic and manual searches were conducted in five databases and gray literature to identify studies that answered the question in this review. The selection of studies, data extraction, and analysis of the risk of bias of the included studies were performed. In total, seven studies were included in this systematic review. Most studies presented a minimal risk of bias, and their main methodological limitation was related to the sample inclusion criteria. Stimulation of the dorsal or ventral borders of the STN resulted in improved motor signs of Parkinson's disease, with some of the studies tending towards the choice of dorsal border stimulation for better motor effects, while the improvement in non-motor symptoms and inhibitory control was due to stimulation of the ventral border. The findings of this systematic review suggest that the improvement in the motor signs of Parkinson's disease can be brought about by stimulating the dorsal or ventral borders of the subthalamic nucleus, whereas non-motor symptoms such as anxiety improve with stimulation of the ventral border.

Pacientes com doença de Parkinson frequentemente experimentam sinais motores e sintomas não motores ocasionados pela doença. A estimulação cerebral profunda do Núcleo Subtalâmico (NST) ou de suas bordas ventral ou dorsal é uma das opções de tratamento indicada para tratar sintomas refratários dessa doença. No entanto, ainda não se sabe qual a borda que, ao ser estimulada, gera mais efeitos benéficos a esses pacientes, sendo esse o objetivo dessa revisão sistemática. Para responder essa questão foram realizadas buscas eletrônicas e manuais em cinco bancos de dados e na literatura cinzenta para identificar estudos que abordassem essa temática. Foram executados a seleção dos estudos, extração de dados e análise do risco de viés dos estudos incluídos. No total, sete artigos foram selecionados para comporem o estudo. A maioria dos estudos apresentou baixo risco de viés, sendo que a principal limitação metodológica deles se relacionou com os critérios de inclusão da amostra. A estimulação da borda dorsal ou ventral do NST resultou na melhora dos sinais motores da doença de Parkinson, com alguns dos estudos inclusos com tendência para a escolha da estimulação da borda dorsal para melhores efeitos motores, enquanto a melhora dos sintomas não motores e do controle inibitório foi devido à estimulação da borda ventral. Os achados sugerem que a melhora dos sinais motores da doença de Parkinson pode ser ocasionada ao estimular a borda dorsal ou ventral do Núcleo subtalâmico, enquanto os sintomas não motores, como a ansiedade, melhoram com a estimulação da borda ventral.

Emotional state and self-perception of quality of life of patients with Parkinson's disease in the first wave of COVID-19 in Cali, Colombia / Estado emocional y autopercepción de la calidad de vida de pacientes con enfermedad de Parkinson en la primera ola de COVID-19, en Cali, Colombia

Abstract Introducción: Desde marzo del año 2020, la Organización Mundial de la Salud (OMS) declaró como pandemia al COVID-19 y esta situación representó grandes retos para los pacientes con enfermedad de Parkinson (EP). Los efectos en los cambios de las rutinas diarias, la práctica de actividades lúdicas, el relacionamiento y la salud mental, conllevaron a un deterioro secundario. Nuestro objetivo fue caracterizar el estado emocional y la calidad de vida de una cohorte de pacientes con enfermedad de Parkinson, así como explorar cuál fue la percepción de la calidad de vida en la pandemia causada por COVID-19. Métodos: Esta fue una investigación mixta que incluyó un análisis descriptivo para los datos sociodemográficos y las variables clínicas, y un análisis del discurso con base a las categorías relacionadas con la percepción de la calidad de vida de los pacientes con EP. Las categories analizadas fueron: pandemia COVID-19, cuidadores, estrategias de adaptación, manejo de la enfermedad y actividades lúdicas. Resultados: En este estudio hubo 12 pacientes, de los cuales el 75 % tenían una media de edad de 75 años (DE 2,9), donde el 50 % presentó niveles leves de ansiedad y el 41 % presentó niveles leves y graves de depresión. La calidad de vida (CV) estuvo afectada por: la movilidad 37,5 (RIC 10,6-45), seguida por el malestar corporal 25 (RIC 10,4-45,8) y la cognición 21,9 (RIC 14-34,3). El 89 % de los hombres vivía con su esposa y el 67 % de las mujeres vivían con uno de sus hijos. Discusión: La entrevista sobre la percepción de la CV durante la pandemia COVID-19 permitió comprender que la experiencia personal es fundamental para mejorar el manejo y el empoderamiento de los pacientes, cuidadores y familiares. Conclusiones: La calidad de vida es un factor mediado por dimensiones dinámicas y es afectada por la percepción subjetiva y los cambios en el entorno como la pandemia COVID-19.

Resumen Introduction: Since March 2020, the World Health Organization (WHO) declared COVID-19 as a pandemic. This crisis had big challenges for the patients with Parkinson's disease (PD), due to the effects related to changes in daily routines, the practice of leisure activities, relationships and mental health leading to secondary deterioration. Our aim was to characterize the emotional state and quality of life in a cohort of patients with Parkinson's disease as well as to explore the perception of the quality of life during the COVID-19 pandemic. Materials and methods: This investigation was conducted as an exploratory mixed study. Descriptive analysis for sociodemographic and clinical variables and, a discourse analysis was carried out based on categories related to the perception of quality of life of patients with PD. Categories analyzed were: Covid-19 pandemic, caregivers, adaptation strategies, management of the disease, and leisure activities. Results: There were twelve patients total in this study. 75% were men with a median age of 75 (SD 2.9). 50% presented mild levels of anxiety and 41% presented mild and severe depression. The QoL was affected for: mobility 37.5 (IRC 10.6-45), body discomfort 25 (IQR 10.4-45.8) and, cognition 21.9 (IQR 14-34.3). 89% lived with their wife and 67% of women lived with one of their children. Discussion: The interview about perception of QoL during Covid-19 pandemic allowed to understand that individual experiences are crucial to improve the management and empowerment the patients, caregivers and families. Conclusion: Quality of life is a factor made up of dynamic dimensions and it is influenced for subjective perspective and changes in environment as a Covid-19 pandemic.

Ethanolic Extract of Alternanthera Sessilis: A Potential Therapeutic Agent for Behavioral Improvements in Reserpine-Induced Parkinsonian Rats

The present study evaluated the potential of an ethanol extract from Alternanthera sessilis to alleviate reserpine-induced Parkinson's disease (PD) like behavioural manifestations in rats. The animals were grouped into five: a control group, a group receiving only reserpine, a group treated with levodopa and carbidopa, and two groups given different doses of the Alternanthera sessilis extract. Reserpine was used to mimic PD symptoms, while the extract was administered orally at two different concentrations. The behavioral tests were conducted to assess locomotor activity, grip strength, catalepsy, and rearing activity. Locomotor activity was measured using an actophotometer, where interruptions in light beams caused by the rates were recorded over a 10-minute period. Grip strength was evaluated using a rotarod apparatus, measuring the time taken for rats to fall off individual rods. Catalepsy was assessed through a bar test, measuring the time for rats to descend from a horizontal bar to the base. Rearing activity was observed in a round open field arena, with parameters including the occurrence rate of rearing, general movements score, and duration spent in the center of the arena. The results revealed administration of reserpine led to a decrease in body weight, locomotor activity, muscle coordination, catalepsy score, rearing activity, and grip strength compared to the control group. Conversely, treatment with levodopa and carbidopa resulted in increased values for these parameters. Importantly, administration of Alternanthera sessilis extract showed a dose-dependent reversal of the effects induced by reserpine, with significant increases observed in body weight, locomotor activity, muscle coordination, rearing activity, general movement, and grip strength, indicating its potential therapeutic effects. In conclusion, the present study results suggest that the extract from the Alternanthera sessilis plant might protect brain cells and improve symptoms of Parkinson's disease. However, more research is needed to understand how it works and if it can be used safely and effectively clinical trails.

Effect of Random, Blocked, and Mixed Practice Order on Upper Extremity Motor Learning in Subjects with Parkinson’s Disease

Background: Random practice order has been shown to improve motor learning in normal individuals as well as sports players. The purpose of this study is to investigate which practice order is beneficial in subjects with Parkinson’s disease. Methodology: The total number of Subjects included in this study was 32. Blocked practice order followed by random followed by mixed practice order was given. In between washout period of 1 week was given. Response time during acquisition and retention was assessed. Data were analyzed statistically by using one-way ANOVA. Results: The mean time taken by the subjects was maximum with Randomnn practice order with (p=0.001, SD= 10.73) during Acquisition and (p=0.003, SD=8.88). The mean time difference was maximum with random (p= 0.001) in both the acquisitions as well as retention phases. On comparing the difference between the 1st and 10th trials of all three practice orders by using Analysis of Variance (ANOVA) post hoc analysis by using Tukey’s test, we observed that in subjects with PD Random practice order is more beneficial than mixed and blocked respectively. Discussion: On comparing all three practice orders we can infer that Upper Extremity motor learning skill was superior with Random practice orders followed by Mixed and blocked practice orders respectively in both the acquisition and retention phases.

The effect of dyskinesia on postural control, balance, gait, and fall risk in people with Parkinson's disease: a systematic review protocol

Dyskinesia affects the limbs, trunk, and head and is more prevalent in people with Parkinson's disease (PD) and a history of falls. More evidence about the effects of dyskinesia on postural control, balance, gait, and fall risk could help improve the quality of life of individuals with PD. This review aims to examine associations between dyskinesia and postural control, balance, gait, and fall risk in individuals with PD. Such information could lead to new approaches to quality of life improvement among individuals with PD. PubMed, CINAHL, PsycInfo, Scopus, and SciELO will be searched for longitudinal, cohort, and case-control studies published in English or Portuguese in any year that investigated the association between dyskinesia and postural control, balance, gait, and fall risk in individuals with PD. Two reviewers will independently evaluate the titles, abstracts, and full texts according to PRISMA guidelines to select eligible studies for the review. Data on participants, dyskinesia, postural control, balance, gait, and fall risk will be extracted and summarized in tables. Two reviewers will independently assess the methodological quality of each study using the Newcastle Ottawa quality assessment scale. Meta-analysis will not be performed. The results of this systematic review will offer insight into the effects of dyskinesia on postural control, balance, gait, and fall risk. Such information could significantly contribute to informed decisions about early motor intervention in individuals with PD. (AU)

Entrenamiento de la marcha con la cinta rodante antigravitatoria en pacientes con Parkinson / Gait training with the anti-gravity treadmill in Parkinson's patients / Treinamento de marcha com fita rolante antigravitatoria em pacientes com Parkinson

La enfermedad de Parkinson (EP) es una condición neurodegenerativa caracterizada por alteraciones motoras que afectan principalmente el desarrollo de la marcha, produciéndose generalmente el fenómeno del congelamiento de la marcha con la posibilidad del riesgo de caída. Objetivo: Analizar los beneficios del entrenamiento de la marcha con la cinta rodante antigravitatoria en pacientes con EP. Materiales y métodos: Es un estudio pre-experimental con un solo grupo de intervención. Se llevó a cabo el entrenamiento de la marcha a través de una cinta rodante antigravitatoria (AlterG) durante un mes dividido en 2 sesiones por semana. Los parámetros de la marcha arrojados por el equipo AlterG fueron la descarga de peso, cadencia, tiempo de apoyo y longitud del paso; además se valoró el congelamiento de la marcha con el cuestionario (FOGQ) y el riesgo de caída con el test Timed Up and Go (TUG). Resultados: En los parámetros de la marcha y en el FOGQ se encontró diferencias significativas (p<0,05) entre los valores de pre y post intervención, exceptuando a la variable cadencia. El riesgo de caída disminuyó 4,6 y 4,3 segundos promedio en el test TUG en hombres y mujeres respectivamente. Conclusión: El entrenamiento de la marcha en la cinta rodante antigravitatoria mejora las condiciones de la marcha y reduce el riesgo de caídas en pacientes con EP.

Parkinson's disease (PD) is a neurodegenerative condition characterized by motor alterations that mainly affect the development of gait, generally producing the phenomenon of freezing of gait with the possibility of risk of falling. Objective: To analyze the benefits of gait training with the antigravity treadmill in patients with PD. Materials and methods: It is a pre-experimental study with a single intervention group. Gait training was carried out using an antigravity treadmill (AlterG) for one month divided into 2 sessions per week. The gait parameters returned by the AlterG team were weight unloading, cadence, support time and step length; Furthermore, freezing of gait was assessed with the questionnaire (FOGQ) and the risk of falling with the Timed Up and Go test (TUG). Results: In the gait parameters and in the FOGQ, significant differences (p<0.05) were found between the pre- and post-intervention values, except for the cadence variable. The risk of falling decreased by 4.6 and 4.3 seconds on average in the TUG test in men and women respectively. Conclusion: Antigravity treadmill gait training improves walking conditions and reduces the risk of falls in PD patients.

A doença de Parkinson (DP) é uma condição neurodegenerativa caracterizada por alterações motoras que afetam principalmente o desenvolvimento da marcha, geralmente produzindo o fenômeno de congelamento da marcha com possibilidade de risco de queda. Objetivo: Analisar os benefícios do treino de marcha com esteira antigravitacional em pacientes com DP. Materiais e métodos: Trata-se de um estudo pré-experimental com um único grupo de intervenção. O treinamento de marcha foi realizado em esteira antigravitacional (AlterG) durante um mês dividido em 2 sessões semanais. Os parâmetros de marcha retornados pela equipe AlterG foram descarga de peso, cadência, tempo de apoio e comprimento do passo; Além disso, o congelamento da marcha foi avaliado com o questionário (FOGQ) e o risco de queda com o teste Timed Up and Go (TUG). Resultados: Nos parâmetros da marcha e no FOGQ foram encontradas diferenças significativas (p<0,05) entre os valores pré e pós-intervenção, exceto na variável cadência. O risco de queda diminuiu em média 4,6 e 4,3 segundos no teste TUG em homens e mulheres respectivamente. Conclusão: O treino de marcha em esteira antigravitacional melhora as condições de marcha e reduz o risco de quedas em pacientes com DP.

FNDC5/Irisin in dementia and cognitive impairment: update and novel perspective

Epidemiological surveys show that the incidence of age-related dementia and cognitive impairment is increasing and it has been a heavy burden for society, families, and healthcare systems, making the preservation of cognitive function in an increasingly aging population a major challenge. Exercise is beneficial for brain health, and FDNC5/irisin, a new exercise-induced myokine, is thought to be a beneficial mediator to cognitive function and plays an important role in the crosstalk between skeletal muscle and brain. This review provides a critical assessment of the recent progress in both fundamental and clinical research of FDNC5/irisin in dementia and cognitive impairment-related disorders. Furthermore, we present a novel perspective on the therapeutic effectiveness of FDNC5/irisin in alleviating these conditions.

Correlato neurobiológico de los síntomas premotores del parkinson: el origen en la teoría de Braak / Neurobiological correlate of parkinson's premotor symptoms: the origin in Braak's theory / Correlação neurobiológica dos sintomas pré-motores de parkinson: a origem na teoria de Braak

El diagnóstico de enfermedad de Parkinson (ED) se basa en las principales manifestaciones motoras: bradicinesia en combinación con temblor en reposo, rigidez o ambos. Cuando se realiza el diagnóstico basado en la sintomatología motora clínica típica ya se han perdido hasta el 60 % de las neuronas dopaminérgicas de la sustancia negra pars compacta mesencefálica. La identificación de los síntomas premotores son un marcador temprano para sospechar la aparición futura de la enfermedad, así como su progresión y gravedad. La hipótesis sobre la patogénesis que mejor expone la progresión de la enfermedad es la teoría de Braak. Esta se basa en la aparición y presencia de cuerpos de Lewy en diferentes estructuras anatómicas, las cuales representadas en cada uno de sus seis estadios y podrían ser la explicación biológica de los síntomas premotores, motores y no motores. La detección temprana de los síntomas premotores puede tener repercusiones positivas en el enfoque, seguimiento, diagnóstico y tratamiento de la EP. El propósito de este artículo es identificar las aproximaciones neurológicas descritas por la teoría de Braak para los síntomas premotores de la enfermedad de Parkinson de acuerdo con la literatura publicada en los últimos 20 años.

The diagnosis of Parkinson's disease (PD) is based on the main motor manifestations: bradykinesia in combination with tremor at rest, rigidity, or both. When the diagnosis is made based on typical clinical motor symptoms, up to 60 % of the dopaminergic neurons of the mesencephalic substantia nigra pars compacta have already been lost. The identification of premotor symptoms is an early marker to suspect the future appearance of the disease, as well as its progression and severity. The hypothesis about the pathogenesis that best exposes the progression of the disease is Braak's theory. It is based on the appearance and presence of Lewy bodies in different anatomical structures, which are represented in each of its six stages and could be the biological explanation biological of premotor, motor, and non-motor symptoms. Early detection of premotor symptoms can have positive repercussions in the approach, follow-up, diagnosis and treatment of PD. The purpose of this article is to identify the neurological approaches described by Braak's theory for the premotor symptoms of Parkinson's disease according to the literature published in the last 20 years.

O diagnóstico da doença de Parkinson (DP) baseia-se nas principais manifestações motoras: bradicinesia combinada com tremor de repouso, rigidez ou ambos. Quando o diagnóstico é feito com base em sintomas clínicos motores típicos, até 60% dos neurônios dopaminérgicos da substância negra pars compacta mesencefálica já foram perdidos. A identificação de sintomas pré-motores é um marcador precoce para suspeitar do futuro aparecimento da doença, bem como da sua progressão e gravidade. A hipótese sobre a patogênese que melhor expõe a progressão da doença é a teoria de Braak. Isto se baseia no aparecimento e presença de corpos de Lewy em diferentes estruturas anatômicas, que estão representados em cada uma de suas seis etapas e podem ser a explicação biológica dos sintomas pré-motores, motores e não motores. A detecção precoce de sintomas pré-motores pode repercutir positivamente na abordagem, acompanhamento, diagnóstico e tratamento da DP. O objetivo deste artigo é identificar as abordagens neurológicas descritas pela teoria de Braak para os sintomas pré-motores da doença de Parkinson de acordo com a literatura publicada nos últimos 20 anos.

Alteraciones genéticas asociadas a la enfermedad de Parkinson y Alzheimer: evolución y respuesta al tratamiento / Genetic Alterations Associated with Parkinson's and Alzheimer's Disease: Evolution and Response to Treatment

La enfermedad de Parkinson y Alzheimer son las enfermedades neurodegenerativas más frecuentes a nivel mundial. Tienen etiología multifactorial, entre ellas, la genética; y son motivo de interés en la investigación científica actual. Se realizó una revisión narrativa con el objetivo de determinar las alteraciones genéticas asociadas a estas patologías, además su influencia en la evolución y respuesta al tratamiento de ellas. Se consultaron artículos originales, revisiones bibliográficas, sistemáticas, metaanálisis en inglés y español, con fecha de publicación entre el 1 enero de 2018 y el 20 de mayo de 2023, en bases como PubMed y Medline. Se utilizaron los términos MeSH «Alzheimer Disease¼, «Parkinson Disease¼, «Drug Therapy¼ y «Mutations¼. El riesgo hereditario para la enfermedad de Parkinson suele ser poligenético, sin embargo, existen genes relacionados con mutaciones monogénicas. Se identifican alteraciones en genes de α-sinucleína, glucocerebrosidasa y quinasa 2 rica en leucina que se relacionan con mayor riesgo de desarrollar Parkinson, además de variaciones en el cuadro clínico y edad de inicio de síntomas. En cuanto a la enfermedad de Alzheimer, las alteraciones en los genes de la proteína precursora amiloide, presenilina 1 y 2 se relacionan con la forma familiar de la enfermedad; por otra parte, las de apolipoproteína E4 se han identificado en la forma esporádica, por lo que se consideran como el factor de riesgo genético más importante para su desarrollo

Parkinson's and Alzheimer's are the most frequent neurodegenerative diseases worldwide. They have a multifactorial etiology, including genetics, and are of interest in current scientific research. A narrative review was carried out with the aim of determining the genetic alterations associated with these pathologies, as well as their influence on their evolution and response to treatment. Original articles, literature reviews, systematic reviews, meta-analyses in English and Spanish, with publication date between January 1, 2018 and May 20, 2023, were consulted in databases such as PubMed and Medline. MeSH terms "Alzheimer Disease", "Parkinson Disease", "Drug Therapy" and "Mutation" were used. Hereditary risk for Parkinson's disease is usually polygenetic, however, there are genes related to monogenic mutations. Alterations in α-synuclein, glucocerebrosidase and leucine-rich kinase 2 genes have been identified that are related to an increased risk of developing Parkinson's disease, in addition to variations in the clinical picture and age of symptom onset. As for Alzheimer's disease, alterations in the genes of the amyloid precursor protein, presenilin 1 and 2 are related to the familial form of the disease; on the other hand, those of apolipoprotein E4 have been identified in the sporadic form, and are therefore considered to be the most important genetic risk factor for its development

Exploration of Role of Yin and Yang Syndrome Differentiation in Parkinson's Disease / 中国实验方剂学杂志

The syndrome differentiation of Yin and Yang has the function of controlling the other six principles in the eight principles syndrome differentiation，which is a higher level or general induction of the disease. In the clinical process of traditional Chinese medicine，syndrome differentiation of Yin and Yang runs through the whole process of disease diagnosis and treatment. For Parkinson's disease，syndrome differentiation of Yin and Yang is particularly important. Different symptoms，the transformation of pathogenesis during the development of the disease and the treatment of traditional Chinese and western medicine all reflect the characteristics of Yin and Yang opposition restriction，mutual root and mutual use，and the transformation of ebb and flow. This article discusses the background，application and value of Yin-Yang syndrome differentiation from three aspects：the origin and application of yin-yang syndrome differentiation，the basis of Parkinson's disease syndrome differentiation，and the status and role of Yin-Yang syndrome differentiation in Parkinson's disease. It is of great significance to guide the diagnosis and treatment of Parkinson's disease with "Yin-Yang as the key point".

Tianma Goutengyin and Its Single Herb in Treatment of Parkinson's Disease： A Review / 中国实验方剂学杂志

Parkinson's disease （PD） is a kind of chronic progressive neurodegenerative disease that has a high prevalence rate in recent years， especially in the elderly. PD belongs to the category of "tremor disease" and "tremor" in traditional Chinese medicine， and Tianma Goutengyin is a classic prescription contained in the Synopsis of The New Significance of Patterns and Treatment in Miscellaneous Diseases（《中医内科杂病证治新义》）. This article explored the theory of Tianma Goutengyin in the treatment of PD， and based on network pharmacological research， the article summarized relevant research on Tianma Goutengyin and its single herb in the treatment of PD. Moreover， it discussed the clinical applications and mechanisms of Tianma Goutengyin and its single herb in the treatment of PD. It is found that the mechanisms of Tianma Goutengyin in treating PD may be related to resisting oxidative stress， inhibiting inflammatory response， regulating neurotransmitters， and protecting dopamine （DA） neurons. Besides， the main components of the single herb in Tianma Goutengyin for treating PD are gastrodin， rhynchophylline， geniposide， gardenial alcohol， eucommitol glycoside， motherwort alkaloid， baicalin， pachyman， and achyranthes bidentata sterol. They can improve the related symptoms of PD patients by inhibiting inflammatory response， resisting oxidative stress， affecting calcium ion concentration， restoring mitochondrial function， and and protecting DA neurons. This article summarized the research progress of Tianma Goutengyin and its single herb in treating PD， so as to provide a reference for the prescription and medication of Tianma Goutengyin in the treatment of PD and subsequent research on the mechanisms of Tianma Goutengyin and its single herb in the treatment of PD and give play to the advantages of traditional Chinese medicine in the treatment of PD.

Juvenile Parkinson's disease caused by PRKN gene compound heterozygous mutation:A case report and literature review / 吉林大学学报(医学版)

Objective:To conduct the genetic analysis of a family with one patient suffering from juvenile Parkinson's disease(JP)and discuss the clinical manifestations,genetic mutation characteristics,and treatment plans prompted by PRKN gene compound heterozygous mutations,and to enhance the clinicians'awareness of this disease.Methods:The clinical data of one patient with JP caused by PRKN gene mutations was analyzed,the clinical manifestations and genetic mutation features of the patient were summarized,and the related literatures were reviewed.Results:The patient,a 16-year-old male,was admitted to the hospital due to unstable gait,trembling limbs with rigidity in both lower limbs for three years.The examination results revealed a panic gait,clear consciousness,fluent speech,normal muscle strength in limbs,increased"gear-like"muscle tone in both upper limbs,and"lead-pipe"rigidity in both lower limbs;the sensory functions and tendon reflexes were normal.The head,neck,and thoracic magnetic resonance imaging(MRI)results showed no abnormalities.18F-fluorodeoxyglucose(18F-FDG)positron emission tomography/computed tomography(PET/CT)results showed that the head size and shape were normal,the glucose metabolism in the left cerebellum and middle temporal gyrus was slightly decreased,and the glucose metabolism in bilateral thalami,right frontal lobe,parietotemporal lobe,and left medial frontal lobe was increased.The dopamine transporter(DAT)PET/CT results showed that there was no radioactive distribution in the brain cortex and the DAT distribution in the posterior part of both striata was decreased.The whole-exome sequencing results showed the patient had two PRKN gene mutations,such as codons c.8T>A and c.850G>C compound heterozygous mutations,and each mutation was from one parent;the patient's father carried the c.8T>A mutation,the patient's mother carried the c.850G>C mutation,and the patient's sister had the same genetic mutation site as the patient's father.Conclusion:PRKN gene compound heterozygous mutations may be the basis of the disease in this family.Identification of the mutation c.8T>A expands the mutation spectrum of the PRKN gene,and provides the valuable information for the research on the pathogenic genetic mutations of the JP patients.

Research progress in pathogenesis and treatment of gastrointestinal motility disorders in Parkinson's disease / 吉林大学学报(医学版)

The gastrointestinal motility disorder of the patients with Parkinson's disease(PD)occurs in the early stages of this disease,even before the onset of motor symptoms.The gastrointestinal motility disorder is one type of gastrointestinal dysfunction,not only affect the absorption of medication,exacerbating the progression of PD,but also severely impact the quality of life of the patients.Therefore,it is essential to find new therapeutic targets to alleviate PD-induced gastrointestinal dysmotility in order to improve the progression of the disease and the quality of life of the patients.The gastrointestinal motility function is highly dependent on the health of the gut and central nervous regulating the gastrointestinal movements.A healthy gut is closely related to the integrity of the intestinal barrier,gut microbiota,neuroinflammation,and the normal function of enteric neurons responsible for the contraction and relaxation of the gastrointestinal tract.The gut function of the PD patients is compromised to some extent.This review summarizes the effects of the enteric nervous system,central nervous system,and gut microbiota on the development of gastrointestinal motility disorder of the PD patients;it also outlines the current therapeutic methods available and their limitations,with the aim of providing the new insights into the treatment of gastrointestinal motility disorder of the PD patients.

Correlation analysis of serum dopamine,5-hydroxytryptamine,homovanillic acid levels and cognitive dysfunction in patients with Parkinson's disease / 国际检验医学杂志

Objective To explore the relationship between the levels of serum dopamine,5-hydroxytryptamine,homovanillic acid and cognitive dysfunction in patients with Parkinson's disease.Methods A total of 118 Parkinson's disease patients admitted to Bazhong Central Hospital from February 2020 to February 2022 were selected as the disease group,and 106 healthy patients who underwent physical examination in the hospital during the same period were selected as the control group.The levels of serum do-pamine,5-hydroxytryptamine and homovanillic acid were measured in all subjects,and the cognitive function was evaluated with Montreal Cognitive Assessment Scale(MoCA).Parkinson's disease patients were divided into cognitive impairment group and non cognitive impairment group according to MoCA score.The serum do-pamine,5-hydroxytryptamine,homovanillic acid levels of the cognitive impairment group and the non cogni-tive impairment group were compared.Pearson correlation analysis was used to analyze the correlation be-tween serum dopamine,5-hydroxytryptamine and homovanillic acid levels and cognitive function of Parkinson's disease patients,and the receiver operating characteristic curve was drawn to analyze the evaluation value of serum dopamine,5-hydroxytryptamine and homovanillic acid levels on cognitive dysfunction of Parkinson's disease patients.Results The levels of serum dopamine,5-hydroxytryptamine,homovanillic acid and MoCA score in the disease group were lower than those in the control group,with statistical significance(P＜0.05).The levels of serum dopamine,5-hydroxytryptamine,homovanillic acid and MoCA score in advanced patients were lower than those in early patients,and the difference was statistically significant(P＜0.05).The levels of serum dopamine,serotonin and homovanillic acid in the cognitive dysfunction group were lower than those in the non-cognitive dysfunction group,and the difference was statistically significant(P＜0.05).The results of Pearson analysis showed that the levels of serum dopamine,5-hydroxytryptamine and homovanillic acid in Parkinson's disease patients were positively correlated with MoCA score(P＜0.05).The sensitivity of the combined assessment of serum dopamine,serotonin and homovanillic acid in Parkinson's disease patients was higher than that in Parkinson's disease patients alone(x2=7.413,P=0.006;x2=9.714,P=0.002;x2=8.541,P=0.003),the area under the curve(AUC)was higher than the AUC for assessing cognitive impair-ment in Parkinson's disease alone(Z=2.479,P=0.013;Z=2.271,P=0.023;Z=2.451,P=0.014).Conclusion There are differences in serum levels of dopamine,5-hydroxytryptamine,homovanillic acid and cognitive function among different stages of Parkinson's disease patients.Serum levels of dopamine,5-hydroxytryptamine,and homovanillic acid are closely related to cognitive function in Parkinson's disease pa-tients,all of which have evaluation value for the occurrence of cognitive dysfunction in Parkinson's disease pa-tients.However,the combination of the three serum indicators is more helpful for clinical evaluation and diag-nosis.

Propofol Regulates MPP+-induced Mitochondrial Oxidative Stress and Apoptosis in SH-SY5Y Cells / 昆明医科大学学报

Objective To investigate the effects of different concentrations of PPF on oxidative stress and apoptosis of PD model cells induced by MPP+.Methods The human neuroblastoma cell SH-SY5Y was induced by 1 mM MPP+ to establish PD cell model.In PPF treatment group,SH-SY5Y cells were stimulated with 10,20,40 and 80 μM PPF for 4 h before MPP+ induction.Cell counting kit-8(CCK-8)was performed to evaluate cell proliferation activity.H2DCF-DA fluorescent probe was used to detect ROS in cells.The levels of MDA and NADPH oxidase were analyzed by the kit.Western blot examined the protein expression of cytochrome c in mitochondria and cytoplasm,as well as the relative expression of Bcl-2,Bax and cleaved caspase-3 in SH-SY5Y cells.Apoptosis rate was analyzed by flow cytometry.Results MPP+ significantly inhibited the proliferation of SH-SY5Y cells(P<0.001),promoted the level of ROS(P<0.001),MDA(P<0.001),NADPH oxidase(P<0.01),cytochrome c in cytoplasm(P<0.01)and induced apoptosis(P<0.001)and the relative expression of pro-apoptosis protein Bax and cleaved caspase-3(P<0.01),reduced cytochrome c protein in mitochondria(P<0.01)and the relative expression of anti-apoptosis protein(P<0.01).PPF pretreatment alleviated the proliferation inhibition,oxidative stress and apoptosis promotion of SH-SY5Y cells induced by MPP+(P<0.001),and the effects of 40 μM and 80 μM on cells were more significant.Conclusion PPF pretreatment can alleviate the oxidative stress of SH-SY5Y cells induced by MMP+ and reduce apoptosis rate.

Research progress in the treatment of Parkinson's disease with depression / 临床神经病学杂志

Parkinson's disease(PD)depression is one of the most common non-motor symptoms of PD,but depression is often ignored in the early stages of PD and is not treated in time.With the progression of the disease,the symptoms of depression become more prominent,and patients tend to commit suicide in severe cases,which seriously reduces the quality of life of patients.At present,although there are many clinical treatment methods for PD with depression,but the clinical effect is not clear,and there is still a lack of effective therapeutic intervention means and methods.In this paper,the more common treatment methods are summarized,to develop an individualized treatment plan for PD patients with depression.

Prevalence and related risk factors of minor hallucinations in newly diagnosed Parkinson's disease patients / 临床神经病学杂志

Objective To screen the prevalence and related risk factors of minor hallucinations(MH)in newly diagnosed Parkinson's disease(PD).Methods From November 2018 to December 2022,274 newly diagnosed patients with untreated PD were enrolled in the PD Clinic of Brain Hospital Affiliated to Nanjing Medical University.According to the score of item 2 of the unified PD rating scale Ⅰ(UPDRSⅠ),the PD patients with MH were selected(MH group,score≥2).The patients matched in age,sex,education and course of disease level were screened in non-MH PD patients(NMH group,score = 0).Cognitive function,depressive symptoms,anxiety symptoms,sleep quality,non-motor symptoms,rapid eye movement sleep disorder(RBD)symptoms,activities of daily life,motor function and disease severity were evaluated with appropriate scales.The differences between two groups were compared,and the risk factors of MH in PD patients were analyzed by univariate and multivariate progressive Logistic regression.Results Among the 274 newly diagnosed PD patients,11 cases(4.01%)had MH.Compared with those in NMH group(22 cases),MH group had higher Hamilton depression scale(HAMD)scores,higher Hamilton anxiety scale(HAMA)scores,higher PD non motor symptoms(PDNMS)scores and higher RBD scores(all P＜0.05).Univariate Logistic regression analysis showed that high HAMD scores,high HAMA scores,high PDNMS scores and high RBD scores were risk factors for MH in PD patients(all P＜0.05).Multivariate Logistic regression analysis showed that high HAMD score(OR =1.182,95%CI:1.004-1.392,P =0.045)and high RBD score(OR =4.448,95%CI:1.066-18.557,P =0.041)were independent risk factors for MH in PD patients.Conclusions MH may occur in newly diagnosed PD patients with probability.Depression and RBD are independent risk factors for MH in PD patients.Attention should be paid to screening patients like this and early intervention measures should be taken.