Manifestations Of Parkinson's Disease Research Articles

Molecular Imaging Findings on Acute and Long-Term Effects of COVID-19 on the Brain: A Systematic Review.

Molecular imaging techniques such as PET and SPECT have been used to shed light on how coronavirus disease 2019 (COVID-19) affects the human brain. We provide a systematic review that summarizes the current literature according to 5 predominant topics. First, a few case reports have suggested reversible cortical and subcortical metabolic alterations in rare cases with concomitant para- or postinfectious encephalitis. Second, imaging findings in single patients with the first manifestations of parkinsonism in the context of COVID-19 resemble those in neurodegenerative parkinsonism (loss of nigrostriatal integrity), but scarceness of data and a lack of follow-up preclude further etiologic conclusions (e.g., unmasking/hastening of neurodegeneration vs. infectious or parainfectious parkinsonism). Third, several case reports and a few systematic studies have addressed focal symptoms and lesions, most notably hyposmia. The results have been variable, although some studies found regional hypometabolism of regions related to olfaction (e.g., orbitofrontal and mesiotemporal). Fourth, a case series and systematic studies in inpatients with COVID-19–related encephalopathy (acute to subacute stage) consistently found a frontoparietal-dominant neocortical dysfunction (on imaging and clinically) that proved to be grossly reversible in most cases until 6 mo. Fifth, studies on post–COVID-19 syndrome have provided controversial results. In patients with a high level of self-reported complaints (e.g., fatigue, memory impairment, hyposmia, and dyspnea), some authors found extensive areas of limbic and subcortical hypometabolism, whereas others found no metabolic alterations on PET and only minor cognitive impairments (if any) on neuropsychologic assessment. Furthermore, we provide a critical appraisal of studies with regard to frequent methodologic issues and current pathophysiologic concepts. Finally, we devised possible applications of PET and SPECT in the clinical work-up of diagnostic questions related to COVID-19.

2021 Workshop: Neurodegenerative Diseases in the Gut-Brain Axis—Parkinson's Disease

2021 Workshop: Neurodegenerative Diseases in the Gut-Brain Axis—Parkinson's Disease

Inflammatory markers and BDNF in obstructive sleep apnea (OSA) in Parkinson's disease (PD)

ObjectiveObstructive sleep apnea (OSA) exacerbates Parkinson's disease (PD) manifestations including cognitive dysfunction. Both OSA and PD have been associated with inflammation. Brain-derived neurotrophic factor (BDNF) has been implicated in cognitive function. We aimed to investigate inflammatory cytokines and BDNF in relation to OSA and PD symptoms. MethodsIn a prospective observational study, patients with PD underwent overnight polysomnography. Morning serum levels of interleukin (IL)-1β, IL-6, IL-8, TNFα, and BDNF were quantified at baseline (n = 64) and 6 months (n = 38). Outcomes included non-motor and motor standard scores; Montreal Cognitive Assessment (MoCA); and Epworth Sleepiness scale (ESS). Associations were assessed using linear regression, adjusting for age, sex and body mass index. ResultsAt baseline, IL-6 was associated with the Apnea–Hypopnea Index (β = 0.013, p = 0.03), and the Oxygen Desaturation Index (β = 0.028, p = 0.002). No other associations between cytokines and sleep parameters were found. Motor dysfunction was associated with IL-6 (β = 0.03, p = 0.001). ESS was associated non-significantly with IL-6 (β = 0.04, p = 0.07) and BDNF (β = 555, p = 0.06). At follow-up, change in IL-6 was associated with change in non-motor (β = 0.08, p = 0.007), and motor (β = 0.03, p = 0.001) symptoms. Change in BDNF was associated with change in ESS (β = 1450, p = 0.02). InterpretationWe found an association between IL-6 levels and both OSA severity and PD motor dysfunction. At follow-up, increasing IL-6 correlated with deterioration of motor and non-motor PD symptoms. Increasing BDNF correlated with increasing sleepiness. Further work with a larger sample size is needed, but our results support the hypothesis that OSA-related inflammation plays a role in PD manifestations and progression.

Провокуючі фактори дебюту моторних симптомів хвороби Паркінсона

Актуальність. Хвороба Паркінсона (ХП) — одне з найбільш частих нейродегенеративних захворювань. Незважаючи на 200-річчя його наукового вивчення, етіологія ХП залишається до кінця невідомою. Раніше встановлено, що латентна і премоторна фаза на 4–10 років передують розвитку класичних проявів ХП. Залишається відкритим питання виділення провокуючого фактора клінічної маніфестації моторних симптомів ХП. Мета дослідження: визначити найбільш часті провокуючі фактори розвитку моторних симптомів ХП шляхом проведення анкетного опитування пацієнтів. Матеріали та методи. Опитано 120 пацієнтів з ХП. Анкета розроблена автором для виявлення факторів, що провокують маніфестацію ХП. Отримані клінічні дані й результати анкетування піддали статистичній обробці. Рівень значущості р приймали рівним 0,05. Результати. 53,33 % (64 пацієнта) зв’язали розвиток моторних симптомів ХП із перенесеною значущою гострою психотравмуючою ситуацією. Часовий інтервал між дією стресового чинника і дебютом захворювання варіював від 1 дня до 4 років (медіана (Me) 5,2 місяця; 95% ДІ 2,1–9,1 місяця). Перенесені гострі респіраторні інфекції в дебюті розвитку або за 2–4 місяці до розвитку ХП відзначили 3,33 % (4 людини). Больові синдроми різної локалізації були виявлені у 8,33 % (10 осіб). Відсутність будь-якого провокуючого фактора відзначили 35 % (42 опитаних). Обробка клінічних даних (стать, вік дебюту ХП і склад за клінічними формами ХП) не виявила статистично значущих відмінностей між групами з різними провокуючими факторами дебюту ХП. Висновки. Розвиток моторних симптомів ХП у багатьох пацієнтів може бути спровоковано низкою факторів, серед яких переважав дистрес. Сформульована автором гіпотеза формування зони абсолютної рефрактерності в дофамінергічній системі після стресового впливу в дебюті моторних симптомів ХП потребує експериментального підтвердження.

COVID-19: The cynosure of rise of Parkinson's disease.

Parkinson's disease (PD) is one of the most common age-related disorders globally. The pathophysiological mechanisms and precipitating factors underlying PD manifestations, including genetic and environmental parameters, inflammation/stress and ageing, remain elusive. Speculations about whether the Coronavirus Disease 2019 (Covid-19) pandemic could be a pivotal factor in affecting the prevalence and severity of PD or triggering a wave of new-onset parkinsonism in both the near and distant future have recently become very popular, with researchers wondering if there is a changing trend in current parkinsonism cases. Could the current understanding of the Covid-19 pathophysiology provide clues for an impending rise of parkinsonism cases in the future? Are there any lessons to learn from previous pandemics? Our aim was to look into these questions and available current literature in order to investigate if Covid-19 could constitute a cardinal event affecting the parkinsonism landscape.

Motor and non-motor circuit disturbances in early Parkinson disease: which happens first?

For the last two decades, pathogenic concepts in Parkinson disease (PD) have revolved around the toxicity and spread of α-synuclein. Thus, α-synuclein would follow caudo-rostral propagation from the periphery to the central nervous system, first producing non-motor manifestations (such as constipation, sleep disorders and hyposmia), and subsequently impinging upon the mesencephalon to account for the cardinal motor features before reaching the neocortex as the disease evolves towards dementia. This model is the prevailing theory of the principal neurobiological mechanism of disease. Here, we scrutinize the temporal evolution of motor and non-motor manifestations in PD and suggest that, even though the postulated bottom-up mechanisms are likely to be involved, early involvement of the nigrostriatal system is a key and prominent pathophysiological mechanism. Upcoming studies of detailed clinical manifestations with newer neuroimaging techniques will allow us to more closely define, in vivo, the role of α-synuclein aggregates with respect to neuronal loss during the onset and progression of PD.

A Markerless 2D Video, Facial Feature Recognition-Based, Artificial Intelligence Model to Assist With Screening for Parkinson Disease: Development and Usability Study.

BackgroundMasked face is a characteristic clinical manifestation of Parkinson disease (PD), but subjective evaluations from different clinicians often show low consistency owing to a lack of accurate detection technology. Hence, it is of great significance to develop methods to make monitoring easier and more accessible.ObjectiveThe study aimed to develop a markerless 2D video, facial feature recognition–based, artificial intelligence (AI) model to assess facial features of PD patients and investigate how AI could help neurologists improve the performance of early PD diagnosis.MethodsWe collected 140 videos of facial expressions from 70 PD patients and 70 matched controls from 3 hospitals using a single 2D video camera. We developed and tested an AI model that performs masked face recognition of PD patients based on the acquisition and evaluation of facial features including geometric and texture features. Random forest, support vector machines, and k-nearest neighbor were used to train the model. The diagnostic performance of the AI model was compared with that of 5 neurologists.ResultsThe experimental results showed that our AI models can achieve feasible and effective facial feature recognition ability to assist with PD diagnosis. The accuracy of PD diagnosis can reach 83% using geometric features. And with the model trained by random forest, the accuracy of texture features is up to 86%. When these 2 features are combined, an F1 value of 88% can be reached, where the random forest algorithm is used. Further, the facial features of patients with PD were not associated with the motor and nonmotor symptoms of PD.ConclusionsPD patients commonly exhibit masked facial features. Videos of a facial feature recognition–based AI model can provide a valuable tool to assist with PD diagnosis and the potential of realizing remote monitoring of the patient’s condition, especially during the COVID-19 pandemic.

The role of frailty in Parkinson's disease: a cross-sectional study.

Frailty is an age-related state of increased risk for health-related adverse outcomes that reflects multisystem physiological changes and likely influences the clinical expression and disease progression of neurodegenerative disorders. The aim of the present study was to assess the potential relationship between frailty, as assessed by a frailty index (FI), and motor symptom severity, motor subtypes, and non-motor domains in Parkinson's disease (PD). We consecutively enrolled 150 PD patients. We administered an FI specifically designed for PD that included 50 age-related multidimensional biological deficits. Patients underwent a clinical assessment that evaluated motor and non-motor manifestations of PD. Using the FI score, we classified PD patients as relatively fit (FI ≤ 0.10), less fit (0.10 < FI ≤ 0.21), or frail (FI > 0.21). A linear regression model was designed to explore possible associations between frailty level and PD motor and non-motor manifestations. Frail patients showed greater motor symptom severity and motor complications than fitter patients. A trend towards a higher prevalence of the postural instability/gait disorder subtype was also observed in frail versus relatively fit and less fit patients. The global burden of non-motor symptoms was higher in frail patients. Increased frailty was associated with more severe motor and non-motor symptoms, as well as with more pronounced cognitive deficits. These associations remained significant even when "traditional" predictors of PD severity (age, disease duration, and levodopa equivalent daily dose) were considered. The present findings indicate that the FI is associated with both motor and non-motor features of PD.

Prestimulus Low-Alpha Frontal Networks Are Associated with Pareidolias in Parkinson's Disease.

Background: Pareidolias are visual phenomena wherein ambiguous, abstract forms or shapes appear meaningful due to incorrect perception. In Parkinson's disease (PD), patients susceptible to visual hallucinations experience visuo-perceptual deficits in the form of pareidolias. Although pareidolias necessitate top-down modulation of visual processing, the cortical dynamics of internally generated perceptual priors on these visual misperceptions is unknown. Objectives: To study prestimulus-related electroencephalography (EEG) spectral and network abnormalities in PD patients experiencing pareidolias. Methods: Twenty-one PD in-patients and 10 age-matched controls were evaluated. Neuropsychological assessments included tests for cognition, attention, and executive functions. Pareidolias were quantified by using the "noise pareidolia test" with simultaneous EEG recording. The PD patients were subdivided into two groups-those with high pareidolia counts (n = 10) and those without (n = 11). The EEG was analyzed 1000 msec before stimulus presentation in the spectral domain (theta, low-alpha, and high-alpha frequencies) with corresponding graph networks to evaluate network properties. Statistical analysis included analysis of variance and multiple regression to evaluate the differences. Results: The PD patients with high pareidolia counts were older with lower scores on neuropsychological tests. Their prestimulus EEG low-alpha band showed a tendency toward higher frontal activity (p = 0.07). Graph networks showed increased normalized clustering coefficient (p = 0.05) and lower frontal degree centrality (p = 0.005). These network indices correlated positively to patients' pareidolia scores. Discussion: We suggest that pareidolias in PD are a consequence of an abnormal top-down modulation of visual processing; they are defined by their frontal low-alpha spectral and network alterations in the prestimulus phase due to a dissonance between patients' internally generated mental processing with external stimuli. Impact statement Pareidolias in Parkinson's disease (PD) are considered to be promising early markers of visual hallucinations and an indicator of PD prognosis. In certain susceptible PD patients, pareidolias can be evoked and studied. Here, via electroencephalography, we aimed at understanding this visual phenomenon by studying how neural information is processed before stimulus presentation in such patients. Using spectral and graph network measures, we revealed how top-down modulated internally generated processes affect visual perception in patients with pareidolias. Our findings highlight how prestimulus network alterations in the frontal cortex shape poststimulus pareidolic manifestations in PD.

Transcutaneous vagus nerve stimulation (tVNS) as a potential therapeutic application for neurodegenerative disorders - A focus on dysautonomia in Parkinson's disease.

The understandings of pathogenic processes in major neurodegenerative diseases has significantly advanced in recent years, with evidence showing pathological spread of intraneuronal proteinaceous inclusions as a fundamental factor. In Parkinson's disease (PD), the culprit protein has been identified as α-synuclein as the main component for mediating progressive neurodegeneration. With severe pathology evident in the autonomic nervous system prior to clinical manifestations of PD, pathogenic spread can occur from the peripheral nervous system through key nuclei, such as the anterior olfactory nucleus and dorsal motor nucleus of the glossopharyngeal and vagal nerves, gradually reaching the brainstem, midbrain and cerebral cortex. With this understanding and the proposed involvement of the vagus nerve in disease progression in PD, notably occurring prior to characterized clinical motor features, it raises intriguing questions as to whether vagal nerve pathology can be accurately detected, and importantly used as a reliable marker for determining early neurodegeneration. Along with this is the potential use of vagus nerve neuromodulation for treatment of early disease symptoms like dysautonomia, for modulating sympatho-vagal imbalances and easing severe comorbidities of the disease. In this article, we take a closer look at the pathogenic transmission processes in neurodegenerative disorders that impact the vagus nerve, and how vagus nerve neuromodulation can be potentially applied as a therapeutic approach for major neurodegenerative disorders.

Review of medicine utilization for Parkinson's disease management: the Bulgarian perspective.

Background: Parkinson’s disease (PD), which occurs in 1% of the population, is the second most common neurodegenerative disorder. Despite the broad spectrum of PD manifestations and high disease prevalence, there are insufficient data on medicine utilization and prescription strategies. The purpose of the current study was to analyze published data concerning treatment approaches and to compare them with Bulgarian therapeutic practice.Design and methods: We conducted a systematic review of the PubMed and Google Scholar databases, and we calculated medicine utilization in Bulgaria during 2018 and 2019 using the WHO methodology.Results: The literature search identified a total of 311 publications, but only 12 met the inclusion criteria. Eleven studies pointed out that levodopa-containing medicine are the most frequently used, followed by dopamine agonists. The highest rate was found for levodopa-containing products and decarboxylase inhibitor (1.06 and 1.33 DDD/1000 inh/day), followed by anticholinergic Biperiden (0.494 and 0.455 DDD/1000 inh/day) during 2018 and 2019 in Bulgaria.Conclusion: Overall, the treatment approaches used in the last decade comply with guideline recommendations, despite variations in levodopa and dopamine agonist utilization. Even though new medicines have been approved for PD management, levodopa- containing products are still most often prescribed and used worldwide. Significance for public health Parkinson’s disease is the second most common neurodegenerative disorder affecting high number of the population. The achieved clinical results and disease control depending on early patients’ diagnostic and treatment. This study emphasizes on medicines utilization and most often used treatment approaches on Parkinson’s disease management. In addition, this is the first study exploring medicines utilization in Bulgaria. The findings reveal real medicines utilization in Bulgaria during 2018-2019 and its comparison with those found in the other countries. Regardless development of new therapies, levodopa-containing products reveals the highest rate of utilization as in most of the compared countries as in Bulgaria

Gait based Parkinson’s disease diagnosis and severity rating using multi-class support vector machine

To diagnose Parkinson’s disease (PD) in a clinical setting, generally clinicians utilize several clinical manifestations such as motor impairments and non-motor symptoms and predict the severity level based on unified Parkinson’s disease rating scale (UPDRS). Such a clinical evaluation highly depends on the expertise and experience of the clinicians and results in variation in assessment among clinicians. Hence, to assist the clinicians to diagnose the PD and rate the severity level, we present a gait classification based decision support system using multi-class support vector machine (MCSVM). As the gait alterations are the initial manifestations of PD, we utilize the publicly available vertical ground reaction force (VGRF) dataset and perform the kinematic analysis to extract the spatiotemporal features. To identify the prominent gait biomarkers, this work utilizes a correlation based feature selection approach and employs multi-regression approach to normalize the gait time series data. Moreover, transforming the multi-class classification problem into multiple binary classification problem using one-versus-one (OVO) strategy, the proposed PD severity rating framework tests the performance of four SVM kernel functions for three different walking tests. Experimental results highlight that the quadratic SVM classifier offers an average accuracy of 98.65% and outperforms several other state-of-the-art methods that utilized gait dataset for PD diagnosis.

Serum 25-Hydroxyvitamin D Level Estimation among Patients with Parkinson's Disease in West Bengal, India, and its Relationship with Motor Impairment

Context: Worldwide, the association of Vitamin D deficiency in Parkinson's disease (PD) has recently been proposed. However, to the best of our knowledge, such studies are lacking from eastern India. Aims: This study compares the prevalence of Vitamin D deficiency in a cohort of patients with PD with the prevalence in age-matched healthy controls. It also aimed at determining a significant correlation of the severity of the various motor manifestations in PD with low serum vitamin levels. Settings and Design: It was a prospective observational case–control study to estimate the level of serum 25-hydroxyvitamin D (25[OH] D) concentrations of the sample population. Subjects and Methods: One hundred consecutive PD patients were selected for this study between 2015 and 2018 from the patients attending neurology outpatient department. Control (n = 100) participants were randomly selected after matching for age sex, and geographic location. Statistical Analysis Used: Statistical Package for the Social Sciences version 15 with multivariate logistic regression (the Pearson correlation coefficient (r) and P value) was applied. Results: Among 100 PD patients 48, patients (48%) had Vitamin D deficiency, 34 patients (34%) had Vitamin D insufficiency, and 18 patients (18%) had normal Vitamin D level; whereas age- and sex-matched control population shows Vitamin D deficiency in 46% people, normal vitamin level in 42%, and insufficient Vitamin D level in 12% control population. The mean (standard deviation) 25(OH) D concentration in the PD cohort was significantly lower than in the control cohorts (20.72 [8.21] ng/mL vs. 25.56 [11.99] ng/mL, respectively; P = 0.001). There was major association between 25(OH) D levels and severity of motor scores (P = 0.028), tremor (P = 0.0001), bradykinesia (P = 0.001), and severity of freezing (P = 0.002), whereas no significant association was found between Vitamin D levels and rigidity (P = 0.05) and postural instability (P = 0.395). Conclusions: This study demonstrates a significantly higher prevalence of hypovitaminosis in PD versus healthy controls. The severity of motor scores, tremor, and bradykinesia and severity of freezing were found to have a direct inverse correlation with low serum Vitamin D levels which further emphasizes the provision of preventive and therapeutic supplementation of Vitamin D in PD.

Narcolepsy genetic marker HLA DQB1*06:02 and excessive daytime sleepiness in Parkinson disease patients treated with dopaminergic agents.

To determine whether narcolepsy Human Leukocyte Antigen (HLA) risk allele DQB1*0602 is associated with excessive daytime sleepiness (EDS) and inappropriate sleep in patients with Parkinson disease (PD). EDS is a common and disabling non-motor manifestation of PD, affecting quality of life and driving performance. DQB1*0602 is an HLA risk allele for narcolepsy. It is present in 12-30% of the general population. We hypothesize that DQB1*0602 is associated with an increased risk of EDS and inappropriate sleep in PD patients. This was a cross-sectional observational study of 150 PD individuals on dopaminergic agents. Main outcome measures were DQB1*0602 status and the modified Epworth Sleepiness Scale. Individuals with dementia, loss of independence, narcolepsy and untreated sleep apnea were excluded. Confounding variables for EDS were assessed using Parkinson Disease Sleep Scale, Mayo Sleep Questionnaire, Unified PD Rating Scale, Hoehn and Yahr scale. DQB1*06:02 positive PD patients were approximately three times more likely to experience EDS and fall asleep inappropriately during activities that required sustained alertness (e.g. driving, eating, attending work etc.). Exploratory post hoc analysis showed a dopaminergic drug dose- and type- dependent effect on daytime sleepiness in DQB1*06:02 positive individuals. No significant differences were found in confounding variables. PD individuals are more likely to experience EDS and fall asleep inappropriately during activities if DQB1*0602 positive. Genetic vulnerability may explain EDS risk in PD.

Antiparkinsonian activity of new N-methyl-D-aspartate receptor ligands in the arecoline hyperkinesis test

Introduction. Parkinson’s disease (PD) is one of the most common neurodegenerative diseases in the population of older patients. Even though long-term combination therapy helps to cope with the main manifestations of PD. It inevitably leads to the appearance of such side effects as drowsiness, hallucinations, dyskinesia, and many others. [12]. Therefore, the search for effective antiparkinsonian drugs devoid of the above-mentioned adverse reactions remains an urgent task of modern neuropharmacology.The explored substances are derivatives of imidazole-4,5-dicarboxylic acid. These compounds belong to a fundamentally new class of N-methyl-D-aspartate ligands (NMDA) that are not channel blockers. Their pharmacological effect is realized due to interaction with the NMDA receptor recognition site, which, along with high efficiency, allows us to assume their higher safety, compared to previously existing channel blockers from the NMDA ligand group.Objective. Studing of the antiparkinsonian activity of new ligands of the glutamate NMDA-receptor complex-1,2-substituted imidazole-4,5-dicarboxylic acids on an experimental model of arecoline hyperkinesis.Materials and methods. Imidazole-dicarboxylic acid derivatives (IEM2258, IEM2248, IEM2247, and IEM1574) were injected into the lateral ventricles of the mouse brain 10 minutes before arecoline in a volume of 5 µl at doses of 0.1-0.5 µmol, then the latent period, intensity, and duration of tremor were recorded. Amantadine was used as a comparison drug.Results. Preliminary administration of the studied examined substances led to a significant decrease in the intensity and duration of arecoline tremor. The highest inhibitory activity with respect to the intensity and duration of the experimental tremor was demonstrated with the introduction of the compound IEM-2247 (at a dose of 0.1-0.5 mmol, the duration of the latent period of the tremor was 1.7-2.3 times longer than the control one, respectively, the duration of the tremor decreased by 1.5 - 2.5 times).Conclusions. The dose-dependent antiparkinsonian activity of imidazole-dicarboxylic acid derivatives is shown, indicating the prospects for the development of these substances and the further search for effective and safe antiparkinsonian agents among the compounds of this class.

Retinal Diseases and Parkinson Disease: A Population-Based Study.

IntroductionPatients with Parkinson disease (PD) tend to have ophthalmic symptoms. Retinal diseases are associated with central nervous system diseases, especially neurodegenerative diseases. Here, we investigated the association of retinal diseases with PD, especially the temporal relationship before and after PD diagnosis.MethodsData were obtained from the National Health Insurance Research Database of Taiwan. In total, 21,845 patients with newly diagnosed PD were matched with four controls each on the basis of propensity score. This study was bidirectional. A case–control study evaluated the adjusted odds ratio (aOR) of retinal disease before PD diagnosis by using conditional logistic regression. Furthermore, a cohort study evaluated the adjusted subdistribution hazard ratio (aSHR) for new-onset retinal and optic nerve diseases after PD diagnosis by using competing risk analysis. The association between PD with optic nerve diseases and glaucoma (another common ophthalmic diseases with the consequence of retinal dysfunction) were also analyzed as reference.ResultsIn the case–control study, PD was found to be significantly comorbid with recent and remote retinal disease [recent: ≤ 5 years, aOR: 1.12, 95% confidence interval (CI): 1.03–1.23; remote: > 5 years, aOR: 1.18, 95% CI: 1.04–1.34]. No similar association was identified between optic nerve disease or glaucoma with PD. In the cohort study, patients with PD were found to have a low risk of retinal disease in short-term (≤ 5 years, aSHR: 0.81, 95% CI: 0.71–0.93) and long-term (> 5 years, aSHR: 0.82, 95% CI: 0.72–0.93) follow-up.ConclusionThe study findings demonstrated that patients with prediagnostic PD were at greater risk of retinal disease than non-PD participants, but the risk reversed afterward. Thus, retinal disease may be a premotor manifestation of PD, and there may be some possible effect of dopamine supplements on retina.

Nonmotor symptoms and quality of life in Parkinson's disease with different motor subtypes.

To explore the differences in the features and impact on quality of life (QOL) of nonmotor symptoms (NMS) of the tremor dominant (TD) and non-tremor dominant (NTD) subtypes of Parkinson's disease (PD) and elucidate the characteristic NMS and determinants of QOL for the subtypes. This cross-sectional study included 77patients with PD. The NMS questionnaire was used to assess the range and prevalence of NMS. The modified Hoehn and Yahr staging and the unified PD rating scale (UPDRS) were used to assess symptom severity. Cognitive abilities were investigated using the mini-mental status examination (MMSE). Emotional state was assessed using the Hamilton depression scale (HAMD) and the Hamilton anxiety scale (HAMA) and QOL was evaluated using the Parkinson's disease questionnaire-39 (PDQ-39). Overall, 39(50.65%) patients were classified as the TD subtype, and 38(49.35%) were classified as the NTD subtype. Patients with NTD subtype presented a significantly higher number of NMS total scores (P = 0.007) and significantly higher score in the cognition domain of PDQ-39 (P = 0.021) than patients with TD subtype. Patients with NTD subtype had significantly higher NMS prevalence than patients with TD subtype with constipation (P = 0.021), incomplete bowel emptying (P = 0.050), anxiety (P = 0.030), daytime sleepiness (P = 0.017) and intense vivid dreams (P = 0.016). The predictors for the NTD subtype were intense vivid dreams (P = 0.012), anxiety (P = 0.030) and constipation (P = 0.044). The UPDRS, NMS total, and MMSE scores were the determinants of QOL in patients with PD (P < 0.05). The NMS is aprominent manifestation of PD. Patients with the NTD subtype had ahigher prevalence of NMS than those with the TD subtype and intense vivid dreams, anxiety and constipation were characteristic of the NTD subtype. NMS is one of the important factors that determine the QOL of patients with PD especially those with the NTD subtype.

The Impact of SNCA Variations and Its Product Alpha-Synuclein on Non-Motor Features of Parkinson’s Disease

Parkinson’s disease (PD) is a common and progressive neurodegenerative disease, caused by the loss of dopaminergic neurons in the substantia nigra pars compacta in the midbrain, which is clinically characterized by a constellation of motor and non-motor manifestations. The latter include hyposmia, constipation, depression, pain and, in later stages, cognitive decline and dysautonomia. The main pathological features of PD are neuronal loss and consequent accumulation of Lewy bodies (LB) in the surviving neurons. Alpha-synuclein (α-syn) is the main component of LB, and α-syn aggregation and accumulation perpetuate neuronal degeneration. Mutations in the α-syn gene (SNCA) were the first genetic cause of PD to be identified. Generally, patients carrying SNCA mutations present early-onset parkinsonism with severe and early non-motor symptoms, including cognitive decline. Several SNCA polymorphisms were also identified, and some of them showed association with non-motor manifestations. The functional role of these polymorphisms is only partially understood. In this review we explore the contribution of SNCA and its product, α-syn, in predisposing to the non-motor manifestations of PD.

Parkinson’s disease: epidemiology and pathogenesis

This review presents data on the etiology, epidemiology, and pathogenesis of Parkinsons disease from National Center for Biotechnology Information (NCBI), eLibrary, CyberLeninka, and from monographs and textbooks. The prevalence, classification, genetic variability, main pathogenetic links, and potential disease development mechanisms are described. Both classic Parkinsons disease and variable manifestations of parkinsonism are considered. The factors that contribute to disease progression and inhibit its development are described. The main hypotheses of the pathogenetic mechanisms of Parkinsons disease are presented. These are protein misfolding, mitochondrial dysfunction, impaired protein purification systems, neuroinflammation, and pathology of the gut-brain axis.

Animal Models of Autosomal Recessive Parkinsonism.

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder. The neuropathological hallmark of the disease is the loss of dopamine neurons of the substantia nigra pars compacta. The clinical manifestations of PD are bradykinesia, rigidity, resting tremors and postural instability. PD patients often display non-motor symptoms such as depression, anxiety, weakness, sleep disturbances and cognitive disorders. Although, in 90% of cases, PD has a sporadic onset of unknown etiology, highly penetrant rare genetic mutations in many genes have been linked with typical familial PD. Understanding the mechanisms behind the DA neuron death in these Mendelian forms may help to illuminate the pathogenesis of DA neuron degeneration in the more common forms of PD. A key step in the identification of the molecular pathways underlying DA neuron death, and in the development of therapeutic strategies, is the creation and characterization of animal models that faithfully recapitulate the human disease. In this review, we outline the current status of PD modeling using mouse, rat and non-mammalian models, focusing on animal models for autosomal recessive PD.