Environmental Risk Factors for Parkinson's Disease: A Critical Review and Policy Implications.

The age-standardized prevalence of Parkinson's disease (PD) has increased substantially over the years and is expected to increase further. This emphasizes the need to identify modifiable risk factors of PD, which could form a logical entry point for the prevention of PD. The World Health Organization (WHO) has recommended reducing exposure to specific environmental factors that have been reported to be associated with PD, in particular pesticides, trichloroethylene (TCE), and air pollution.

Ethical Considerations for Identifying Individuals in the Prodromal/Early Phase of Parkinson's Disease: A Narrative Review.

The ability to identify individuals in the prodromal phase of Parkinson's disease has improved in recent years, raising the question of whether and how those affected should be informed about the risk of future disease. Several studies investigated prognostic counselling for individuals with isolated REM sleep behavior disorder and have shown that most patients want to receive information about prognosis, but autonomy and individual preferences must be respected. However, there are still many unanswered questions about risk disclosure or early diagnosis of PD, including the impact on personal circumstances, cultural preferences and specific challenges associated with different profiles of prodromal symptoms, genetic testing or biomarker assessments.

Association of Misfolded α-Synuclein Derived from Neuronal Exosomes in Blood with Parkinson's Disease Diagnosis and Duration.

Background: Misfolded α-synuclein can be detected in blood samples of Parkinson's disease (PD) patients by a seed amplification assay (SAA), but the association with disease duration is not clear, yet.

Objective: In the present study we aimed to elucidate whether seeding activity of misfolded α-synuclein derived from neuronal exosomes in blood is associated with PD diagnosis and disease duration.

Methods: Cross-sectional samples of PD patients were analyzed and compared to samples of age- and gender-matched healthy controls using a blood-based SAA.

Detecting Misfolded α-Synuclein in Blood Years before the Diagnosis of Parkinson's Disease.

Background: Identifying individuals with Parkinson's disease (PD) already in the prodromal phase of the disease has become a priority objective for opening a window for early disease-modifying therapies.

Objective: The aim was to evaluate a blood-based α-synuclein seed amplification assay (α-syn SAA) as a novel biomarker for diagnosing PD in the prodromal phase.

Methods: In the TREND study (University of Tuebingen) biennial blood samples of n = 1201 individuals with/without increased risk for PD were taken prospectively over 4 to 10 years.

Large-Scale Screening: Phenotypic and Mutational Spectrum in Isolated and Combined Dystonia Genes.

Background: Pathogenic variants in several genes have been linked to genetic forms of isolated or combined dystonia. The phenotypic and genetic spectrum and the frequency of pathogenic variants in these genes have not yet been fully elucidated, neither in patients with dystonia nor with other, sometimes co-occurring movement disorders such as Parkinson's disease (PD).

Objectives: To screen >2000 patients with dystonia or PD for rare variants in known dystonia-causing genes.

Pesticides and the Microbiome-Gut-Brain Axis: Convergent Pathways in the Pathogenesis of Parkinson's Disease.

The increasing global burden of Parkinson's disease (PD), termed the PD pandemic, is exceeding expectations related purely to population aging and is likely driven in part by lifestyle changes and environmental factors. Pesticides are well recognized risk factors for PD, supported by both epidemiological and experimental evidence, with multiple detrimental effects beyond dopaminergic neuron damage alone. The microbiome-gut-brain axis has gained much attention in recent years and is considered to be a significant contributor and driver of PD pathogenesis.

Can Digital Mobility Assessment Enhance the Clinical Assessment of Disease Severity in Parkinson's Disease?

Background: Real-world walking speed (RWS) measured using wearable devices has the potential to complement the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) for motor assessment in Parkinson's disease (PD).

Objective: Explore cross-sectional and longitudinal differences in RWS between PD and older adults (OAs), and whether RWS was related to motor disease severity cross-sectionally, and if MDS-UPDRS III was related to RWS, longitudinally.

Methods: 88 PD and 111 OA participants from ICICLE-GAIT (UK) were included.

Thyroid [I]MIBG uptake in Parkinson's disease and diabetes mellitus.

Thyroid [I]MIBG uptake is proposed as a tool for differentiating between Parkinson's disease (PD) and diabetes mellitus (DM) on [I]MIBG scintigraphies since both patient groups show decreased cardiac uptake. One study compared thyroid [I]MIBG uptake in DM and PD patients and reported reduced [I]MIBG uptake only in the PD group. Here, we investigated thyroid [I]MIBG uptake in patients with PD and DM and found severely reduced thyroid [I]MIBG uptake in DM.

Dermal Real-Time Quaking-Induced Conversion Is a Sensitive Marker to Confirm Isolated Rapid Eye Movement Sleep Behavior Disorder as an Early α-Synucleinopathy.

Background: Skin biopsy is a potential tool for the premortem confirmation of an α-synucleinopathy.

Objective: The aim was to assess the aggregation assay real-time quaking-induced conversion (RT-QuIC) of skin biopsy lysates to confirm isolated rapid eye movement sleep behavior disorder (iRBD) as an α-synucleinopathy.

Methods: Skin biopsies of patients with iRBD, Parkinson's disease (PD), and controls were analyzed using RT-QuIC and immunohistochemical detection of phospho-α-synuclein.

Microbiome and Metabolome Insights into the Role of the Gastrointestinal-Brain Axis in Parkinson's and Alzheimer's Disease: Unveiling Potential Therapeutic Targets.

Neurodegenerative diseases such as Parkinson's (PD) and Alzheimer's disease (AD), the prevalence of which is rapidly rising due to an aging world population and westernization of lifestyles, are expected to put a strong socioeconomic burden on health systems worldwide. Clinical trials of therapies against PD and AD have only shown limited success so far. Therefore, research has extended its scope to a systems medicine point of view, with a particular focus on the gastrointestinal-brain axis as a potential main actor in disease development and progression.

Parkinson's Disease and Sugar Intake-Reasons for and Consequences of a Still Unclear Craving.

Lately, studies have shown that patients with Parkinson's disease (PD) report a strong craving for sweets and consume significantly more fast-acting carbohydrates than healthy controls. Consuming food with a high-sugar content is assumed to lead to an increase in insulin concentration, which could positively influence dopamine concentration in the brain and unconsciously be used by patients as kind of "self-medication" to compensate for a lack of dopamine in PD. On the other hand, high-sugar intake could also lead to insulin resistance and diabetes, which is discussed as a causative factor for progressive neurodegeneration in PD.

Detection of neuron-derived pathological α-synuclein in blood.

To date, no reliable clinically applicable biomarker has been established for Parkinson's disease. Our results indicate that a long anticipated blood test for Parkinson's disease may be realized. Following the isolation of neuron-derived extracellular vesicles of Parkinson's disease patients and non-Parkinson's disease individuals, immunoblot analyses were performed to detect extracellular vesicle-derived α-synuclein.

Increased Intake of Fast-Acting Carbohydrates in Patients with Parkinson's Disease.

Background: Patients with Parkinson's disease (PD) regularly report an increased desire for food or beverages with high sugar content.

Objective: The aim of this study was to verify the hypothesis of an increased intake of fast-acting carbohydrates in PD patients.

Methods: This study investigated the consumption of high-sugar content food products in 221 PD patients compared with 184 healthy controls using a self-administered questionnaire.

Effects of exergaming on hippocampal volume and brain-derived neurotrophic factor levels in Parkinson's disease.

Background And Objective: Cognitive impairment is among the most burdensome non-motor symptoms in Parkinson's disease (PD) and has been associated with hippocampal atrophy. Exercise has been reported to enhance neuroplasticity in the hippocampus in correlation with an improvement of cognitive function. We present data from the Training-PD study, which was designed to evaluate effects of an "" training protocol on neuronal plasticity in PD.

Risk Disclosure in Prodromal Parkinson's Disease.

Background: Impressive progress in the understanding of the prodromal phase of Parkinson's disease (PD) in recent years has enabled the generation of disease prediction models. However, a remaining diagnostic uncertainty and lack of therapeutic options for affected individuals has resulted in a variety of ethical issues that have not to date been addressed sufficiently. Moreover, differences in the specificity of prodromal symptoms and possible subtypes of PD, especially the presence of rapid eye movement (REM) sleep behavior disorder (RBD), may have an important impact on prognostic counseling.

Asymmetric Dopaminergic Dysfunction in Brain-First versus Body-First Parkinson's Disease Subtypes.

Background: We have hypothesized that Parkinson's disease (PD) comprises two subtypes. Brain-first, where pathogenic α-synuclein initially forms unilaterally in one hemisphere leading to asymmetric nigrostriatal degeneration, and body-first with initial enteric pathology, which spreads through overlapping vagal innervation leading to more symmetric brainstem involvement and hence more symmetric nigrostriatal degeneration. Isolated REM sleep behaviour disorder has been identified as a strong marker of the body-first type.

Short-term physical exercise impacts on the human holobiont obtained by a randomised intervention study.

Background: Human well-being has been linked to the composition and functional capacity of the intestinal microbiota. As regular exercise is known to improve human health, it is not surprising that exercise was previously described to positively modulate the gut microbiota, too. However, most previous studies mainly focused on either elite athletes or animal models.

Prodromal Parkinson disease subtypes - key to understanding heterogeneity.

In Parkinson disease (PD), pathological processes and neurodegeneration begin long before the cardinal motor symptoms develop and enable clinical diagnosis. In this prodromal phase, risk and prodromal markers can be used to identify individuals who are likely to develop PD, as in the recently updated International Parkinson and Movement Disorders Society research criteria for prodromal PD. However, increasing evidence suggests that clinical and prodromal PD are heterogeneous, and can be classified into subtypes with different clinical manifestations, pathomechanisms and patterns of spatial and temporal progression in the CNS and PNS.

Complications following REM sleep behavior disorder.

REM sleep behavior disorder (RBD) is gaining increasing attention as important prodromal marker for the development of neurodegenerative disorders such as Parkinson's Disease. However, the clinical relevance of this disorder and its association with other prodromal markers is often underestimated in clinical routine. We here report a case of severe clinical complications following extensive nocturnal movements due to RBD, aggravated by occurrence of additional prodromal non-motor symptoms.

Effects of Levodopa on quality of sleep and nocturnal movements in Parkinson's Disease.

Background: Sleep disturbances are common in Parkinson's Disease (PD), with nocturnal akinesia being one of the most burdensome. Levodopa is frequently used in clinical routine to improve nocturnal akinesia, although evidence is not well proven.

Methods: We assessed associations of Levodopa intake with quality of sleep and perception of nocturnal akinesia in three PD cohorts, using the Parkinson's Disease Sleep Scale (PDSS-2) in two cohorts and a question on nocturnal immobility in one cohort.

Expression Profiling of Rectal Biopsies Suggests Altered Enteric Neuropathological Traits in Parkinson's Disease Patients.

Still little is known about the nature of the gastrointestinal pathological alterations occurring in Parkinson's disease (PD). Here, we used multiplexed mRNA profiling to measure the expression of a panel of 770 genes related to neuropathological processes in deep submucosal rectal biopsies of PD patients and healthy controls. Altered enteric neuropathological traits based on the expression of 22 genes related to neuroglial and mitochondrial functions, vesicle trafficking and inflammation was observed in 9 out of 12 PD patients in comparison to healthy controls.

Cognitive impairment and sedentary behavior predict health-related attrition in a prospective longitudinal Parkinson's disease study.

Introduction: In Parkinson's disease (PD), the high burden of motor and non-motor symptoms, such as cognitive impairment or falls, is associated with rapid disease progression and mortality. This is often reflected by an increased drop-out rate of PD patients in longitudinal studies. Active physical behavior can impact the disease course beneficially and has an overall positive effect on health.