Parkinson’s disease is a progressive neurodegenerative disorder mainly distinguished by sporadic etiology, although a genetic component is also well established. Variants in the LRRK2 gene are associated with both familiar and sporadic disease. We have previously shown that PAK6 and 14-3-3γ protein interact with and regulate the activity of LRRK2.
The aim of this study is to quantify PAK6 and 14-3-3γ in plasma as reliable biomarkers for the diagnosis of both sporadic and LRRK2-linked Parkinson’s disease.
After an initial quantification of PAK6 and 14-3-3γ expression by means of Western blot in post-mortem human brains, we verified the presence of the two proteins in plasma by using quantitative ELISA tests. We analyzed samples obtained from 39 healthy subjects, 40 patients with sporadic Parkinson’s disease, 50 LRRK2-G2019S non-manifesting carriers and 31 patients with LRRK2-G2019S Parkinson’s disease.
The amount of PAK6 and 14-3-3γ is significantly different in patients with Parkinson’s disease compared to healthy subjects. Moreover, the amount of PAK6 also varies with the presence of the G2019S mutation in the LRRK2 gene. Although the generalized linear models show a low association between the presence of Parkinson’s disease and PAK6, the kinase could be added in a broader panel of biomarkers for the diagnosis of Parkinson’s disease.
Changes of PAK6 and 14-3-3γ amount in plasma represent a shared readout for patients affected by sporadic and LRRK2-linked Parkinson’s disease. Overall, they can contribute to the establishment of an extended panel of biomarkers for the diagnosis of Parkinson’s disease.
Task prioritization involves allocating brain resources in a dual-task scenario, but the mechanistic details of how prioritization strategies affect dual-task walking performance for Parkinson’s disease (PD) are little understood.
We investigated the performance benefits and corresponding neural signatures for people with PD during dual-task walking, using gait-prioritization (GP) and manual-prioritization (MP) strategies.
Participants (N = 34) were asked to hold two inter-locking rings while walking and to prioritize either taking big steps (GP strategy) or separating the two rings (MP strategy). Gait parameters and ring-touch time were measured, and scalp electroencephalograph was performed.
Compared with the MP strategy, the GP strategy yielded faster walking speed and longer step length, whereas ring-touch time did not significantly differ between the two strategies. The MP strategy led to higher alpha (8–12 Hz) power in the posterior cortex and beta (13–35 Hz) power in the left frontal-temporal area, but the GP strategy was associated with stronger network connectivity in the beta band. Changes in walking speed and step length because of prioritization negatively correlated with changes in alpha power. Prioritization-related changes in ring-touch time correlated negatively with changes in beta power but positively with changes in beta network connectivity.
A GP strategy in dual-task walking for PD can enhance walking speed and step length without compromising performance in a secondary manual task. This strategy augments attentional focus and facilitates compensatory reinforcement of inter-regional information exchange.
Persons with Parkinson’s disease (PD) and society at large can profit from a strategic investment into a forward leaning, practical, preventative, and proactive multidisciplinary care policy. The American healthcare system is not easily bent to accommodate this type of care, and thus a tax benefit is an attractive option. An individual federal income tax benefit of $6200 each year for every person residing in the US with a diagnosis of PD, could among other offerings provide monthly access to a licensed clinical social worker and access to mental health services. The implementation of more coordinated care has the potential reduce the burden of depression, anxiety, and demoralization. Personal training would also be covered and directed by physical and occupational therapists. The combination of home-based and telemedicine services would have the added benefit of improving access. The tax benefit would also provide access to a dietician. This type of care strategy could be designed to proactively identify early signs of aspiration and urinary tract infections to ‘head off’ significant morbidity. A $6200/year individual tax benefit for those diagnosed with PD will thus translate into more fall prevention, more care in the home setting, less hospitalizations, less depression, less anxiety, less demoralization, better diets, and less persons placed in nursing facilities. Additionally, this tax benefit will provide the potential for billions of dollars in savings to the healthcare system. A tax benefit for PD is a practical preventative and proactive strategy which can serve to advantage both this generation and the next.
Several dietary patterns and nutritional supplements have been linked to the development, progression, and symptomatic treatment of Parkinson’s disease (PD). Most of the evidence, at this point, is preliminary and based largely on observational studies. Interventional studies are scarce, so the evidence on effectiveness remains inconclusive. Dietary interventions could, analogous to exercise, potentially have a beneficial effect on disease symptoms as well as on the progression of the disease and should therefore be researched in high quality studies. Further work is also needed to study whether dietary interventions, when applied to an at-risk population, have any potential to postpone the onset of manifest PD. In this paper, we summarize all ongoing clinical trials on dietary interventions in PD. We found 10 ongoing studies, all aimed at a different intervention. These studies are mostly exploratory in nature or represent phase I or phase II trials focusing on safety, biological responses, and symptomatic effects. Taken together, we conclude that research on dietary interventions in persons with PD is still in its early days. The results of the various ongoing trials are expected to generate new hypotheses and will help to shape the agenda for future research on this important topic.
Background: Mutations in the Leucine Rich Repeat Kinase 2 gene are highly relevant in both sporadic and familial cases of Parkinson's disease. Specific therapies are entering clinical trials but patient stratification remains challenging. Dysregulated microRNA expression levels have been proposed as biomarker candidates in sporadic Parkinson's disease.
Objective: In this proof-of concept study we evaluate the potential of extracellular miRNA signatures to identify LRRK2-driven molecular patterns in Parkinson's disease.
Methods: We measured expression levels of 91 miRNAs via RT-qPCR in ten individuals with sporadic Parkinson's disease, ten LRRK2 mutation carriers and eleven healthy controls using both plasma and cerebrospinal fluid. We compared miRNA signatures using heatmaps and t-tests. Next, we applied group sorting algorithms and tested sensitivity and specificity of their group predictions.
Results: miR-29c-3p was differentially expressed between LRRK2 mutation carriers and sporadic cases, with miR-425-5p trending towards significance. Individuals clustered in principal component analysis along mutation status. Group affiliation was predicted with high accuracy in the prediction models (sensitivity up to 89%, specificity up to 70%). miRs-128-3p, 29c-3p, 223-3p, and 424-5p were identified as promising discriminators among all analyses.
Conclusions: LRRK2 mutation status impacts the extracellular miRNA signature measured in plasma and separates mutation carriers from sporadic Parkinson's disease patients. Monitoring LRRK2 miRNA signatures could be an interesting approach to test drug efficacy of LRRK2-targeting therapies. In light of small sample size, the suggested approach needs to be validated in larger cohorts.
Background: Non-motor symptoms (NMS) reduce quality of life in Parkinson's disease (PD) patients, who experience three times more NMS than individuals without PD. While there are international and national NMS treatment guidelines, their implication in clinical practice remains unclear.
Objective: This study aimed to investigate the adherence to pharmacological NMS treatment guidelines in patients with mild to moderately severe PD.
Methods: 220 PD patients with ≥1 NMS based on the Non-Motor Symptom Questionnaire and a Hoehn and Yahr stage ≤4 were randomly selected from the Swedish Parkinson registry and screened for inclusion. NMS were evaluated using the International Parkinson and Movement Disorder Society-Non-Motor Rating Scale (MDS-NMS), Parkinson's Disease Sleep Scale 2, Epworth Sleepiness Scale, and Hospital Anxiety and Depression Scale. Treatment was compared with Swedish national guidelines and international guidelines from the MDS Evidence-Based Medicine Committee.
Results: Among 165 included patients, the median number of NMS was 14, and in median 7 symptoms were estimated to require treatment. The most common NMS requiring treatment were pain (69%) and urinary problems (56%). Treatment of depression and constipation demonstrated the highest adherence to guidelines (79% and 77%), while dysphagia and excessive daytime sleepiness exhibited the lowest adherence (0% and 4%). On average, only 32% of NMS were treated in accordance with guidelines.
Conclusions: Adherence to pharmacological guidelines for NMS in patients with mild to severe PD was low. This study highlights the need for improved evaluation and treatment of NMS to enhance symptom management and quality of life among PD patients.
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