• Behavioural changes
• Neuropsychiatric symptoms
• Non-motor symptoms
• Parkinson's disease

• Aged
• Female
• Humans
• Male
• Middle Aged
• Cognition Disorders/etiology
• Cognition Disorders/psychology
• Cognition Disorders/therapy
• Cognition Disorders/diagnosis
• Cognitive Dysfunction/etiology
• Cognitive Dysfunction/psychology
• Cognitive Dysfunction/therapy
• Disruptive, Impulse Control, and Conduct Disorders/etiology
• Mental Disorders/etiology
• Mental Disorders/psychology
• Mental Disorders/therapy
• Mental Disorders/diagnosis
• Parkinson Disease/psychology
• Parkinson Disease/complications
• Parkinson Disease/therapy
• Parkinson Disease/diagnosis
• Quality of Life

• Motor fluctuations
• Non-motor fluctuations
• Non-motor symptoms
• Parkinson’s disease

• Ablation
• Deep brain stimulation (DBS)
• Invasive therapies
• Parkinson’s disease
• Pump therapy

• Humans
• Parkinson Disease/therapy
• Parkinson Disease/diagnosis
• Deep Brain Stimulation/methods
• Deep Brain Stimulation/standards
• Germany
• Neurology/standards
• Societies, Medical/standards
• Practice Guidelines as Topic/standards

• Universitätsmedizin Rostock (8980)

• Advanced
• Fluctuations
• Non-motor
• Parkinson’s disease
• Therapy

• parkinson's disease
• neurodegeneration

• Humans
• Parkinson Disease/psychology
• Parkinson Disease/epidemiology
• Parkinson Disease/physiopathology
• United Arab Emirates/epidemiology
• Male
• Female
• Cross-Sectional Studies
• Middle Aged
• Sexual Dysfunction, Physiological/epidemiology
• Aged
• Quality of Life
• Surveys and Questionnaires
• Adult

• Early onset Parkinson’s disease
• Non-motor symptoms
• Parkinson’s disease
• Quality of life

• Humans
• Parkinson Disease/psychology
• Parkinson Disease/complications
• Parkinson Disease/physiopathology
• Male
• Quality of Life/psychology
• Female
• Middle Aged
• Adult
• Age of Onset
• Young Adult
• Sleep Wake Disorders/etiology
• Sleep Wake Disorders/psychology

• Non-motor symptoms
• ON response
• Parkinson's disease

• Humans
• Male
• Female
• Aged
• Parkinson Disease/drug therapy
• Parkinson Disease/complications
• Parkinson Disease/physiopathology
• Middle Aged
• Reproducibility of Results
• Surveys and Questionnaires
• Antiparkinson Agents/therapeutic use

• MOVEMENT DISORDERS
• PARKINSON'S DISEASE
• SCALES

• Humans
• Parkinson Disease/physiopathology
• Parkinson Disease/drug therapy
• Parkinson Disease/complications
• Male
• Female
• Levodopa/therapeutic use
• Middle Aged
• Deep Brain Stimulation
• Aged
• Antiparkinson Agents/therapeutic use
• Surveys and Questionnaires
• Severity of Illness Index
• Subthalamic Nucleus/physiopathology

• PD home diary
• Parkinson’s disease
• diary
• dyskinesia
• fatigue
• motor fluctuations
• non-motor fluctuations
• pain

• Humans
• Parkinson Disease/complications
• Parkinson Disease/physiopathology
• Male
• Female
• Aged
• Middle Aged
• Pain/etiology
• Pain/physiopathology
• Prospective Studies
• Quality of Life
• Severity of Illness Index
• Fatigue/etiology
• Fatigue/physiopathology

• Parkinson‘s disease
• neuropsychiatric fluctuations
• psychometric characteristics
• scale
• validation

• Apomorphine
• Levodopa
• On-demand therapy
• Parkinson’s disease
• Rescue therapy

• Acorda Therapeutics

• Parkinson’s disease
• motor impairment
• non-motor fluctuations
• non-motor symptoms

• Parkinson's disease
• active standing test
• multiple system atrophy
• orthostatic hypotension
• the ΔHR/ΔSBP

• Antipsychotics
• Delusions
• Hallucinations
• Parkinson’s disease
• Psychosis

Non‐motor fluctuations (NMF) in people with Parkinson's disease (PwP) are clinically important yet understudied.

To study NMF in PwP using both the Movement Disorder Society Non‐Motor Rating Scale (MDS‐NMS) NMF subscale and wearable sensors.

We evaluated differences in overall burden of NMF and of specific NMF across disease durations: <2 years (n = 33), 2–5 years (n = 35), 5–10 years (n = 33), and > 10 years (n = 31). In addition, wearable triaxial sensor output was used as an exploratory outcome for early morning “off” periods.

Significant between‐group differences were observed for MDS‐NMS NMF total scores (P < 0.001), and specifically for depression, anxiety, fatigue and cognition, with both NMF prevalence and burden increasing in those with longer disease duration. Whereas only 9.1% with a short disease duration had NMF (none of whom had dyskinesia), in PwP with a disease duration of >10 years this was 71.0% (P < 0.001). From a motor perspective, dyskinesia severity increased evenly with increasing disease duration, while NMF scores in affected individuals showed an initial increase with largest differences between 2–5 years disease duration (P < 0.001), with plateauing afterwards. Finally, we observed that the most common NMF symptoms in patients with sensor‐confirmed early morning “off” periods were fluctuations in cognitive capabilities, restlessness, and excessive sweating.

Non‐motor fluctuations prevalence in PwP increases with disease duration, but in a pattern different from motor fluctuations. Moreover, NMF can occur in PwP without dyskinesia, and in those with NMF the severity of NMF increases most during years 2–5 after diagnosis.

Non-manifesting carriers (NMCs) of Parkinson’s disease (PD)-related mutations such as LRRK2 and GBA are at an increased risk for developing PD. Dopamine transporter (DaT)-spectral positron emission computed tomography is widely used for capturing functional nigrostriatal dopaminergic activity. However, it does not reflect other ongoing neuronal processes; especially in the prodromal stages of the disease. Resting-state fMRI (rs-fMRI) has been proposed as a mode for assessing functional alterations associated with PD, but its relation to dopaminergic deficiency remains unclear. We aimed to study the association between presynaptic striatal dopamine uptake and functional connectivity (FC) patterns among healthy first-degree relatives of PD patients with mutations in LRRK2 and GBA genes. N = 85 healthy first-degree subjects were enrolled and genotyped. All participants underwent DaT and rs-fMRI scans, as well as a comprehensive clinical assessment battery. Between-group differences in FC within striatal regions were investigated and compared with striatal binding ratios (SBR). N = 26 GBA-NMCs, N = 25 LRRK2-NMCs, and N = 34 age-matched nonmanifesting noncarriers (NM-NCs) were included in each study group based on genetic status. While genetically-defined groups were similar across clinical measures, LRRK2-NMCs demonstrated lower SBR in the right putamen compared with NM-NCs, and higher right putamen FC compared to GBA-NMCs. In this group, higher striatal FC was associated with increased risk for PD. The observed differential SBR and FC patterns among LRRK2-NMCs and GBA-NMCs indicate that DaTscan and FC assessments might offer a more sensitive prediction of the risk for PD in the pre-clinical stages of the disease.

Neuropsychiatric symptoms in Parkinson's disease (PD) have been shown to significantly affect quality of life (QOL). We investigated the impact of safinamide on depression and apathy when administered as an adjunct to levodopa in Japanese patients with PD.

This was a post-hoc analysis of data from a phase 2/3 clinical study of safinamide in Japanese patients with PD experiencing wearing-off (JapicCTI-153056; https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-153056). Patients received placebo, safinamide 50 mg, or safinamide 100 mg as an adjunct therapy. The endpoints for this analysis were changes from baseline to Week 24 in the Unified Parkinson's Disease Rating Scale (UPDRS) Part I item 3 (depression) and item 4 (apathy) scores and the Parkinson's Disease Questionnaire (PDQ-39) “emotional well-being” domain score. Subgroup analyses investigated the relationship between neuropsychologic symptoms and improvements in motor fluctuation and assessed which patient populations might be expected to obtain neuropsychologic benefit from safinamide.

Compared with placebo, safinamide (both doses) significantly improved UPDRS Part I item 3 scores in the overall analysis population, and the 100-mg dose improved UPDRS Part I item 4 scores in the population with apathy at baseline. Changes in the PDQ-39 “emotional well-being” score showed numerical, but not significant, dose-related improvements. Notable reductions in depression were associated with a change in daily ON-time ≥1 h, pain during OFF-time at baseline, and female sex.

The results from this post-hoc analysis of the Japanese phase 2/3 study suggest that safinamide could bring benefits to patients with PD who have mild depression, pain during the OFF phase. In addition, safinamide might provide particular benefits for patients with PD who have mild apathy and female.

• MAO-B inhibitor
• Parkinson's disease
• apathy
• clinical trial
• depression
• post-hoc analysis
• safinamide

• National Natural Science Foundation of China
• Zhejiang Public Welfare Technology Application Research Project
• Shaanxi Province
• Major Scientific Project of Zhejiang Lab
• Chinese Academy of Engineering
• Natural Science Foundation of Zhejiang Province
• China Postdoctoral Science Foundation
• Ministry of Science and Technology of the People''s Republic of China

• Non-motor fluctuations
• Parkinson's disease
• Questionnaire

Inflammation is an integral part of neurodegeneration including in Parkinson’s disease (PD). Ashkenazi Jews have high rates of genetic PD with divergent phenotypes among GBA-PD and LRRK2-PD. The role of inflammation in the prodromal phase of PD and the association with disease phenotype has yet to be elucidated.

To assess central and peripheral cytokines among PD patients with mutations in the LRRK2 and GBA genes and among non-manifesting carriers (NMC) of these mutations in order to determine the role of inflammation in genetic PD.

The following cytokines were assessed from peripheral blood and cerebrospinal fluid (CSF): TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10 and INF- γ. A comprehensive intake including general medical conditions, use of anti-inflammatory treatments, motor and cognitive assessments and additional laboratory measures were recorded, enabling the construction of the MDS probable prodromal score.

Data from 362 participants was collected: 31 idiopathic PD (iPD), 30 LRRK2-PD, 77 GBA-PD, 3 homozygote GBA-PD, 3 GBA-LRRK2-PD, 67 LRRK2-NMC, 105 GBA-NMC, 14 LRRK2-GBA-NMC, and 32 healthy controls. No between-group differences in peripheral or CSF cytokines were detected. No correlation between disease characteristics or risk for prodromal PD could be associated with any inflammatory measure.

In this study, we could not detect any evidence on dysregulated immune response among GBA and LRRK2 PD patients and non-manifesting mutation carriers.

• GBA
• LRRK2
• Parkinson’s disease
• inflammation

• Administration, Cutaneous
• Dopamine Agonists/administration & dosage
• Dopamine Agonists/adverse effects
• Humans
• Parkinson Disease/drug therapy
• Parkinson Disease/physiopathology
• Quality of Life
• Restless Legs Syndrome/drug therapy
• Tetrahydronaphthalenes/administration & dosage
• Tetrahydronaphthalenes/adverse effects
• Thiophenes/administration & dosage
• Thiophenes/adverse effects
• Transdermal Patch

• GBA
• Glomerular filtration rate
• LRRK2
• Parkinson’s disease
• Renal functions

• Biomarkers
• Glucosylceramidase/genetics
• Heterozygote
• Humans
• Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics
• Mutation/genetics
• Parkinson Disease/genetics

Non‐motor fluctuations are a major concern in Parkinson's disease (PD), and they have been categorized into neuropsychiatric, autonomic and sensory fluctuations. However, this categorization does not include sleep and sleep‐related features, and the association between daytime sleepiness and other motor and/or non‐motor fluctuations in PD remains to be elucidated.

To investigate the relationship between daytime sleepiness and other non‐motor and motor fluctuations in people with PD.

A three‐day home diary recording daytime sleepiness, mood, anxiety, and motor symptoms was used along with the Karolinska Sleepiness Scale (KSS) and 6 days of accelerometer (Parkinson's KinetiGraph™; PKG™) registration to detect motor fluctuations among people with a DaTSCAN verified clinical PD diagnosis (32 men; mean PD duration, 8.2 years). Participants were categorized as motor fluctuators or non‐fluctuators according to the UPDRS part IV and/or the presence of motor and non‐motor fluctuations.

Fifty‐two people with PD participated. Daytime sleepiness correlated significantly with motor symptoms, mood and anxiety among those classified as motor fluctuators (n = 28). Motor fluctuators showed stronger correlations between the individual mean level of all diary variables (daytime sleepiness, anxiety, mood and motor symptoms) when compared to the non‐fluctuators (n = 24). Stronger positive within‐individual correlations were found among fluctuators in comparison to non‐fluctuators. In general, PKG data did not correlate with diary data.

Episodes of daytime sleepiness, as reported by home diaries, were associated with other self‐reported non‐motor and motor fluctuations, but were not supported by PKG data.

• daytime sleepiness, Parkinson's disease, motor fluctuations and non‐motor fluctuations, home diary, PKG

• Parkinson’s disease
• anxiety
• fear of falling
• freezing of gait
• multidisciplinary
• neuropsychiatry
• symptom interaction

In order toevaluate the influence of the metabolic syndrome (MS) (obesity, hypertension, elevated triglycerides, reduced levels of HDL cholesterol and glucose impairment) on the phenotype of LRRK2 and GBA Parkinson’s disease (PD), and on the prevalence of prodromal features among individuals at risk, we collected, laboratory test results, blood pressure, demographic, cognitive, motor, olfactory and affective information enabling the assessment of each component of MS and the construction of the MDS prodromal probability score. The number of metabolic components and their levels were compared between participants who were separated based on disease state and genetic status. One hundred and four idiopathic PD, 40 LRRK2-PD, 70 GBA-PD, 196 healthy non-carriers, 55 LRRK2-NMC and 97 GBA-NMC participated in this study. PD groups and non manifesting carriers (NMC) did not differ in the number of metabolic components (p = 0.101, p = 0.685, respectively). LRRK2-PD had higher levels of triglycerides (p = 0.015) and higher rates of prediabetes (p = 0.004), while LRRK2-NMC had higher triglyceride levels (p = 0.014). NMC with probability rates for prodromal PD above 50% had higher frequencies of hypertriglyceridemia and prediabetes (p < 0.005, p = 0.023 respectively). While elevated triglycerides and prediabetes were more frequent among LRRK2 carriers, MS does not seem to influence GBA and LRRK2-PD phenotype.

• motor fluctuations
• patient‐reported outcomes
• wearing off

• GLP-1 agonist
• Parkinson’s disease
• clinical trial
• exenatide
• non-motor symptoms

• Parkinson’s disease
• apathy
• fatigue
• fluctuations
• late stage
• levodopa
• levodopa test
• mood
• non-motor symptoms
• sleep

• Aged
• Aged, 80 and over
• Antiparkinson Agents/therapeutic use
• Cognition Disorders/drug therapy
• Cognition Disorders/etiology
• Dopamine Agents/therapeutic use
• Fatigue/drug therapy
• Fatigue/etiology
• Female
• Humans
• Levodopa/therapeutic use
• Male
• Mood Disorders/drug therapy
• Mood Disorders/etiology
• Parkinson Disease/complications
• Parkinson Disease/drug therapy
• Treatment Outcome

• Parkinson's disease
• dyskinesias
• fluctuations
• levodopa
• nonmotor
• personalized medicine

SNCA-rs11931074 had been demonstrated to be strongly correlated with PD risk. However, there was lack of comprehensive analysis of SNCA-rs11931074-related clinical features which may help explain clinical heterogeneity of PD. In our study, we performed association analyses on the relationship between SNCA-rs11931074 and motor symptoms, nonmotor symptoms, and comorbidities in PD. 611 rs11931074 carriers and 113 rs11931074 noncarriers were enrolled. In the clinical phenotype analyses, the Unified Parkinson's Disease Rating Scale part II (UPDRS II) and part III (UPDRS III) scores of rs11931074 carriers were lower than those of noncarriers (SC: −0.083, p=0.035; SC: −0.140, p ≤ 0.001). The Charlson Comorbidity Index (CCI) score of carriers was lower than that of noncarriers (SC: −0.097, p=0.009). No significant statistical differences were found between the variant and other clinical features such as motor complications and nonmotor symptoms. The SNCA-rs11931074 carriers may present with more benign clinical profiles than noncarriers with less severe motor symptoms and comorbidity burden.

• Follow-up studies
• Incidence
• Levodopa
• Parkinson disease
• Prospective studies
• Surveys and questionnaires

• Motor complications
• Motor fluctuations
• Non-motor fluctuations
• Off
• Parkinson's disease
• Wearing off

• Non-motor assessment
• Non-motor fluctuations
• Non-motor symptoms
• Parkinson’s disease
• Pathophysiology