Aims

Hypokinetic dysarthria is a common symptom of Parkinson’s disease (PD) which does not respond well to PD treatments. We investigated the long-term effects of multiple-session repetitive transcranial magnetic stimulation on hypokinetic dysarthria in PD.

Methods

A randomized parallel-group sham stimulation-controlled design was used. Patients were randomly assigned to ten sessions of real (1 Hz) or sham stimulation over the right superior temporal gyrus (STG). Stimulation effects were evaluated at weeks 2, 6, and 10 after the baseline assessment. Articulation, prosody, and speech intelligibility were quantified by speech therapist using a validated tool (Phonetics score). Activations of the speech network regions, structural and functional connectivity were measured.

Results

Altogether 33 PD patients completed the study. Linear mixed model showed significant time-by-group interactions for the Phonetics score (p = 0.040). Real as compared to sham stimulation led to increased activations of the left orofacial sensorimotor cortex (OFSM1) (p = 0.032) and left caudate nucleus (p = 0.029) and to increased intrinsic connectivity of the OFSM1 with the stimulated area (p = 0.045). A significant positive correlation was found between the temporal evolution of the Phonetics score and the STG-OFSM1 functional connectivity changes in the real stimulation group (R = 0.449, p = 0.013). DTI analysis revealed that real as compared to sham stimulation significantly increased fractional anisotropy and decreased mean diffusivity in the left anterior arcuate fasciculus (p = 0.002; p = 0.036).

Conclusions

This is the first study to show the long-lasting clinically relevant effects of low-frequency rTMS on hypokinetic dysarthria in PD.

Aims

Abstract

Background: Disorders of gait are a very common feature of Parkinson’s Disease. We examined how deep brain stimulation of the subthalamic nucleus (STN DBS) and dopaminergic medication affect gait and more specifically its rhythmicity.

Objectives: We accurately quantified multiple gait parameters in Parkinson’s patients during on and off stages of their treatment (levodopa or STN DBS) to compare and contrast the treatment-induced changes in gait.

Methods

Methods: We studied 11 patients with STN DBS, 15 patients on levodopa and 42 healthy controls. They all completed the MDS-UPDRS part III along with a gait assessment protocol while wearing six nine-axis inertial measurement units (lumbar, sternal, and all four extremities).

Results

Results: Both medication and stimulation significantly improved stride length, while medication further significantly increased gait speed. In the lower limbs, both medication and stimulation had a normalising effect on lower limb angles, significantly increasing the foot strike angle and toe-off angle.

Conclusions

Conclusions: STN DBS reduced the step to step variability in a range of lower limb gait parameters in PD, while antiparkinsonian medication had no significant effect. This suggests that STN stimulation, but not dopaminergic medication, has access to circuits that control gait rhythm, and that the resulting effect of stimulation on gait is beneficial. However, the results we observed for movement of the trunk and upper limbs were strikingly different to those seen in the lower limbs. We propose a hypothesis to explain why we observe these results, focusing on cholinergic pedunculopontine projections.

Aims

The aim of this study was to identify early neuroimaging biomarkers of the need for deep brain stimulation (DBS) use in patients with Parkinson’s Disease (PD).

Methods

PD patients performed clinical-cognitive evaluations and resting-state functional MRI (RS-fMRI) at baseline and every year for 4 years. Patients were divided into two groups: 19 patients eligible for DBS (PD-DBS) over 48 months and 41 patients who did not meet the criteria to undergo DBS surgery (PD-noDBS). 60 age- and sex-matched controls performed baseline assessments. Graph analysis/connectomics assessed global and local topological network properties and regional functional connectivity (FC) at baseline and changes over-time.

Results

Lobar network analysis showed a significant higher mean nodal strength, local efficiency and clustering coefficient of the occipital areas in PD-DBS relative to both controls and PD-noDBS at baseline. These results were then confirmed by regional analysis. A significant increased FC between frontal and basal ganglia networks was found in PD-noDBS compared to both controls and PD-DBS patient at baseline. Referring to longitudinal analysis, PD-DBS patients showed a progressive decreased FC within occipital and between occipital and parietal networks compared to PD-noDBS (stable over time). Progressive decreased FC between frontal and basal ganglia networks occurred in PD-noDBS relative to PD-DBS (stable over time). Functional alterations within occipital network were positively related to tremor only in PD-DBS at baseline and over time.

Conclusions

RS-fMRI analysis might represent an early biomarker that helps clinicians to establish the correct indication for DBS in PD patients. Funding:Ministry of Education and Science Republic of Serbia (Grant#175090).

Aims

To extend research on the short-term benefits of Dance for Parkinson’s Disease (PD) and determine improvements over 3 years while participating in weekly classes.

Methods

We collected EEG, mood (PANAS-X), cognitive (MMSE, PD-NMS & MDS-UPDRS Parts I, II & IV) and motor (MDS-UPDRS Part III) assessments. We conducted two studies: (1) examined the short-term benefits of dance (N=17) and (2) measured PD symptom progression over a 3-year period (N=32).

Results

rsEEG global alpha power was highest after a single dance class in comparison to before, F(1,26) = 6.928, p < .025, η² = .210. Individuals with PD participating in 3-yrs of dance showed no progression of motor symptoms across time (p=0.817). Further no impairment was shown for daily living (p=0.329), motor experiences of daily living (p=0.540) and for non-motor complications (p=0.390). To examine disease progression directly in our cohort, we matched data from Parkinson’s Progression Markers Initiative as our non-dance PD comparison group (PD-MJFF-Com). A significant Group (PD-Dancers and PD-MJFF-Com) by Days interaction showed that PD who train in dance have less motor impairment (M=18.75) than PD-MJFF-Com who do not dance (M=24.61) and over time (p< 0.05). As expected, and in stark contrast to our PD-Dancers the PD-MJFF-Com showed motor impairment (UPDRS III) across time (p< 0.01). UPDRS I and II showed disease progression of PD over time (p<0.005), and (p<0.01), whereas UPDRS IV showed no progression (p= 0.365) over the same 2-year period.

Conclusions

Multinetwork training to music is effective at slowing motor and non-motor PD symptoms.

Aims

Dance is a sensorimotor and cognitive activity providing variety of positive effects for elderly. Our previous research revealed positive behavioral effects of dance intervention(DI) on attention, executive function, and fitness in non-demented elderly. Here we explored whether DI-induced changes in functional connectivity(rsFC) of brain networks are moderated by cognitive reserve(CR).

Methods

68 non-demented elderly were analysed: 36 in DI group and 32 controls. All participants underwent cognitive and fitness testing and (f)MRI at baseline and six months after DI. Moderation analyses tested the effect of the CR (moderator, years of education-YoE) on the relationship between the DI/controls and change in the rs-FC of sensorimotor network (SMN), dorsal attention network (DAN), their interconnectivity.

Results

The SMN and the SMN-DAN rs-FC significantly improved in the DI group relative to the control group, this change depended on CR. DI significantly contributed to improved rs-FC of SMN t(64) = 3.20; p = 002) and SMN-DAN t(64) = 2.28; p = 026) when the education was 1 SD above the mean (≥17.5 YoE; p < .05), but not when it was at the mean/below the mean (p = > .17). The CR*DI moderator, nor the separate variables predicted change in DAN.

Conclusions

The magnitude of DI-induced increases of rs-FC within the SMN and the SMN-DAN networks, engaged in movement execution and attention, is dependent on high CR. The relationship between the intervention and brain changes dissolved with low CR, so this is important as it shows the degree of CR linked to differing ability to benefit from DI.

Aims

Methods

Results

Conclusions

Aims

To assess the safety and efficacy of mevidalen, a D1 receptor positive allosteric modulator, for the treatment of cognition in patients with LBD.

Methods

PRESENCE (NCT03305809) was a Phase 2, 12-week study in LBD participants with mild-to-moderate dementia randomized (1:1:1:1) to once-daily doses of mevidalen (10 mg, 30 mg, or 75 mg) or placebo. The primary outcome measure was change from baseline on the Cognitive Drug Research Continuity of Attention (CDR-CoA) composite score using a Bayesian mixed model repeated measures (MMRM) model. Success criterion was defined as at least a 67% probability of an effect size (ES)≥0.2. Key study eligibility requirements were age of 40-85 years, Hoehn and Yahr score of 0-4, and Montreal Cognitive Assessment (MoCA) score of 10 to 23. Participants were randomized (1:1:1:1) to once-daily doses of mevidalen (10 mg, 30 mg, or 75 mg) or placebo. Secondary outcomes included Alzheimer’s Disease Assessment Scale cognitive subscale 13 (ADAS-cog₁₃), Alzheimer’s Disease Cooperative Study – Clinical Global Impression of Change (ADCS-CGIC), Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), and Epworth Sleepiness Scale (ESS). Numerous safety measures were collected.

Results

No dose met the primary success criterion. Dose dependent and statistically significant effects were seen on secondary measures of motor and non-motor symptoms of LBD and global functioning. Significant increases in vital signs, nervous system adverse events, and cardiovascular SAEs occurred at 75 mg and resulted in discontinuing this dose during the study.

Conclusions

Mevidalen failed to demonstrate cognitive efficacy. However, improvements in motor and non-motor symptoms with benefit on global functioning suggest a unique profile for the potential symptomatic treatment of LBD. The balance of risk to benefit may be less favorable for the 75 mg dose thereby limiting its utility.