Association of liver fibrosis with cognitive decline in Parkinson's disease.

BACKGROUND: Cognitive decline is a common but variable non-motor manifestation of Parkinson's disease. Chronic liver disease contributes to dementia, but its impact on cognitive performance in Parkinson's disease is unknown. We assessed the effect of liver fibrosis on cognition in Parkinson's disease. METHODS: We conducted a retrospective cohort study using data from the Parkinson's Progression Markers Initiative. Our exposure was liver fibrosis at baseline, based on the validated Fibrosis-4 score. Our primary outcome was the Montreal Cognitive Assessment, and additional outcome measures were the Symbol Digit Modalities Test, the Benton Judgement of Line Orientation, the Letter-Number Sequencing Test, and the Modified Semantic Fluency Test. We used linear regression models to assess the relationship between liver fibrosis and scores on cognitive assessments at baseline and linear mixed models to evaluate the association between baseline Fibrosis-4 score with changes in each cognitive test over five years. Models were adjusted for demographics, comorbidities, and alcohol use. RESULTS: We included 409 participants (mean age 61, 40 % women). There was no significant association between liver fibrosis and baseline performance on any of the cognitive assessments in adjusted models. However, over the subsequent five year period, liver fibrosis was associated with more rapid decline in scores on the Montreal Cognitive Assessment (interaction coefficient, -0.07; 95 % CI, -0.12, -0.02), the Symbol Digit Modalities Test, the Benton Judgement of Line Orientation, and the Modified Semantic Fluency Test. CONCLUSION: In people with Parkinson's disease, the presence of comorbid liver fibrosis was associated with more rapid decline across multiple cognitive domains.

Dystonia phenomenology and treatment response in migraine.

OBJECTIVE: To describe the phenomenology of cervical dystonia (CD) in patients with migraine and the effect of its treatment on migraine frequency. BACKGROUND: Preliminary studies demonstrate that treatment of CD with botulinum toxin in those with migraine can improve both conditions. However, the phenomenology of CD in the setting of migraine has not been formally described. METHODS: We conducted a single-center, descriptive, retrospective case series of patients with a verified diagnosis of migraine who were referred to our movement disorder center for evaluation of co-existing, untreated CD. Patient demographics, characteristics of migraine and CD, and effects of cervical onabotulinumtoxinA (BoTNA) injections were recorded and analyzed. RESULTS: We identified 58 patients with comorbid CD and migraine. The majority were female (51/58 [88%]) and migraine preceded CD in 72% (38/53) of patients by a mean (range) of 16.0 (0-36) years. Nearly all the patients had laterocollis (57/58) and 60% (35/58) had concurrent torticollis. Migraine was found to be both ipsilateral and contralateral to the dystonia in a comparable proportion of patients (11/52 [21%] vs. 15/52 [28%]). There was no significant relationship between migraine frequency and dystonia severity. Treatment of CD with BoTNA reduced migraine frequency in most patients (15/26 [58%] at 3 months and 10/16 [63%] at 12 months). CONCLUSIONS: In our cohort, migraine often preceded dystonia symptoms and laterocollis was the most described dystonia phenotype. The lateralization and severity/frequency of these two disorders were unrelated, but dystonic movements were a common migraine trigger. We corroborated previous reports that cervical BoTNA injections reduced migraine frequency. Providers treating patients with migraine and neck pain who are not fully responding to typical therapies should screen for possible CD as a confounding factor, which when treated can reduce migraine frequency.

Context-dependent representations of movement in Drosophila dopaminergic reinforcement pathways.

Dopamine plays a central role in motivating and modifying behavior, serving to invigorate current behavioral performance and guide future actions through learning. Here we examine how this single neuromodulator can contribute to such diverse forms of behavioral modulation. By recording from the dopaminergic reinforcement pathways of the Drosophila mushroom body during active odor navigation, we reveal how their ongoing motor-associated activity relates to goal-directed behavior. We found that dopaminergic neurons correlate with different behavioral variables depending on the specific navigational strategy of an animal, such that the activity of these neurons preferentially reflects the actions most relevant to odor pursuit. Furthermore, we show that these motor correlates are translated to ongoing dopamine release, and acutely perturbing dopaminergic signaling alters the strength of odor tracking. Context-dependent representations of movement and reinforcement cues are thus multiplexed within the mushroom body dopaminergic pathways, enabling them to coordinately influence both ongoing and future behavior.