Semantic Memory and Lexical Availability in Parkinson's Disease: A Statistical Learning Study.

Parkinson's disease (PD) is a neurodegenerative disorder that causes a progressive impairment in motor and cognitive functions. Although semantic fluency deficits have been described in PD, more specific semantic memory (SM) and lexical availability (LA) domains have not been previously addressed. Here, we aimed to characterize the cognitive performance of PD patients in a set of SM and LA measures and determine the smallest set of neuropsychological (lexical, semantic, or executive) variables that most accurately classify groups. Thirty early-stage non-demented PD patients (age 35-75, 10 females) and thirty healthy controls (age 36-76, 12 females) were assessed via general cognitive, SM [three subtests of the CaGi battery including living (i.e., elephant) and non-living things (i.e., fork)], and LA (eliciting words from 10 semantic categories related to everyday life) measures. Results showed that PD patients performed lower than controls in two SM global scores (picture naming and naming in response to an oral description). This impairment was particularly pronounced in the non-living things subscale. Also, the number of words in the LA measure was inferior in PD patients than controls, in both larger and smaller semantic fields, showing a more inadequate recall strategy. Notably, the classification algorithms indicated that the SM task had high classification accuracy. In particular, the denomination of non-living things had a classification accuracy of ∼80%. These results suggest that frontostriatal deterioration in PD leads to search strategy deficits in SF and the potential disruption in semantic categorization. These findings are consistent with the embodied view of cognition.

Rekindling Action Language: A Neuromodulatory Study on Parkinson's Disease Patients.

Impairments of action semantics (a cognitive domain that critically engages motor brain networks) are pervasive in early Parkinson's disease (PD). However, no study has examined whether action semantic skills in persons with this disease can be influenced by non-invasive neuromodulation. Here, we recruited 22 PD patients and performed a five-day randomized, blinded, sham-controlled study to assess whether anodal transcranial direct current stimulation (atDCS) over the primary motor cortex, combined with cognitive training, can boost action-concept processing. On day 1, participants completed a picture-word association (PWA) task involving action-verb and object-noun conditions. They were then randomly assigned to either an atDCS (n = 11, 2 mA for 20 m) or a sham tDCS (n = 11, 2 mA for 30 s) group and performed an online PWA practice over three days. On day 5, they repeated the initial protocol. Relative to sham tDCS, the atDCS group exhibited faster reaction times for action (as opposed to object) concepts in the post-stimulation test. This result was exclusive to the atDCS group and held irrespective of the subjects' cognitive, executive, and motor skills, further attesting to its specificity. Our findings suggest that action-concept deficits in PD are distinctively grounded in motor networks and might be countered by direct neuromodulation of such circuits. Moreover, they provide new evidence for neurosemantic models and inform a thriving agenda in the embodied cognition framework.

Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial.

Importance: Ivermectin is widely prescribed as a potential treatment for COVID-19 despite uncertainty about its clinical benefit. Objective: To determine whether ivermectin is an efficacious treatment for mild COVID-19. Design, Setting, and Participants: Double-blind, randomized trial conducted at a single site in Cali, Colombia. Potential study participants were identified by simple random sampling from the state's health department electronic database of patients with symptomatic, laboratory-confirmed COVID-19 during the study period. A total of 476 adult patients with mild disease and symptoms for 7 days or fewer (at home or hospitalized) were enrolled between July 15 and November 30, 2020, and followed up through December 21, 2020. Intervention: Patients were randomized to receive ivermectin, 300 µg/kg of body weight per day for 5 days (n = 200) or placebo (n = 200). Main Outcomes and Measures: Primary outcome was time to resolution of symptoms within a 21-day follow-up period. Solicited adverse events and serious adverse events were also collected. Results: Among 400 patients who were randomized in the primary analysis population (median age, 37 years [interquartile range {IQR}, 29-48]; 231 women [58%]), 398 (99.5%) completed the trial. The median time to resolution of symptoms was 10 days (IQR, 9-13) in the ivermectin group compared with 12 days (IQR, 9-13) in the placebo group (hazard ratio for resolution of symptoms, 1.07 [95% CI, 0.87 to 1.32]; P = .53 by log-rank test). By day 21, 82% in the ivermectin group and 79% in the placebo group had resolved symptoms. The most common solicited adverse event was headache, reported by 104 patients (52%) given ivermectin and 111 (56%) who received placebo. The most common serious adverse event was multiorgan failure, occurring in 4 patients (2 in each group). Conclusion and Relevance: Among adults with mild COVID-19, a 5-day course of ivermectin, compared with placebo, did not significantly improve the time to resolution of symptoms. The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand the effects of ivermectin on other clinically relevant outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT04405843.

Classifying Parkinson's Disease Patients With Syntactic and Socio-emotional Verbal Measures.

Frontostriatal disorders, such as Parkinson's disease (PD), are characterized by progressive disruption of cortico-subcortical dopaminergic loops involved in diverse higher-order domains, including language. Indeed, syntactic and emotional language tasks have emerged as potential biomarkers of frontostriatal disturbances. However, relevant studies and models have typically considered these linguistic dimensions in isolation, overlooking the potential advantages of targeting multidimensional markers. Here, we examined whether patient classification can be improved through the joint assessment of both dimensions using sentential stimuli. We evaluated 31 early PD patients and 24 healthy controls via two syntactic measures (functional-role assignment, parsing of long-distance dependencies) and a verbal task tapping social emotions (envy, Schadenfreude) and compared their classification accuracy when analyzed in isolation and in combination. Complementarily, we replicated our approach to discriminate between patients on and off medication. Results showed that specific measures of each dimension were selectively impaired in PD. In particular, joint analysis of outcomes in functional-role assignment and Schadenfreude improved the classification accuracy of patients and controls, irrespective of their overall cognitive and affective state. These results suggest that multidimensional linguistic assessments may better capture the complexity and multi-functional impact of frontostriatal disruptions, highlighting their potential contributions in the ongoing quest for sensitive markers of PD.