Search

Introduction: Parkinson's disease (PD) is associated with a range of cognitive deficits. Few studies have carefully examined the subtle impacts of PD on cognition among patients who do not meet formal criteria for MCI or dementia. The aim of the current study was thus to describe the impact of PD on cognition in those without cognitive impairment in a well-characterized cohort.Methods: Non-cognitively impaired participants (122 with PD, 122 age- and sex-matched healthy volunteers) underwent extensive cognitive testing. Linear regression analyses compared diagnostic group performance across cognitive measures. For cognitive tasks that were significantly different between groups, additional analyses examined group differences restricting the group inclusion to PD participants with mild motor symptoms or disease duration less than 10years.Results: Processing speed and semantic verbal fluency were significantly lower in the PD group (B =-3.77, 95% CIs [-5.76 to -1.77], p

BACKGROUND: Aggregated α-synuclein plays an important role in Parkinson's disease pathogenesis. Cinpanemab, a human-derived monoclonal antibody that binds to α-synuclein, is being evaluated as a disease-modifying treatment for Parkinson's disease. METHODS: In a 52-week, multicenter, double-blind, phase 2 trial, we randomly assigned, in a 2:1:2:2 ratio, participants with early Parkinson's disease to receive intravenous infusions of placebo (control) or cinpanemab at a dose of 250 mg, 1250 mg, or 3500 mg every 4 weeks, followed by an active-treatment dose-blinded extension period for up to 112 weeks. The primary end points were the changes from baseline in the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score (range, 0 to 236, with higher scores indicating worse performance) at weeks 52 and 72. Secondary end points included MDS-UPDRS subscale scores and striatal binding as assessed on dopamine transporter single-photon-emission computed tomography (DaT-SPECT). RESULTS: Of the 357 enrolled participants, 100 were assigned to the control group, 55 to the 250-mg cinpanemab group, 102 to the 1250-mg group, and 100 to the 3500-mg group. The trial was stopped after the week 72 interim analysis owing to lack of efficacy. The change to week 52 in the MDS-UPDRS score was 10.8 points in the control group, 10.5 points in the 250-mg group, 11.3 points in the 1250-mg group, and 10.9 points in the 3500-mg group (adjusted mean difference vs. control, -0.3 points [95% confidence interval {CI}, -4.9 to 4.3], P = 0.90; 0.5 points [95% CI, -3.3 to 4.3], P = 0.80; and 0.1 point [95% CI, -3.8 to 4.0], P = 0.97, respectively). The adjusted mean difference at 72 weeks between participants who received cinpanemab through 72 weeks and the pooled group of those who started cinpanemab at 52 weeks was -0.9 points (95% CI, -5.6 to 3.8) for the 250-mg dose, 0.6 points (95% CI, -3.3 to 4.4) for the 1250-mg dose, and -0.8 points (95% CI, -4.6 to 3.0) for the 3500-mg dose. Results for secondary end points were similar to those for the primary end points. DaT-SPECT imaging at week 52 showed no differences between the control group and any cinpanemab group. The most common adverse events with cinpanemab were headache, nasopharyngitis, and falls. CONCLUSIONS: In participants with early Parkinson's disease, the effects of cinpanemab on clinical measures of disease progression and changes in DaT-SPECT imaging did not differ from those of placebo over a 52-week period. (Funded by Biogen; SPARK ClinicalTrials.gov number, NCT03318523.).

The SARS-CoV-2 (COVID-19) pandemic has rapidly moved telemedicine from discretionary to necessary. Here, we describe how the Stanford Neurology Department (1) rapidly adapted to the COVID-19 pandemic, resulting in over 1,000 video visits within 4 weeks, and (2) accelerated an existing quality improvement plan of a tiered roll out of video visits for ambulatory neurology to a full-scale roll out. Key issues we encountered and addressed were related to equipment/software, provider engagement, workflow/triage, and training. On reflection, the key drivers of our success were provider engagement and dedicated support from a physician champion, who plays a critical role understanding stakeholder needs. Before COVID-19, physician interest in telemedicine was mixed. However, in response to county and state stay-at-home orders related to COVID-19, physician engagement changed completely; all providers wanted to convert a majority of visits to video visits as quickly as possible. Rapid deployment of neurology video visits across all its subspecialties is feasible. Our experience and lessons learned can facilitate broader utilization, acceptance, and normalization of video visits for neurology patients in the present as well as the much anticipated postpandemic era.

Introduction Gait and balance impairments are cardinal features of Parkinson's disease (PD) that require cognitive input. However, the extent to which specific gait and balance characteristics relate to cognition in PD is unclear. In addition, independent models of gait and balance have not been developed from the same cohort. We aimed to i) develop models of gait and balance in a large PD cohort and ii) determine which gait and balance characteristics best related to cognition. Methods One hundred and ninety-eight people with PD were recruited to the Pacific Udall Center. Using six inertial sensors (APDM, Inc.), comprehensive gait measurements were collected over a 2-min continuous walk and comprehensive static balance measures were collected during a 60-second standing task. Six domains of cognition were assessed: global cognition, attention, executive function, language, memory, and visuospatial function. Correlations and hierarchical linear regression determined independent associations. Results Principal components analysis identified a gait model containing four domains accounting for 80.1% of total variance: pace/turning, rhythm, variability, and trunk. The balance model contained four independent domains accounting for 84.5% of total variance: sway area/jerkiness, sway velocity, sway frequency anteroposterior, and sway frequency mediolateral. Gait domains of pace/turning and variability were strongly associated with attention and executive function. Sway area and jerkiness of balance associated with attention and visuospatial function. Conclusions Gait and balance characteristics were associated with specific types of cognition. The specific relationships between gait or balance with cognitive functions suggests shared cerebral cortical circuitry for mobility and cognitive functions.

Dopaminergic medication is widely used to alleviate motor symptoms of Parkinson’s disease, but these medications also impact cognition with significant variability across patients. It is hypothesized that dopaminergic medication impacts cognition and working memory in Parkinson’s disease by modulating frontoparietal-basal ganglia cognitive control circuits, but little is known about the underlying causal signalling mechanisms and their relation to individual differences in response to dopaminergic medication. Here we use a novel state-space computational model with ultra-fast (490 ms resolution) functional MRI to investigate dynamic causal signalling in frontoparietal-basal ganglia circuits associated with working memory in 44 Parkinson’s disease patients ON and OFF dopaminergic medication, as well as matched 36 healthy controls. Our analysis revealed aberrant causal signalling in frontoparietal-basal ganglia circuits in Parkinson’s disease patients OFF medication. Importantly, aberrant signalling was normalized by dopaminergic medication and a novel quantitative distance measure predicted individual differences in cognitive change associated with medication in Parkinson’s disease patients. These findings were specific to causal signalling measures, as no such effects were detected with conventional non-causal connectivity measures. Our analysis also identified a specific frontoparietal causal signalling pathway from right middle frontal gyrus to right posterior parietal cortex that is impaired in Parkinson’s disease. Unlike in healthy controls, the strength of causal interactions in this pathway did not increase with working memory load and the strength of load-dependent causal weights was not related to individual differences in working memory task performance in Parkinson’s disease patients OFF medication. However, dopaminergic medication in Parkinson’s disease patients reinstated the relation with working memory performance. Our findings provide new insights into aberrant causal brain circuit dynamics during working memory and identify mechanisms by which dopaminergic medication normalizes cognitive control circuits.

Background Telemedicine has been used for decades. Despite its many advantages, its uptake and rigorous evaluation of feasibility across neurology’s ambulatory subspecialties has been sparse. However, the COVID-19 pandemic prompted health care systems worldwide to reconsider traditional health care delivery. To safeguard health care workers and patients, many health care systems quickly transitioned to telemedicine, including across neurology subspecialties, providing a new opportunity to evaluate this modality of care. Objective To evaluate the accelerated implementation of video visits in ambulatory neurology during the COVID-19 pandemic, we used mixed methods to assess adoption, acceptability, appropriateness, and perceptions of potential sustainability. Methods Video visits were launched rapidly in ambulatory neurology clinics of a large academic medical center. To assess adoption, we analyzed clinician-level scheduling data collected between March 22 and May 16, 2020. We assessed acceptability, appropriateness, and sustainability via a clinician survey (n=48) and semistructured interviews with providers (n=30) completed between March and May 2020. Results Video visits were adopted rapidly; overall, 65 (98%) clinicians integrated video visits into their workflow within the first 6 implementation weeks and 92% of all visits were conducted via video. Video visits were largely considered acceptable by clinicians, although various technological issues impacted their satisfaction. Video visits were reported to be more convenient for patients, families, and caregivers than in-person visits; however, access to technology, the patient’s technological capacity, and language difficulties were considered barriers. Many clinicians expressed optimism about future utilization of video visits in neurology. They believed that video visits promote continuity of care and can be incorporated into their practice long-term, although several insisted that they can never replace the in-person examination. Conclusions Video visits are an important addition to clinical care in ambulatory neurology and are anticipated to remain a permanent supplement to in-person visits, promoting patient care continuity, and flexibility for patients and clinicians alike.

Parkinson disease (PD) is the second most common neurodegenerative disorder, after Alzheimer disease,1 and the number of individuals with PD worldwide more than doubled between 1990 and 2015.2 In 2016, PD affected an estimated 6.1 million people globally.3 In the United States, an estimated 680,000 individuals ≥45 years of age had PD in 2010.4 These numbers were projected to rise to 930,000 in 2020 and to reach 1,238,000 by 2030.4 Both motor (rest tremor, bradykinesia, rigidity) and nonmotor (including but not limited to neuropsychiatric, autonomic, and sensory) symptoms of PD contribute to decreased quality of life5 and neurologic disability.3

Neuropsychiatric symptoms are common in Parkinson’s disease (PD). We investigated the relationship between neuropsychiatric symptoms and current and future diagnosis of PD dementia (PDD). Individuals with PD who had a study partner were enrolled (n = 696). Study partners were administered the Neuropsychiatric Inventory or Neuropsychiatric Inventory Questionnaire at baseline. Participants were assigned a cognitive diagnosis at baseline and follow up visits. Hallucinations were significantly associated with a diagnosis of PDD cross-sectionally (p

Mitochondrial dysfunction has been implicated in the pathogenesis of Parkinson's disease (PD), but the cause of this dysfunction is unclear.Platelet mitochondrial complex I and I/III (nicotinamide adenine dinucleotide cytochrome c reductase, NCCR) activities were measured in early PD patients and matched controls enrolled in a population-based case-control study. Ambient agricultural pesticide exposures were assessed with a geographic information system and California Pesticide Use Registry.In contrast to some previous reports, we found no differences in complex I and I/III activities in subjects with PD and controls. We did find that NCCR activity correlated with subjects' exposure to pesticides known to inhibit mitochondrial activity regardless of their diagnosis.Electron transport chain (ETC) activity is not altered in PD in this well-characterized cohort when compared with community-matched controls but appears to be affected by environmental toxins, such as mitochondria-inhibiting pesticides.