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Alzheimer's disease (AD) is a challenging medical issue that requires efficacious treatment options to improve long-term quality of life. Cannabidiol (CBD) is a cannabis-derived phytocannabinoid with potential health benefits, including reports from our laboratory and others showing a therapeutic role in the pre-clinical treatment of AD; however, the mechanisms whereby CBD affects AD progression remain undefined. Innate lymphoid cells (ILCs) are recently discovered immune cells that initiate and orchestrate inflammatory responses. ILC2, a sub-class of ILCs, is proposed to have a role in cognitive function via unknown mechanisms. In this present study, we explored whether CBD ameliorates AD symptoms via the enhancement of acetylcholine (ACh), a cholinergic neurotransmitter involved in cognition that may regulate ILC2. 5xFAD mice were chronically treated by inhalation of a formulation of broad-spectrum CBD for seven months. ACh production, ILC2s profile, brain histopathology, and long-term behavior were assessed. Together, our studies showed that long-term inhalation of CBD improved cognitive function and reduced senile plaques in a murine AD model, effects that were associated with enhanced ACh production and altered ILC2s distribution within the CNS. These findings indicate that inhaled CBD could offer a cost-effective, non-invasive, and effective treatment for managing AD. The beneficial effects of CBD inhalation may be linked to increased ACh production and an altered distribution of ILC2s, highlighting the need for further research in this area. [ABSTRACT FROM AUTHOR]

ObjectiveTo determine whether providing remote neurologic care into the homes of people with Parkinson disease (PD) is feasible, beneficial, and valuable.MethodsIn a 1-year randomized controlled trial, we compared usual care to usual care supplemented by 4 virtual visits via video conferencing from a remote specialist into patients' homes. Primary outcome measures were feasibility, as measured by the proportion who completed at least one virtual visit and the proportion of virtual visits completed on time; and efficacy, as measured by the change in the Parkinson's Disease Questionnaire-39, a quality of life scale. Secondary outcomes included quality of care, caregiver burden, and time and travel savings.ResultsA total of 927 individuals indicated interest, 210 were enrolled, and 195 were randomized. Participants had recently seen a specialist (73%) and were largely college-educated (73%) and white (96%). Ninety-five (98% of the intervention group) completed at least one virtual visit, and 91% of 388 virtual visits were completed. Quality of life did not improve in those receiving virtual house calls (0.3 points worse on a 100-point scale; 95% confidence interval [CI] -2.0 to 2.7 points; p = 0.78) nor did quality of care or caregiver burden. Each virtual house call saved patients a median of 88 minutes (95% CI 70-120; p < 0.0001) and 38 miles per visit (95% CI 36-56; p < 0.0001).ConclusionsProviding remote neurologic care directly into the homes of people with PD was feasible and was neither more nor less efficacious than usual in-person care. Virtual house calls generated great interest and provided substantial convenience.Clinicaltrialsgov identifierNCT02038959.Classification of evidenceThis study provides Class III evidence that for patients with PD, virtual house calls from a neurologist are feasible and do not significantly change quality of life compared to in-person visits. The study is rated Class III because it was not possible to mask patients to visit type.

BackgroundRecognizing the factors associated with falling in Parkinson's disease (PD) would improve identification of at-risk individuals.ObjectiveTo examine frequency of falling and baseline characteristics associated with falling in PD using the National Institute of Neurological Disorders and Stroke (NINDS) Exploratory Trials in PD Long-term Study-1 (NET-PD LS-1) dataset.MethodsThe LS-1 database included 1741 early treated PD subjects (median 4year follow-up). Baseline characteristics were tested for a univariate association with post-baseline falling during the trial. Significant variables were included in a multivariable logistic regression model. A separate analysis using a negative binomial model investigated baseline factors on fall rate.Results728 subjects (42%) fell during the trial, including at baseline. A baseline history of falls was the factor most associated with post-baseline falling. Men had lower odds of post-baseline falling compared to women, but for men, the probability of a post-baseline fall increased with age such that after age 70, men and women had similar odds of falling. Other baseline factors associated with a post-baseline fall and increased fall rate included the Unified PD Rating Scale (UPDRS) Activities of Daily Living (ADL) score, total functional capacity (TFC), baseline ambulatory capacity score and dopamine agonist monotherapy.ConclusionFalls are common in early treated PD. The biggest risk factor for falls in PD remains a history of falling. Measures of functional ability (UPDRS ADL, TFC) and ambulatory capacity are novel clinical risk factors needing further study. A significant age by sex interaction may help to explain why age has been an inconsistent risk factor for falls in PD.

BackgroundDelivering specialty care remotely directly into people's homes can enhance access for and improve the healthcare of individuals with chronic conditions. However, evidence supporting this approach is limited.Materials and methodsConnect.Parkinson is a randomized comparative effectiveness study that compares usual care of individuals with Parkinson's disease in the community with usual care augmented by virtual house calls with a Parkinson's disease specialist from 1 of 18 centers nationally. Individuals in the intervention arm receive four virtual visits from a Parkinson's disease specialist over 1 year via secure, Web-based videoconferencing directly into their homes. All study activities, including recruitment, enrollment, and assessments, are conducted remotely. Here we report on interest, feasibility, and barriers to enrollment in this ongoing study.ResultsDuring recruitment, 11,734 individuals visited the study's Web site, and 927 unique individuals submitted electronic interest forms. Two hundred ten individuals from 18 states enrolled in the study from March 2014 to June 2015, and 195 were randomized. Most participants were white (96%) and college educated (73%). Of the randomized participants, 73% had seen a Parkinson's disease specialist within the previous year.ConclusionsAmong individuals with Parkinson's disease, national interest in receiving remote specialty care directly into the home is high. Remote enrollment in this care model is feasible but is likely affected by differential access to the Internet.

BackgroundThe effects of dopaminergic therapy in parkinson's disease (PD) can vary depending on the class of medication selected.ObjectiveThe aim of this post hoc study was to determine if the class of dopaminergic therapy correlated with disease severity in persons with early, treated PD.MethodsA non-parametric global statistical test (GST) was used to assess the status of participants treated with dopamine agonist (DA) monotherapy, levodopa (LD) monotherapy or combined LD and DA therapy on multiple PD outcomes encompassing motor, cognitive, psychiatric and autonomic function, as well as disability and quality of life.ResultsThe outcomes measured at the beginning of the study showed lower disease burden for participants on initial DA monotherapy compared to those taking combined LD and DA therapy after controlling for age, education, taking cog-meds and amantadine.ConclusionThis observation suggests that clinicians treating early PD patients favor combined LD and DA therapy in patients with more disabling features over DA monotherapy. As such, studies of PD progression in treated PD patients may be affected by the class of symptomatic dopaminergic therapy.

ImportanceThere are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies.ObjectiveTo determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease.Design, setting, and patientsThe Long-term Study 1, a multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1741 men and women with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) Parkinson disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013.InterventionsParticipants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years).Main outcomes and measuresThe primary outcome measure was a difference in clinical decline from baseline to 5-year follow-up, compared between the 2 treatment groups using a global statistical test. Clinical status was defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity. All outcomes were coded such that higher scores indicated worse outcomes and were analyzed by a global statistical test. Higher summed ranks (range, 5-4775) indicate worse outcomes.ResultsThe trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2360 (95% CI, 2249-2470) and for creatine was 2414 (95% CI, 2304-2524). The global statistical test yielded t1865.8 = -0.75 (2-sided P = .45). There were no detectable differences (P

Background: Parkinson's disease (PD) is a neurodegenerative movement disorder with prodromal and highly prevalent gastrointestinal (GI) symptoms, especially constipation. Although PD models suggest gut‐brain axis dysfunction, the mechanistic underpinnings and their correlation with GI symptoms are poorly understood. Aim: To examine the bidirectional gut‐brain axis function in PD and correlate it with constipation severity, PD duration, and severity. Methods: Rectal sensory thresholds and afferent cortical evoked potentials (CEP) were assessed using a 4‐ring EMG electrode probe. Efferent anal and rectal motor evoked potentials (MEPs) were obtained following transcranial and lumbosacral magnetic stimulation. Bowel symptoms were assessed by prospective stool diary. The CEP and MEP latencies, rectal sensory thresholds, and anorectal sensorimotor data were compared between PD subjects and age‐adjusted healthy subjects. Key Results: Twenty‐five PD subjects with constipation (F/M = 6/19) and 20 healthy subjects (F/M = 14/6) were enrolled. The first and pain sensation thresholds were higher in PD subjects than healthy subjects (p < 0.002) but lost significance after adjustment for age. Age‐adjusted rectal CEP and right‐sided cortico‐anal MEP latencies were prolonged in PD subjects compared to healthy subjects (p < 0.04). Also, half (4 of 8) age‐adjusted spino‐anal and rectal MEP latencies in PD subjects were significantly longer. In multivariate linear analysis, first rectal sensation and right‐sided MEP latencies showed moderate correlation with constipation severity. Conclusions & Inferences: Parkinson's disease is associated with significant bidirectional gut‐brain axis dysfunction as evidenced by prolonged afferent and efferent neuronal signaling. Constipation severity in PD is correlated to abnormal rectal sensation and lateralized disturbance of efferent brain‐gut signaling. [ABSTRACT FROM AUTHOR]