From Awareness to Understanding: A Knowledge-Focused Framework for Parkinson's Disease Communication.

There is no question that the stigma and discrimination associated with HIV and AIDS can be reduced through intervention. The inclusion of stigma and discrimination reduction as a critical component of achieving an AIDS-free generation in recent UNAIDS, UN and PEPFAR political initiatives is promising. Yet national governments need evidence on effective interventions at the individual, community and societal levels in order to strategically incorporate stigma and discrimination reduction into national AIDS plans. Currently, the heterogeneity of stigma and discrimination reduction approaches and measurement makes it challenging to compare and contrast evaluated interventions. Moving forward, it is critical for the research community to: (1) clearly link intervention activities to the domains of stigma to be shifted; (2) assess the stigma domains in a consistent manner; and (3) link stigma and discrimination reduction with HIV prevention, care and treatment outcomes (e.g., uptake, adherence and retention of ART). These steps would further advance the scientific evidence base of stigma and discrimination reduction and allow for the identification of effective interventions that could be scaled up by national governments. 10.7448/IAS.16.3.18881 © 2013 Grossman C I et al; licensee International AIDS Society Published 13 November 2013 Corresponding author: Cynthia I Grossman, HIV Care Engagement and Secondary Prevention Program, Division of AIDS Research, National Institutes of Mental Health, 6001 Executive Boulevard, RM 6201, MSC 9619, Bethesda, MD 20892, USA. ([email protected])

Dysregulation of microRNA gene expression has been implicated in many neurodegenerative diseases, including Parkinson's disease. However, the individual dysregulated microRNAs remain largely unknown. Previous meta-analyses have highlighted several microRNAs being differentially expressed in post-mortem Parkinson's disease and Alzheimer's disease brains versus controls, but they were based on small sample sizes. In this study, we quantified the expression of the most compelling Parkinson's and Alzheimer's disease microRNAs from these meta-analyses ('candidate miRNAs') in one of the largest Parkinson's/Alzheimer's disease case-control post-mortem brain collections available (n = 451), thereby quadruplicating previously investigated sample sizes. Parkinson's disease candidate microRNA hsa-miR-132-3p was differentially expressed in our Parkinson's (P = 4.89E-06) and Alzheimer's disease samples (P = 3.20E-24) compared with controls. Alzheimer's disease candidate microRNAs hsa-miR-132-5p (P = 4.52E-06) and hsa-miR-129-5p (P = 0.0379) were differentially expressed in our Parkinson's disease samples. Combining these novel data with previously published data substantially improved the statistical support (α = 3.85E-03) of the corresponding meta-analyses, clearly implicating these microRNAs in both Parkinson's and Alzheimer's disease. Furthermore, hsa-miR-132-3p/-5p (but not hsa-miR-129-5p) showed association with α-synuclein neuropathological Braak staging (P = 3.51E-03/P = 0.0117), suggesting that hsa-miR-132-3p/-5p play a role in α-synuclein aggregation beyond the early disease phase. Our study represents the largest independent assessment of recently highlighted candidate microRNAs in Parkinson's and Alzheimer's disease brains, to date. Our results implicate hsa-miR-132-3p/-5p and hsa-miR-129-5p to be differentially expressed in both Parkinson's and Alzheimer's disease, pinpointing shared pathogenic mechanisms across these neurodegenerative diseases. Intriguingly, based on publicly available high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation data, hsa-miR-132 may interact with SNCA messenger RNA in the human brain, possibly pinpointing novel therapeutic approaches in fighting Parkinson's disease.

Occupational exposures to magnetic fields and neurodegenerative disease risks

BackgroundLittle has been quantified, at a population‐level, about the magnitude of heath service disruption to persons living with dementia in community settings during the COVID‐19 pandemic. Sustained access to health care services is particularly important for persons with dementia and other neurodegenerative diseases as they are vulnerable to decline.MethodHealth administrative data from Ontario, Canada were used to examine patterns of health service use among all persons with Alzheimer disease and related dementias (dementia) who were alive and living in the community. This cohort was compared to persons with Parkinson’s disease (PD) as well as all older adults (age 65+ years) without neurodegenerative diseases. Rates of all‐cause hospital admissions, emergency department visits, primary care and specialist physician visits and home care visits were analyzed for all individuals alive and eligible for provincial health insurance at the start of each weekly period from March 1, 2020 to September 20, 2020 (pandemic period) and from March 3, 2019 to September 22, 2019 (pre‐pandemic period). Rates of health service use during specific weeks in the pandemic period (i.e., lowest week, last available week) were compared to corresponding weeks in the pre‐pandemic period within each cohort using percent changes.ResultsOn March 1, 2020, 128,696 persons with dementia, 30,099 with PD and 2,460,358 older adults were eligible for provincial health services. Across cohorts and services, dramatic declines in use of health services were observed at the lowest week: hospitalization (‐38.7% dementia, ‐72.3% PD, ‐44.2% older adults); emergency department (‐54.9% dementia, ‐57.7% PD, ‐53.6% older adults); home care (‐14.8% dementia, ‐19.4% PD, ‐7.4% older adults). Health services varied in how quickly they rebounded to pre‐pandemic levels within cohorts; notably, by the end of the study period, emergency department visits had increased to a level higher than corresponding 2019 weekly rates (24.2% dementia, 15.2% PD, 7.4% older adults).ConclusionsThe first wave of the COVID‐19 pandemic meaningfully and immediately disrupted use of health care services for persons living with dementia and PD and may have resulted in long‐term consequences that should be monitored.

The Role of Focused Ultrasound in the Management of Movement Disorders: Insights after 5 Years of Experience.

Although neurodegenerative diseases are a leading cause of death, little is known about health care utilization and cost during the end-of-life (EoL) period or how it compares with that of other life-limiting conditions. We aimed to describe and compare resource utilization among US Medicare decedents with neurodegenerative diseases with decedents with cancer. We conducted a retrospective study of Medicare Part A and B beneficiaries with Alzheimer disease (AD), Parkinson disease (PD), or amyotrophic lateral sclerosis (ALS) who died in 2018. Decedents diagnosed with malignant brain tumors or pancreatic cancer served as non-neurodegenerative comparators. Descriptive analyses examined demographic and clinical characteristics in the last year of life. The probabilities and associated costs of emergency department (ED), inpatient, skilled nursing facility (SNF), and hospice utilization during the last 12 and 6 months of life were also compared between persons with neurodegenerative diseases and cancer, adjusting for sociodemographic factors and comorbidity burden. A total of 1,126,799 Medicare beneficiaries died in 2018, of which 357,926 had a qualifying diagnosis. Persons with neurodegenerative diseases were older and more frequently received Medicaid assistance than persons with brain or pancreatic cancer. In all groups, health care service utilization increased over the last year of life, and total costs were predominantly attributable to inpatient care. In the last 6 months of life, neurologist care was infrequent among patients with neurodegenerative disease (AD: 1.5%; PD: 8.6%; ALS: 32.0%). Persons with neurodegenerative diseases as compared to persons with malignant brain tumors also had greater odds of ED use (AD: adjusted odds ratio [aOR] 1.17, 95% CI 1.11-1.23; PD: aOR 1.18, 95% CI 1.11-1.25; ALS: aOR 1.11, 95% CI 1.01-1.23), lower odds of hospitalization (AD: aOR 0.64, 95% CI 0.60-0.68; PD: aOR 0.65, 95% CI 0.61-0.69; ALS: aOR 0.33, 95% CI 0.30-0.37), and lower odds of hospice enrollment (AD: aOR 0.33, 95% CI 0.31-0.36; PD: aOR 0.33, 95% CI 0.31-0.36; ALS: aOR 0.41, 95% CI 0.36-0.46). The findings were similar in pancreatic cancer. Persons with neurodegenerative diseases in the United States are more likely to visit the ED and less likely to use inpatient and hospice services at EoL than persons with brain or pancreatic cancer. These group differences may stem from prognostic uncertainty and reflect inadequate EoL care practices, requiring further investigation to ensure more timely palliative care and hospice referrals.

Background:Adult-onset neurodegenerative diseases affect millions and negatively impact health care systems worldwide. Evidence suggests that air pollution may contribute to aggravation of neurodegeneration, but studies have been limited.Objective:We examined the potential association between long-term exposure to particulate matter in aerodynamic diameter [fine particulate matter ()] and disease aggravation in Alzheimer’s (AD) and Parkinson’s (PD) diseases and amyotrophic lateral sclerosis (ALS), using first hospitalization as a surrogate of clinical aggravation.Methods:We used data from the New York Department of Health Statewide Planning and Research Cooperative System (SPARCS 2000–2014) to construct annual county counts of first hospitalizations with a diagnosis of AD, PD, or ALS (total, urbanicity-, sex-, and age-stratified). We used annual concentrations estimated by a prediction model at a resolution, which we aggregated to population-weighted county averages to assign exposure to cases based on county of residence. We used outcome-specific mixed quasi-Poisson models with county-specific random intercepts to estimate rate ratios (RRs) for a 1-y exposure. We allowed for nonlinear exposure–outcome relationships using penalized splines and accounted for potential confounders.Results:We found a positive nonlinear association that plateaued above (, 95% CI: 1.04, 1.14 for a increase from 8.1 to ). We also found a linear positive association (, 95% CI: 1.01, 1.09 per increase), and suggestive evidence of an association with AD. We found effect modification by age for PD and ALS with a stronger positive association in patients of age but found insufficient evidence of effect modification by sex or urbanization level for any of the outcomes.Conclusion:Our findings suggest that annual increase in county-level concentrations may contribute to clinical aggravation of PD and ALS. Importantly, the average annual concentration in our study was , below the current American national standards, suggesting the standards may not adequately protect the aging population. https://doi.org/10.1289/EHP7425

In this review I outline the arguments as to whether we should consider Parkinson disease one or more than one entity and discuss genetic findings from Mendelian and whole-genome association analysis in that context. I discuss what the demonstration of disease spread implies for our analysis of the genetic and epidemiologic risk factors for disease and outline the surprising fact that we now have genetically identified on the order of half our risk for developing the disease.

tranSMART Foundation Datathon 1.0: The cross neurodegenerative diseases challenge

Editorial: A Trends guide to Neurodegenerative Disease and Repair

SUMMARYα-synuclein (α-syn) aggregation and accumulation drive neurodegeneration in Parkinson’s disease (PD). The substantia nigra of patients with PD contains excess iron, yet the underlying mechanism accounting for this iron accumulation is unclear. Here, we show that misfolded α-syn activates microglia, which release interleukin 6 (IL-6). IL-6, via its trans-signaling pathway, induces changes in the neuronal iron transcriptome that promote ferrous iron uptake and decrease cellular iron export via a pathway we term the cellular iron sequestration response, or CISR. The brains of patients with PD exhibit molecular signatures of the IL-6-mediated CISR. Genetic deletion of IL-6, or treatment with the iron chelator deferiprone, reduces pathological α-syn toxicity in a mouse model of sporadic PD. These data suggest that IL-6-induced CISR leads to toxic neuronal iron accumulation, contributing to synuclein-induced neurodegeneration.

Persons with dementia and Parkinson disease (PD) are vulnerable to disruptions in health care and services. To examine changes in health service use among community-dwelling persons with dementia, persons with PD, and older adults without neurodegenerative disease during the first wave of the COVID-19 pandemic. Repeated cross-sectional analysis using population-based administrative data among community-dwelling persons with dementia, persons with PD, and adults 65 years and older at the start of each week from March 1 through the week of September 20, 2020 (pandemic period), and March 3 through the week of September 22, 2019 (historical period), in Ontario, Canada. COVID-19 pandemic as of March 1, 2020. Main outcomes were weekly rates of emergency department visits, hospitalizations, nursing home admissions, home care, virtual and in-person physician visits, and all-cause mortality. Poisson regression models were used to calculate weekly rate ratios (RRs) with 95% CIs comparing pandemic weeks with historical levels. Among those living in the community as of March 1, 2020, persons with dementia (n = 131 466; mean [SD] age, 80.1 [10.1] years) were older than persons with PD (n = 30 606; 73.7 [10.2] years) and older adults (n = 2 363 742; 74.0 [7.1] years). While all services experienced declines, the largest drops occurred in nursing home admissions (RR for dementia: 0.10; 95% CI, 0.07-0.15; RR for PD: 0.03; 95% CI, 0.00-0.21; RR for older adults: 0.11; 95% CI, 0.06-0.18) and emergency department visits (RR for dementia: 0.45; 95% CI, 0.41-0.48; RR for PD: 0.40; 95% CI, 0.34-0.48; RR for older adults: 0.45; 95% CI, 0.44-0.47). After the first wave, most services returned to historical levels except physician visits, which remained elevated (RR for dementia: 1.07; 95% CI, 1.05-1.09; RR for PD: 1.10, 95% CI, 1.06-1.13) and shifted toward virtual visits. Older adults continued to experience lower hospitalizations. All-cause mortality was elevated across cohorts. In this population-based repeated cross-sectional study in Ontario, Canada, those with dementia, those with PD, and older adults sought hospital care far less than usual, were not admitted to nursing homes, and experienced excess mortality during the first wave of the pandemic. Most services returned to historical levels, but virtual physician visits remained a feature of care. While issues of equity and quality of care are still emerging among persons with neurodegenerative diseases, policies to support virtual care are necessary.

The term neurodegeneration defines numerous conditions that modify neuron’s normal functions in the human brain where is possible to observe a progressive and consistent neuronal loss. The mechanisms involved in neurodegenerative chronic and acute diseases evolution are not completely understood yet, however they share common characteristics such as misfolded proteins, oxidative stress, inflammation, excitotoxicity, and neuronal loss. Many studies have shown the frequency to develop neurodegenerative chronic diseases several years after an acute brain injury. In addition, many patients show, after a traumatic brain injury, motor and cognitive manifestations that are close to which are observed in neurodegenerative chronic patients. For this reason it is evident how is fundamental the concept of neuroprotection as a way to modulate the neurodegenerative processes evolution. Neuroinflammation, oxidative stress and the apoptotic process may be functional targets where operate to this end. Taking into account these considerations, the aim of the present study is to identify potential common pathogenetic pathways in neurodegenerative diseases using an integrated approach of preclinical studies. The goal is to delineate therapeutic strategies for the prevention of neuroinflammation, neurodegeneration and dysfunctions associated to Parkinson’s disease (PD) and cerebral ischemia. In the present study we used a murine model of PD treated with an isothiocyanate, 6-MSITC, able to quench ROS formation, restore the antioxidant GSH system, slow down the apoptotic neuronal death and counteract motor dysfunction induced by 6-OHDA. In the second study we utilized a transgenic mouse model knockout for CD36 receptor to investigate the inflammation involvement in a long term study of MCAo, which shows a better outcome after the damage induced. In conclusion, results in this study allow underlying the connection among these pathologies, and the importance of a neuroprotective strategy able to restore neurons activity where current drugs therapies have shown palliative but not healing abilities.

Feasibility, appropriateness, meaningfulness and effectiveness of nursing interventions on the well-being of people with Parkinsonʼs disease and their caregivers living in the community: a mixed-methods systematic review protocol

The second brain in Parkinson's disease: fact or fantasy?