Explore the vast range of titles available.

Objective To determine the evolution of numerous neuropsychiatric symptoms and cognitive abilities in Parkinson disease from disease onset. Methods Prospectively collected, longitudinal (untreated, disease onset to year 5), observational data from Parkinson's Progression Markers Initiative annual visits was used to evaluate prevalence, correlates, and treatment of 10 neuropsychiatric symptoms and cognitive impairment in Parkinson disease participants and matched healthy controls. Results Of 423 Parkinson disease participants evaluated at baseline, 315 (74.5%) were assessed at year 5. Eight neuropsychiatric symptoms studied increased in absolute prevalence by 6.2–20.9% at year 5 relative to baseline, and cognitive impairment increased by 2.7–6.2%. In comparison, the frequency of neuropsychiatric symptoms in healthy controls remained stable or declined over time. Antidepressant and anxiolytic/hypnotic use in Parkinson disease were common at baseline and increased over time (18% to 27% for the former; 13% to 24% for the latter); antipsychotic and cognitive‐enhancing medication use was uncommon throughout (2% and 5% of patients at year 5); and potentially harmful anticholinergic medication use was common and increased over time. At year 5 the cross‐sectional prevalence for having three or more neuropsychiatric disorders/cognitive impairment was 56% for Parkinson disease participants versus 13% for healthy controls, and by then seven of the examined disorders had either occurred or been treated at some time point in the majority of Parkinson disease patients. Principal component analysis suggested an affective disorder subtype only. Interpretation Neuropsychiatric features in Parkinson disease are common from the onset, increase over time, are frequently comorbid, and fluctuate in severity.

Delirium in elderly patients is common and dangerous. Major risk factors include aging and exogenous insults, such as infection or surgery. In animal models, aging enhances pro-inflammatory cytokine release from microglia in response to exogenous insults. The epigenetic mechanism DNA methylation (DNAm) regulates gene expression and changes with age. Older individuals may have methylation changes that influence the increased cytokine upon insult, but the degree to which aging affects DNAm of cytokine genes is not fully understood. The relationship between DNAm and aging of pro-inflammatory cytokine genes (TNF-alpha, IL1-beta, IL-6) was investigated using methylation array data in two cohorts. Brain and blood samples were collected from a neurosurgery cohort (NSG) of 21 subjects who underwent brain resection. A second cohort, the Grady Trauma Project (GTP), included blood samples from 265 subjects. In the NSG cohort, a significant negative correlation between age and DNAm in brain was found at a CpG in IL-6. With the GTP dataset, significant negative correlations between age and DNAm were seen at most of the CpGs in TNF-alpha. Also, TNF-Alpha expression increases with age. These GTP DNAm correlations were also nominally significant in NSG blood samples. In neuronal negative NSG brain tissue, a similar negative trend was observed. With aging, a decrease in DNAm of cytokines gene CpGs in glia and blood was seen. As this can affect their expression, additional research is needed to fully elucidate the role of DNAm in aging and how it may influence the pathogenesis of delirium.

Introduction Individuals with idiopathic rapid eye movement sleep behavior disorder (iRBD) are at high risk for a clinical diagnosis of an α‐synucleinopathy (aSN). They could serve as a key population for disease‐modifying trials. Abnormal dopamine transporter (DAT) imaging is a strong candidate biomarker for risk of aSN diagnosis in iRBD. Our primary objective was to identify a quantitative measure of DAT imaging that predicts diagnosis of clinically‐defined aSN in iRBD. Methods The sample included individuals with iRBD, early Parkinson’s Disease (PD), and healthy controls (HC) enrolled in the Parkinson Progression Marker Initiative, a longitudinal, observational, international, multicenter study. The iRBD cohort was enriched with individuals with abnormal DAT binding at baseline. Motor and nonmotor measures were compared across groups. DAT specific binding ratios (SBR) were used to calculate the percent of expected DAT binding for age and sex using normative data from HCs. Receiver operative characteristic analyses identified a baseline DAT binding cutoff that distinguishes iRBD participants diagnosed with an aSN in follow‐up versus those not diagnosed. Results The sample included 38 with iRBD, 205 with PD, and 92 HC who underwent DAT‐SPECT at baseline. Over 4.7 years of mean follow‐up, 14 (36.84%) with iRBD were clinically diagnosed with aSN. Risk of aSN diagnosis was significantly elevated among those with baseline putamen SBR ≤ 48% of that expected for age and sex, relative to those above this cutoff (hazard ratio = 17.8 [95%CI: 3.79–83.3], P = 0.0003). Conclusion We demonstrate the utility of DAT SBR to identify individuals with iRBD with increased short‐term risk of an aSN diagnosis.

Abstract Background: Identification of risk factors is critical to preventing the childhood obesity epidemic. Risk factors that contribute to obesity are multifactorial. However, limited research has focused on identifying obesity risk factors using an ecological approach. Methods: Baseline self-report survey data from the STRONG Kids program were used. The sample consisted of 329 parent-child dyads recruited from childcare programs in east-central Illinois. Child height and weight were measured and converted to age- and sex-specific z-scores using standard growth charts. An ecological model provided the theoretical framework for the selection of 22 previously reported childhood obesity risk factors. Multiple logistic regression analyses were used to identify risk factors. Results: Of 22 potential risk factors, three were found to be significantly associated with child overweight/obesity. These included child nighttime sleep duration (χ2=8.56; p=0.003), parent BMI (χ2=5.62; p=0.01), and parental restrictive feeding for weight control (χ2=4.77; p=0.02). Children who slept for 8 hours and less were 2.2 times more likely to be overweight/obese [95% confidence interval (CI): 1.3–3.7), whereas children with an overweight/obese parent were 1.9 times more likely to be overweight/obese (95% CI: 1.12–3.2). Finally, children whose parents used restrictive feeding practices were 1.75 times more likely to be overweight/obese (95% CI: 1.06–2.9). Conclusions: Using an ecological approach, we conclude that childhood obesity prevention efforts may benefit from targeting the key risk factors of child sleep duration, parent BMI, and parental restrictive feeding practices as focus areas for obesity prevention.

Aims: There is no previous study demonstrating the differences of genome-wide DNA methylation (DNAm) profiles between patients with and without postoperative delirium (POD). We aimed to discover epigenetic (DNAm) markers that are associated with POD in blood obtained from patients before and after neurosurgery. Methods: Pre- and post-surgical blood DNA samples from 37 patients, including 10 POD cases, were analyzed using the Illumina EPIC array genome-wide platform. We examined DNAm differences in blood from patients with and without POD. Enrichment analysis with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes terms were also conducted. Results: When POD cases were tested for DNAm change before and after surgery, enrichment analyses showed many relevant signals with statistical significance in immune response related-pathways and inflammatory cytokine related-pathways such as 'cellular response to cytokine stimulus', 'regulation of immune system process', 'regulation of cell activation', and 'regulation of cytokine production'. Furthermore, after excluding the potential effect of common factors related to surgery and anesthesia between POD cases and non-POD controls, the enrichment analyses showed significant signals such as 'immune response' and 'T cell activation', which are same pathways previously identified from an independent non-surgical inpatient cohort. Conclusions: Our first genome-wide DNAm investigation of POD showed promising signals related to immune response, inflammatory response and other relevant signals considered to be associated with delirium pathophysiology. Our data supports the hypothesis that epigenetics are playing an important role in pathophysiological mechanism of delirium and suggest the potential usefulness of epigenetics based biomarker of POD. Competing Interest Statement Funding: This work was supported by research grants from the National Institute of Mental Health, United States (R01 MH119165). Gen Shinozaki receives research grant support from National institute of health (NIH), National Science Foundation (NSF), Sumitomo Pharma LTD, and Fujitsu Laboratories LTD. Role of the Sponsors: The supporters had no role in the design, analysis, interpretation, or publication of this study. Declaration of Interest: Gen Shinozaki has pending patents 'Epigenetic Biomarker of Delirium Risk' in the PCT Application No. PCT/US19/51276, in the PCT Application No. PCT/US21/63166, and in U.S. Provisional Patent No. 62/731,599. All other authors have declared that no conflict of interest exists.

INTRODUCTION: We previously reported the association between DNA methylation (DNAm) of pro-inflammatory cytokine genes and aging. Neurotrophic factors are also known to be associated with aging and neurocognitive disorders. Thus, we hypothesized that DNAm of neurotrophic genes change with aging, especially in delirium patients. METHODS: DNAm were analyzed using HumanMethylationEPIC BeadChip Kit in 3 independent cohorts; blood from 383 Grady Trauma Project subjects, brain from 21 neurosurgery patients, and blood from 87 inpatients with and without delirium. RESULTS: Both blood and brain samples showed that most of the DNAm of neurotrophic genes were positively correlated with aging. Furthermore, DNAm of neurotrophic genes were positively correlated with aging in delirium cases than in non-delirium controls. DISCUSSION: These findings support our hypothesis that the neurotrophic genes may be epigenetically modulated with aging, and this process may be contributing to the pathophysiology of delirium.

Background: The authors previously hypothesized the role of epigenetics in pathophysiology of delirium, and tested DNA methylation (DNAm) change among pro-inflammatory cytokines along with aging in blood, glia and neuron. The authors reported that DNAm level of the TNF-alpha decreases along with aging in blood and glia, but not in neuron; however, DNAm differences between delirium cases and non-delirium controls have not been investigated directly. Therefore, in the present study, DNAm differences in blood between delirium patients and controls without delirium were examined. Methods: A case-control study with 92 subjects was conducted. Whole blood samples were collected and genome-wide DNAm was measured by the Infinium HumanMethylationEPIC BeadChip arrays. The correlation between DNAm levels in the TNF-alpha and age, network analysis, and the correlation between age and DNAm age were tested. Results: Only delirium cases showed 3 CpGs sites in the TNF-alpha significantly correlated to age after multiple corrections. A genome-wide significant CpG site near the gene of LDLRAD4 was identified. In addition, network analysis showed several significant pathways with false discovery rate adjusted p-value < 0.05. The top pathway with GO was immune response, and the second top pathway with KEGG was cholinergic synapse. Although there was no statistically significant difference, DNAm age among non-delirium controls showed \"slower aging\" compared to delirium cases. Conclusions: DNAm differences were shown both at gene and network levels between delirium cases and non-delirium controls. This finding indicates that DNAm status in blood has a potential to be used as epigenetic biomarkers for delirium.

We have previously developed a bispectral electroencephalography (BSEEG) device, which was shown to be effective in detecting delirium and predicting patient outcomes. In this study we aimed to apply the BSEEG approach for a sepsis. This was a retrospective cohort study conducted at a single center. Sepsis-positive cases were identified based on retrospective chart review. EEG raw data and calculated BSEEG scores were obtained in the previous studies. The relationship between BSEEG scores and sepsis was analyzed, as well as the relationship among sepsis, BSEEG score, and mortality. Data were analyzed from 628 patients. The BSEEG score from the first encounter (1st BSEEG) showed a significant difference between patients with and without sepsis ( p  = 0.0062), although AUC was very small indicating that it is not suitable for detection purpose. Sepsis patients with high BSEEG scores showed the highest mortality, and non-sepsis patients with low BSEEG scores showed the lowest mortality. Mortality of non-sepsis patients with high BSEEG scores was as bad as that of sepsis patients with low BSEEG scores. Even adjusting for age, gender, comorbidity, and sepsis status, BSEEG remained a significant predictor of mortality ( p  = 0.008). These data are demonstrating its usefulness as a potential tool for identification of patients at high risk and management of sepsis.