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ObjectiveTo determine the evolution of numerous neuropsychiatric symptoms and cognitive abilities in Parkinson disease from disease onset.MethodsProspectively 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.ResultsOf 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.InterpretationNeuropsychiatric features in Parkinson disease are common from the onset, increase over time, are frequently comorbid, and fluctuate in severity.

Background: Anxiety and depression are common non‐motor symptoms in Parkinson's disease (PD) but remain under‐recognized and under‐treated. Objectives: To evaluate functional outcomes associated with baseline anxiety or depression and effects related to the initiation of new psychiatric treatment. Methods: We analyzed 7 years of data from patients with de novo PD enrolled in the Parkinson's Progression Markers Initiative. Longitudinal regression models evaluated the association between baseline anxiety and depression with Schwab and England (SE) and MDS‐UPDRS total scores over time. Cox proportional hazard models assessed effects of baseline anxiety and depression on time to initiation of dopaminergic therapy. Piecewise linear regression models examined the association of treatment initiation for anxiety and depression with SE and MDS‐UPDRS. Results: 490 participants with baseline depression and anxiety data were included. Anxiety and depression were associated with lower SE (anxiety: β = −1.31, P = 0.038, depression: β = −1.96, P = 0.012, co‐morbid: β = −2.70, P = 0.003) and higher MDS‐UPDRS scores (anxiety: β = 5.37, P < 0.001, depression: β = 9.17, P < 0.001, co‐morbid: β = 10.50, P < 0.001) longitudinally. Anxiety was associated with faster time to dopamine replacement therapy initiation (HR 1.30, 95% CI 1.03–1.66, P = 0.03). 16 participants with anxiety initiated treatment for anxiety, which was associated with subsequent lower levodopa daily dose (slope change = −218.49, P = 0.018). 10 participants with depression initiated treatment of depression, which was associated with reduced MDS‐UPDRS total scores (slope change = −8.3, P < 0.001) and higher SE scores (slope change = 5.99, P = 0.004). Conclusions: Anxiety and depression at PD onset are associated with multiple negative longitudinal trajectories. However, preliminary findings suggest that anxiety and depression treatment may be linked with improved motor and non‐motor outcomes. [ABSTRACT FROM AUTHOR]

The article discusses the importance of addressing mental health issues such as depression and anxiety in Parkinson's disease patients. It emphasizes the need for comprehensive clinical evaluations and systematic longitudinal assessments to understand the impact of neuropsychiatric complications and their treatment. The study employed statistical techniques like multiple imputation and the generalized estimation equation method to manage missing data and ensure unbiased estimates. While the study had limitations due to data availability and sample size, it highlights the significance of further research to confirm findings and improve the management of psychiatric symptoms in Parkinson's disease. [Extracted from the article]

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 play an important role in the pathophysiological mechanism of delirium and suggest the potential usefulness of an epigenetics‐based biomarker of POD. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Purpose: Metformin has been reported to improve age-related disorders, including dementia, and to lower mortality. This study was conducted to investigate whether metformin use lower delirium risk, as well as long-term mortality., Methods: In this retrospective cohort study, previously recruited 1,404 subjects were analyzed. The relationship between metformin use and delirium, and the relationship between metformin use and 3-year mortality were investigated., Main Findings: 242 subjects were categorized into a type 2 diabetes mellitus (DM)-without-metformin group, and 264 subjects were categorized into a DM-with-metformin group. Prevalence of delirium was 36.0% in the DM-without-metformin group, and 29.2% in the DM-with-metformin group. A history of metformin use reduced the risk of delirium in patients with DM (OR, 0.50 [95% CI, 0.32 to 0.79]) after controlling for confounding factors. The 3-year mortality in the DM-without-metformin group (survival rate, 0.595 [95% CI, 0.512 to 0.669]) was higher than in the DM-with-metformin group (survival rate, 0.695 [95% CI, 0.604 to 0.770]) (p=0.035). A history of metformin use decreased the risk of 3-year mortality after adjustment for confounding factors (HR, 0.69 [95% CI, 0.48 to 0.98])., Conclusions: Metformin use may lower the risk of delirium and mortality in DM patients.

Complications of delirium and dementia increase mortality; however, it is difficult to diagnose delirium accurately, especially among dementia patients. The bispectral electroencephalography score can detect delirium and predict mortality in elderly patients. We aimed to develop an efficient and reliable bispectral electroencephalography device for high-throughput screening. We also hypothesized that bispectral electroencephalography score can predict mortality among dementia patients. A prospective cohort study was conducted between January 2016 and December 2018 to measure bispectral electroencephalography from elderly patients and correlate with outcomes. A total of 502 elderly (55 years old or older) patients with and without dementia were enrolled. For a replication of the utility of bispectral electroencephalography, mortalities between bispectral electroencephalography-positive and bispectral electroencephalography-negative group were compared. In addition, patients with and without dementia status were added to examine the utility of bispectral electroencephalography among dementia patients. The mortality within 180 days in the bispectral electroencephalography-positive group was higher than that of the bispectral electroencephalography-negative group in both the replication and the total cohorts. Mortality of those in the bispectral electroencephalography-positive group showed a dose-dependent increase in both cohorts. When the dementia patients showed bispectral electroencephalography positive, their mortality was significantly higher than those with dementia but who were bispectral electroencephalography-negative. Mortality within 30 days in the bispectral electroencephalography-positive group was significantly higher than that of the bispectral electroencephalography-negative group. The utility of the bispectral electroencephalography to predict mortality among large sample of 502 elderly patients was shown. The bispectral electroencephalography score can predict mortality among elderly patients in general, and even among dementia patients, as soon as 30 days., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Delirium is common and dangerous, yet underdetected and undertreated. Current screening questionnaires are subjective and ineffectively implemented in busy hospital workflows. Electroencephalography (EEG) can objectively detect the diffuse slowing characteristic of delirium, but it is not suitable for high-throughput screening due to size, cost, and the expertise required for lead placement and interpretation. This study hypothesized that an efficient and reliable point-of-care EEG device for high-throughput screening could be developed., Methods: This prospective study, which measured bispectral EEG (BSEEG) from elderly inpatients to assess their outcomes, was conducted at the University of Iowa Hospitals and Clinics from January 2016 to October 2017. A BSEEG score was defined based on the distribution of 2,938 EEG recordings from the 428 subjects who were assessed for delirium; primary outcomes measured were hospital length of stay, discharge disposition, and mortality., Results: A total of 274 patients had BSEEG score data available for analysis. Delirium and BSEEG score had a significant association (P < .001). Higher BSEEG scores were significantly correlated with length of stay (P < .001 unadjusted, P = .001 adjusted for age, sex, and Charlson Comorbidity Index [CCI] score) as well as with discharge not to home (P < .01). Hazard ratio for survival controlling for age, sex, CCI score, and delirium status was 1.35 (95% CI,1.04 to 1.76; P = .025)., Conclusions: In BSEEG, an efficient and reliable device that provides an objective measurement of delirium status was developed. The BSEEG score is significantly associated with pertinent clinical outcomes of mortality, hospital length of stay, and discharge disposition. The BSEEG score better predicts mortality than does clinical delirium status. This study identified a previously unrecognized subpopulation of patients without clinical features of delirium who are at increased mortality risk., (© Copyright 2019 Physicians Postgraduate Press, Inc.)