Current methods for screening and detecting delirium are not practical in clinical settings. We previously showed that a simplified EEG with bispectral electroencephalography (BSEEG) algorithm can detect delirium in elderly inpatients. In this study, we performed a post-hoc BSEEG data analysis using larger sample size and performed topological data analysis to improve the BSEEG method. Data from 274 subjects included in the previous study were analyzed as a 1st cohort. Subjects were enrolled at the University of Iowa Hospitals and Clinics (UIHC) between January 30, 2016, and October 30, 2017. A second cohort with 265 subjects was recruited between January 16, 2019, and August 19, 2019. The BSEEG score was calculated as a power ratio between low frequency to high frequency using our newly developed algorithm. Additionally, Topological data analysis (TDA) score was calculated by applying TDA to our EEG data. The BSEEG score and TDA score were compared between those patients with delirium and without delirium. Among the 274 subjects from the first cohort, 102 were categorized as delirious. Among the 206 subjects from the second cohort, 42 were categorized as delirious. The areas under the curve (AUCs) based on BSEEG score were 0.72 (1st cohort, Fp1-A1), 0.76 (1st cohort, Fp2-A2), and 0.67 (2nd cohort). AUCs from TDA were much higher at 0.82 (1st cohort, Fp1-A1), 0.84 (1st cohort, Fp2-A2), and 0.78 (2nd cohort). When sensitivity was set to be 0.80, the TDA drastically improved specificity to 0.66 (1st cohort, Fp1-A1), 0.72 (1st cohort, Fp2-A2), and 0.62 (2nd cohort), compared to 0.48 (1st cohort, Fp1-A1), 0.54 (1st cohort, Fp2-A2), and 0.46 (2nd cohort) with BSEEG. BSEEG has the potential to detect delirium, and TDA is helpful to improve the performance.

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

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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.