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.

Background We have developed the bispectral electroencephalography (BSEEG) method for detection of delirium and prediction of poor outcomes. Aims To improve the BSEEG method by introducing a new EEG device. Method In a prospective cohort study, EEG data were obtained and BSEEG scores were calculated. BSEEG scores were filtered on the basis of standard deviation (s.d.) values to exclude signals with high noise. Both non-filtered and s.d.-filtered BSEEG scores were analysed. BSEEG scores were compared with the results of three delirium screening scales: the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), the Delirium Rating Scale-Revised-98 (DRS) and the Delirium Observation Screening Scale (DOSS). Additionally, the 365-day mortalities and the length of stay (LOS) in the hospital were analysed. Results We enrolled 279 elderly participants and obtained 620 BSEEG recordings; 142 participants were categorised as BSEEG-positive, reflecting slower EEG activity. BSEEG scores were higher in the CAM-ICU-positive group than in the CAM-ICU-negative group. There were significant correlations between BSEEG scores and scores on the DRS and the DOSS. The mortality rate of the BSEEG-positive group was significantly higher than that of the BSEEG-negative group. The LOS of the BSEEG-positive group was longer compared with that of the BSEEG-negative group. BSEEG scores after s.d. filtering showed stronger correlations with delirium screening scores and more significant prediction of mortality. Conclusions We confirmed the usefulness of the BSEEG method for detection of delirium and of delirium severity, and prediction of patient outcomes with a new EEG device.

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 longterm 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.

Importance: Metformin, an oral medication for type 2 diabetes mellitus (DM), has been reported to improve age-related disorders, including dementia, and to lower mortality. Objective: To investigate the relationship between history of metformin use and delirium risk, as well as long-term mortality. Design, setting, and participants: In this retrospective cohort study, subjects recruited in the University of Iowa Hospitals and Clinics between January 2016 and March 2020 were analyzed. Main outcomes and measures: Logistic regression analysis was performed to investigate the relationship between metformin use and delirium. Log-rank analysis and Cox proportional hazards model were used to investigate the relationship between metformin use and 3-year mortality. Results: The data from 1404 subjects (mean [SD] age, 68.6 [13.6] years; 48.7% female) were analyzed. 242 subjects (mean [SD] age, 69.9 [12.8] years; 45.5% female) were categorized into a DM-without-metformin group, and 264 subjects (mean [SD] age, 69.5 [10.0] years; 42.4% female) 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 age, sex, and dementia status, body mass index (BMI), and insulin use. 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 age, sex, Charlson Comorbidity Index, BMI, history of insulin use, and delirium status (HR, 0.69 [95% CI, 0.48 to 0.98]). Conclusions and relevance: In this cohort study, it was found that metformin usage was associated with decreased delirium prevalence and lower 3-year mortality. The potential benefit of metformin on delirium risk and mortality were shown, although true causal relationship needs to be examined in a future experimental trial.

Background: Metformin, a commonly prescribed anti-diabetic medication, has repeatedly been shown to hinder aging in pre-clinical models and to be associated with lower mortality for humans. It is, however, not well understood how metformin can potentially prolong lifespan from a biological standpoint. We hypothesized that metformin's potential mechanism of action for longevity is through its epigenetic modifications. Methods: To test our hypothesis, we conducted a post-hoc analysis of available genome-wide DNA methylation (DNAm) data obtained from whole blood collected from inpatients with and without a history of metformin use. We assessed the methylation profile of 171 patients (first run) and only among 63 diabetic patients (second run) and compared the DNAm rates between metformin users and nonusers. Results: Enrichment analysis from the Kyoto Encyclopedia of Genes and Genome (KEGG) showed pathways relevant to metformin's mechanism of action, such as longevity, AMPK, and inflammatory pathways. We also identified several pathways related to delirium whose risk factor is aging. Moreover, top hits from the Gene Ontology (GO) included HIF-1α pathways. However, no individual CpG site showed genome-wide statistical significance (p < 5E-08). Conclusion: This study may elucidate metformin's potential role in longevity through epigenetic modifications and other possible mechanisms of action.