Multimorbidity Pattern and Risk for Mortality Among Patients With Dementia: A Nationwide Cohort Study Using Latent Class Analysis

Objective@#Individuals with dementia are at a substantially elevated risk for mortality; however, few studies have examined multimorbidity patterns and determined the inter-relationship between these comorbidities in predicting mortality risk. @*Methods@#This is a prospective cohort study. Data from 6,556 patients who were diagnosed with dementia between 1997 and 2012 using the Taiwan National Health Insurance Research Database were analyzed. Latent class analysis was performed using 16 common chronic conditions to identify mortality risk among potentially different latent classes. Logistic regression was performed to determine the adjusted association of the determined latent classes with the 5-year mortality rate. @*Results@#With adjustment for age, a three-class model was identified, with 42.7% of participants classified as “low comorbidity class (cluster 1)”, 44.2% as “cardiometabolic multimorbidity class (cluster 2)”, and 13.1% as “FRINGED class (cluster 3, characterized by FRacture, Infection, NasoGastric feeding, and bleEDing over upper gastrointestinal tract).” The incidence of 5-year mortality was 17.6% in cluster 1, 26.7% in cluster 2, and 59.6% in cluster 3. Compared with cluster 1, the odds ratio for mortality was 9.828 (95% confidence interval [CI]=6.708–14.401; p<0.001) in cluster 2 and 1.582 (95% CI=1.281–1.953; p<0.001) in cluster 3. @*Conclusion@#Among patients with dementia, the risk for 5-year mortality was highest in the subpopulation characterized by fracture, urinary and pulmonary infection, upper gastrointestinal bleeding, and nasogastric intubation, rather than cancer or cardiometabolic comorbidities. These findings may improve decision-making and advance care planning for patients with dementia.

Inflammatory Bowel Disease and Neurodegenerative Diseases

A growing body of evidence has demonstrated an intricate association between inflammatory bowel disease (IBD) and neurodegenerative conditions, expanding beyond previous foci of comorbidities between IBD and mood disorders. These new discoveries stem from an improved understanding of the gut-microbiome-brain axis: specifically, the ability of the intestinal microbiota to modulate inflammation and regulate neuromodulatory compounds. Clinical retrospective studies incorporating large sample sizes and population-based cohorts have demonstrated and confirmed the relevance of IBD and chronic neurodegeneration in clinical medicine. In this review, we expound upon the current knowledge on the gut-microbiome-brain axis, highlighting several plausible mechanisms linking IBD with neurodegeneration. We also summarize the known associations between IBD with Parkinson disease, Alzheimer disease, vascular dementia and ischemic stroke, and multiple sclerosis in a clinical context. Finally, we discuss the implications of an improved understanding of the gut-microbiome-brain axis in preventing, diagnosing, and managing neurodegeneration among IBD and non-IBD patients.

Identifying Ketamine Responses in Treatment-Resistant Depression Using a Wearable Forehead EEG.

This study explores responses to ketamine in patients with treatment-resistant depression (TRD) using a wearable forehead electroencephalography (EEG) device. We recruited and randomly assigned 55 outpatients with TRD into three approximately equal-sized groups (A: 0.5-mg/kg ketamine; B: 0.2-mg/kg ketamine; and C: normal saline) under double-blind conditions. The ketamine responses were measured by EEG signals and Hamilton depression rating scale scores. At baseline, the responders showed significantly weaker EEG theta power than the non-responders (p < 0.05). Compared to the baseline, the responders exhibited higher EEG alpha power but lower EEG alpha asymmetry and theta cordance post-treatment (p < 0.05). Furthermore, our baseline EEG predictor classified the responders and non-responders with 81.3 ± 9.5% accuracy, 82.1 ± 8.6% sensitivity, and 91.9 ± 7.4% specificity. In conclusion, the rapid antidepressant effects of mixed doses of ketamine are associated with prefrontal EEG power, asymmetry, and cordance at baseline and early post-treatment changes. Prefrontal EEG patterns at baseline may serve as indicators of ketamine effects. Our randomized double-blind placebo-controlled study provides information regarding the clinical impacts on the potential targets underlying baseline identification and early changes from the effects of ketamine in patients with TRD.

Comparison of inflammatory cytokine levels among type I/type II and manic/hypomanic/euthymic/depressive states of bipolar disorder.

OBJECTIVE: Inflammatory cytokines have been suggested to be the trait or state markers of bipolar disorder, but with inconsistent results. This may be related to small sample sizes and poor control of some important confounding factors. METHODS: Gender/age-matched outpatients with bipolar disorder and normal controls were enrolled. The clinical symptoms were rated using the Montgomery Åsberg Depression Rating Scale and Young Mania Rating Scale. Inflammatory cytokines, including soluble interleukin-6 receptor (sIL-6R), soluble interleukin-2 receptor (sIL-2R), C-reactive protein (CRP), soluble tumor necrosis factor receptor type 1 (sTNF-R1), soluble P-selectin receptor (sP-selectin), and monocyte chemotactic protein-1 (MCP-1), were assessed by enzyme-linked immunosorbent assays. RESULTS: In total, 130 patients with bipolar disorder and 130 normal subjects were enrolled. Among the patients with bipolar disorder, 77 (59.2%) had bipolar I disorder, 53 (40.8%) had bipolar II disorder; 75 (57.7%) were in a euthymic state, 14 (10.8%) were in a manic/hypomanic state, and 41 (31.5%) were in a depressive state. The 130 bipolar patients had significantly higher levels of all cytokines than the normal controls (all p<0.0001). Using multivariate regression analysis with controlling of age, gender, BMI, smoking, duration of illness, and medication grouping, the patients with bipolar II disorder had significantly lower levels of sTNF-R1 than the patients with bipolar I disorder (p=0.038); the patients in a depressive state had significantly lower levels of sTNF-R1 than the patients in manic/hypomanic and euthymic states (p=0.009). CONCLUSION: The study supported the association of bipolar disorder with inflammatory dysregulation, and sTNF-R1 may be a potential biomarker for staging bipolar disorder.