Citations

Abstract The Alzheimer's Disease Neuroimaging Initiative (ADNI) recently celebrated its 20th anniversary, reflecting two decades of major contributions to Alzheimer's research through open data sharing and longitudinal multimodal assessments. This review synthesizes 122 high‐impact studies using ADNI data or biospecimens from 2023 to mid‐2025 to clarify mechanisms of Alzheimer's disease (AD) progression. Studies describe impairment of glymphatic clearance and the impact of cerebral small vessel disease, trajectories of amyloid beta and tau deposition, inflammation, metabolic disturbances, synaptic dysfunction, and neurodegeneration, leading to cognitive impairment and neuropsychiatric symptoms. Multifactorial contributions from genetic and epigenetic influences, co‐pathologies and comorbidities, and mechanisms of resilience modulate disease progression. Finally, heterogeneity of clinical presentation and disease course is described in the context of multiple contributing factors, highlighting the complexity of AD. By integrating imaging, fluid biomarkers, genetics, and clinical measures, ADNI provides a comprehensive research dataset for unraveling mechanisms underlying AD progression.

Objectives: The electroconvulsive therapy for the acute management of severe agitation in dementia (ECT-AD) trial is a multisite study evaluating the effectiveness of ECT for severe agitation in individuals with advanced dementia. Given that participants lack decisional capacity because of advanced cognitive impairment, the trial required a structured and ethically sound approach to obtaining informed consent and assent across jurisdictions with differing legal requirements, including Massachusetts, New York, Georgia, Minnesota, and Michigan. This paper describes the approach used in the study. Methods: We describe the consent framework developed for the ECT-AD trial, including procedures for identifying legally authorized representatives, complying with state-specific laws for ECT consent, obtaining surrogate consent for research participation, and assessing patient assent and dissent using a standardized tool. Conclusions: The approach used in this study may serve as a practical model for future research involving individuals without decision-making capacity and legally complex interventions such as ECT.

This secondary analysis of a nonrandomized clinical trial identifies which participant characteristics were associated with selection of centralized or remote trial engagement.

Abstract Background The Global Bipolar Cohort (GBC) was established to identify existing bipolar disorder (BD) cohorts worldwide and foster collaborations focused on descriptive and analytic outcomes relevant to BD. A distributed analytic framework has been implemented to engage multiple sites without the need for central data pooling. This report describes the GBC endeavor and global functional impairment patterns. Cross-cohort comparisons of functional correlates are limited by heterogeneous measures and data-sharing constraints. Large, culturally diverse comparisons are needed to distinguish broadly reproducible correlates from cohort-specific effects. Participating sites completed a 28-item descriptive survey covering diagnostic methods, cognition, genetics, treatment, functioning, and follow-up strategies. We implemented a harmonized local logistic regression model of dichotomized functional outcome and shared summary statistics only. Results We identified 69 cohorts across five continents. Thirty-seven cohorts contributed functional outcome analyses from 17,130 participants. Outcome measures included clinician-rated disability scales and social indicators such as employment and marital status. The proportion classified with poor functioning ranged from 16% to 77% (mean 50%). In 32 of 37 cohorts, the overall regression model significantly explained variance in functioning. Current depressive symptoms were the most robust and reproducible correlate of poor functional outcome: they were assessed in 29 cohorts, significant in 22 (75.8%), ranked among the top three correlates in 22, and were the top-ranked correlates in 19. Associations between depressive burden and poor functioning were observed across clinician-rated disability scales and work or social indicators, and across geographically diverse cohorts. Comorbid substance use disorder and medication-related variables were associated with poorer functioning in subsets of cohorts, whereas sex, ancestry, bipolar subtype, psychosis history, and premorbid IQ showed weak or inconsistent associations. Cognitive measures, available in a minority of regression models, showed modest and non-uniform effects. Conclusions Across heterogeneous international cohorts, current depressive symptom burden emerged as the most consistent correlate of poor functioning in bipolar disorder. These findings replicate earlier multisite work at a larger scale, show that protocol-based distributed analyses can identify reproducible clinical signals without sharing individual-level data, and support prioritizing detection and treatment of depressive symptoms when aiming to improve real-world functioning. Future work should expand longitudinal harmonization and representation of under-studied populations.

Abstract Background Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and are increasingly associated with cardiovascular toxicities, including myocarditis and accelerated atherosclerosis. While ICI myocarditis has received substantial attention, thrombotic complications remain underrecognized and may be difficult to distinguish from immune-mediated cardiac inflammation and cancer-related hypercoagulable state. We present a case of non-bacterial thrombotic endocarditis (NBTE) and myocardial microthrombi mimicking ICI myocarditis. Case summary A 76-year-old woman with metastatic adenosquamous lung carcinoma presented with progressive dyspnoea 3 weeks after initiating pembrolizumab. Pulmonary arterial and coronary imaging were unremarkable, but cardiac magnetic resonance imaging (MRI) showed late gadolinium enhancement (LGE) and myocardial oedema suggestive of ICI myocarditis. Chest computed tomography revealed inflammatory lung changes, and empirical corticosteroids were initiated with initial clinical improvement. One week later, brain MRI showed multifocal infarcts, and Doppler ultrasound identified bilateral lower extremity deep vein thromboses. Transoesophageal echocardiography showed thickened mitral and aortic valves with moderate regurgitation. Non-bacterial thrombotic endocarditis with embolic phenomena was suspected. Anticoagulation was escalated from apixaban to therapeutic enoxaparin, followed by warfarin. Despite initial stabilization, the patient died 2 months later. Post-mortem examination revealed fibrin-rich valvular vegetations consistent with NBTE, widespread intramyocardial thrombi, and no histopathologic evidence of myocarditis. Discussion This case underscores how microthrombotic complications of ICI therapy may closely mimic myocarditis on imaging. Nonspecific cardiac MRI findings, such as LGE and T2 signal elevation, can result from thrombotic or ischaemic injury alike. Histopathologic confirmation may be required for accurate diagnosis, as misclassification can lead to suboptimal treatment.

Abstract Introduction Chronic and episodic headaches have a strong bidirectional relationship with insomnia and poor sleep outcomes. AM (morning) headaches are common among chronic pain populations, but additional research is needed to understand their pain experiences and potentially inform targeted interventions. Herein, we investigated whether presence of AM headaches is associated with differences in diary-based sleep parameters and pain ratings in women with pain and sleep complaints. We hypothesize individuals with AM headaches will have more sleep disturbances and fatigue as well as greater pain intensity and unpleasantness. Methods Women (N=293, Mage=39.59, SD 12.65, 65% with morning headaches) reporting insomnia and pain complaints (65% also reporting morning headaches) were recruited in mid-Missouri for an RCT (R01NR017168, ClinicalTrials.gov Identifier: NCT03744156). During baseline assessment, participants completed 2 weeks of daily electronic diaries and reported AM headache presence (Y/N). Independent samples t-tests (SPSS) evaluated differences in sleep parameters and pain ratings in those with and without AM headaches. Participants reporting diagnosed sleep apnea were excluded. Results Morning fatigue was higher among individuals with AM headaches (M=54.72+/-18.25) than those without (M=50.02+/-19.12), t(291)=-2.07, p=.04. Pain intensity was greater in the AM headache group in the morning (M=47.65+/-19.73 vs. M=42.52+/-21.91), t(291)=-2.04, p=.042, and evening, (M=49.62+/-19.10 vs. M=44.23+/-20.66), t(283)=-2.21, p=.028. Evening pain unpleasantness was also rated as higher among those with AM headaches (M=45.90+/-19.55) compared to those without (M=40.82+/-22.52), t(283)=-1.99, p=.048, but morning pain unpleasantness ratings only trended towards significance. Conclusion AM headaches can present as a chronic condition or as a symptom of other sleep disorders. Individuals with AM headaches had minimal sleep differences overall, but morning fatigue, pain intensity (AM and PM), and evening pain unpleasantness ratings were all significantly greater in those with AM headaches. Undiagnosed sleep disorders other than insomnia (i.e., obstructive sleep apnea) or other health concerns, like increased intracranial pressure, may have contributed to pain-related findings. Considering the high prevalence of COMISA in chronic pain populations, further investigation should examine its impact on sleep and headache severity. Support (if any) National Institute of Nursing Research (NR017168; Clinical trial: NCT03744156; PI: McCrae).

Abstract Introduction Individuals with ostomies commonly report poor sleep quality years after ostomy surgery; however, little is known about the trajectory of insomnia and objective sleep characteristics in the early postoperative period. The purpose of this study was to describe the trajectory of insomnia and sleep characteristics in the first 3 months following ileostomy surgery. Methods We conducted a prospective, observational feasibility study of adults (18-65 years) undergoing ileostomy surgery. Sleep characteristics were obtained via Garmin smartwatches (vívosmart® 5) worn from 2 weeks to 3 months postoperatively. The Insomnia Severity Index (ISI) was used to elicit insomnia severity perioperatively and at postoperative months 1, 2, and 3. Descriptive and univariate statistics were used. Results We enrolled 22 participants [Mean age 41.55 years (SD 10.77), 10 female (45.5%), 19 White (86.4%), 9 colorectal cancer (40.9%), and 8 inflammatory bowel disease (36.3%)]. There was little change in insomnia severity from the perioperative period (mean = 9.95, SD 5.57) to 3 months after surgery (∆ = 0.76). At the time of ostomy surgery, most participants (n = 13, 59.1%) had insomnia (ISI≥8). Fifteen participants completed the postoperative surveys. Of those, 2 participants (13.3%) experienced resolution of insomnia symptoms, 3 participants (20%) continued to report no insomnia symptoms, 5 participants (33.3%) developed new insomnia symptoms, and 5 (33.3%) experienced persistent insomnia symptoms. There was little change in sleep duration (m = 462.10 min, SD = 79.07, ∆ = -24.1), deep sleep (m = 81.21 min, SD = 16.97, ∆ = -8.01), light sleep (m = 297.93 min, SD = 44.26, ∆ = -3.93), REM sleep (m = 82.82 min, SD = 44.50, ∆ = -12.02), wake after sleep onset (m = 51.87 min, SD = 29.93, ∆ = -3.05), or sleep score out of 100 (m = 59.15, SD = 11.83, ∆ = -1.74) from month 1 to month 3 after surgery. Conclusion Individuals undergoing ileostomy surgery experience symptoms of insomnia which often persist throughout the early postoperative period. Future research should explore the impact of insomnia on ostomy outcomes and should test interventions to treat insomnia in the early postoperative period. Support (if any) LabfrontXGarmin

Objective: To evaluate the effectiveness of a standardized hazardous medication surveillance program and identify occupational factors associated with adverse health outcomes among healthcare workers (HCWs). Methods: We analyzed data from 2,625 HCWs enrolled in a multi-site surveillance program (2020–2022). Participants completed a standardized questionnaire and underwent complete blood count testing. Exposure was categorized by weekly time handling hazardous medications. Associations were evaluated using univariate and multivariable analyses. Results: Higher exposure (>8 hours/week) was associated with increased symptom reporting, hazardous medication spills, and adverse reproductive outcomes. Female sex, older age, and spill exposure independently predicted symptom reporting and reproductive outcomes. No significant association was observed between exposure intensity and abnormal blood counts. Conclusion: Questionnaire-based surveillance effectively identified exposure-related health risks, whereas routine complete blood count testing showed limited utility.