Biomarkers.

Background: Emerging evidence underscores the significant influence of diet on risk for Alzheimer's disease and related dementias (ADRD). In particular, a Western dietary pattern associates with increased risk for ADRD, with proposed mediation via inflammatory mechanisms, among others. Although a Western dietary pattern associates with gut microbiome alterations, it remains unclear whether microbial alterations mediate Western diet-associated inflammation and neurodegeneration.

Biomarkers.

Background: Heavy alcohol consumption is associated with increased risk for Alzheimer's disease and related dementias (ADRD), with mixed evidence suggesting a dose-dependent nonlinear effect of alcohol on ADRD. Potential mechanisms by which alcohol may promote or attenuate brain pathology need further exploration. Although chronic alcohol consumption associates with gut microbiome alterations, it remains unclear whether microbial alterations mediate alcohol-associated neurodegeneration and cognitive decline.

Public Health.

Background: Little is known about how education in later life is related to cognitive function in older adults. This study assessed whether participating in later-life education was associated with better cognitive function over time and whether the benefits differed by sex, race/ethnicity, and prior education level in a nationally-representative sample of U.S.

Public Health.

Background: Many studies have demonstrated an association between sleep and cognition in older adults. The Long Life Family Study (LLFS) has followed families enriched with longevity since 2006 and has shown that this cohort has slower rates of cognitive decline than their spouse controls and the general public. Understanding how sleep and cognition are related in this population can improve our understanding of the key to long life.

Public Health.

Background: Although visual and hearing impairment have been identified as established risk factors for dementia, evidence was limited on the association of the coexistence of these two sensory impairments with incident dementia, especially in the U.S. The study aimed to examine the associations between sensory impairment and 10-year risk of dementia or Alzheimer's disease.

Public Health.

Background: Pesticide exposure may contribute to cognitive decline, but empirical evidence is limited. We examined high pesticide exposure events (HPEE) in relation to subjective cognitive decline among farmers in the Pesticide and Sense of Smell Study (PASS), a sub-cohort of the Agricultural Health Study (AHS).

Method: This analysis included 2365 predominantly white male farmers from Iowa and North Carolina (aged 70±10 years) who enrolled in AHS from 1993-1997 and participated in PASS in 2020-2021.

Biomarkers.

Background: Postoperative delirium (POD) is characterized by fluctuating attention after surgery and is associated with increased risk of developing Alzheimer's Disease (AD). While the neurophysiological changes that underlie POD and increased risk of AD are unclear, recent data has raised the possibility that an exaggerated brain response to anesthetics may be a biomarker for POD risk and preclinical AD-like pathology. Thus, we examined whether anesthetic-dose-adjusted intraoperative brain activity is associated with POD or preoperative brain vulnerabilities (preclinical AD-like pathology, preoperative inattention) that may contribute to risk of POD (and later AD).

Biomarkers.

Background: Subjective cognitive decline (SCD), or a person's perception of changes in their cognitive abilities, has been identified as a possible early marker of preclinical Alzheimer's disease (AD) in non-Hispanic Whites; however, research is lacking about the clinical utility of SCD in diverse populations. This study investigated the associations of self and informant reports of SCD, plasma biomarker profiles of AD, and objective cognitive performance in Hispanic older adults living in Miami.

Method: Hispanic participants enrolled in the 1Florida Alzheimer's Disease Research Center who completed neuropsychological testing and blood draws for biomarker analysis were eligible.

Biomarkers.

Background: Metabolomics captures net influences of exposome, diet, gut microbiome, and genome, informing about individuality and how we respond to interventions. Applications of metabolomics in pharmacology are starting to enable a Systems Pharmacology approach, where the outcome of a treatment is considered to evolve from effects on complex molecular networks, enabling insights into response variations. We bring the power of these approaches to the study of the MIND, a Mediterranean DASH diet for prevention of cognitive decline.

Biomarkers.

Background: The aim of this study was to identify a gut microbial signature associated with patterns of gray matter volume in AD, and to validate the microbial signature by testing it against measures of AD pathology and cognitive performance. Prior literature suggests that microbial species involved in bile acid production and inflammation may be implicated in the microbial signature.

Method: The sample comprised 204 Microbiome in Alzheimer's Risk Study participants (22 AD, 10 MCI, and 172 CN; 129 Females, 78 APOE+) from the Wisconsin Alzheimer's Disease Research Center and Wisconsin Registry for Alzheimer's Prevention.

Biomarkers.

Background: Increasingly, research participants in Alzheimer's studies are seeking disclosure of research results. However, there are no guidelines for result disclosure and specifically, few studies report on their biomarker disclosure procedure. The Duke/UNC ADRC seeks to disclose research results to participants in a standardized fashion with high participant satisfaction.

Biomarkers.

Background: While we do not yet have the means to detect early Alzheimer's disease (AD), studying subjects at risk conferred by the presence of the APOE4 allele, can provide useful information before clinical onset. We show that using symmetric bilinear regression with L1 penalty (SBL) of individual (DTI, fMRI) and fused connectomes, we can identify vulnerable regions changing in association with hallmark AD biomarkers measured in cerebrospinal fluid: amyloid beta Aβ42/40, phosphorylated tau (PTAU), and neurofibrillary light (NfL) as a proxy for neurodegeneration.

Methods: We use structural connectomes derived from diffusion-weighted MRI (DTI) and functional connectomes (fMRI) from 57 subjects, 45 normal controls and 12 cognitively impaired to predict CSF Aβ42/40, PTAU, and NfL to reflect neurodegeneration.

Developing Topics.

Background: Alzheimer's disease (AD) is a devastating form of dementia, and its prevalence is rising as human lifespan increases. Our lab created the AD-BXD mouse model, which expresses AD mutations across a genetically diverse reference panel (BXD), to identify factors that confer resilience to cognitive decline in AD. This model mimics key characteristics of human AD including variation in age of onset and severity of cognitive decline.

Developing Topics.

Background: The rapid development of blood-based biomarkers (BBMs) has improved Alzheimer's disease (AD) diagnostics with some tests now potentially suitable for clinical use. This aligns with the clinical availability of anti-Aβ immunotherapies for early symptomatic AD, where BBMs can help address the increasing need for more rapid and early diagnosis. Clinical practice guidelines (CPG) can help guide healthcare professionals in incorporating BBMs into their clinical practice.

Developing Topics.

Background: APOE4 leads to increased neuroinflammation, neurocognitive decline, increased risk of Alzheimer's disease, and may be associated with increased delirium risk. However, the safety and feasibility of pharmacologic modulation of APOE to prevent neuroinflammation and postoperative delirium is unclear.

Methods: We performed a Phase II, triple blind, escalating dose, randomized controlled trial to determine the safety, feasibility, and efficacy of the APOE mimetic peptide CN-105 for preventing postoperative neuroinflammation and delirium.

Dementia Care Research and Psychosocial Factors.

Background: African Americans (AA) are underrepresented in Alzheimer's disease (AD) brain donation research, making up approximately 2% of brain donations to the National Alzheimer's Coordinating Center (NACC). Focus groups were conducted to obtain qualitative information to expand upon survey data that was collected previously to gain additional insights into the attitudes of Black∖AA individuals toward brain donation and perceptions of medical research.

Method: A brain donation focus group facilitator guide was created based upon earlier survey findings.

Trends and disparities in cardiovascular disease-related mortality among adults with myeloproliferative neoplasms in USA.

Aims: We aimed to perform a retrospective cohort study using the Centers for Disease Control and Prevention's (CDC's) Wide-Ranging Online Data for Epidemiologic Research (WONDER) database to analyse the trends in cardiovascular disease (CVD)-related mortality in patients with myeloproliferative neoplasms (MPNs) from 1999 to 2020.

Methods And Results: We analysed the death certificate data from the CDC WONDER database from 1999 to 2020 for CVD with co-morbid myeloproliferative disorders in the US population. Age-adjusted mortality rates (AAMRs) and 95% confidence intervals (CIs) were computed per 1 million population by standardizing crude mortality rates to the 2000 US census population.

A scoping review on peer-led interventions to improve youth mental health in low- and middle-income countries.

Youth living in low- and middle-income countries (LMICs) have an increased vulnerability to mental illnesses, with many lacking access to adequate treatment. There has been a growing body of interventions using task sharing with trained peer leaders to address this mental health gap. This scoping review examines the characteristics, effectiveness, components of peer delivery and challenges of peer-led mental health interventions for youth aged 10-24 in LMICs.

Intracranial Gunshot Wounds: An Assessment of Patient Characteristics on Surgical Outcomes.

Background/objective: Intracranial gunshot wounds (GSW) are often fatal, with most patients dying before intervention can occur. Surgical management, when indicated, results in decreased mortality. We sought to assess the neurosurgical outcomes and economic costs of intracranial GSW.

Intraoperative right ventricular end-systolic pressure-volume loop analysis in patients undergoing cardiac surgery: A proof-of-concept methodology.

Background: Perioperative right ventricular (RV) dysfunction is associated with increased morbidity and mortality in cardiac surgery patients. This study aimed to demonstrate proof of concept in generating intraoperative RV pressure-volume (PV) loops and conducting an end-systolic PV relationship (ESPVR) analysis using data obtained from routinely used intraoperative monitors.

Methods: Adult patients undergoing cardiac surgery with the placement of a pulmonary artery catheter (PAC) between May 2023 and March 2024 were included prospectively.

Heart transplant survival and the use of donors with intracranial bleeding: United Network for Organ Sharing Registry propensity-score matched analysis.

Objective: The transplantation of hearts from donors who experienced intracranial bleeding (ICB) has been associated with inferior long-term survival in both single-center analyses and, more recently, with the United Network for Ogan Sharing Registry. The purpose of this study was to further explore this relationship through propensity score matching in recipients receiving donor hearts from ICB and non-ICB donors in a large national registry.

Methods: We performed a retrospective cohort analysis of the United Network for Organ Sharing Registry Organ Procurement and Transplantation Network between 2006 and 2018 for adult candidates wait-listed for isolated heart transplantation.

Gene signatures derived from transcriptomic-causal networks stratify colorectal cancer patients for effective targeted therapy.

Background: Gene signatures derived from transcriptomic-causal networks offer potential for tailoring clinical care in cancer treatment by identifying predictive and prognostic biomarkers. This study aimed to uncover such signatures in metastatic colorectal cancer (CRC) patients to aid treatment decisions.

Methods: We constructed transcriptomic-causal networks and integrated gene interconnectivity into overall survival (OS) analysis to control for confounding genes.

Functional evaluation and clinical classification of BRCA2 variants.

Germline BRCA2 loss-of function variants, which can be identified through clinical genetic testing, predispose to several cancers. However, variants of uncertain significance limit the clinical utility of test results. Thus, there is a need for functional characterization and clinical classification of all BRCA2 variants to facilitate the clinical management of individuals with these variants.

Microglia depletion reduces neurodegeneration and remodels extracellular matrix in a mouse Parkinson's disease model triggered by α-synuclein overexpression.

Chronic neuroinflammation with sustained microglial activation occurs in Parkinson's disease (PD), yet the mechanisms and exact contribution of these cells to the neurodegeneration remains poorly understood. In this study, we induced progressive dopaminergic neuron loss in mice via rAAV-hSYN injection to cause the neuronal expression of α-synuclein, which produced neuroinflammation and behavioral alterations. We administered PLX5622, a colony-stimulating factor 1 receptor inhibitor, for 3 weeks prior to rAAV-hSYN injection, maintaining it for 8 weeks to eliminate microglia.

Diuretic Potentiation Strategies in Acute Heart Failure.

Several trials have evaluated diuretic-based strategies to improve symptoms and outcomes in patients with acute heart failure (AHF). The authors sought to summarize the effect of different combination strategies on symptoms, physical signs, physiological variables, and outcomes in patients with AHF. Twelve trials were identified that assessed the addition of thiazide diuretics, sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists, vasopressin receptor antagonists, carbonic anhydrase inhibitors, or loop diuretic intensification to conventional therapy for AHF.