Cognitive reserve is associated with education, social determinants, and cognitive outcomes among older American Indians in the Strong Heart Study.

Cognitive reserve, a component of resilience, may be conceptualized as the ability to overcome accumulating neuropathology and maintain healthy aging and function. However, research measuring and evaluating it in American Indians is needed. We recruited American Indians from 3 regional centers for longitudinal examinations (2010-13, n = 818; 2017-19, n = 403) including MRI, cognitive, clinical, and questionnaire data.

Pharmacokinetic Interaction Between Olaparib and Regorafenib in an Animal Model.

Background: Olaparib (OLA) and regorafenib (REG) are metabolized by the CYP3A4 isoenzyme of cytochrome P450. Both drugs are also substrates and inhibitors of the membrane transporters P-glycoprotein and BCRP. Therefore, the potential concomitant use of OLA and REG may result in clinically relevant drug-drug interactions.

A Pharmacokinetic Study of the Interaction Between Regorafenib and Paracetamol in Male Rats.

: In clinical practice, the prevalent problem of polypharmacy could result in increased risks of drug-drug interactions. Regorafenib (REG) is commonly co-administered with paracetamol (PA) as a treatment protocol in cancer patients with pain therapy. : This study aimed to demonstrate the effect of paracetamol on the pharmacokinetic parameters of regorafenib and its metabolites following a single administration of both substances in rats.

Integrated multimodal cell atlas of Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia in older adults. Although AD progression is characterized by stereotyped accumulation of proteinopathies, the affected cellular populations remain understudied. Here we use multiomics, spatial genomics and reference atlases from the BRAIN Initiative to study middle temporal gyrus cell types in 84 donors with varying AD pathologies.

SEA-AD is a multimodal cellular atlas and resource for Alzheimer's disease.

The Seattle Alzheimer’s Disease Brain Cell Atlas (SEA-AD) is a multifaceted open data resource designed to identify cellular and molecular pathologies that underlie Alzheimer’s disease. Integrating neuropathology, single cell and spatial genomics, and longitudinal clinical metadata, SEA-AD is a unique resource for studying the pathogenesis of Alzheimer’s and related dementias.

Iterative Data-adaptive Autoregressive (IDAR) whitening procedure for long and short TR fMRI.

Introduction: Functional magnetic resonance imaging (fMRI) has become a fundamental tool for studying brain function. However, the presence of serial correlations in fMRI data complicates data analysis, violates the statistical assumptions of analyses methods, and can lead to incorrect conclusions in fMRI studies.

Methods: In this paper, we show that conventional whitening procedures designed for data with longer repetition times (TRs) (>2 s) are inadequate for the increasing use of short-TR fMRI data.

Algorithm-defined memory impairment in older American Indians: The Strong Heart Study.

Objective: Assessment of cognition in American Indians poses challenges, including barriers to healthcare, unvalidated clinical standards, and confounding social determinants of health. Alternative strategies for case identification include algorithmic methods, which can outperform clinical judgment in some circumstances.

Method: Algorithmic methods can be maximized using single-domain tests with multiple-serial trial tasks, such as the California Verbal Learning Test II-Short Form (CVLT-SF).

Unraveling Alzheimer's Disease: Investigating Dynamic Functional Connectivity in the Default Mode Network through DCC-GARCH Modeling.

Alzheimer's disease (AD) has a prolonged latent phase. Sensitive biomarkers of amyloid beta ( ), in the absence of clinical symptoms, offer opportunities for early detection and identification of patients at risk. Current biomarkers, such as CSF and PET biomarkers, are effective but face practical limitations due to high cost and limited availability.

Epidemiology and prevalence of dementia and Alzheimer's disease in American Indians: Data from the Strong Heart Study.

Introduction: Accurate epidemiologic estimates for dementia are lacking for American Indians, despite substantive social and health disparities.

Methods: The Strong Heart Study, a population-based cohort of 11 American Indian tribes, conducted detailed cognitive testing and examinations over two visits approximately 7 years apart. An expert panel reviewed case materials for consensus adjudication of cognitive status (intact; mild cognitive impairment [MCI]; dementia; other impaired/not MCI) and probable etiology (Alzheimer's disease [AD], vascular bain injury [VBI], traumatic brain injury [TBI], other).

Multiomics Blood-Based Biomarkers Predict Alzheimer's Predementia with High Specificity in a Multicentric Cohort Study.

Background: The primary criteria for diagnosing mild cognitive impairment (MCI) due to Alzheimer's Disease (AD) or probable mild AD dementia rely partly on cognitive assessments and the presence of amyloid plaques. Although these criteria exhibit high sensitivity in predicting AD among cognitively impaired patients, their specificity remains limited. Notably, up to 25% of non-demented patients with amyloid plaques may be misdiagnosed with MCI due to AD, when in fact they suffer from a different brain disorder.

Assessment of omeprazole and famotidine effects on the pharmacokinetics of tacrolimus in patients following kidney transplant-randomized controlled trial.

Tacrolimus is metabolized in the liver with the participation of the CYP3A4 and CYP3A5 enzymes. Proton pump inhibitors are used in kidney transplant patients to prevent duodenal and gastric ulcer disease due to glucocorticoids. Omeprazole, unlike famotidine, is a substrate and inhibitor of the enzymes CYP2C19, CYP3A4, CYP3A5.

Bidirectional pharmacokinetic drug interactions between olaparib and metformin.

Objective: Olaparib is a PARP (poly-ADP-ribose polymerase) inhibitor used for maintenance therapy in BRCA-mutated cancers. Metformin is a first-choice drug used in the treatment of type 2 diabetes. Both drugs are commonly co-administered to oncologic patients with add-on type 2 diabetes mellitus.

Integrated multimodal cell atlas of Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia in older adults. Neuropathological and imaging studies have demonstrated a progressive and stereotyped accumulation of protein aggregates, but the underlying molecular and cellular mechanisms driving AD progression and vulnerable cell populations affected by disease remain coarsely understood. The current study harnesses single cell and spatial genomics tools and knowledge from the BRAIN Initiative Cell Census Network to understand the impact of disease progression on middle temporal gyrus cell types.

Pandemic-driven changes in the nearshore non-commercial fishery in Hawai'i: catch photos posted to social media capture changes in fisher behavior.

Using social media, we collect evidence for how nearshore fisheries are impacted by the global COVID-19 pandemic in Hawai'i. We later confirm our social media findings and obtain a more complete understanding of the changes in nearshore non-commercial fisheries in Hawai'i through a more conventional approach-speaking directly with fishers. Resource users posted photographs to social media nearly three times as often during the pandemic with nearly double the number of fishes pictured per post.

Protocol for the Systematic Fixation, Circuit-Based Sampling, and Qualitative and Quantitative Neuropathological Analysis of Human Brain Tissue.

Human brain tissue has long been a critical resource for neuroanatomy and neuropathology, but with the advent of advanced imaging and molecular sequencing techniques, it has become possible to use human brain tissue to study, in great detail, the structural, molecular, and even functional underpinnings of human brain disease. In the century following the first description of Alzheimer's disease (AD), numerous technological advances applied to human tissue have enabled novel diagnostic approaches using diverse physical and molecular biomarkers, and many drug therapies have been tested in clinical trials (Schachter and Davis, Dialogues Clin Neurosci 2:91-100, 2000). The methods for brain procurement and tissue stabilization have remained somewhat consistently focused on formalin fixation and freezing.

Göttingen pigs as a potential model for natalizumab pharmacokinetics, pharmacodynamics, and immunogenicity evaluation.

Natalizumab is a recombinant, humanized form of a monoclonal antibody that binds to CD49d. The presented study was conducted to explore the suitability of Göttingen pigs as a pharmacokinetic/pharmacodynamic model in the preclinical phase of biosimilar natalizumab development. The minipigs were treated with 1.

Educational and Clinical Associations With Longitudinal Cognitive Function and Brain Imaging in American Indians: The Strong Heart Study.

Background And Objectives: Little is known about incidence of vascular and Alzheimer dementias in American Indians.

Methods: We conducted a large, heterogeneous, population-based, longitudinal cohort study of brain aging in community-dwelling American Indians aged 64-95 years from 11 tribes across 3 states, with neurologic examinations, 1.5T MRI, and extensive cognitive testing.

Brain-Aware Replacements for Supervised Contrastive Learning in Detection of Alzheimer's Disease.

We propose a novel framework for Alzheimer's disease (AD) detection using brain MRIs. The framework starts with a data augmentation method called Brain-Aware Replacements (BAR), which leverages a standard brain parcellation to replace medically-relevant 3D brain regions in an anchor MRI from a randomly picked MRI to create synthetic samples. Ground truth "hard" labels are also linearly mixed depending on the replacement ratio in order to create "soft" labels.

Effects of Bisphenol A and Bisphenol F on Porcine Uterus Contractility.

Introduction: Bisphenols, as endocrine disruptors, may cause a wide range of health problems in humans, but so far, not all of them have been confirmed in animals, including pigs. Since animals are also exposed to bisphenols, we hypothesised that these substances may have an effect on uterine contractility in pigs. Therefore, the aim of the study was to investigate the effect of the most-used bisphenol, bisphenol A (BPA), and a selected analogue, bisphenol F (BPF), on the contractile activity of the pig uterus.

Prediction of Naming Outcome With fMRI Language Lateralization in Left Temporal Epilepsy Surgery.

Background And Objectives: Naming decline after left temporal lobe epilepsy (TLE) surgery is common and difficult to predict. Preoperative language fMRI may predict naming decline, but this application is still lacking evidence. We performed a large multicenter cohort study of the effectiveness of fMRI in predicting naming deficits after left TLE surgery.

Increased Basal Ganglia Modulatory Effective Connectivity Observed in Resting-State fMRI in Individuals With Parkinson's Disease.

Alterations to interactions between networked brain regions underlie cognitive impairment in many neurodegenerative diseases, providing an important physiological link between brain structure and cognitive function. Previous attempts to characterize the effects of Parkinson's disease (PD) on network functioning using resting-state functional magnetic resonance imaging (rs-fMRI), however, have yielded inconsistent and contradictory results. Potential problems with prior work arise in the specifics of how the area targeted by the diseases (the basal ganglia) interacts with other brain regions.