Digital Commons Network^™

Prediction Of Continuous Amyloid Positron Emission Tomography With Fluid Measures Of Phosphorylated Tau And Β-Amyloid, Niklas Mattsson-Carlgren, Linda Karlsson, Weizhong Tang, Kaj Blennow, Henrik Zetterberg, Randall J Bateman, Suzanne E Schindler, Nicolas Barthelemy, Sebastian Palmqvist, Erik Stomrud, Shorena Janelidze, Oskar Hansson

2020-Current year OA Pubs

Brain amyloid-β (Aβ) pathology is a core feature of Alzheimer disease (AD) and can be quantified using positron emission tomography (PET). Cerebrospinal fluid (CSF) and plasma biomarkers detect abnormal Aβ, but it is unclear to what degree they can predict quantitative Aβ-PET. We explored plasma and CSF biomarkers in relation to Aβ-PET in the BioFINDER-2 study (N = 1053), and the BioFINDER-1 study (N = 238). We developed a machine learning pipeline to predict Aβ-PET using CSF and plasma measures. The best models achieved R

Application Of Machine Learning To Blood-Based Biomarkers Of Alzheimer's Disease In Down Syndrome, Patrick H Luckett, Melissa Petersen, Sid O'Bryant, Mark Mapstone, Brad T Christian, Benjamin Handen, Elizabeth Head, Beau M Ances, Alzheimer's Biomarker Consortium‐Down Syndrome

2020-Current year OA Pubs

INTRODUCTION: Blood-based biomarkers can improve Alzheimer's disease (AD) characterization in Down syndrome (DS). This study applied hierarchical clustering and machine learning-based feature selection to identify biomarkers associated with disease progression.

METHODS: Cross-sectional blood-based biomarkers were analyzed from 211 DS participants (

RESULTS: The strongest predictors overall were neurofilament light chain (NfL), tau/amyloid beta (Aβ)40, Aβ42/Aβ40, alpha-2-macroglobulin (A2M), and interleukin (IL)-10. Within the CS group, NfL, tau/Aβ40, A2M, and IL-10 were strong predictors. In MCI, Aβ42/Aβ40, NfL, A2M, and IL-10 were strong predictors. In DS-AD, Aβ42/Aβ40, NfL, and tau/Aβ40 were the top predictors. Cluster membership varied based on disease stage.

DISCUSSION: …

Perception Of Dementia Risk Among Black Adults: An Ecological Analysis Of Causal Loop Diagrams With A Structural And Social Determinant Of Health Composite Index, Jean-Francois Trani, Ramkrishna K Singh, Alexis Ib Walker, Semere Bekena, Yiqi Zhu, Ganesh M Babulal, Robbie Hart

2020-Current year OA Pubs

INTRODUCTION: To investigate drivers of dementia risk disparities among older Black Americans using a community-based system dynamics (CBSD) approach.

METHODS: Over 18 months, 234 participants created 36 causal loop diagrams (CLDs) on dementia risk. An ecological analysis compared structural differences across groups based on scores on a structural and social determinants of health composite index (S/SDOH-CI).

RESULTS: Groups in the highest SDOH-CI quantile were more likely to identify key protective pathways linking mental health, substance use, exercise, medication, and community support to reduce dementia risk. In contrast, fewer than 25% of low-SDOH-CI groups identified these connections, and under 15% recognized …

Towards Precision Functional Brain Network Mapping In Parkinson's Disease, Jacob Chernicky, Ally Dworetsky, Sarah Grossen, Emma Carr, Abdulmunaim Eid, Meghan C Campbell, Caterina Gratton

2020-Current year OA Pubs

BACKGROUND: Parkinson's disease (PD) is a complex neurodegenerative condition that leads to widespread disruption of large-scale brain networks and is further complicated by substantial individual variability in symptomology, progression rates, and treatment response. Consequently, the investigation of individual differences in networks measured via resting state functional connectivity (RSFC) may provide insight. However, most RSFC studies are unable to identify interindividual differences due to poor reliability and group average network definitions. "Precision" RSFC addresses these shortcomings through extended data collection, strict denoising, and individual network definition, but remains untested in PD.

OBJECTIVES: To evaluate the feasibility and reliability of precision RSFC …

Novel Insights Into Early Alzheimer's Disease: Quantitative Gradient Recalled Echo Mri Reveals Preatrophic Neuronal And Myelin Injury Concurrent With Emerging Amyloid Pathology, Satya V V N Kothapalli, Tammie L S Benzinger, Randall J Bateman, Melody Li, Cihat Eldeniz, John C Morris, Dmitriy A Yablonskiy

2020-Current year OA Pubs

BACKGROUND: Brain amyloid accumulation is considered an early sign of Alzheimer's disease (AD) pathology, appearing decades before manifestation of clinical symptoms. However, very little is known about neurodegeneration during this early AD stage. Herein we use quantitative gradient recalled echo (qGRE) magnetic resonance imaging (MRI) to reveal preatrophic microstructural neuronal and myelin damage concurrent with amyloid pathology.

METHODS: qGRE MRI and positron emission tomography (PET) amyloid [

RESULTS: qGRE detected significantly lower gray matter neuronal density and white matter myelination in the group of participants with amyloid level below the conventional amyloid-positive threshold (mean cortical standardized uptake value ratio of …

Biological Aging Acceleration In Major Depressive Disorder: A Multi-Omics Analysis, Breno Satler Diniz, Shangshu Zhao, Gabin Drouard, Eero Vuoksimaa, Miina Ollikainen, Eric J Lenze, Ming Xu, Richard H Fortinsky, George A Kuchel, Jaakko Kaprio, Chia-Ling Kuo

2020-Current year OA Pubs

Major depressive disorder (MDD) is linked to a higher risk of premature aging, but the mechanisms underlying this association remain unclear. Using data from two population cohorts (UK Biobank and Finnish Twin Cohort), we evaluate the relationship between systemic and organ-specific proteomic and epigenetic aging acceleration and MDD. A lifetime history of MDD was associated with accelerated proteomic aging at both systemic and organ-specific levels-including the brain-in both cohorts, with stronger associations than those observed with systemic epigenetic aging. Systemic and brain-specific proteomic aging acceleration were linked to higher risks of incident MDD and a greater risk of Alzheimer's disease, …

Excellent Survival Following Low-Intensity Approaches Prior To Allo-Hsct In Ph+ All: A Comprehensive Meta-Analysis, Lacey S. Williams, Wenners Ballard Iii, Deniz Ozisik, Charles Scott Dorris, Kepher Makambi, Scott Rowley, Kieron Dunleavy, John Dipersio, Alaa Ali

2020-Current year OA Pubs

No abstract provided.

Comparison Of Positive Dysphotopsia Rates Between Au00t0, Mx60e, Pcb00/Zcb00, And Sn60wf Intraocular Lenses, Jonathan L. Tong, Maggie J. Xing, Arsham Sheybani

2020-Current year OA Pubs

No abstract provided.

Reliability Of Remote Self-Administered Web-Based Digital Cognitive Measures And Comparison To In-Person Neuropsychological Tests: Stricker Learning Span, Symbols Test, And The Mayo Test Drive Screening Battery Composite, Morgan A Hughes, Jason Hassenstab, Et Al.

2020-Current year OA Pubs

INTRODUCTION: We describe the reliability of remote self-administered digital cognitive measures completed via the Mayo Test Drive (MTD) web-based platform.

METHODS: A total of 1846 participants (mean age = 70, SD = 12, range 31-101; 48% male; 96% White; 99% non-Hispanic; 97% cognitively unimpaired) with two to four complete MTD sessions at ∼7.5-month intervals were included. Test-retest reliability was assessed using single-rating, absolute-agreement, and two-way mixed intraclass correlation coefficients (ICCs) with 95% confidence intervals. ICCs for in-person-administered traditional neuropsychological measures were compared to MTD for a subset of 244 participants. Analyses also compared reliability across demographic, residential, and session context …

The Association Between Major Depressive Disorder, Plasma Biomarkers Of Alzheimer's Disease, And Mild Behavioral Impairment Among Older Adults, Yiqi Zhu, Jean-Francois Trani, Ramkrishna K Singh, Semere Bekena, Jonathan Williams, Eric J Lenze, Ganesh M Babulal

2020-Current year OA Pubs

INTRODUCTION: Plasma biomarkers and mild behavioral impairment (MBI) are associated with dementia risk, but their relationships with major depressive disorder (MDD) are understudied. This study aimed to examine associations between plasma biomarkers of Alzheimer's disease (AD) and MBI among older adults with and without MDD.

METHODS: Older adults aged ≥65 were recruited from longitudinal studies of depression and AD (

RESULTS: Older adults with MDD were more likely to endorse MBI. After adjustment, Aβ42/Aβ40 and p-tau217/np-tau217 positivity were associated with MBI among those with MDD but not among those without.

DISCUSSION: Neuropsychatric symptoms (NPS) and biomarkers are AD risk factors. …

The Impact Of Congenital Heart Disease On The Timing Of Alzheimer's Disease In Down Syndrome, Julianne G Clina, Beau Ances, Et Al.

2020-Current year OA Pubs

INTRODUCTION: The incidence of Alzheimer's disease (AD) in Down syndrome (DS) exceeds 90%. Approximately 50% of people with DS have congenital heart disease (CHD). Having CHD increases risk for early-onset AD in populations without DS, but it is unclear if CHD influences AD in DS.

METHODS: Data from the Alzheimer Biomarker Consortium-Down Syndrome (ABC-DS) were used. Participants with CHD (

RESULTS: People with CHD scored lower for visuospatial ability (

DISCUSSION: Presence of CHD may influence AD progression in DS.

HIGHLIGHTS: In adults with Down syndrome (DS), those with congenital heart disease (CHD) had higher amyloid beta and reached the …

Antihypertensive Medications And Risk Of Alzheimer's Disease: Evidence For Specific Medication Use, Osvaldo J. Laurido-Soto, Alejandra Camacho-Soto, Irene M. Faust, Kassu M. Beyene, Aaron Katz, Jordan A. Killion, Brad A. Racette

2020-Current year OA Pubs

No abstract provided.

Criterion And Convergent Validity Of Plasma Biomarkers In Early-Onset Alzheimer's Disease: Initial Findings From Leads, Dustin B Hammers, Kyle Womack, Erik Musiek, Et Al.

2020-Current year OA Pubs

No abstract provided.

Alzheimer's Disease Stage 1 And 2: Biology, Diagnostics, And Treatment, Suzanne E. Schindler, Sarah M. Hartz, Et Al.

2020-Current year OA Pubs

No abstract provided.

Eligibility For Anti-Amyloid Treatment In A Multiethnic Community-Based Study, Lydia Trudel, Joseph Therriault, Arthur C Macedo, Karin L Meeker, Meredith N Braskie, Arthur W Toga, Serge Gauthier, Paolo Vitali, Suzanne E Schindler, Sid E O'Bryant, Pedro Rosa-Neto

2020-Current year OA Pubs

INTRODUCTION: The approval of anti-amyloid monoclonal antibodies (mAbs), including lecanemab and donanemab, represents a significant advance in disease-modifying therapies (DMTs) for early Alzheimer's disease (AD). While appropriate use recommendations (AURs) have been established to guide clinical decision-making, the proportion of individuals with cognitive impairment in real-world, multiethnic populations meeting eligibility criteria remains unknown, as do potential differences in treatment-related risks across ethnic groups.

METHODS: We included 513 cognitively impaired individuals from the Health and Aging Brain Study-Health Disparities study, a multiethnic community-based cohort. Eligibility for lecanemab and donanemab was determined using published AUR criteria. Counts of amyloid-related imaging abnormalities were …

Plasma P-Tau217 And Apoe Genotype: Prodromal Alzheimer's Disease Staging, Ann M Stowe, Ellen Binder, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Plasma phosphorylated tau (p-tau)217 levels and apolipoprotein E (

METHODS: We measured

RESULTS: Plasma p-tau217 was 57% higher in subjects with at least one

DISCUSSION: Plasma p-tau217 demonstrated elevation in the

Effect Of A Pregnancy Lifestyle Intervention Embedded Into A Home Visiting Program On Child Neurodevelopment, Sarah S Farabi, Rosemary Bass, Amit Mathur, Cindy Schwarz, Candice Woolfolk, Richard Stein, Samuel Klein, Debra Haire-Joshu, Alison G Cahill

2020-Current year OA Pubs

Maternal obesity is associated with a higher risk of abnormal child neurodevelopment. The aim of this study was to determine the effect of a lifestyle intervention embedded into a home visiting program, Parents as Teachers (PAT), on 18-month neurodevelopment in the offspring. Pregnant women (9-15 weeks) of African American Race, 18-45 years old, first-trimester BMI 25.0-45.0 kg/m

Rationale And Trial Design Of Ribolaris: A Phase Ii Trial Of Neoadjuvant And Adjuvant Ribociclib Plus Endocrine Therapy For Clinically High-Risk Hr+/Her2-Negative Breast Cancer, Paul Cottu, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite advances in endocrine therapy, patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) early breast cancer (eBC) remain at risk of recurrence (ROR). Chemotherapy is often used in high-risk cases, but not all patients benefit.

OBJECTIVES: To evaluate whether chemotherapy can be safely omitted in patients with stage II, grade 2/3 HR+/HER2- eBC who convert to low genomic risk (ROR-low) following neoadjuvant ribociclib plus letrozole.

METHODS: RIBOLARIS (NCT05296746) is an open-label, multicenter phase II trial in patients with stage II, grade 2 or 3, HR+/HER2- eBC defined as high risk based on a Ki-67 index ⩾20% …

The Role Of Home Visiting In Addressing Postpartum Care Gaps: Evidence From A Large Community Sample, Aishwarya Vijay, Allison Kemner, Karen Hoerchler, Abigail Edwards, Jeannie C Kelly, Rachel G Tabak, Mark D Huffman, Zainab Mahmoud

2020-Current year OA Pubs

BackgroundMaternal mortality in the United States has doubled over the last two decades, primarily due to cardiovascular disease, with more than half of deaths occurring postpartum. Despite national calls to action, attendance at postpartum clinic visits remains low. The role of alternative care delivery strategies, such as home visiting, remains insufficiently studied.ObjectiveTo describe postpartum clinic visit attendance among participants in a large national home visiting program, identify sociodemographic and clinical factors associated with attendance, and examine how timing and duration of enrollment relate to postpartum follow-up.DesignWe conducted a retrospective cohort study of pregnancy episodes among mothers enrolled in the Parents …

Strategies To Optimize Skill Acquisition And Prevent Skill Decay For The Air Transport Clinician, Mckayley Green, Aaron J Lacy, James L Li, John E Schneider

2020-Current year OA Pubs

No abstract provided.

Focused Ultrasound-Enhanced Nose-To-Brain Delivery Of A Therapeutic Antibody In A Large-Animal Model, Siaka Fadera, Cristian Antonio Wieczorek Villas Boas, Yimei Yue, Zhaoning Gu, Jinyun Yuan, Debolina De, Buck E Rogers, Arash Nazeri, Hong Chen

2020-Current year OA Pubs

No abstract provided.

A Survey-Based Assessment Of Treatment Preferences For Distal Radius Fractures In Participants Aged 65 Years And Older, Zayd Al Rawi, Elizabeth Graesser, Lindley B Wall

2020-Current year OA Pubs

PURPOSE: The management of distal radius fractures (DRF) in patients aged ≥65 years is debated because there is evidence that operative and nonsurgical treatment yield similar outcomes 1 year after injury. When more than one reasonable treatment option exists, shared decision-making between the patient and physician should be used. This study elicited preferences for the treatment of DRF using a survey of participants aged ≥65 years.

METHODS: A survey for participants ≥65 years was administered using Amazon Mechanical Turk. Participants were presented with a theoretical scenario in which they sustained a DRF, followed by two treatment options (surgery or casting) …

Phase I Trial Of Adp-A2afp Tcr T-Cell Therapy In Patients With Advanced Hepatocellular Or Gastric Hepatoid Carcinoma, Tim Meyer, Benjamin R Tan, Et Al.

2020-Current year OA Pubs

BACKGROUND & AIMS: Patients with advanced hepatocellular carcinoma (HCC) generally experience poor outcomes despite current therapies, necessitating the development of alternative treatments. ADP-A2AFP is an investigational autologous T-cell therapy with an affinity-enhanced T-cell receptor (TCR) targeting alpha-fetoprotein (AFP).

METHODS: We describe a phase I, open-label, first-in-human clinical trial of ADP-A2AFP (NCT03132792) in human leukocyte antigen-eligible participants with AFP-expressing HCC (or other tumor) not amenable to transplant/resection who progressed on, were intolerant to, or refused prior systemic therapy. Participants received lymphodepletion chemotherapy (cyclophosphamide 500 mg/m

RESULTS: Twenty-one participants, 20 with advanced HCC and one with gastric hepatoid carcinoma received ≥1 ADP-A2AFP …

Cutibacterium Adaptation To Life On Humans Provides A Potential C Acnes Infection Biomarker, Md Shafiuddin, Wen-Chi Huang, Gabriel William Prather, Jeffrey Ryan Anton, Andrew Lawrence Martin, Sydney Brianna Sillart, Jonathan Z Tang, Michael R Vittori, Michael J Prinsen, Jessica Jane Ninneman, Chandrashekhara Manithody, Jeffrey P Henderson, Alexander W Aleem, Ma Xenia Garcia Ilagan, William H Mccoy 4th

2020-Current year OA Pubs

Propionibacteriaceae appear to have adapted to life on humans during the domestication of cattle. These microbial immigrants formed the genus Cutibacterium, and a descendent of those microbial trailblazers (C acnes) now dominates 25% of human skin. C acnes colonization of human skin requires the protein RoxP. Although all Cutibacteria encode this adaptation to life on humans, nothing like RoxP has been found in any other organism. In this study, we report an extensive assessment of 21 RoxP orthologs, which identified conserved molecular surfaces linked to heme-dependent oligomerization and low pH stability. Our investigation suggests how RoxP helps C acnes dominate …

Diverse Misfolding Mutant Digestive Enzymes Cause Chronic Pancreatitis Through Common Pathways, Steven J Wilhelm, Grace E Curry, Neel Matiwala, Jianguo Lin, Tran Quach, Mark E Lowe, Miklós Sahin-Tóth, Xunjun K Xiao

2020-Current year OA Pubs

BACKGROUND & AIMS: Increasing evidence suggests that protein misfolding and proteotoxicity is an important mechanism of chronic pancreatitis (CP) in patients with genetic variants. Two mouse models carrying misfolding digestive enzyme variants, CPA1 N256K and PNLIP T221M, recapitulate the human CP phenotype. We hypothesized that both models develop CP through similar disease mechanisms.

METHODS: We conducted a comprehensive analysis of mice aged 1 to 6 months using histology, immunohistochemistry, protein immunoblotting, quantitative polymerase chain reaction (qPCR), transmission electron microscopy (TEM), and RNA sequencing (RNA-seq) analysis to characterize pancreatic pathological changes.

RESULTS: Both homozygous models exhibited CP hallmarks, including progressive acinar …

Coordinated Regulation Of Capping Protein By Carmil And V-1/Myotrophin, John A Hammer, John A Cooper

2020-Current year OA Pubs

Capping Protein (CP) plays a central role in controlling actin filament dynamics in almost all eukaryotic cell types by virtue of its ability to block monomer addition and loss at the barbed end of the actin filament. Like other proteins that control actin assembly, CP is subject to regulation. Here we focus on two direct regulators of CP-CARMIL and V-1/Myotrophin. Specifically, we review recent biochemical, structural, imaging, and cell biological data that argue these two proteins cooperate to create a regulatory cycle for CP that controls its availability, activity, and site of action in the cell. Finally, we discuss unresolved …

Dysregulated Lactate Metabolism Synergizes With Als Genetic Risk Factors To Accelerate Motor Decline, Shweta Tendulkar, Tong Wu, Amy Strickland, Amber R. Hackett, Yurie Sato-Yamada, Xianrong Mao, Yo Sasaki, Jeffrey Milbrandt, A. Joseph Bloom, Aaron Diantonio

2020-Current year OA Pubs

Neurons rely on glial 'lactate shuttling' for metabolic support, which declines with aging and in neurodegenerative disease. Full disruption of lactate shuttling in peripheral nerves causes progressive axon degeneration, but we were interested to understand how partial disruption, a scenario more relevant to aging and disease, contributes to neurodegeneration risk. Pyruvate and lactate are interconverted by lactate dehydrogenases (LDHA and LDHB) in both lactate producing and consuming cells. We therefore began by investigating Ldhb knockout mice (loss of LDHA, the dominant LDH in liver and muscle, caused embryonic lethality), and discovered that they develop progressive neuromuscular junction atrophy and functional …

An Emerging Timer-2c Framework For Addressing Barriers To Research Culture And Productivity Among Local Healthcare Providers In The Middle East And Sub-Saharan Africa: A Qualitative Study And Modified Delphi Approach, Beryne Odeny, Dorothy Mangale, Dhananjaya Sharma, Mariam Balogun, Elizabeth Bukusi, Fatima Suleman, Miliard Derbew, Juliet Iwelunmor, Ermyas Birru, Isaac Che Ngang, Akila Anandarajah, Vaishnavi Mamillapalle, Wael Almahmeed

2020-Current year OA Pubs

Contributions from healthcare professionals in the Middle East and North Africa (MENA) and sub-Saharan Africa (SSA) to global health research remain disproportionately low. We conceptualized the TIMER-2C framework to capture the multi-level barriers and facilitators shaping research productivity among local healthcare professionals in MENA and SSA. We conducted qualitative interviews using a modified Delphi approach comprising two rounds to: 1) identify barriers and facilitators, and 2) establish consensus on the most prominent factors influencing research productivity. We purposively sampled 17 participants from Jordan, Qatar, Egypt, Lebanon, North Sudan, South Sudan, Nigeria, Ghana, Kenya, Uganda, Ethiopia, South Africa and India. Interview …

A Deep Learning Model To Guide Personalized Mechanical Circulatory Support Use In Cardiogenic Shock Patients Undergoing Pci, Amit P Amin, Richard G Bach, Darren C Tsang, Weili S Zheng, Raed A Qarajeh, Emmanouil S Brilakis, Hemant Kulkarni

2020-Current year OA Pubs

BACKGROUND: Cardiogenic shock (CS) in patients undergoing percutaneous coronary intervention (PCI) involves rapidly changing clinical, hemodynamic, and metabolic factors that current models cannot effectively integrate.

OBJECTIVES: The purpose of this study was to develop and validate a deep learning (DL) model to guide personalized use of mechanical circulatory support (MCS) devices in CS patients undergoing PCI.

METHODS: The authors analyzed data from 1,408 CS patients treated with intra-aortic balloon pump (IABP) or microaxial flow-pump (mAFP) at multiple hospitals (2004-2019). Clinical, hemodynamic, and metabolic variables from admission to MCS placement were compiled into longitudinal vectors. Using Python 3.7 and TabNet in …

Oculomics And Ai: The Eye As A Biomarker For Health Span, Joy Le Yi Wong, Rajendra S Apte, Et Al.

2020-Current year OA Pubs

As the world's population ages, the focus of healthcare is shifting from extending life span to promoting health span. There is an unmet need to identify sensitive and reliable markers of health span through more cost-effective and non-invasive methods, to enable early and effective intervention on modifiable aging factors. The eye offers a unique window into systemic health, providing direct visualization of the body's vascular and neural health. This review presents an overview of how various ocular structures can serve as biomarkers of health span-drawing on insights from ocular imaging, metabolomics, and proteomics, with evidence from basic science, animal models, …