Neurosciences Commons^™

Testing The Motivational Tradeoffs Between Pathogen Avoidance And Status Acquisition, Mitch Brown, Donald F. Sacco

Psychological Science Faculty Publications and Presentations

To reduce disease transmission through interpersonal contact, humans have evolved a behavioral immune system that facilitates identification and avoidance of pathogens. One behavioral strategy in response to pathogenic threat is the adoption of interpersonal reticence. However, reticence may impede status acquisition. This program of research tested whether activating pathogen-avoidant motives through priming fosters reticence related to status, namely disinterest in pursuing a group leadership position (Study 1) or disinterest in accepting a group leadership position bestowed onto them (Study 2). Individuals high in germ aversion were particularly interested in pursuing leadership as a form of status, with disease salience unexpectedly …

Current Role Of Laser Interstitial Thermal Therapy In The Treatment Of Intracranial Tumors, Farhan A. Mirza, Rida Mitha, Muhammad Shahzad Shamim

Neurosurgery Faculty Publications

Laser interstitial thermal therapy (LITT) is gaining popularity in the treatment of both primary and secondary intracranial tumors. The goal of LITT is to deliver thermal energy in a predictable, controlled, and minimally invasive fashion. It can be particularly valuable in patients with recurrent tumors who, due to previous radiation or surgery, may have a potentially higher risk of wound breakdown or infection with repeat craniotomy. Deep-seated lesions that are often inaccessible through open approaches (thalamus, hypothalamus, mesial basal temporal lobe, brainstem) may also be suitable targets. The experience and data published thus far on this modality is limited but …

Ssh1 Impedes P62/Sqstm1 Flux And Tau Clearance Independent Of Cofilin Activation, Cenxiao Fang

USF Tampa Graduate Theses and Dissertations

Accumulation of toxic protein assemblies and damaged mitochondria are key features of neurodegenerative diseases, which arise in large part from clearance defects in the autophagy-lysosome system. The autophagy cargo receptor p62/SQSTM1 plays a major role in the clearance of ubiquitinated cargo through Ser403 phosphorylation by multiple kinases. However, no phosphatase is known to physiologically dephosphorylate p62 on this activating residue. RNAi-mediated knockdown and overexpression experiments using genetically encoded fluorescent reporters and defined mutant constructs in cell lines, primary neurons, and brains show that SSH1, the canonical cofilin phosphatase, mediates the dephosphorylation of phospho-Ser403-p62, thereby impairing p62 flux and phospho-tau clearance. …

Uncovering The Complex Genetics Of Human Temperament, Igor Zwir, Javier Arnedo, Coral Del-Val, Laura Pulkki-Råback, Bettina Konte, Sarah S. Yang, Rocio Romero-Zaliz, Mirka Hintsanen, Kevin M. Cloninger, Gabriel A. De Erausquin

School of Medicine Publications

Experimental studies of learning suggest that human temperament may depend on the molecular mechanisms for associative conditioning, which are highly conserved in animals. The main genetic pathways for associative conditioning are known in experimental animals, but have not been identified in prior genome-wide association studies (GWAS) of human temperament. We used a data-driven machine learning method for GWAS to uncover the complex genotypic–phenotypic networks and environmental interactions related to human temperament. In a discovery sample of 2149 healthy Finns, we identified sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (i.e., SNP sets) regardless of phenotype. Second, we identified …

Mental Health & Drugs; A Map Of The Mind, Wylie Jones Jordan

Journal of Mind and Medical Sciences

The practice of physical medicine underwent a sea change at the turn of the 20th century, but the management of mental disorders stayed much the same as it had been since Rome. New names have been coined for disorders, and synthetic drugs are advertised as a solution to every problem, but the causes are still largely unknown and, although spontaneous remission can occur, there are no cures. This review of psychiatric diagnosis and treatment from Rome to the 21st century offers a rationale to support the classic (and still current) classification of disorders. It offers a method of distinguishing the …

Tdp-43 Mediated Blood-Brain Barrier Permeability And Leukocyte Infiltration Promote Neurodegeneration In A Low-Grade Systemic Inflammation Mouse Model, Frank Zamudio, Anjanet R. Loon, Shayna Smeltzer, Khawla Benyamine, Nanda K. Navalpur Shanmugam, Nicholas J. F. Stewart, Daniel C. Lee, Kevin Nash, Maj-Linda B. Selenica

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Neuronal cytoplasmic inclusions containing TAR DNA-binding protein 43 (TDP-43) are a neuropathological feature of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's Disease (AD). Emerging evidence also indicates that systemic inflammation may be a contributor to the pathology progression of these neurodegenerative diseases.

METHODS: To investigate the role of systemic inflammation in the progression of neuronal TDP-43 pathology, AAV9 particles driven by the UCHL1 promoter were delivered to the frontal cortex of wild-type aged mice via intracranial injections to overexpress TDP-43 or green fluorescent protein (GFP) in corticospinal motor neurons. Animals were then subjected …

Effects Of Neuronic Shutter Observed In The Eeg Alpha Rhythm, Kevin E. Alexander, Justin R. Estepp, Sherif M. Elbasiouny

Neuroscience, Cell Biology & Physiology Faculty Publications

The posterior alpha (α) rhythm, seen in human electroencephalogram (EEG), is posited to originate from cycling inhibitory/excitatory states of visual relay cells in the thalamus. These cycling states are thought to lead to oscillating visual sensitivity levels termed the “neuronic shutter effect.” If true, perceptual performance should be predictable by observed α phase (of cycling inhibitory/excitatory states) relative to the timeline of afferentiation onto the visual cortex. Here, we tested this hypothesis by presenting contrast changes at near perceptual threshold intensity through closed eyelids to 20 participants (balanced for gender) during times of spontaneous α oscillations. To more accurately and …

Facial Grimace Testing As An Assay Of Neuropathic Pain-Related Behavior In A Mouse Model Of Cervical Spinal Cord Injury., Nicolette M Heinsinger, Gabrielle Spagnuolo, R Vivian Allahyari, Simon Galer, Tyler Fox, David A Jaffe, Samantha J Thomas, Lorraine Iacovitti, Angelo C Lepore

Department of Neuroscience Faculty Papers

A major portion of individuals affected by traumatic spinal cord injury (SCI) experience one or more types of chronic neuropathic pain (NP), which is often intractable to currently available treatments. The availability of reliable behavioral assays in pre-clinical models of SCI-induced NP is therefore critical to assess the efficacy of new potential therapies. Commonly used assays to evaluate NP-related behavior in rodents, such as Hargreaves thermal and von Frey mechanical testing, rely on the withdrawal response to an evoked stimulus. However, other assays that test spontaneous/non-evoked NP-related behavior or supraspinal aspects of NP would be highly useful for a more …

I. Interventions To Decrease Stroke Patient Falls On The Stroke Unit, Courtney Herron

Year of the Nurse: Clinical Scholarship Presentations

No abstract provided.

Microglial-Associated Responses To Comorbid Amyloid Pathology And Hyperhomocysteinemia In An Aged Knock-In Mouse Model Of Alzheimer's Disease, David J. Braun, Edgardo R. Dimayuga, Josh M. Morganti, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Elevated blood homocysteine levels, termed hyperhomocysteinemia (HHcy), is a prevalent risk factor for Alzheimer's disease (AD) in elderly populations. While dietary supplementation of B-vitamins is a generally effective method to lower homocysteine levels, there is little if any benefit to cognition. In the context of amyloid pathology, dietary-induced HHcy is known to enhance amyloid deposition and certain inflammatory responses. Little is known, however, about whether there is a more specific effect on microglia resulting from combined amyloid and HHcy pathologies.

METHODS: The present study used a knock-in mouse model of amyloidosis, aged to 12 months, given 8 weeks of …

Functional Outcome Of Traumatic Spinopelvic Instabilities Treated With Lumbopelvic Fixation., Emre Yilmaz, Martin F Hoffmann, Alexander Von Glinski, Christiane Kruppa, Uwe Hamsen, Cameron K Schmidt, Ahmet Oernek, Matthias Koenigshausen, Marcel Dudda, Thomas A Schildhauer

Articles, Abstracts, and Reports

The aim of this study was to assess the functional outcome after lumbopelvic fixation (LPF) using the SMFA (short musculoskeletal functional assessment) score and discuss the results in the context of the existing literature. The last consecutive 50 patients who underwent a LPF from January 1st 2011 to December 31st 2014 were identified and administered the SMFA-questionnaire. Inclusion criteria were: (1) patient underwent LPF at our institution, (2) complete medical records, (3) minimum follow-up of 12 months. Out of the 50 recipients, 22 questionnaires were returned. Five questionnaires were incomplete and therefore seventeen were included for analysis. The mean age …

Syllables In Sync Form A Link: Neural Phase-Locking Reflects Word Knowledge During Language Learning, Laura Batterink

Brain and Mind Institute Researchers' Publications

Language is composed of small building blocks, which combine to form larger meaningful structures. To understand language, we must process, track, and concatenate these building blocks into larger linguistic units as speech unfolds over time. An influential idea is that phase-locking of neural oscillations across different levels of linguistic structure provides a mechanism for this process. Building on this framework, the goal of the current study was to determine whether neural phase-locking occurs more robustly to novel linguistic items that are successfully learned and encoded into memory, compared to items that are not learned. Participants listened to a continuous speech …

Pain In The Newborn Brain: A Neural Signature, Emma G. Duerden, Steven P. Miller

Brain and Mind Institute Researchers' Publications

No abstract provided.

An Auditory-Perceptual And Pupillometric Study Of Vocal Strain And Listening Effort In Adductor Spasmodic Dysphonia, Mojgan Farahani, Vijay Parsa, Björn Herrmann, Mason Kadem, Ingrid Johnsrude, Philip C. Doyle

Brain and Mind Institute Researchers' Publications

© 2020 by the authors. This study evaluated ratings of vocal strain and perceived listening effort by normal hearing participants while listening to speech samples produced by talkers with adductor spasmodic dysphonia (AdSD). In addition, objective listening effort was measured through concurrent pupillometry to determine whether listening to disordered voices changed arousal as a result of emotional state or cognitive load. Recordings of the second sentence of the "Rainbow Passage" produced by talkers with varying degrees of AdSD served as speech stimuli. Twenty naïve young adult listeners perceptually evaluated these stimuli on the dimensions of vocal strain and listening effort …

Decoding Motor Imagery And Action Planning In The Early Visual Cortex: Overlapping But Distinct Neural Mechanisms, Simona Monaco, Giulia Malfatti, Jody C. Culham, Luigi Cattaneo, Luca Turella

Brain and Mind Institute Researchers' Publications

Recent evidence points to a role of the primary visual cortex that goes beyond visual processing into high-level cognitive and motor-related functions, including action planning, even in absence of feedforward visual information. It has been proposed that, at the neural level, motor imagery is a simulation based on motor representations, and neuroimaging studies have shown overlapping and shared activity patterns for motor imagery and action execution in frontal and parietal cortices. Yet, the role of the early visual cortex in motor imagery remains unclear. Here we used multivoxel pattern analyses on functional magnetic resonance imaging (fMRI) data to examine whether …

Covid-19-Associated Cns Demyelinating Diseases, Dhanashri Miskin, Md

Department of Neuroscience Faculty Papers

Neurological manifestations of SARS-CoV-2 infection are increasingly being recognized. The most common neurologic symptoms include headache, anosmia, and dysgeusia, but patients may also develop other central nervous system (CNS) diseases.

Gsj Gets A Fresh New Look, Jeffrey C Wang, Jens R Chapman, Karsten Wiechert

Articles, Abstracts, and Reports

No abstract provided.

Nine-Year Prospective Efficacy And Safety Of Brain-Responsive Neurostimulation For Focal Epilepsy., Dileep R Nair, Kenneth D Laxer, Peter B Weber, Anthony M Murro, Yong D Park, Gregory L Barkley, Brien J Smith, Ryder P Gwinn, Michael J Doherty, Katherine H Noe, Richard S Zimmerman, Gregory K Bergey, William S Anderson, Christianne Heck, Charles Y Liu, Ricky W Lee, Toni Sadler, Robert B Duckrow, Lawrence J Hirsch, Robert E Wharen, William Tatum, Shraddha Srinivasan, Guy M Mckhann, Mark A Agostini, Andreas V Alexopoulos, Barbara C Jobst, David W Roberts, Vicenta Salanova, Thomas C Witt, Sydney S Cash, Andrew J Cole, Gregory A Worrell, Brian N Lundstrom, Jonathan C Edwards, Jonathan J Halford, David C Spencer, Lia Ernst, Christopher T Skidmore, Michael R Sperling, Ian Miller, Eric B Geller, Michel J Berg, A James Fessler, Paul Rutecki, Alica M Goldman, Eli M Mizrahi, Robert E Gross, Donald C Shields, Theodore H Schwartz, Douglas R Labar, Nathan B Fountain, W Jeff Elias, Piotr W Olejniczak, Nicole R Villemarette-Pittman, Stephan Eisenschenk, Steven N Roper, Jane G Boggs, Tracy A Courtney, Felice T Sun, Cairn G Seale, Kathy L Miller, Tara L Skarpaas, Martha J Morrell, Rns System Ltt Study

Neuroscience Articles

OBJECTIVE: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.

METHODS: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.

RESULTS: Of 256 patients treated in the initial trials, 230 participated in …

Neurotoxicity Of Isomers Of The Environmental Toxin L-Bmaa, Thomas Schneider, Catherine Simpson, Prachi Desai, Madeleine Tucker, Doug Lobner

Biomedical Sciences Faculty Research and Publications

There is evidence that the environmental toxin β-N-methylamino-L-alanine (L-BMAA) may be involved in neurodegenerative diseases. However, a number of controversies exist regarding L-BMAA, one of which is the possibility that when assaying for L-BMAA, its isomers are being detected instead. There are at least four isomers of BMAA that are known to occur: L-BMAA, β-N-methylamino-D-alanine (D-BMAA), 2,4-diaminobutyric acid (DAB), and N-(2-aminoethyl)glycine (AEG). The fact that isomers of BMAA exist in nature also leads to the possibility that they are involved in toxicity. We set out to determine both the potency and the mechanism of toxicity of L-BMAA, D-BMAA, DAB, and …

Conditional Loss Of Engrailed 1/2 In Rhombic Lip-Derived Neurons Increases Intrinsic Rhythmicity And Decreases Overall Variability Of Eupneic Respiration, Angela P. Taylor

Theses and Dissertations (ETD)

Evidence for a cerebellar role during cardiopulmonary challenges has long been established, but investigation into cerebellar involvement in eupneic breathing has been inconclusive. Given the view of the cerebellum (CRB) as a temporally coordinating structure, any investigation into the CRB during respiration must evaluate rhythm and variability of the respiratory sequence. In this study, we chose an elegant model of cerebellar neuropathology, Atoh1-En1/2 CKO, where mutant animals have conditional loss of the developmental patterning gene Engrailed 1/2 in rhombic lip-lineage neurons and exhibit a proportional scaling-down of neuron number in hypoplastic lobules of the CRB. We utilized whole-body unrestrained plethysmography …

Genomic Instability And The Oncohistone H3k27m Drive Gliomagenesis In A Murine Model, Lee J. Pribyl

Theses and Dissertations (ETD)

Maintaining genome stability is crucial for human health and it is of particular importance in neural cells during early brain development. Genome maintenance occurs at two broad stages; surveillance during DNA replication and DNA damage repair in differentiating and mature cells. Neural cells are particularly sensitive to DNA strand breaks and defective DNA damage responses can result in detrimental effects on the nervous system, including cancer. Multiple DNA repair pathways play critical roles in preventing DNA damage accumulation in stem and neural progenitor cells. The mechanisms that protect progenitor genomes also suppress DNA mutations that can result in cancer. A …

Hypusination Of Eif5a Regulates Cytoplasmic Tdp-43 Aggregation And Accumulation In A Stress-Induced Cellular Model, Shayna Smeltzer, Zainuddin Quadri, Abraian Miller, Frank Zamudio, Jordan Hunter, Nicholas J.F. Stewart, Sheba Saji, Daniel C. Lee, Dale Chaput, Maj-Linda B. Selenica

Sanders-Brown Center on Aging Faculty Publications

TAR DNA-binding protein 43 (TDP-43) is a nuclear RNA/DNA binding protein involved in mRNA metabolism. Aberrant mislocalization to the cytoplasm and formation of phosphorylated/aggregated TDP-43 inclusions remains the hallmark pathology in a spectrum of neurodegenerative diseases, including frontotemporal disorders and Alzheimer's disease. Eukaryotic Translation Initiation Factor 5A undergoes a unique post-translation modification of lysine to hypusine (K50), which determines eIF5A binding partners. We used a sodium arsenite-induced cellular stress model to investigate the role of hypusinated eIF5A (eIF5A^HypK50) in governing TDP-43 cytoplasmic mislocalization and accumulation in stress granule. Our proteomics and functional data provide evidence that eIF5A interacts …

Cardiorespiratory Fitness Diminishes The Effects Of Age On White Matter Hyperintensity Volume, Nathan F. Johnson, Ahmed A. Bahrani, David K. Powell, Gregory A. Jicha, Brian T. Gold

Physical Therapy Faculty Publications

White matter hyperintensities (WMHs) are among the most commonly observed marker of cerebrovascular disease. Age is a key risk factor for WMH development. Cardiorespiratory fitness (CRF) is associated with increased vessel compliance, but it remains unknown if high CRF affects WMH volume. This study explored the effects of CRF on WMH volume in community-dwelling older adults. We further tested the possibility of an interaction between CRF and age on WMH volume. Participants were 76 adults between the ages of 59 and 77 (mean age = 65.36 years, SD = 3.92) who underwent a maximal graded exercise test and structural brain …

Combination Of A Gellan Gum-Based Hydrogel With Cell Therapy For The Treatment Of Cervical Spinal Cord Injury, Eduardo D Gomes, Biswarup Ghosh, Rui Lima, Miguel Goulão, Tiago Moreira-Gomes, Joana Martins-Macedo, Mark W Urban, Megan C Wright, Jeffrey M Gimble, Nuno Sousa, Nuno A Silva, Angelo C Lepore, António J Salgado

Department of Neuroscience Faculty Papers

Cervical spinal cord trauma represents more than half of the spinal cord injury (SCI) cases worldwide. Respiratory compromise, as well as severe limb motor deficits, are among the main consequences of cervical lesions. In the present work, a Gellan Gum (GG)-based hydrogel modified with GRGDS peptide, together with adipose tissue-derived stem/stromal cells (ASCs) and olfactory ensheathing cells (OECs), was used as a therapeutic strategy after a C2 hemisection SCI in rats. Hydrogel or cells alone, and a group without treatment, were also tested. Four weeks after injury, compound muscle action potentials (CMAPs) were performed to assess functional phrenic motor neuron …

Folic Acid Supplementation In Patients With Elevated Homocysteine Levels, Alan D. Kaye, George M. Jeha, Alex D. Pham, Mitchell C. Fuller, Zachary I. Lerner, Gerald T. Sibley, Elyse M. Cornett, Ivan Urits, Omar Viswanath, Christopher G. Kevil

School of Medicine Faculty Publications

Introduction: Folic acid is the most important dietary determinant of homocysteine (Hcy). Hcy serves as a critical intermediate in methylation reactions. It is created from methionine and either converted back to methionine or transformed into cysteine. This process is aided through several enzymes and three vitamins, folic acid, B12, and B6. Daily supplementation with 0.5–5.0 mg of folic acid typically lowers plasma Hcy levels by approximately 25%. Hyperhomocysteinemia is a known risk factor for coronary artery disease. In this regard, elevated levels of Hcy have been found in a majority of patients with vascular disease. Methods: A literature review of …

The Bach1/Nrf2 Axis In Brain In Down Syndrome And Transition To Alzheimer Disease-Like Neuropathology And Dementia, Marzia Perluigi, Antonella Tramutola, Sara Pagnotta, Eugenio Barone, D. Allan Butterfield

Chemistry Faculty Publications

Down syndrome (DS) is the most common genetic cause of intellectual disability that is associated with an increased risk to develop early-onset Alzheimer-like dementia (AD). The brain neuropathological features include alteration of redox homeostasis, mitochondrial deficits, inflammation, accumulation of both amyloid beta-peptide oligomers and senile plaques, as well as aggregated hyperphosphorylated tau protein-containing neurofibrillary tangles, among others. It is worth mentioning that some of the triplicated genes encoded are likely to cause increased oxidative stress (OS) conditions that are also associated with reduced cellular responses. Published studies from our laboratories propose that increased oxidative damage occurs early in life in …

Covid-19 And Possible Links With Parkinson's Disease And Parkinsonism: From Bench To Bedside, David Sulzer, Angelo Antonini, Valentina Leta, Anna Nordvig, Richard Jay Smeyne, James E Goldman, Osama Al-Dalahmah, Luigi Zecca, Alessandro Sette, Luigi Bubacco, Olimpia Meucci, Elena Moro, Ashley S Harms, Yaqian Xu, Stanley Fahn, K Ray Chaudhuri

Department of Neuroscience Faculty Papers

This Viewpoint discusses insights from basic science and clinical perspectives on coronavirus disease 2019 (COVID-19)/severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection in the brain, with a particular focus on Parkinson's disease. Major points include that neuropathology studies have not answered the central issue of whether the virus enters central nervous system neurons, astrocytes or microglia, and the brain vascular cell types that express virus have not yet been identified. Currently, there is no clear evidence for human neuronal or astrocyte expression of angiotensin-converting enzyme 2 (ACE2), the major receptor for viral entry, but ACE2 expression may be activated by inflammation, and …

Dementia-Related Psychosis And The Potential Role For Pimavanserin, Jeffery L. Cummings, D. P. Devanand, Stephen M. Stahl

School of Medicine Faculty Research

Dementia-related psychosis is prevalent across dementias and typically manifests as delusions and/or hallucinations. The mechanisms underlying psychosis in dementia are unknown; however, neurobiological and pharmacological evidence has implicated multiple signaling pathways and brain regions. Despite differences in dementia pathology, the neurobiology underlying psychosis appears to involve dysregulation of a cortical and limbic pathway involving serotonergic, GABAergic, glutamatergic, and dopaminergic signaling. Thus, an imbalance in cortical and mesolimbic excitatory tone may drive symptoms of psychosis. Delusions and hallucinations may result from (1) hyperactivation of pyramidal neurons within the visual cortex, causing visual hallucinations, and (2) hyperactivation of the mesolimbic pathway, causing …

Artificial Intelligence For Rapid Meta-Analysis: Case Study On Ocular Toxicity Of Hydroxychloroquine., Matthew Michelson, Tiffany Chow, Neil A Martin, Mike Ross, Amelia Tee Qiao Ying, Steven Minton

Articles, Abstracts, and Reports

BACKGROUND: Rapid access to evidence is crucial in times of an evolving clinical crisis. To that end, we propose a novel approach to answer clinical queries, termed rapid meta-analysis (RMA). Unlike traditional meta-analysis, RMA balances a quick time to production with reasonable data quality assurances, leveraging artificial intelligence (AI) to strike this balance.

OBJECTIVE: We aimed to evaluate whether RMA can generate meaningful clinical insights, but crucially, in a much faster processing time than traditional meta-analysis, using a relevant, real-world example.

METHODS: The development of our RMA approach was motivated by a currently relevant clinical question: is ocular toxicity and …

Trc-Pad: Accelerating Recruitment Of Ad Clinical Trials Through Innovative Information Technology, G. A. Jimenez-Maggiora, S. Bruschi, R. Raman, O. Langford, M. Donohue, M. S. Rafii, R. A. Sperling, J. L. Cummings, P. S. Aisen, Trc-Pad Investigators

School of Medicine Faculty Research

Background The Trial-Ready Cohort for Preclinical/ Prodromal Alzheimer's Disease (TRC-PAD) Informatics Platform (TRC-PAD IP) was developed to facilitate the efficient selection, recruitment, and assessment of study participants in support of the TRC-PAD program. Objectives Describe the innovative architecture, workflows, and components of the TRC-PAD IP. Design The TRC-PAD IP was conceived as a secure, scalable, multi-tiered information management platform designed to facilitate high-throughput, cost-effective selection, recruitment, and assessment of TRC-PAD study participants and to develop a learning algorithm to select amyloid-bearing participants to participate in trials of early-stage Alzheimer's disease. Setting TRC-PAD participants were evaluated using both web-based and in-person …