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Mechanisms Of Memory Updating: State Dependency Vs. Reconsolidation, Christopher Kiley, Colleen M. Parks Jan 2022

Mechanisms Of Memory Updating: State Dependency Vs. Reconsolidation, Christopher Kiley, Colleen M. Parks

Psychology Faculty Research

Reactivating a memory trace has been argued to put it in a fragile state where it must undergo a stabilization process known as reconsolidation. During this process, memories are thought to be susceptible to interference and can be updated with new information. In the spatial context paradigm, memory updating has been shown to occur when new information is presented in the same spatial context as old information, an effect attributed to a reconsolidation process. However, the integration concept holds that memory change can only occur when reactivation and test states are the same, similar to a state-dependent effect. Thus, in …


The Costs Of Developing Treatments For Alzheimer’S Disease: A Retrospective Exploration, Jeffrey L. Cummings, Dana P. Goldman, Nicholas R. Simmons-Stern, Eric Ponton Sep 2021

The Costs Of Developing Treatments For Alzheimer’S Disease: A Retrospective Exploration, Jeffrey L. Cummings, Dana P. Goldman, Nicholas R. Simmons-Stern, Eric Ponton

School of Medicine Faculty Publications

Introduction: With the exception of the recent accelerated approval of aducanumab, in over 26 years of research and development (R&D) investment in Alzheimer's disease (AD), only five novel drugs—all for symptomatic treatment only—have reached FDA approval. Here, we estimate the costs of AD drug development during this period in the private sector. Methods: To estimate private R&D funding, we collected information on AD clinical trials (n = 1099; phases 1–4) conducted between January 1, 1995 and June 21, 2021 from various databases. Costs were derived using previously published methodologies and adjusted for inflation. Results: Since 1995, cumulative private expenditures on …


Developing Methods To Detect And Diagnose Chronic Traumatic Encephalopathy During Life: Rationale, Design, And Methodology For The Diagnose Cte Research Project, Jeffrey Cummings, Numerous Authors, See Full List Below Aug 2021

Developing Methods To Detect And Diagnose Chronic Traumatic Encephalopathy During Life: Rationale, Design, And Methodology For The Diagnose Cte Research Project, Jeffrey Cummings, Numerous Authors, See Full List Below

School of Medicine Faculty Publications

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been neuropathologically diagnosed in brain donors exposed to repetitive head impacts, including boxers and American football, soccer, ice hockey, and rugby players. CTE cannot yet be diagnosed during life. In December 2015, the National Institute of Neurological Disorders and Stroke awarded a seven-year grant (U01NS093334) to fund the “Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project.” The objectives of this multicenter project are to: develop in vivo fluid and neuroimaging biomarkers for CTE; characterize its clinical presentation; refine …


Scaling Up Information Sharing On Hiv-Associated Neurocognitive Disorder: Raising Awareness And Knowledge Among Key Stakeholders, Renato M. Liboro, Paul A. Shuper, Lori E. Ross May 2021

Scaling Up Information Sharing On Hiv-Associated Neurocognitive Disorder: Raising Awareness And Knowledge Among Key Stakeholders, Renato M. Liboro, Paul A. Shuper, Lori E. Ross

Psychology Faculty Research

Although the majority of specialists and researchers in the field of HIV/AIDS are aware and knowledgeable about HIV-associated neurocognitive disorder (HAND) as a condition that affects as much as 50% of people living with HIV/AIDS (PLWH), research has documented that many health care and service providers who work directly with PLWH are either unaware of HAND or believe they do not know enough information about HAND to effectively support their clients experiencing neurocognitive challenges. Based on the findings of a qualitative study that interviewed 33 health care and service providers in HIV/AIDS services to identify and examine their awareness and …


Influence Of Previous Covid-19 And Mastitis Infections On The Secretion Of Brain-Derived Neurotrophic Factor And Nerve Growth Factor In Human Milk, Veronique Demers-Mathieu, Dustin J. Hines, Rochelle M. Hines, Sirima Lavangnananda, Shawn Fels, Elena Medo Apr 2021

Influence Of Previous Covid-19 And Mastitis Infections On The Secretion Of Brain-Derived Neurotrophic Factor And Nerve Growth Factor In Human Milk, Veronique Demers-Mathieu, Dustin J. Hines, Rochelle M. Hines, Sirima Lavangnananda, Shawn Fels, Elena Medo

Psychology Faculty Research

Background: Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) play a critical role in neurodevelopment, where breast milk is a significant dietary source. The impact of previous COVID-19 infection and mastitis on the concentration of BDNF and NGF in human milk was investigated. Methods: Concentrations of BDNF and NGF were measured via ELISA in human milk samples collected from 12 mothers with a confirmed COVID-19 PCR, 13 mothers with viral symptoms suggestive of COVID-19, and 22 unexposed mothers (pre-pandemic Ctl-2018). These neurotrophins were also determined in 12 mothers with previous mastitis and 18 mothers without mastitis. Results: The NGF …


Intepirdine As Adjunctive Therapy To Donepezil For Mild-To-Moderate Alzheimer’S Disease: A Randomized, Placebo-Controlled, Phase 3 Clinical Trial (Mindset), Frederick M. Lang, Yi Mo, Marwan Sabbagh, Paul Solomon, Merce Boada, Roy W. Jones, Giovanni B. Frisoni, Timo Grimmer, Bruno Dubois, Mark Harnett, Sarah R. Friedhoff, Shari Coslett, Jeffrey L. Cummings Mar 2021

Intepirdine As Adjunctive Therapy To Donepezil For Mild-To-Moderate Alzheimer’S Disease: A Randomized, Placebo-Controlled, Phase 3 Clinical Trial (Mindset), Frederick M. Lang, Yi Mo, Marwan Sabbagh, Paul Solomon, Merce Boada, Roy W. Jones, Giovanni B. Frisoni, Timo Grimmer, Bruno Dubois, Mark Harnett, Sarah R. Friedhoff, Shari Coslett, Jeffrey L. Cummings

Brain Health Faculty Publications

Introduction: A previous phase 2b study supported the use of the 5-HT6 receptor antagonist intepirdine as adjunctive therapy to donepezil for Alzheimer's disease (AD) dementia. A phase 3 study, MINDSET, was performed to test this hypothesis. Methods: MINDSET was a global, double-blind, randomized, placebo-controlled trial in 1315 mild-to-moderate AD dementia patients on stable donepezil. Patients received 35 mg/day intepirdine or placebo for 24 weeks. The co-primary endpoints were change from baseline to week 24 on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL). Results: There were no statistically significant differences between intepirdine …


A Conformation Variant Of P53 Combined With Machine Learning Identifies Alzheimer Disease In Preclinical And Prodromal Stages, Giulia Abate, Marika Vezzoli, Letizia Polito, Antonio Guaita, Diego Albani, Moira Marizzoni, Emirena Garrafa, Alessandra Marengoni, Gianluigi Forloni, Giovanni B. Frisoni, Jeffrey L. Cummings, Maurizio Memo, Daniela Uberti Dec 2020

A Conformation Variant Of P53 Combined With Machine Learning Identifies Alzheimer Disease In Preclinical And Prodromal Stages, Giulia Abate, Marika Vezzoli, Letizia Polito, Antonio Guaita, Diego Albani, Moira Marizzoni, Emirena Garrafa, Alessandra Marengoni, Gianluigi Forloni, Giovanni B. Frisoni, Jeffrey L. Cummings, Maurizio Memo, Daniela Uberti

School of Medicine Faculty Publications

© 2020 by the authors. Li-censee MDPI, Basel, Switzerland. Early diagnosis of Alzheimer’s disease (AD) is a crucial starting point in disease man-agement. Blood-based biomarkers could represent a considerable advantage in providing AD-risk information in primary care settings. Here, we report new data for a relatively unknown blood-based biomarker that holds promise for AD diagnosis. We evaluate a p53-misfolding conformation rec-ognized by the antibody 2D3A8, also named Unfolded p53 (U-p532D3A8+), in 375 plasma samples derived from InveCe.Ab and PharmaCog/E-ADNI longitudinal studies. A machine learning approach is used to combine U-p532D3A8+ plasma levels with Mini-Mental State Examination (MMSE) and apolipoprotein E …


Long-Term Impact Of Mild Traumatic Brain Injuries On Multiple Functional Outcomes And Epigenetics: A Pilot Study With College Students, Hyunhwa Lee, Sungchul Lee, Ipuna Black, Laura Salado, Jonica Estrada, Katrina Isla Jun 2020

Long-Term Impact Of Mild Traumatic Brain Injuries On Multiple Functional Outcomes And Epigenetics: A Pilot Study With College Students, Hyunhwa Lee, Sungchul Lee, Ipuna Black, Laura Salado, Jonica Estrada, Katrina Isla

Nursing Faculty Publications

People who suffer a mild traumatic brain injury (mTBI) have heterogeneous symptoms and disease trajectories, which make it difficult to precisely assess long-term complications. This pilot study assessed and compared deficits in cognitive, psychosocial, visual functions, and balance performance between college students with and without histories of mTBI. Global DNA methylation ratio (5-mC%) in blood was also compared as a peripheral epigenetic marker. Twenty-five volunteers participated, including 14 healthy controls (64.3% females; mean age of 22.0) and 11 mTBI cases (27.3% females; mean age of 28.7 years) who self-reported mTBI history (63.6% multiple; 2.5 ± 1.29 injuries) with 7.1 years …


Cognitively Normal Women With Alzheimer’S Disease Proteinopathy Show Relative Preservation Of Memory But Not Of Hippocampal Volume, Jessica Z.K. Caldwell, Jeffrey L. Cummings, Sarah J. Banks, Sebastian Palmqvist, Oskar Hansson Dec 2019

Cognitively Normal Women With Alzheimer’S Disease Proteinopathy Show Relative Preservation Of Memory But Not Of Hippocampal Volume, Jessica Z.K. Caldwell, Jeffrey L. Cummings, Sarah J. Banks, Sebastian Palmqvist, Oskar Hansson

School of Medicine Faculty Publications

Background: We examined interactive effects of sex, diagnosis, and cerebrospinal fluid (CSF) amyloid beta/phosphorylated tau ratio (Aβ/P-tau) on verbal memory and hippocampal volumes. Methods: We assessed 682 participants (350 women) from BioFINDER (250 cognitively normal [CN]; and 432 symptomatic: 186 subjective cognitive decline [SCD], 246 mild cognitive impairment [MCI]). General linear models evaluated effects of Alzheimer’s disease (AD) proteinopathy (CSF Aß/p-tau ratio), diagnosis, and sex on verbal memory (ADAS-cog 10-word recall), semantic fluency (animal naming fluency), visuospatial skills (cube copy), processing speed/attention functions (Symbol Digit Modalities Test and Trail Making Part A), and hippocampal volumes. Results: Amyloid-positive (Aβ/P-tau+) CN women …


Meta-Analysis Of Cognitive Performance By Novel Object Recognition After Proton And Heavy Ion Exposures, Eliedonna Cacao, Francis A. Cucinotta Aug 2019

Meta-Analysis Of Cognitive Performance By Novel Object Recognition After Proton And Heavy Ion Exposures, Eliedonna Cacao, Francis A. Cucinotta

Health Physics & Diagnostic Sciences Faculty Publications

Experimental studies of cognitive detriments in mice and rats after proton and heavy ion exposures have been performed by several laboratories to investigate possible risks to astronauts exposed to cosmic rays in space travel and patients treated for brain cancers with proton and carbon beams in Hadron therapy. However, distinct radiation types and doses, cognitive tests and rodent models have been used by different laboratories, while few studies have considered detailed dose-response characterizations, including estimates of relative biological effectiveness (RBE). Here we report on the first quantitative meta-analysis of the dose response for proton and heavy ion rodent studies of …


Developmental Dependence For Functional Eye Regrowth In Xenopus Laevis, Cindy X. Kha, Kelly Ai-Sun Tseng Aug 2018

Developmental Dependence For Functional Eye Regrowth In Xenopus Laevis, Cindy X. Kha, Kelly Ai-Sun Tseng

Life Sciences Faculty Research

A key challenge in designing tissue repair strategies is knowing whether and how developmental mechanisms are used for successful repair of mature/adult tissues. Although it is known that developmental components are used in repair, it remains mostly unclear which ones are required and whether they act similarly as during development. This issue is further complicated by the fact that it is difficult to assess the similarities and differences between development and the repair of mature tissues, since the two contexts are highly dissimilar. A potentially useful yet underutilized approach is to understand developmental regrowth (defined here as the ability to …


An Integrative Neurological Model For Basic Observable Human Behavior, Ryan M. Francis Jan 2016

An Integrative Neurological Model For Basic Observable Human Behavior, Ryan M. Francis

Calvert Undergraduate Research Awards

The scientific method uncovers information from the natural world in small increments. This spurs the design of models to explain how the pieces fit together and to identify future targets of research. This is especially the case in psychology, where visualizing concepts is an advantageous practice. One all too common criticism of cognitive and behavioral models in psychology is the lack of a biological basis. This paper aims to alleviate part of this issue by integrating currently understood biological and neurological mechanisms that drive psychological phenomena into a predictive and descriptive model for basic human behavior. To accomplish this task, …


Induction Of Integral Membrane Pam Expression In Att-20 Cells Alters The Storage And Trafficking Of Pomc And Pc1, Giuseppe D. Ciccotosto, Martin R. Schiller, Betty A. Eipper, Richard E. Mains Feb 1999

Induction Of Integral Membrane Pam Expression In Att-20 Cells Alters The Storage And Trafficking Of Pomc And Pc1, Giuseppe D. Ciccotosto, Martin R. Schiller, Betty A. Eipper, Richard E. Mains

Life Sciences Faculty Research

Peptidylglycine alpha-amidating monooxygenase (PAM) is an essential enzyme that catalyzes the COOH-terminal amidation of many neuroendocrine peptides. The bifunctional PAM protein contains an NH2-terminal monooxygenase (PHM) domain followed by a lyase (PAL) domain and a transmembrane domain. The cytosolic tail of PAM interacts with proteins that can affect cytoskeletal organization. A reverse tetracycline-regulated inducible expression system was used to construct an AtT-20 corticotrope cell line capable of inducible PAM-1 expression. Upon induction, cells displayed a time- and dose-dependent increase in enzyme activity, PAM mRNA, and protein. Induction of increased PAM-1 expression produced graded changes in PAM-1 metabolism. Increased expression of …