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Articles 31 - 60 of 63
Full-Text Articles in Cognitive Neuroscience
Altered Theta Rhythm And Hippocampal-Cortical Interactions Underlie Working Memory Deficits In A Hyperglycemia Risk Factor Model Of Alzheimer’S Disease, Ryan A. Wirt, Lauren A. Crew, Andrew A. Ortiz, Adam M. Mcneela, Emmanuel Flores, Jefferson W. Kinney, James M. Hyman
Altered Theta Rhythm And Hippocampal-Cortical Interactions Underlie Working Memory Deficits In A Hyperglycemia Risk Factor Model Of Alzheimer’S Disease, Ryan A. Wirt, Lauren A. Crew, Andrew A. Ortiz, Adam M. Mcneela, Emmanuel Flores, Jefferson W. Kinney, James M. Hyman
Integrated Health Sciences Faculty Research
Diabetes mellitus is a metabolic disease associated with dysregulated glucose and insulin levels and an increased risk of developing Alzheimer’s disease (AD) later in life. It is thought that chronic hyperglycemia leads to neuroinflammation and tau hyperphosphorylation in the hippocampus leading to cognitive decline, but effects on hippocampal network activity are unknown. A sustained hyperglycemic state was induced in otherwise healthy animals and subjects were then tested on a spatial delayed alternation task while recording from the hippocampus and anterior cingulate cortex (ACC). Hyperglycemic animals performed worse on long delay trials and had multiple electrophysiological differences throughout the task. We …
The Amyloid-Β Pathway In Alzheimer’S Disease, Harald Hampel, John Hardy, Kaj Blennow, Christopher Chen, George Perry, Seung Hyun Kim, Victor L. Villemagne, Paul Aisen, Michele Vendruscolo, Takeshi Iwatsubo, Colin L. Masters, Min Cho, Lars Lannfelt, Jeffrey L. Cummings, Andrea Vergallo
The Amyloid-Β Pathway In Alzheimer’S Disease, Harald Hampel, John Hardy, Kaj Blennow, Christopher Chen, George Perry, Seung Hyun Kim, Victor L. Villemagne, Paul Aisen, Michele Vendruscolo, Takeshi Iwatsubo, Colin L. Masters, Min Cho, Lars Lannfelt, Jeffrey L. Cummings, Andrea Vergallo
School of Medicine Faculty Research
Breakthroughs in molecular medicine have positioned the amyloid-β (Aβ) pathway at the center of Alzheimer’s disease (AD) pathophysiology. While the detailed molecular mechanisms of the pathway and the spatial-temporal dynamics leading to synaptic failure, neurodegeneration, and clinical onset are still under intense investigation, the established biochemical alterations of the Aβ cycle remain the core biological hallmark of AD and are promising targets for the development of disease-modifying therapies. Here, we systematically review and update the vast state-of-the-art literature of Aβ science with evidence from basic research studies to human genetic and multi-modal biomarker investigations, which supports a crucial role of …
Estimating Progression Rates Across The Spectrum Of Alzheimer’S Disease For Amyloid-Positive Individuals Using National Alzheimer’S Coordinating Center Data, Michele Potashman, Marric Buessing, Mihaela Levitchi Benea, Jeffrey Cummings, Soo Borson, Peter Pemberton-Ross, Andrew J. Epstein
Estimating Progression Rates Across The Spectrum Of Alzheimer’S Disease For Amyloid-Positive Individuals Using National Alzheimer’S Coordinating Center Data, Michele Potashman, Marric Buessing, Mihaela Levitchi Benea, Jeffrey Cummings, Soo Borson, Peter Pemberton-Ross, Andrew J. Epstein
School of Medicine Faculty Research
Introduction: Published estimates of Alzheimer’s disease (AD) progression do not capture the full disease continuum. This study provides transition probabilities of individuals with amyloid-β (Aβ+) pathology across the disease continuum. Methods: Patient-level longitudinal data from the National Alzheimer’s Coordinating Center were used to estimate progression rates. Progression rates through five clinically defined AD stages—asymptomatic, mild cognitive impairment due to AD (MCI-AD), mild AD dementia, moderate AD dementia, severe AD dementia—and death were measured as transition probabilities. Rates were assessed in “incident” patients who recently entered the stage, controlling for covariates. Transition probabilities were generated from multinomial logit regression models that …
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
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 Research
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 …
Aducanumab: Appropriate Use Recommendations, Jeffrey Cummings, Steve Salloway
Aducanumab: Appropriate Use Recommendations, Jeffrey Cummings, Steve Salloway
School of Medicine Faculty Research
Aducanumab recently received accelerated approval by the FDA. An Expert Panel was comprised to provide recommendations on appropriate use of aducanumab in real world practices. Patient selection, aducanumab administration and monitoring, management of ARIA, and best practices in patient care in the context of aducanumab therapy are described. The paper was published in the Journal of Prevention of Alzheimer's Disease.
Severe Covid-19 In Alzheimer’S Disease: Apoe4’S Fault Again?, Nian Xiong, Martin R. Schiller, Jingwen Li, Xiaowu Chen, Zhicheng Lin
Severe Covid-19 In Alzheimer’S Disease: Apoe4’S Fault Again?, Nian Xiong, Martin R. Schiller, Jingwen Li, Xiaowu Chen, Zhicheng Lin
Life Sciences Faculty Research
Challenges have been recognized in healthcare of patients with Alzheimer’s disease (AD) in the COVID-19 pandemic, given a high infection and mortality rate of COVID-19 in these patients. This situation urges the identification of underlying risks and preferably biomarkers for evidence-based, more effective healthcare. Towards this goal, current literature review and network analysis synthesize available information on the AD-related gene APOE into four lines of mechanistic evidence. At a cellular level, the risk isoform APOE4 confers high infectivity by the underlying coronavirus SARS-CoV-2; at a genetic level, APOE4 is associated with severe COVID-19; at a pathway level, networking connects APOE …
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
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 …
Value-Generating Exploratory Trials In Neurodegenerative Dementias, Lauren G. Friedman, Nicholas Mckeehan, Yuko Hara, Jeffrey L. Cummings, Dawn C. Matthews, Jian Zhu, Richard C. Mohs, Deli Wang, Suzanne B. Hendrix, Melanie Quintana, Lon S. Schneider, Michael Grundman, Samuel P. Dickson, Howard H. Feldman, Judith Jaeger, Elizabeth C. Finger, J. Michael Ryan, Debra Niehoff, Susan L.J. Dickinson, Jessica T. Markowitz, Meriel Owen, Alessio Travaglia, Howard M. Fillit
Value-Generating Exploratory Trials In Neurodegenerative Dementias, Lauren G. Friedman, Nicholas Mckeehan, Yuko Hara, Jeffrey L. Cummings, Dawn C. Matthews, Jian Zhu, Richard C. Mohs, Deli Wang, Suzanne B. Hendrix, Melanie Quintana, Lon S. Schneider, Michael Grundman, Samuel P. Dickson, Howard H. Feldman, Judith Jaeger, Elizabeth C. Finger, J. Michael Ryan, Debra Niehoff, Susan L.J. Dickinson, Jessica T. Markowitz, Meriel Owen, Alessio Travaglia, Howard M. Fillit
School of Medicine Faculty Research
Drug development for Alzheimer disease and other neurodegenerative dementias, including frontotemporal dementia, has experienced a long history of phase 2 and phase 3 clinical trials that failed to show efficacy of investigational drugs. Despite differences in clinical and behavioral characteristics, these disorders have shared pathologies and face common challenges in designing early-phase trials that are predictive of late-stage success. Here, we discuss exploratory clinical trials in neurodegenerative dementias. These are generally phase 1b or phase 2a trials that are designed to assess pharmacologic effects and rely on biomarker outcomes, with shorter treatment durations and fewer patients than traditional phase 2 …
Aducanumab Produced A Clinically Meaningful Benefit In Association With Amyloid Lowering, Jeffrey Cummings, Paul Aisen, Cynthia Lemere, Alireza Atri, Marwan Sabbagh, Stephen Salloway
Aducanumab Produced A Clinically Meaningful Benefit In Association With Amyloid Lowering, Jeffrey Cummings, Paul Aisen, Cynthia Lemere, Alireza Atri, Marwan Sabbagh, Stephen Salloway
School of Medicine Faculty Research
No abstract provided.
Diagnostic Criteria For Apathy In Neurocognitive Disorders, David S. Miller, Philippe Robert, Larry Ereshefsky, Lawrence Adler, Daniel Bateman, Jeff Cummings, Steven T. Dekosky, Corinne E. Fischer, Masud Husain, Zahinoor Ismail, Judith Jaeger, Alan J. Lerner, Abby Li, Constantine G. Lyketsos, Valeria Manera, Jacobo Mintzer, Hans J. Moebius, Moyra Mortby, Didier Meulien, Stephane Pollentier, Anton Porsteinsson, Jill Rasmussen, Paul B. Rosenberg, Myuri T. Ruthirakuhan, Mary Sano, Carla Zucchero Sarracini, Krista L. Lanctôt
Diagnostic Criteria For Apathy In Neurocognitive Disorders, David S. Miller, Philippe Robert, Larry Ereshefsky, Lawrence Adler, Daniel Bateman, Jeff Cummings, Steven T. Dekosky, Corinne E. Fischer, Masud Husain, Zahinoor Ismail, Judith Jaeger, Alan J. Lerner, Abby Li, Constantine G. Lyketsos, Valeria Manera, Jacobo Mintzer, Hans J. Moebius, Moyra Mortby, Didier Meulien, Stephane Pollentier, Anton Porsteinsson, Jill Rasmussen, Paul B. Rosenberg, Myuri T. Ruthirakuhan, Mary Sano, Carla Zucchero Sarracini, Krista L. Lanctôt
School of Medicine Faculty Research
Introduction: Apathy is common in neurocognitive disorders (NCD) but NCD-specific diagnostic criteria are needed. Methods: The International Society for CNS Clinical Trials Methodology Apathy Work Group convened an expert group and sought input from academia, health-care, industry, and regulatory bodies. A modified Delphi methodology was followed, and included an extensive literature review, two surveys, and two meetings at international conferences, culminating in a consensus meeting in 2019. Results: The final criteria reached consensus with more than 80% agreement on all parts and included: limited to people with NCD; symptoms persistent or frequently recurrent over at least 4 weeks, a change …
A Randomized, Double-Blind, Phase 2b Proof-Of-Concept Clinical Trial In Early Alzheimer’S Disease With Lecanemab, An Anti-Aβ Protofibril Antibody, Chad J. Swanson, Yong Zhang, Shobha Dhadda, Jinping Wang, June Kaplow, Robert Y.K. Lai, Lars Lannfelt, Heather Bradley, Martin Rabe, Akihiko Koyama, Larisa Reyderman, Donald A. Berry, Scott Berry, Robert Gordon, Lynn D. Kramer, Jeffrey L. Cummings
A Randomized, Double-Blind, Phase 2b Proof-Of-Concept Clinical Trial In Early Alzheimer’S Disease With Lecanemab, An Anti-Aβ Protofibril Antibody, Chad J. Swanson, Yong Zhang, Shobha Dhadda, Jinping Wang, June Kaplow, Robert Y.K. Lai, Lars Lannfelt, Heather Bradley, Martin Rabe, Akihiko Koyama, Larisa Reyderman, Donald A. Berry, Scott Berry, Robert Gordon, Lynn D. Kramer, Jeffrey L. Cummings
School of Medicine Faculty Research
Background: Lecanemab (BAN2401), an IgG1 monoclonal antibody, preferentially targets soluble aggregated amyloid beta (Aβ), with activity across oligomers, protofibrils, and insoluble fibrils. BAN2401-G000-201, a randomized double-blind clinical trial, utilized a Bayesian design with response-adaptive randomization to assess 3 doses across 2 regimens of lecanemab versus placebo in early Alzheimer’s disease, mild cognitive impairment due to Alzheimer’s disease (AD) and mild AD dementia. Methods: BAN2401-G000-201 aimed to establish the effective dose 90% (ED90), defined as the simplest dose that achieves ≥90% of the maximum treatment effect. The primary endpoint was Bayesian analysis of 12-month clinical change on the Alzheimer’s Disease Composite …
#Eegmanylabs: Investigating The Replicability Of Influential Eeg Experiments, Yuri G. Pavlov, Nika Adamian, Stefan Appelhoff, Mahnaz Arvaneh, Christopher S.Y. Benwell, Christian Beste, Amy R. Bland, Daniel E. Bradford, Florian Bublatzky, Niko A. Busch, Peter E. Clayson, Damian Cruse, Artur Czeszumski, Anna Dreber, Guillaume Dumas, Benedikt Ehinger, Giorgio Ganis, Xun He, José A. Hinojosa, Christoph Huber-Huber, Michael Inzlicht, Bradley N. Jack, Magnus Johannesson, Rhiannon Jones, Evgenii Kalenkovich, Laura Kaltwasser, Hamid Karimi-Rouzbahani, Andreas Keil, Peter Koning, Layla Kouara
#Eegmanylabs: Investigating The Replicability Of Influential Eeg Experiments, Yuri G. Pavlov, Nika Adamian, Stefan Appelhoff, Mahnaz Arvaneh, Christopher S.Y. Benwell, Christian Beste, Amy R. Bland, Daniel E. Bradford, Florian Bublatzky, Niko A. Busch, Peter E. Clayson, Damian Cruse, Artur Czeszumski, Anna Dreber, Guillaume Dumas, Benedikt Ehinger, Giorgio Ganis, Xun He, José A. Hinojosa, Christoph Huber-Huber, Michael Inzlicht, Bradley N. Jack, Magnus Johannesson, Rhiannon Jones, Evgenii Kalenkovich, Laura Kaltwasser, Hamid Karimi-Rouzbahani, Andreas Keil, Peter Koning, Layla Kouara
Psychology Faculty Research
There is growing awareness across the neuroscience community that the replicability of findings about the relationship between brain activity and cognitive phenomena can be improved by conducting studies with high statistical power that adhere to well-defined and standardised analysis pipelines. Inspired by recent efforts from the psychological sciences, and with the desire to examine some of the foundational findings using electroencephalography (EEG), we have launched #EEGManyLabs, a large-scale international collaborative replication effort. Since its discovery in the early 20th century, EEG has had a profound influence on our understanding of human cognition, but there is limited evidence on the replicability …
Prediction Of Alzheimer’S Disease-Specific Phospholipase C Gamma-1 Snv By Deep Learning-Based Approach For High-Throughput Screening, Sung Hyun Kim, Sumin Yang, Key Hwan Lim, Euiseng Ko, Hyun Jun Jang, Mingon Kang, Pann Ghill Suh, Jae Yeol Joo
Prediction Of Alzheimer’S Disease-Specific Phospholipase C Gamma-1 Snv By Deep Learning-Based Approach For High-Throughput Screening, Sung Hyun Kim, Sumin Yang, Key Hwan Lim, Euiseng Ko, Hyun Jun Jang, Mingon Kang, Pann Ghill Suh, Jae Yeol Joo
Computer Science Faculty Research
© 2021 National Academy of Sciences. All rights reserved. Exon splicing triggered by unpredicted genetic mutation can cause translational variations in neurodegenerative disorders. In this study, we discover Alzheimer’s disease (AD)-specific single-nucleotide variants (SNVs) and abnormal exon splicing of phospholipase c gamma-1 (PLCγ1) gene, using genome-wide association study (GWAS) and a deep learning-based exon splicing prediction tool. GWAS revealed that the identified single-nucleotide variations were mainly distributed in the H3K27ac-enriched region of PLCγ1 gene body during brain development in an AD mouse model. A deep learning analysis, trained with human genome sequences, predicted 14 splicing sites in human PLCγ1 gene, …
Practical Recommendations For Timely, Accurate Diagnosis Of Symptomatic Alzheimer’S Disease (Mci And Dementia) In Primary Care: A Review And Synthesis, J. L. Liss, S. Seleri Assunção, Jeffrey Cummings, A. Atri, D. S. Geldmacher, S. F. Candela, D. P. Devanand, H. M. Fillit, J. Susman, J. Mintzer, T. Bittner, S. A. Brunton, D. R. Kerwin, W. C. Jackson, G. W. Small, G. T. Grossberg, C. K. Clevenger, V. Cotter, R. Stefanacci, A. Wise-Brown, M. N. Sabbagh
Practical Recommendations For Timely, Accurate Diagnosis Of Symptomatic Alzheimer’S Disease (Mci And Dementia) In Primary Care: A Review And Synthesis, J. L. Liss, S. Seleri Assunção, Jeffrey Cummings, A. Atri, D. S. Geldmacher, S. F. Candela, D. P. Devanand, H. M. Fillit, J. Susman, J. Mintzer, T. Bittner, S. A. Brunton, D. R. Kerwin, W. C. Jackson, G. W. Small, G. T. Grossberg, C. K. Clevenger, V. Cotter, R. Stefanacci, A. Wise-Brown, M. N. Sabbagh
School of Medicine Faculty Research
The critical role of primary care clinicians (PCCs) in Alzheimer’s disease (AD) prevention, diagnosis and management must evolve as new treatment paradigms and disease-modifying therapies (DMTs) emerge. Our understanding of AD has grown substantially: no longer conceptualized as a late-in-life syndrome of cognitive and functional impairments, we now recognize that AD pathology builds silently for decades before cognitive impairment is detectable. Clinically, AD first manifests subtly as mild cognitive impairment (MCI) due to AD before progressing to dementia. Emerging optimism for improved outcomes in AD stems from a focus on preventive interventions in midlife and timely, biomarker-confirmed diagnosis at early …
Alzgps: A Genome-Wide Positioning Systems Platform To Catalyze Multi-Omics For Alzheimer’S Drug Discovery, Yadi Zhou, Jiansong Fang, Lynn M. Bekris, Yeon Heon Kim, Andrew A. Pieper, James B. Leverenz, Jeffrey Cummings, Feixiong Cheng
Alzgps: A Genome-Wide Positioning Systems Platform To Catalyze Multi-Omics For Alzheimer’S Drug Discovery, Yadi Zhou, Jiansong Fang, Lynn M. Bekris, Yeon Heon Kim, Andrew A. Pieper, James B. Leverenz, Jeffrey Cummings, Feixiong Cheng
School of Medicine Faculty Research
Background: Recent DNA/RNA sequencing and other multi-omics technologies have advanced the understanding of the biology and pathophysiology of AD, yet there is still a lack of disease-modifying treatments for AD. A new approach to integration of the genome, transcriptome, proteome, and human interactome in the drug discovery and development process is essential for this endeavor. Methods: In this study, we developed AlzGPS (Genome-wide Positioning Systems platform for Alzheimer’s Drug Discovery, https://alzgps.lerner.ccf.org), a comprehensive systems biology tool to enable searching, visualizing, and analyzing multi-omics, various types of heterogeneous biological networks, and clinical databases for target identification and development of effective prevention …
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
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 Research
© 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 …
Sex Moderates The Relationship That Number Of Professional Fights Has With Cognition And Brain Volumes, Lauren L. Bennett, Steve J. Stephen, Charles Bernick, Guogen Shan, Sarah J. Banks
Sex Moderates The Relationship That Number Of Professional Fights Has With Cognition And Brain Volumes, Lauren L. Bennett, Steve J. Stephen, Charles Bernick, Guogen Shan, Sarah J. Banks
School of Public Health Faculty Research
Objective: Incidence of concussions and report of symptoms are greater among women across sports. While structural brain changes and cognitive declines are associated with repetitive head impact (RHI), the role of sex is not well-understood. This study aimed to determine if there is a moderating effect of sex on the relationship the number of professional fights has with cognitive functioning and regional brain volumes in a cohort of boxers, mixed martial artists, and martial artists. Methods: A total of 55 women were matched with 55 men based on age, years of education, ethnicity, and fighting style. Cognition was assessed via …
An Acute Application Of Cerebellar Transcranial Direct Current Stimulation Does Not Improve Motor Performance In Parkinson’S Disease, Lidio Lima De Albuquerque, Milan Pantovic, Mitchel Clingo, Katherine Fischer, Sharon Jalene, Merrill Landers, Zoltan Mari, Brach Poston
An Acute Application Of Cerebellar Transcranial Direct Current Stimulation Does Not Improve Motor Performance In Parkinson’S Disease, Lidio Lima De Albuquerque, Milan Pantovic, Mitchel Clingo, Katherine Fischer, Sharon Jalene, Merrill Landers, Zoltan Mari, Brach Poston
Integrated Health Sciences Faculty Research
Transcranial direct current stimulation of the cerebellum (c-tDCS) improves motor performance in young and old adults. Based on the cerebellar involvement in Parkinson’s disease (PD), c-tDCS could have potential to improve motor function in PD. The purpose was to determine the effects of c-tDCS on motor performance in PD while participants were on medications. The study was a randomized, double-blind, SHAM-controlled, between-subjects design. Twenty-two participants with PD were allocated to either a c-tDCS group or a SHAM group. All participants completed one experimental session and performed two motor tasks with their most affected hand in a Baseline condition (no stimulation) …
Non-Amyloid Approaches To Disease Modification For Alzheimer’S Disease: An Eu/Us Ctad Task Force Report, Serge Gauthier, P. S. Aisen, J. Cummings, M. J. Detke, F. M. Longo, R. Raman, M. Sabbagh, L. Schneider, R. Tanzi, P. Tariot, M. Weiner, J. Touchon, B. Vellas
Non-Amyloid Approaches To Disease Modification For Alzheimer’S Disease: An Eu/Us Ctad Task Force Report, Serge Gauthier, P. S. Aisen, J. Cummings, M. J. Detke, F. M. Longo, R. Raman, M. Sabbagh, L. Schneider, R. Tanzi, P. Tariot, M. Weiner, J. Touchon, B. Vellas
School of Medicine Faculty Research
© 2020, The Author(s). While amyloid-targeting therapies continue to predominate in the Alzheimer’s disease (AD) drug development pipeline, there is increasing recognition that to effectively treat the disease it may be necessary to target other mechanisms and pathways as well. In December 2019, The EU/US CTAD Task Force discussed these alternative approaches to disease modification in AD, focusing on tau-targeting therapies, neurotrophin receptor modulation, anti-microbial strategies, and the innate immune response; as well as vascular approaches, aging, and non-pharmacological approaches such as lifestyle intervention strategies, photobiomodulation and neurostimulation. The Task Force proposed a general strategy to accelerate the development of …
New Approaches To Symptomatic Treatments For Alzheimer’S Disease, Jeffrey Cummings
New Approaches To Symptomatic Treatments For Alzheimer’S Disease, Jeffrey Cummings
School of Medicine Faculty Research
Background: Successful development of agents that improve cognition and behavior in Alzheimer’s disease (AD) is critical to improving the lives of patients manifesting the symptoms of this progressive disorder. Discussion: There have been no recent approvals of cognitive enhancing agents for AD. There are currently 6 cognitive enhancers in Phase 2 trials and 4 in phase 3. They represent a variety of novel mechanisms. There has been progress in developing new treatments for neuropsychiatric symptoms in AD with advances in treatment of insomnia, psychosis, apathy, and agitation in AD. There are currently 4 AD-related psychotropic agents in Phase 2 trials …
Alzheimer's Disease Drug Development Pipeline: 2020, Jeffrey Cummings, Garam Lee, Aaron Ritter, Marwan Sabbagh, Kate Zhong
Alzheimer's Disease Drug Development Pipeline: 2020, Jeffrey Cummings, Garam Lee, Aaron Ritter, Marwan Sabbagh, Kate Zhong
School of Medicine Faculty Research
© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association. Introduction: Alzheimer's disease (AD) is a growing public health concern affecting millions of patients worldwide and costing billions of dollars annually. We review the pipeline of drugs and biologics in clinical trials for the treatment of AD. We use the Common Alzheimer's and Related Dementias Research Ontology (CADRO) to classify treatment targets and mechanisms of action. We review our annual pipeline reports for the past 5 years to provide longitudinal insight into clinical trials and drug development for …
Open Peer Commentary To “Failure To Demonstrate Efficacy Of Aducanumab: An Analysis Of The Emrge And Engage Trials As Reported By Biogen December 2019”, Marwan Noel Sabbagh, Jeffrey Cummings
Open Peer Commentary To “Failure To Demonstrate Efficacy Of Aducanumab: An Analysis Of The Emrge And Engage Trials As Reported By Biogen December 2019”, Marwan Noel Sabbagh, Jeffrey Cummings
School of Medicine Faculty Research
No abstract provided.
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
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 Research
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 …
Biological And Practical Implications Of Genome-Wide Association Study Of Schizophrenia Using Bayesian Variable Selection, Benazir Rowe, Xiangning Chen, Zuoheng Wang, Jingchun Chen, Amei Amei
Biological And Practical Implications Of Genome-Wide Association Study Of Schizophrenia Using Bayesian Variable Selection, Benazir Rowe, Xiangning Chen, Zuoheng Wang, Jingchun Chen, Amei Amei
School of Medicine Faculty Research
Genome-wide association studies (GWAS) have identified over 100 loci associated with schizophrenia. Most of these studies test genetic variants for association one at a time. In this study, we performed GWAS of the molecular genetics of schizophrenia (MGS) dataset with 5334 subjects using multivariate Bayesian variable selection (BVS) method Posterior Inference via Model Averaging and Subset Selection (piMASS) and compared our results with the previous univariate analysis of the MGS dataset. We showed that piMASS can improve the power of detecting schizophrenia-associated SNPs, potentially leading to new discoveries from existing data without increasing the sample size. We tested SNPs in …
Clinical Drug Development For Dementia With Lewy Bodies: Past And Present, Garam Lee, Jeffrey Cummings, Boris Decourt, James B. Leverenz, Marwan N. Sabbagh
Clinical Drug Development For Dementia With Lewy Bodies: Past And Present, Garam Lee, Jeffrey Cummings, Boris Decourt, James B. Leverenz, Marwan N. Sabbagh
School of Medicine Faculty Research
Introduction: Dementia with Lewy bodies (DLB) is an under-researched area despite being the second most common type of degenerative dementia after Alzheimer’s disease. It is an area of unmet need with no approved symptomatic or disease-modifying therapies. The pharmacological management of DLB is complex and challenging because early trials of drugs for DLB have resulted in no demonstrable efficacy. Randomized controlled trials (RCTs) in the DLB population have only recently been initiated. Understanding results from previous and current clinical trials in DLB can provide insights for future research and development. Areas covered: We provide an overview of the DLB drug …
Sex Moderates Amyloid And Apolipoprotein Ε4 Effects On Default Mode Network Connectivity At Rest, Jessica Z.K. Caldwell, Xiaowei Zhuang, Mackenzie J. Leavitt, Sarah J. Banks, Jeffery Cummings, Dietmar Cordes
Sex Moderates Amyloid And Apolipoprotein Ε4 Effects On Default Mode Network Connectivity At Rest, Jessica Z.K. Caldwell, Xiaowei Zhuang, Mackenzie J. Leavitt, Sarah J. Banks, Jeffery Cummings, Dietmar Cordes
School of Medicine Faculty Research
Women are more likely to have Alzheimer's disease (AD) and decline more rapidly once diagnosed despite greater verbal memory early in the disease compared to men—an advantage that has been termed “memory reserve.” Resting state functional MRI (fMRI) investigations demonstrate interactions between sex and AD risk factors in default mode network (DMN) connectivity, a network of brain regions showing progressive dysfunction in AD. Separate work suggests connectivity of left prefrontal cortex (PFC) may correlate with more general cognitive reserve in healthy aging. It is unknown whether left prefrontal functional connectivity with anterior and posterior default mode network (aDMN, pDMN) might …
Souvenaid In The Management Of Mild Cognitive Impairment: An Expert Consensus Opinion, Jeffrey Cummings, Peter Passmore, Bernadette Mcguinness, Vincent Mok, Christopher Chen, Sebastiaan Engelborghs, Michael Woodward, Sagrario Manzano, Guillermo Garcia-Ribas, Stefano Cappa, Paulo Bertolucci, Leung-Wing Chu
Souvenaid In The Management Of Mild Cognitive Impairment: An Expert Consensus Opinion, Jeffrey Cummings, Peter Passmore, Bernadette Mcguinness, Vincent Mok, Christopher Chen, Sebastiaan Engelborghs, Michael Woodward, Sagrario Manzano, Guillermo Garcia-Ribas, Stefano Cappa, Paulo Bertolucci, Leung-Wing Chu
School of Medicine Faculty Research
Background Mild cognitive impairment (MCI) among an aging global population is a growing challenge for healthcare providers and payers. In many cases, MCI is an ominous portent for dementia. Early and accurate diagnosis of MCI provides a window of opportunity to improve the outcomes using a personalized care plan including lifestyle modifications to reduce the impact of modifiable risk factors (for example, blood pressure control and increased physical activity), cognitive training, dietary advice, and nutritional support. Souvenaid is a once-daily drink containing a mixture of precursors and cofactors (long-chain omega-3 fatty acids, uridine, choline, B vitamins, vitamin C, vitamin E, …
Meta-Analysis Of Cognitive Performance By Novel Object Recognition After Proton And Heavy Ion Exposures, Eliedonna Cacao, Francis A. Cucinotta
Meta-Analysis Of Cognitive Performance By Novel Object Recognition After Proton And Heavy Ion Exposures, Eliedonna Cacao, Francis A. Cucinotta
Health Physics and Diagnostic Sciences Faculty Research
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 …
A 24-Week Double-Blind Placebo-Controlled Study Of The Efficacy And Safety Of The Ampa Modulator S47445 In Patients With Mild To Moderate Alzheimer's Disease And Depressive Symptoms, Eileen M. Bulger, Sylvie Gouttefangeas, Sylvie Bretin, Stéphanie Galtier, Philippe Robert, Vjera Holthoff-Detto, Jeffrey Cummings, Maria Pueyo
A 24-Week Double-Blind Placebo-Controlled Study Of The Efficacy And Safety Of The Ampa Modulator S47445 In Patients With Mild To Moderate Alzheimer's Disease And Depressive Symptoms, Eileen M. Bulger, Sylvie Gouttefangeas, Sylvie Bretin, Stéphanie Galtier, Philippe Robert, Vjera Holthoff-Detto, Jeffrey Cummings, Maria Pueyo
School of Medicine Faculty Research
Introduction S47445 is a novel positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors that may emerge as a favorable candidate for the symptomatic treatment of cognitive and depressive disorders in patients suffering from Alzheimer's disease (AD) of mild to moderate severity and with depressive symptoms. Methods For this double-blind, placebo-controlled 24-week phase II trial, 520 outpatients aged between 55 and 85 years, with probable AD at mild to moderate stages (a Mini-Mental State Examination score of 24-15 inclusive) and exhibiting depressive symptoms (Cornell Scale for Depression in Dementia [CSDD] ≥ 8) were recruited in twelve countries and randomized to 3 doses …
Associations Between Comorbid Tdp-43, Lewy Body Pathology And Neuropsychiatric Symptoms In Alzheimer's Disease, Ece Bayram, Guogen Shan, Jeffrey L. Cummings
Associations Between Comorbid Tdp-43, Lewy Body Pathology And Neuropsychiatric Symptoms In Alzheimer's Disease, Ece Bayram, Guogen Shan, Jeffrey L. Cummings
School of Public Health Faculty Research
More than half of the patients with Alzheimer’s disease (AD) have comorbidities including TDP-43 and Lewy bodies, which are also associated with frontotemporal lobar degeneration and dementia with Lewy bodies, respectively. These comorbidities may help explain the overlapping neuropsychiatric symptoms between AD and other dementias. Data on 221 AD patients with Neuropsychiatric Inventory-Questionnaire were obtained from the National Alzheimer’s Coordinating Center. TDP-43 was associated with aberrant motor activity, whereas Lewy bodies were associated with anxiety, irritability, sleep behavior, and appetite problems. The associations between these comorbidities and neuropsychiatric symptoms were more significant for patients with sparse diffuse plaques.