Review
Medicine, Research & Experimental
Shreya Asher, Ronny Priefer
Summary: This article reviews the history of clinical trials for Alzheimer's disease and analyzes the reasons for their failures.
Review
Neurosciences
Simon R. W. Stott, Richard K. Wyse, Patrik Brundin
Summary: The international Linked Clinical Trials program is focused on providing disease-modifying drugs for Parkinson's disease, with seven completed and 15 ongoing clinical trials. This program, which has rapidly grown since its initial planning in 2010, aims to deliver disease modification in PD by evaluating 16 agents in clinical trials. The review provides an overview of the history, structure, process, progress, and examples of agents selected and evaluated by the program.
FRONTIERS IN NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
George E. Barreto
Summary: Alzheimer's disease (AD) is a neurodegenerative disease characterized by amyloid-beta and tau accumulation, leading to memory and cognitive loss. Postmenopausal women have a higher risk of developing AD, possibly due to decreased hormone levels, especially estrogen, and its impact on estrogen receptors, particularly ERβ. Hormone therapies, such as tibolone, which reduces amyloid burden and improves mitochondrial function, could be a potential treatment option for AD. The importance of tibolone has increased due to its implication in AD pathogenesis.
Article
Clinical Neurology
Victoire Leroy, Wassim Gana, Amal Aidoud, Jacques-Alexis N'kodo, Anna-Chloe Balageas, Pascal Blanc, Dominique Bomia, Camille Debacq, Bertrand Fougere
Summary: Decentralized clinical trials (DCTs) have the potential to overcome screening and recruitment challenges in Alzheimer's disease (AD) therapeutic trials, and may facilitate involvement of primary care providers and caregivers. However, further research is needed to assess the feasibility of DCTs in AD.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Computer Science, Artificial Intelligence
Ruoqi Liu, Lai Wei, Ping Zhang
Summary: Drug repurposing is an effective strategy to discover new uses for existing drugs by analyzing real-world data, offering new possibilities for disease treatment.
NATURE MACHINE INTELLIGENCE
(2021)
Article
Clinical Neurology
Terry E. Goldberg, Seonjoo Lee, Davangere P. Devanand, Lon S. Schneider
Summary: Using per cent slowing of decline as a metric of outcome in Alzheimer's disease clinical trials may be misleading, while Cohen's d is a more valid and informative measure of efficacy. Standardised effect size determines group overlap, influences NNT computations, and provides information on the likelihood of minimum clinically important differences.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Kyriaki Savva, Margarita Zachariou, Marilena M. Bourdakou, Nikolas Dietis, George M. Spyrou
Summary: This study proposes a network-based method for drug repurposing against different stages of Alzheimer's disease. It ranks candidate repurposed drugs based on their structural similarity with existing drugs and re-ranks them based on functional, structural, and a priori information. The method also considers the permeability through the Blood Brain Barrier. The proposed methodology has been validated on known clinical trial drugs and shows promising results.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Geriatrics & Gerontology
Laura C. Hanson, Kathryn Wessell, Natalie Meeks, Antonia V. Bennett, Mark Toles, Josh Niznik, Sheryl Zimmerman, Joan Carpenter, Christine S. Ritchie, Natalie C. Ernecoff, Debra Saliba
Summary: This study describes the development and structure of the IMbedded Pragmatic ADRD Clinical Trials Collaboratory (IMPACT) iLibrary of potential outcome measures for ADRD pragmatic trials and evaluates their pragmatic characteristics. The study found that pragmatic outcome measures are brief, meaningful to diverse populations, easily scored and interpreted by clinicians, and available in electronic format for analysis. The iLibrary can aid in the selection of measures for a wide range of outcomes relevant to people with ADRD and their care partners.
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
(2023)
Article
Clinical Neurology
Marina Ritchie, Daniel L. Gillen, Joshua D. Grill
Summary: This study analyzed the recruitment trends of 11 Alzheimer's disease clinical trials conducted over a 20-year period. The study found that there were no significant changes in recruitment planning or overall recruitment rates over time. None of the trials achieved a recruitment rate of more than one participant per site per month. Trials with no competition had the fastest recruitment rates, while trials that overlapped in time had the slowest rates. The study suggests that recruitment projections should plan for less than one participant per site per month and consider the number of other trials being conducted concurrently.
ALZHEIMERS RESEARCH & THERAPY
(2023)
News Item
Multidisciplinary Sciences
Sara Reardon
Summary: Concerns arise due to the lack of representation of people of colour, questioning the safety and effectiveness of drugs in diverse populations.
Review
Cell Biology
Tanzeel Khan, Rashid Waseem, Mohammad Shahid, Jaoud Ansari, Ishfaq Ahmad Ahanger, Imtaiyaz Hassan, Asimul Islam
Summary: Alzheimer's disease is the most prevalent form of dementia, and there is currently no permanent cure. Stem cell therapy has shown promising results in preclinical studies and is being explored as a potential treatment. This article reviews research from the past decade, discusses hypotheses related to the pathology of Alzheimer's disease, and provides an overview of ongoing clinical trials for immunotherapy and stem cell therapy.
AGEING RESEARCH REVIEWS
(2023)
Review
Health Care Sciences & Services
Areeba Rashad, Atta Rasool, Muhammad Shaheryar, Azza Sarfraz, Zouina Sarfraz, Karla Robles-Velasco, Ivan Cherrez-Ojeda
Summary: Amyloid-beta (A beta) plaques and aggregated tau are core mechanisms in the development of Alzheimer's disease (AD). This systematic review examines the efficacy and safety of Donanemab, a humanized antibody targeting A beta plaque reduction, in AD patients. The review found that Donanemab led to reduction in A beta plaque levels and a slowing of tau accumulation, resulting in delayed cognitive decline. However, the therapeutic benefits and long-term clinical improvement in AD patients remain unclear, and further trials are needed to explore the potential benefits of Donanemab in modifying the disease's progression.
Article
Clinical Neurology
Annalise Rahman-Filipiak, Corey Bolton, Joshua D. Grill, Ayda Rostamzadeh, Nathaniel Chin, Judith Heidebrink, Sarah Getz, Nicole R. Fowler, Allyson Rosen, Jennifer Lingler, Ellen Wijsman, Lindsay Clark
Summary: The development of biomarkers for Alzheimer's disease (AD) has allowed researchers to improve sample homogeneity and test candidate treatments earlier in the disease. However, it is unknown to what extent standardized methods for disclosing biomarker testing results to research participants are implemented in trials.
ALZHEIMERS & DEMENTIA
(2023)
Article
Pharmacology & Pharmacy
Line Seguy, Lena Guyon, Manon Maurel, Pascal Verdie, Audrey Davis, Sophie Corvaisier, Vincent Lisowski, Patrick Dallemagne, Anne-Claire Groo, Aurelie Malzert-Freon
Summary: The study investigated the potential therapeutic effects of repurposed tegaserod for treating Alzheimer's disease by enhancing the nonamyloidogenic pathway. By encapsulating tegaserod into 50nm nanoemulsions with neutral zeta potential and functionalizing with peptide-22, the study demonstrated the potential value of tegaserod for AD treatment. The developed functionalized nanoemulsions showed efficiency in adsorption and controlled release of tegaserod without hemolytic properties, indicating their promise for future preclinical studies.
Review
Neurosciences
Jacqui Taryn Nimmo, Louise Kelly, Ajay Verma, Roxana O. Carare, James A. R. Nicoll, Jean-Cosme Dodart
Summary: This article discusses the application of immunotherapy in neurodegenerative diseases, specifically Alzheimer's disease and Lewy body diseases. While immunotherapies have shown promising results in animal models, they have faced challenges in clinical trials, indicating a disconnect between experimental and clinical outcomes.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Mathematics, Interdisciplinary Applications
Kristoffer H. Hellton, Jeffrey Cummings, Audun Osland Vik-Mo, Jan Erik Nordrehaug, Dag Aarsland, Geir Selbaek, Lasse Melvaer Giil
Summary: PCA may not be suitable for analyzing psychiatric syndromes in dementia due to zero-inflation. A new method, ZIBP-PCA, was proposed to address this issue and provide a simpler and more interpretable component structure for characterizing the psychopathology of dementia.
MULTIVARIATE BEHAVIORAL RESEARCH
(2021)
Review
Neurosciences
Jeffrey Cummings
Summary: There have been no recent approvals of cognitive enhancing agents for Alzheimer's disease (AD), but there are several new drugs in trials, including those targeting neuropsychiatric symptoms. Progress is also being made in trial design and outcome measures.
MOLECULAR NEURODEGENERATION
(2021)
Editorial Material
Clinical Neurology
Jeffrey Cummings, Paul Aisen, Cynthia Lemere, Alireza Atri, Marwan Sabbagh, Stephen Salloway
ALZHEIMERS RESEARCH & THERAPY
(2021)
Article
Medicine, General & Internal
Justin Bauzon, Caleb Murphy, Sandhya Wahi-Gururaj
Summary: The study demonstrated that macros can significantly reduce the time spent on data cleaning in clinical research, particularly beneficial for institutions lacking informatics support or EMR functionality for exporting data in analysis-ready format.
JOURNAL OF COMMUNITY HOSPITAL INTERNAL MEDICINE PERSPECTIVES
(2021)
Article
Neurosciences
Jeffrey Cummings, Andrew Ortiz, Janelle Castellino, Jefferson Kinney
Summary: Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) commonly co-occur. Animal models suggest that chronic low-grade inflammation caused by persistent hyperglycemia may contribute to the development of neuroinflammation and accelerate the pathobiology of AD. Epidemiological studies show that T2DM patients treated with specific anti-diabetic agents have a decreased risk for AD.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2022)
Article
Pediatrics
Justin Bauzon, Desiree Morris, Charles St Hill, Taylor Schanda, Michael Scheidler, Shirong Chang
Summary: This article reports an unusual case of rapidly growing hepatic mesenchymal hamartoma (HMH) with associated placental anomalies and elevated AFP. The rapid growth raises concerns for malignancy, and the abnormal placental findings affect surgical management.
JOURNAL OF PEDIATRIC SURGERY CASE REPORTS
(2022)
Article
Pharmacology & Pharmacy
Ariyon Schreiber, Justin S. Bauzon, Kavita Batra, Salman Mohammed, Kevin Lee, Nazanin Houshmand, Uyen Pham, Celica Cosme, Kim Inciong, Omar Al-Taweel, Keaton Nasser, Jibran Rana, Chris Sossou, Ariel Go, Dalia Hawwass, Jimmy Diep, Chowdhury H. Ahsan
Summary: This study investigated the clinical characteristics and outcomes of patients who experienced bradycardia during treatment with remdesivir for COVID-19. The results suggest that bradycardia occurring during or shortly after remdesivir treatment may be associated with an increased rate of in-hospital mortality. However, the potential contribution of COVID-19 and its cardiac complications to the occurrence of bradycardia cannot be excluded.
CLINICAL DRUG INVESTIGATION
(2022)
Review
Geriatrics & Gerontology
Krista L. Lanctot, Zahinoor Ismail, Kritleen K. Bawa, Jeffrey L. Cummings, Masud Husain, Moyra E. Mortby, Philippe Robert
Summary: This narrative review discusses the clinical features of apathy and depression in individuals with neurocognitive disorders, aiming to differentiate the two syndromes based on clinical presentation, diagnostic criteria, neuropathological features, and response to treatments.
INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY
(2023)
Article
Pharmacology & Pharmacy
Jeffrey Cummings
Summary: Two anti-amyloid monoclonal antibodies, lecanemab (Leqembi) and aducanumab (Aduhelm), have been approved in the USA for the treatment of Alzheimer's disease. These breakthrough agents slow the clinical decline of AD by targeting the disease's basic biological processes, supporting the amyloid hypothesis and amyloid as a target for drug development. Monoclonal antibodies bring about a new era in AD therapy and open doors for the development of treatments for various neurodegenerative disorders.
Review
Psychology, Clinical
Mary Sano, Jeffrey Cummings, Stefanie Auer, Sverre Bergh, Corinne E. Fischer, Debby Gerritsen, George Grossberg, Zahinoor Ismail, Krista Lanctot, Maria I. Lapid, Jacobo Mintzer, Rebecca Palm, Paul B. Rosenberg, Michael Splaine, Kate Zhong, Carolyn W. Zhu
Summary: This article summarizes the use and validation of the provisional consensus definition of agitation in cognitive disorders published by the International Psychogeriatric Association (IPA) in 2015. It presents a finalized definition based on the review of academic literature, clinical guidelines, expert surveys, and patient and family advocates' experiences. The article also discusses the development of diagnostic tools and strategies for dissemination and integration of the definition into precision diagnosis and agitation interventions.
INTERNATIONAL PSYCHOGERIATRICS
(2023)
Review
Psychology, Clinical
Jeffrey Cummings, Mary Sano, Stefanie Auer, Sverre Bergh, Corinne E. Fischer, Debby Gerritsen, George Grossberg, Zahinoor Ismail, Krista Lanctot, Maria I. Lapid, Jacobo Mintzer, Rebecca Palm, Paul B. Rosenberg, Michael Splaine, Kate Zhong, Carolyn W. Zhu
Summary: The IPA Agitation Work Group develops an algorithm for reducing and preventing agitation, which emphasizes the integration of psychosocial and pharmacologic interventions, reiterative assessment of response to treatment, adjustment of therapeutic approaches, and shared decision-making. The algorithm includes different treatment choices for different levels of agitation.
INTERNATIONAL PSYCHOGERIATRICS
(2023)
Review
Biochemistry & Molecular Biology
Ramakrishna Nirogi, Pradeep Jayarajan, Anil Shinde, Abdul Rasheed Mohammed, Venkata Ramalingayya Grandhi, Vijay Benade, Vinod Kumar Goyal, Renny Abraham, Venkat Jasti, Jeffrey Cummings
Summary: Serotonin-6 (5-HT6) receptor, a G-protein-coupled receptor, plays a key role in the regulation of various functions in the nervous system. Clinical studies have shown that 5-HT6 receptor antagonists have potential in treating cognitive deficits associated with Alzheimer's disease (AD) and neuropsychiatric symptoms in dementia. However, the outcomes of phase 3 trials for these antagonists have been disappointing. Masupirdine, a selective 5-HT6 receptor antagonist, has shown promise in reducing agitation/aggression-like behaviors in animal models and may have potential benefits for agitation and psychosis in AD, but further trials are needed.
Review
Pharmacology & Pharmacy
Jeffrey L. Cummings, Amanda M. Leisgang Osse, Jefferson W. Kinney
Summary: Novel agents targeting non-amyloid, non-tau proteins in Alzheimer's Disease (AD) account for 70% of the drugs currently in clinical trials. Inflammation and synaptic plasticity/neuroprotection are the most common categories for novel therapies in AD research. Multiple categories, including APOE4 effects, lipids and lipoprotein receptors, neurogenesis, and oxidative stress, are being evaluated. Biomarkers are evolving in parallel with new targets and novel agents, providing a means of supporting disease modification. The identification and development of novel targets offer an important opportunity for advancing new AD treatments.
Review
Medicine, General & Internal
Jeffrey Cummings, Jefferson Kinney
Summary: This review explores the regulatory guidance for the use of biomarkers in clinical trials and clinical care. Biomarkers used in clinical trials must have a defined context of use and follow a specific regulatory pathway. In clinical care, biomarkers can be companion biomarkers, in vitro diagnostic devices, or laboratory developed tests.
MEDICINA-LITHUANIA
(2022)
Article
Education, Scientific Disciplines
Justin Bauzon, Amalie Alver, Vishvaas Ravikumar, Adrian Devera, Tatiana Mikhael, Rafae Nauman, Edward Simanton
Summary: This study found that medical students who felt more prepared for exams performed better, and using resources such as watching didactic lectures online and peer-to-peer tutoring had a positive impact on exam performance. Most students used multiple resources for exam preparation, but there may be a slightly negative association between the quantity of resources used and exam scores.
MEDICAL SCIENCE EDUCATOR
(2021)