VJDementia Podcast

Anti-amyloid antibodies are the first disease-modifying therapies for Alzheimer’s disease (AD), with two agents—lecanemab and donanemab—now fully approved by the U.S. Food and Drug Administration (FDA).

This podcast features experts Paulo Caramelli, MD, PhD, Federal University of Minas Gerais, Belo Horizonte, Brazil, Stephen P. Salloway, MD, MS, Butler Hospital & Warren Alpert Medical School of Brown University, Providence, RI, Suzanne Schindler, MD, PhD, Washington University School of Medicine in St. Louis, St. Louis, MO, and Dorota Religa, MD, PhD, Karolinska Institutet, Solna, Sweden, who discuss the practical considerations when using these therapies.

The discussion explores pivotal clinical trial findings, appropriate use recommendations, the management of amyloid-related imaging abnormalities (ARIA), and patients who may not be eligible for these treatments.

The post Practical considerations when using anti-amyloid antibodies for the treatment of Alzheimer’s disease appeared first on VJDementia.

In this episode, we dive into the latest advancements in Alzheimer’s disease (AD) biomarkers, focusing on the diagnostic and predictive potential of plasma p-tau217.

As an alternative to traditional PET assessment, blood-based biomarker detection has the potential to provide a time-efficient, cost-effective strategy for pre-screening and treatment monitoring in AD clinical trials. Although the widespread use of blood-based biomarkers in clinical practice remains to be seen, they also hold promise in expediting diagnostic/prognostic procedures for AD.

We are joined by renowned researchers who discuss their work to test and validate p-tau217, both as a tool for clinical trials and for use in daily practice. 

With Marco Bucci, PhD, Karolinska Institutet, Stockholm, Sweden; Suzanne Schindler, MD, PhD, Washington University in St. Louis School of Medicine, St. Louis, MO; Pamela Lukasewicz Ferreira, PhD, University of Pittsburgh, Pittsburgh, PA; and Lyduine Collij, PhD, Lund University, Lund, Sweden.

The post Exploring plasma p-tau217: a game-changer in Alzheimer’s trials appeared first on VJDementia.

The retina is often considered an extension of the brain, as they share many functional and structural similarities. Retinal changes have been reported to correspond to brain and cognitive changes seen in patients with Alzheimer’s Disease (AD). These changes include pathologies associated with AD such as amyloid-beta (Aβ) deposition and neurofibrillary tangle build up. The retina has been cited as a way to assess AD, particularly in patients with early AD, in a simple and non-invasive manner. Work is currently being undertaken to detect retinal biomarkers of AD, to allow for earlier diagnosis and the introduction of interventions which are needed to manage the disease effectively.

There are several areas currently being investigated to assess how the retina can provide insights into AD. In today’s episode, we hear from top researchers studying the retina as a window to the Alzheimer’s brain. Hear the latest on retinal biomarkers, the development of a diagnostic ‘eye test’ for Alzheimer’s disease, and the promise of retina organoids for novel drug development. 

With Frederique Hart de Ruyter, MD, Vrije Universiteit Amsterdam; Maya Koronyo-Hamaoui, PhD, Cedars-Sinai Medical Center; Mourad Tayebi, PhD, Western Sydney University; & Natalia Vergara, PhD, University of Colorado.

The post Eyes on Alzheimer’s: the promise of the retina in research and healthcare appeared first on VJDementia.

Genetic studies have shown that the vast majority of risk genes for Alzheimer’s Disease (AD) are highly, or even preferentially, expressed in microglia. Accumulating evidence is demonstrating the importance of microglia in AD development and progression, with experimental models demonstrating both protective and destructive capabilities. It has been suggested that the role of microglia in AD changes depending on the stage of the disease, with protective functions predominating in early-stage AD but more detrimental functions taking over in the later stages.

Intensive research is being conducted to understand more about microglia and their phenotypic transitions over time and in response to their environment. This not only has implications for therapeutic targeting of microglia subsets in disease, but also for conducting research and the need to closely consider the environment when interpreting data from microglia models.

In this episode, VJDementia are joined by Amy Lloyd, PhD, University of Dundee, Dundee; Soyon Hong, PhD, University College London, London, UK; João Pedro Ferrari-Souza, MD-PhD candidate, University of Pittsburgh, Pittsburgh, PA; and Elina Svensson, PhD candidate, University College London, London, UK, who are sharing their work looking at the complex and disparate roles of microglia in health and disease, and the implications of this for understanding how to treat AD.

The post Exciting developments in microglia research in Alzheimer’s disease appeared first on VJDementia.

On January 6, 2023, the US Food and Drug Administration (FDA) approved lecanemab for the treatment of Alzheimer’s disease (AD), making history as the first ever treatment to significantly slow cognitive decline. The approval follows that of aducanumab last year, and together these drugs represent a new category of medications targeting the Aβ pathology associated with AD.

Lecanemab is unique for its preferential binding of soluble amyloid-β protofibrils compared to aggregated amyloid plaques. In the recently completed Phase III trial, Clarity AD (NCT03887455), lecanemab slowed cognitive decline by 27% compared to placebo, as measured by CDR-SB. Similar slowing of decline was reported in other measures of cognitive function such as ADCOMS, ADAS-Cog14 and ADCS MCI-ADL.

Despite the excitement in the field surrounding this breakthrough approval, concerns remain regarding the extent of lecanemab’s clinical benefit and the risks involved with its use. In this episode, experts delve into the evidence we have to date, reflecting on the performance of lecanemab in clinical trials, how it compares to aducanumab, the risk of hemorrhage, its efficacy in women, and future directions for investigating anti-amyloid immunotherapies.

With Lars Lannfelt, MD, PhD, Uppsala University, Uppsala, Sweden; Alvaro Pascual-Leone, MD, PhD, Hebrew SeniorLife & Harvard Medical School, Boston, MA; and Nicolas Villain, MD, PhD, AP-HP Sorbonne University, Paris, France.

The post Expert perspectives on lecanemab appeared first on VJDementia.

Cognitive decline caused by dementia is one of the leading causes of disability and dependency for older adults globally, and due to ageing populations around the world, the estimated 50 million people who currently suffer from dementia is projected to reach 100 million by 2050. Thus, dementia is considered a major public health issue. Considering this, healthcare professionals and researchers are beginning to focus on behaviors which could delay or even prevent the onset of cognitive decline. Research suggests that diet is an important lifestyle factor which could be an integral component in preventing cognitive decline and dementia in older age. Observational studies consistently demonstrate correlations between certain dietary habits and cognitive performance, however randomized clinical trials have struggled to confirm such findings.

In this week’s episode, specialists discuss the results of their recent studies and give insights on the implications that their research could have for dementia prevention. The topics up for discussion this week include: high intake of ultra-processed food associated with cognitive decline, intermittent fasting in Alzheimer’s disease, omega-3 consumption in the prevention of dementia in APOE4 carriers, and the REACTION trial assessing a multi-nutrient drink for age-related cognitive decline.

The post Nutrition and cognitive decline appeared first on VJDementia.

Our current podcast series is focused on Alzheimer’s disease biomarkers. Hundreds of studies have emerged in recent years that have aimed to characterize and validate several blood-based biomarkers and ready them for daily use in the real-world. While a number of well-studied diagnostic markers are beginning to be implemented in clinical practice, many more are still emerging. Biomarkers that can predict prognosis or be used for monitoring and outcome assessment in clinical trials are needed to improve disease management and support the development of novel therapeutics.

In this third and final episode, our guests will discuss their work on the discovery and validation of promising new biomarkers for monitoring, prognostication, and clinical trial outcomes. Novel markers beyond the classical measures of plasma amyloid and phosphorylated tau will be discussed, including TREM2, neurofilament light, retinal imaging, and blood-brain barrier leakage. It is hoped that these features could provide valuable insights beyond those provided by the current biomarker repertoire.

With Charlotte Teunissen, Amsterdam University Medical Center; Estrella Morenas-Rodriguez, German Center for Neurodegenerative Diseases; Natalia Vergara, University of Colorado School of Medicine; Giulia Giacomucci, University of Florence; and Axel Montagne, UK Dementia Research Institute.

The post Novel markers for Alzheimer’s disease monitoring and prognostication appeared first on VJDementia.

Blood biomarkers are taking off in the Alzheimer’s disease field, showing promise for diagnosis, prognostication, and treatment monitoring. As more evidence is collected, it is becoming clear that different markers reflect different stages of progression and thus, perform better at certain stages of disease. For example, phosphorylated-tau-231 has been put forward as the most promising candidate for detecting incipient amyloid-beta (Aβ) pathology. Several studies have also shown that neurofilament light, GFAP, and phosphorylated-tau-181 levels in the blood may help to predict the risk of progression to dementia from subjective cognitive decline (SCD) or mild cognitive impairment (MCI).

Research groups across the globe are assessing biomarkers in the very earliest stages of disease. Identifying measures that reflect early pathology or can predict dementia risk prior to symptom onset could improve early diagnosis and prognostication, as well as recognizing high-risk populations for clinical trial enrolment and public health interventions. In this episode, Marta Milà-Alomà, PhD, Barcelonaβeta Brain Research Center (BBRC), Barcelona; Pamela Lukasewicz Ferreira, PhD, University of Pittsburgh, Pittsburgh; Madison Honey, PhD candidate, Amsterdam University Medical Centre, Amsterdam; and Zahinoor Ismail, MD, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, share their latest work looking at early biomarkers, from plasma biomarkers to mild behavioral impairment.

The post Early biomarkers for Alzheimer’s disease appeared first on VJDementia.

Blood biomarkers are taking off in the Alzheimer’s disease field, showing promise for diagnosis, prognostication, and treatment monitoring. Current diagnostic methods, such as cerebrospinal fluid analysis and amyloid PET scans, are expensive, invasive, and not widely available. Therefore, the development of a blood test which detects amyloid beta (Aβ), phosphorylated tau (p-tau), or other putative objective markers could be the way forward.

Following development, rigorous validation, and retrospective and prospective analyses, several assays are now ready for real-world study and clinical implementation. Many investigations are ongoing to try to determine the optimal combinations of biomarkers, cut-offs for accurate discrimination, and where in the disease spectrum each marker performs best. In today’s podcast, our experts discuss the road to clinical implementation of plasma biomarkers, including the latest data on Aβ, p-tau, and GFAP, development of standard operating procedures and guidelines, and real-world evidence.

The post Alzheimer’s disease blood tests? Bringing plasma biomarkers into clinical practice appeared first on VJDementia.

The complexity of Alzheimer’s disease (AD) pathogenesis has led to difficulties understanding the disease and, therefore, impacted the development of AD drugs. Immunotherapy is a powerful treatment approach that holds considerable promise for the future. Recently, an anti-β-amyloid monoclonal antibody, aducanumab, was approved by the US Food and Drug Administration (FDA), and the current pipeline of anti- β-amyloid monoclonal antibodies in clinical trials and under the evaluation of regulatory agencies continues to grow. Meanwhile, immunotherapy strategies targeting tau are also under development. As the future unfolds, immunotherapies based on β-amyloid and tau may be promising strategies to reduce the devastating effects of AD.

In this episode, AD specialists Philip Tipton, MD, Mayo Clinic, Jacksonville, FL; Johanne Kaplan, PhD, ProMIS Neurosciences, Inc., Cambridge, MA; and Adam Fleisher, MD, MAS, Eli Lilly and Company, Indianapolis, IN, discuss the development of immunotherapeutic strategies for AD targeting β-amyloid and tau.

The post Immunotherapy for Alzheimer’s disease: targeting β-amyloid and tau appeared first on VJDementia.