Browsing by Author "Khachaturian, Ara S."

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    The cholinergic system in the pathophysiology and treatment of Alzheimer's disease
    (Oxford University Press, 2018-07) Hampel, Harald; Mesulam, M.-Marsel; Cuello, A. Claudio; Farlow, Martin R.; Giacobini, Ezio; Grossberg, George T.; Khachaturian, Ara S.; Vergallo, Andrea; Cavedo, Enrica; Snyder, Peter J.; Khachaturian, Zaven S.; Neurology, IU School of Medicine
    Cholinergic synapses are ubiquitous in the human central nervous system. Their high density in the thalamus, striatum, limbic system, and neocortex suggest that cholinergic transmission is likely to be critically important for memory, learning, attention and other higher brain functions. Several lines of research suggest additional roles for cholinergic systems in overall brain homeostasis and plasticity. As such, the brain's cholinergic system occupies a central role in ongoing research related to normal cognition and age-related cognitive decline, including dementias such as Alzheimer's disease. The cholinergic hypothesis of Alzheimer's disease centres on the progressive loss of limbic and neocortical cholinergic innervation. Neurofibrillary degeneration in the basal forebrain is believed to be the primary cause for the dysfunction and death of forebrain cholinergic neurons, giving rise to a widespread presynaptic cholinergic denervation. Cholinesterase inhibitors increase the availability of acetylcholine at synapses in the brain and are one of the few drug therapies that have been proven clinically useful in the treatment of Alzheimer's disease dementia, thus validating the cholinergic system as an important therapeutic target in the disease. This review includes an overview of the role of the cholinergic system in cognition and an updated understanding of how cholinergic deficits in Alzheimer's disease interact with other aspects of disease pathophysiology, including plaques composed of amyloid-β proteins. This review also documents the benefits of cholinergic therapies at various stages of Alzheimer's disease and during long-term follow-up as visualized in novel imaging studies. The weight of the evidence supports the continued value of cholinergic drugs as a standard, cornerstone pharmacological approach in Alzheimer's disease, particularly as we look ahead to future combination therapies that address symptoms as well as disease progression.
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    Considerations for widespread implementation of blood-based biomarkers of Alzheimer's disease
    (Wiley, 2024) Mielke, Michelle M.; Anderson, Matthew; Ashford, J. Wesson; Jeromin, Andreas; Lin, Pei-Jung; Rosen, Allyson; Tyrone, Jamie; VandeVrede, Lawren; Willis, Deanna; Hansson, Oskar; Khachaturian, Ara S.; Schindler, Suzanne E.; Weiss, Joan; Batrla, Richard; Bozeat, Sasha; Dwyer, John R.; Holzapfel, Drew; Jones, Daryl Rhys; Murray, James F.; Partrick, Katherine A.; Scholler, Emily; Vradenburg, George; Young, Dylan; Braunstein, Joel B.; Burnham, Samantha C.; de Oliveira, Fabricio Ferreira; Hu, Yan Helen; Mattke, Soeren; Merali, Zul; Monane, Mark; Sabbagh, Marwan Noel; Shobin, Eli; Weiner, Michael W.; Udeh-Momoh , Chinedu T.; Medicine, School of Medicine
    Diagnosing Alzheimer's disease (AD) poses significant challenges to health care, often resulting in delayed or inadequate patient care. The clinical integration of blood-based biomarkers (BBMs) for AD holds promise in enabling early detection of pathology and timely intervention. However, several critical considerations, such as the lack of consistent guidelines for assessing cognition, limited understanding of BBM test characteristics, insufficient evidence on BBM performance across diverse populations, and the ethical management of test results, must be addressed for widespread clinical implementation of BBMs in the United States. The Global CEO Initiative on Alzheimer's Disease BBM Workgroup convened to address these challenges and provide recommendations that underscore the importance of evidence-based guidelines, improved training for health-care professionals, patient empowerment through informed decision making, and the necessity of community-based studies to understand BBM performance in real-world populations. Multi-stakeholder engagement is essential to implement these recommendations and ensure credible guidance and education are accessible to all stakeholders.
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    Recommendations for clinical implementation of blood-based biomarkers for Alzheimer's disease
    (Wiley, 2024) Mielke, Michelle M.; Anderson, Matthew; Ashford, J. Wesson; Jeromin, Andreas; Lin, Pei-Jung; Rosen, Allyson; Tyrone, Jamie; Vandevrede, Lawren; Willis, Deanna R.; Hansson, Oskar; Khachaturian, Ara S.; Schindler, Suzanne E.; Weiss, Joan; Batrla, Richard; Bozeat, Sasha; Dwyer, John R.; Holzapfel, Drew; Jones, Daryl Rhys; Murray, James F.; Partrick, Katherine A.; Scholler, Emily; Vradenburg, George; Young, Dylan; Braunstein, Joel B.; Burnham, Samantha C.; de Oliveira, Fabricio Ferreira; Hu, Yan Helen; Mattke, Soeren; Merali, Zul; Monane, Mark; Sabbagh, Marwan Noel; Shobin, Eli; Weiner, Michael; Udeh-Momoh, Chinedu T.; Medicine, School of Medicine
    Blood-based biomarkers (BBM) for Alzheimer's disease (AD) are being increasingly used in clinical practice to support an AD diagnosis. In contrast to traditional diagnostic modalities, such as amyloid positron emission tomography and cerebrospinal fluid biomarkers, BBMs offer a more accessible and lower cost alternative for AD biomarker testing. Their unique scalability addresses the anticipated surge in demand for biomarker testing with the emergence of disease-modifying treatments (DMTs) that require confirmation of amyloid pathology. To facilitate the uptake of BBMs in clinical practice, The Global CEO Initiative on Alzheimer's Disease convened a BBM Workgroup to provide recommendations for two clinical implementational pathways for BBMs: one for current use for triaging and another for future use to confirm amyloid pathology. These pathways provide a standardized diagnostic approach with guidance on interpreting BBM test results. Integrating BBMs into clinical practice will simplify the diagnostic process and facilitate timely access to DMTs for eligible patients.