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Preclinical Alzheimer's prevention trials require a multi-year commitment from diverse, cognitively unimpaired individuals willing to receive biomarker results of confirmed Alzheimer's pathology and possible ApoE4 status. Participants learn new terms such as ARIA, edema and microhemorrhage and undergo numerous MRI scans for safety monitoring. They take quarterly composite Alzheimer's assessments that are anxiety-provoking and highlight weaknesses which may have been unrecognized in daily life.
View Article and Find Full Text PDFLecanemab, a humanized IgG1 monoclonal antibody that binds with high affinity to amyloid-beta (Aβ) protofibrils, was formally evaluated as a treatment for early Alzheimer's disease in a phase 2 study (Study 201) and the phase 3 Clarity AD study. These trials both included an 18-month, randomized study (core) and an open-label extension (OLE) phase where eligible participants received open-label lecanemab for up to 30 months to date. Clinical (CDR-SB, ADAS-Cog14, and ADCS-MCI-ADL), biomarker (PET, Aβ42/40 ratio, and ptau181) and safety outcomes were evaluated.
View Article and Find Full Text PDFAlzheimer's disease pathophysiology is believed to involve various abnormalities, including those of amyloid beta (Ab) peptide and tau processing, inflammation, oxidative stress, and vascular risk factors. Aβ peptides exist in a dynamic continuum of conformational states from monomeric Aβ, to soluble progressively larger Aβ assemblies that include a range of low molecular weight oligomers to higher molecular weight protofibrils, and finally to insoluble fibrils (plaques). Various lines of evidence support the "amyloid hypothesis" that Aβ plays a central role in the pathogenesis of AD, and several immunotherapies have been developed to interact with this cascade in various different places which may reduce the number of soluble aggregates and insoluble Aβ fibrils deposited in the brain.
View Article and Find Full Text PDFAmyloid β (Aβ) has been confirmed as a therapeutic target in AD by recent findings in Phase 3 trials with anti-Aβ antibodies. Modulators of γ-secretase (GSMs) are an emerging complementary approach to target amyloid. GSMs "modulate" the interaction between γ-secretase and amyloid precursor protein (APP), leading to a reduced production of long, amyloidogenic Aβ42 and Aβ40 and to concomitantly increased levels of the shorter, non amyloidogenic Aβ37 and Aβ38.
View Article and Find Full Text PDFDementia Care Research and Psychosocial Factors.
Alzheimers Dement
December 2024
University of Virginia, Charlottesville, VA, USA.
Background: For care of persons with dementia (PWDs), the healthcare system relies on informal care partners (CPs), who are disproportionately at risk of detrimental health outcomes. Psychosocial interventions, including via telehealth, have been shown to buffer against negative outcomes and improve CPs' ability to provide care. We aimed to develop and pilot an evidence-informed CP intervention using in-person and telehealth modalities.
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