Alzheimer disease (AD), the most common form of dementia, affects more than 5 million US residents and progressively leads to a loss of memory and cognitive function. The advent of new therapeutic agents for AD has the potential to lessen the enormous patient, family, and societal burden of illness. In this issue of JAMA, phase 3 trial results suggest that donanemab (an infused monoclonal antibody) is efficacious in slowing disease progression based on the Integrated Alzheimer’s Disease Rating Scale in patients with mild to moderate AD with amyloid and tau pathology. Another monoclonal antibody that produced similar improvements, lecanemab, was recently awarded traditional approval by the Food and Drug Administration (FDA). While these new therapies have been welcomed by many stakeholders, they also will challenge the US system of pharmaceutical regulation and reimbursement. In particular—assuming FDA approval is granted—payers and policy makers must design rules that optimize value, affordability, and equity of AD care.
Source: JAMA Online First
In Alzheimer disease (AD) research and care, novel biomarkers that measure amyloid-β (Aβ) and phosphorylated tau (P-tau)–the principal components of amyloid plaques and neurofibrillary tangles–have facilitated early detection and biomarker-supported diagnosis. Therapeutics that modify the biology of AD are being tested in clinical trials, leveraging biomarkers so that investigators select the right patients, evaluate target engagement, and gauge the effects of therapy on AD pathophysiology. The first class of therapies to reach the clinic in this modern era of AD drug development are Aβ-targeting monoclonal antibodies, which bind different species in the Aβ aggregation cascade. This treatment approach is grounded in the “amyloid hypothesis,” which postulates that Aβ aggregation triggers a cascade of pathophysiologic events, including synaptic and network dysfunction, neuroinflammation, and aggregation and spread of P-tau tangles. The spread of tangles is associated with synaptic loss and neurodegeneration, culminating in cognitive decline and dementia. By binding Aβ aggregates, monoclonal antibodies facilitate Aβ clearance from the brain, potentially mitigating both direct and downstream deleterious effects of Aβ and hence slowing cognitive decline.
Source: JAMA Online First
Availability of safe and effective treatments for Alzheimer disease is an urgent challenge given the global shift toward an older population and increased risk of mild cognitive impairment and dementia as people age. Dementia-related burdens are disproportionately felt within historically marginalized communities because structural inequalities rooted in racism, xenophobia, and sexism increase risk factors for cognitive impairment, increase barriers to diagnosis, and reduce access to care.
Source: JAMA Online First
This randomized clinical trial examines the efficacy and adverse effects of donanemab, a monoclonal antibody designed to clear brain amyloid plaque, among patients with early symptomatic Alzheimer disease.
Source: JAMA Online First
An older patient with history of surgical decompression for syringomyelia, poor mobility, and frequent falls presented with pain, numbness, and paresthesias in his left upper extremity. Radiograph showed complete absence of the left humeral head. What is the diagnosis, and what would you do next?
Source: JAMA Online First
Source: JAMA Online First
This study examines the use of COVID-19 antiviral treatments in US nursing homes and the facility characteristics associated with use of oral antivirals and monoclonal antibodies.
Source: JAMA Online First
This Viewpoint argues that making a progestin-only contraceptive pill available for sale as an over-the-counter product will help reduce logistic barriers to safe and effective birth control.
Source: JAMA Online First
This Medical News article discusses the difficulties of studying, diagnosing, and treating bipolar disorder and new research initiatives to improve diagnostic tests and treatments.
Source: JAMA Online First
In this narrative medicine essay, a surgical oncologist joins the hospital chaplain during his rounds to learn how to connect with patients who have strong faith in God, even when her own beliefs afe uncertain.
Source: JAMA Online First