Navigating the Challenges of Shared Decision-Making in Amyloid Immunotherapy for Alzheimer's Disease

Anti-amyloid therapies (AATs), such as lecanemab and donanemab, represent a major therapeutic development for early Alzheimer's disease (AD). However, safety risks and uncertainties regarding long-term effects make treatment decisions complex. These decisions arise when patients remain legally capable of providing informed consent but may experience cognitive vulnerabilities affecting their ability to engage in complex decisions. Shared decision-making (SDM) is therefore particularly relevant, yet its implementation raises ethical and practical challenges.

This position paper draws on a multidisciplinary reflection on decision-making, informed consent, and cognitive vulnerability in early AD and AATs. The authors, with expertise in neurology, geriatrics, law, and history, examined challenges to patient participation and developed a relational framework integrating SDM and supported decision-making.

Impairments in memory, insight, and executive function, together with cognitive biases, stigma, and the complexity of AAT-related information, may compromise patient participation despite preserved legal capacity. Formal capacity assessments and improved information delivery may address some difficulties but are unlikely to provide comprehensive support. We propose a relational framework involving assessment of patients' cognitive vulnerabilities, values, preferences, and informational needs; tailored information; and involvement of a patient-designated care partner to support information exchange, deliberation, and expression of preferences. Consent should be iterative, with safeguards to preserve autonomy and confidentiality, prevent coercion, and avoid excluding socially isolated individuals.

Combining SDM with supported decision-making may provide an ethical and practical framework for autonomous treatment decisions regarding AATs in early AD.