Presentation description

Alzheimer's disease and related dementias (ADRD) affect approximately 55 million people globally, and the search for effective therapies to slow disease progression is crucial. Lecanemab, an anti-amyloid monoclonal antibody, was recently approved to treat mild ADRD following a phase 3 trial showing reduced cognitive decline. However, 20% of patients receiving lecanemab develop brain bleeding known as amyloid-related imaging abnormalities with hemosiderin deposits (ARIA-H). ARIA-H is predominantly asymptomatic but causes symptomatic brain bleeding in about 1% of cases. The exact mechanism of ARIA-H remains unclear, though the involvement of platelet activation and coagulation abnormalities in ADRD and brain hemorrhage suggests their potential role.

Using an observational approach, our study investigates the role of platelet and coagulation function in ARIA-H development. We will compare two cohorts: 20 ADRD patients over age 50 years receiving lecanemab (cases) and 40 eligible patients not receiving it (controls). Functional platelet and coagulation testing will occur at baseline and again after 8-10 weeks. The analysis will employ multivariate logistic regression to control for confounders such as medications, sociodemographics, clinical characteristics, and other laboratory values. The primary composite outcome is ARIA-H, ARIA-E (edema), loss to follow-up, and mortality. Additional secondary outcomes include functional testing changes and clinical efficacy.

To date, 20 patients have been recruited, including 4 receiving lecanemab (cases). Upon completion, the study aims to provide insights into platelet and coagulation factors' contributions to ARIA-H, potentially identifying biomarkers for risk assessment and patient selection and contributing to the safer application of novel ADRD therapies.