Lecanemab, Donanemab, and Emerging Disease Modifying Therapies for Alzheimer Disease: Clinical Evidence and Primary Care Implications in Canada

Introduction: Alzheimer's disease is a progressive neurodegenerative disorder with current treatment limited to symptomatic relief and no alteration in disease progression. Advances in the DMTs (Disease-modifying-therapies) may alter the progression if used in early phase of the disease. Objective: To review and summarize the current evidence on advancements in DMTs in AD; review their regulatory status in Canada; Examine risk vs. benefit and explore implications for Family Physicians. Methods: Narrative review of recent randomized controlled trials. regulatory status and submissions, and Canadian policy documents up to mid-2025. Sources include PubMed, clinical trial registries, Health Canada Notices, Alzheimer's Society of Canada materials. Results: Monoclonal antibodies such as lecanemab and donanemab show reduction in amyloid plaque and slowing of cognitive and functional decline (modest) in early AD (mild cognitive impairment or mild dementia). In contrast, Aducanumab while initially promising ended up showing mixed results and due to inconsistent clinical outcomes, it is not approved by Health Canada at present. Tau‑targeting and anti‑inflammatory agents are under investigation but have not yet demonstrated definitive benefit. Key risks include amyloid‑related imaging abnormalities (ARIA), infusion reactions, cost, and lack of data for long term safety. Canadian health system challenges include lack of access to biomarker testing and imaging, Lack of healthcare specialists, and reimbursement frameworks. Conclusion: Using DMTs in the early phases of AD offers significant promise in altering disease progression. However, Family Physicians needs to thoroughly evaluate the risk to benefit ratio, ensure careful patient selection, and work in close collaboration with specialists. Furthermore, ensuring the healthcare system is ready— with access to proper testing facilities, coverage models, and support systems—is essential for the safe and equitable implementation of these therapies. Key points Monoclonal antibodies (lecanemab, donanemab) are the most advanced DMTs in AD at present with evidence that shows slight slowing in clinical decline in early AD patients. Risks associated to the treatment like ARIA etc. requires biomarker confirmation which is not readily available throughout Canada yet. Family Physicians and Canadian Healthcare System play a crucial role in selection of patient, their monitoring, treatment coverage and testing.