Practical Guide of the Korean Association for Geriatric Psychiatry to Anti-Amyloid Monoclonal Antibody Therapy for Alzheimer's Disease: Focused on Lecanemab

Abstract

The advent of anti-amyloid monoclonal antibody (mAb) therapies represents a paradigm shift in the treatment of Alzheimer's disease (AD), from symptomatic relief to disease modification. Lecanemab, a humanized mAb targeting soluble Aβ protofibrils and plaque, received regulatory approval in Korea in July 2024, following global randomized controlled trial data demonstrating its efficacy to reduce amyloid burden and slow cognitive decline. However, the introduction of such therapies into routine clinical realm presents several practical and systemic challenges, particularly in the context of Korea's unique healthcare infrastructure and reimbursement environment. In response, the Korean Association for Geriatric Psychiatry has developed the first comprehensive domestic guidance to facilitate the safe, evidence-based, and patient-centered use of anti-amyloid mAb therapies, first focused on lecanemab. This practical guide goes beyond simple eligibility criteria. It provides detailed recommendations on clinical and imaging-based candidate selection, amyloid-related imaging abnormalities (ARIA) risk stratification and monitoring protocols, infusion workflows, adverse event management strategies, and multidisciplinary coordination within hospital systems. It also emphasizes shared decision-making and outlines how to navigate situations where treatment is not appropriate, such as in patients with advanced dementia, high-risk magnetic resonance imaging findings, or poor treatment adherence, reinforcing that non-treatment can also represent a legitimate, evidence-based clinical decision. The guidance further highlights the urgent need to generate real-world data that reflect the treatment experiences of Korean patients. Multicenter collaboration will be essential for collecting data on adherence rates, ARIA incidence, cognitive outcomes, and functional trajectories, which in turn can inform policy decisions, insurance reimbursement models, and future updates to clinical guidelines. This publication represents the first nationwide roadmap in Korea to support clinicians in the appropriate integration of monoclonal antibody therapies for AD. By combining scientific rigor, operational feasibility, and ethical sensitivity, it aims to promote safe and responsible adoption of disease-modifying treatment across various clinical settings.

Keywords: Alzheimer's Disease; Antiamyloid Monoclonal Antibodies; Appropriate Use; Donanemab; Lecanemab; Practical Guide.

Fig. 1. Eligibility assessment algorithm for lecanemab treatment. The flowchart is designed to guide clinicians in identifying patients who are appropriate candidates for lecanemab treatment. This algorithm outlines a stepwise approach to evaluating treatment candidacy. It integrates three core evaluation domains: 1) clinical diagnosis and assessment of cognitive impairment severity, 2) confirmation of amyloid pathology via PET or CSF biomarkers, and 3) neuroimaging findings that may raise concerns regarding the use of lecanemab. Additional considerations include comorbid medical conditions, concurrent medications, caregiver support, and treatment adherence. Clinicians are advised to perform a comprehensive risk-benefit analysis and engage in shared decision-making with patients and caregivers to determine the final treatment plan.

MCI = mild cognitive impairment, AD = Alzheimer’s disease, DSM-5-TR = Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision, CDR = Clinical Dementia Rating Scale, GDS = Global Deterioration Scale, NIA-AA = National Institute on Aging–Alzheimer’s Association, PET = positron emission tomography, CSF = cerebrospinal fluid.

Fig. 2. Clinical algorithm for monitoring and management of ARIA. This algorithm outlines the recommended clinical decision-making process for monitoring and managing ARIA (Amyloid-Related Imaging Abnormalities) during lecanemab treatment. (A) Illustrates an ARIA monitoring protocol guided by individual risk stratification using the provisional KAGP risk scale. Patients are categorized into low, intermediate, or high ARIA risk groups. And, the timing of ARIA-monitoring MRI varies accordingly, with earlier imaging (e.g., before the 3rd infusion) recommended for higher-risk individuals. (B) Upon identification of suspected ARIA symptoms, an additional MRI is performed to confirm ARIA-E (edema/effusion) or ARIA-H (microhemorrhage/siderosis). Treatment decisions are guided by the presence or absence of symptoms, as well as the severity of ARIA findings.

ARIA = amyloid-related imaging abnormalities, KAGP = Korean Association for Geriatric Psychiatry, MRI = magnetic resonance imaging.