A How-To Guide to the Use of Anti-Amyloid Therapies in Alzheimer’s Disease

Introduction

The advent of anti-amyloid therapies has ushered in a transformative era in the management of Alzheimer’s disease (AD), offering new hope particularly for patients in the prodromal or early symptomatic stages. These therapies, including monoclonal antibodies such as aducanumab and lecanemab, specifically target amyloid-beta plaques, a hallmark of AD pathology. Clinical trials have demonstrated that these agents can modestly slow the rate of cognitive and functional decline, marking a pivotal shift in how the medical community approaches this neurodegenerative disease (van Dyck et al., 2022). As these treatments become more accessible globally, clinicians must be equipped with the knowledge and infrastructure to safely and effectively incorporate them into routine care. This guide provides a comprehensive roadmap for healthcare professionals worldwide, spanning from patient selection to long-term management and caregiver education.

Section 1: Establishing a Multidisciplinary Team

1.1 Core Team Members

Successful implementation of anti-amyloid therapy requires a coordinated multidisciplinary team. Core members should include:

• Neurologists: Oversee diagnosis, treatment planning, and therapy oversight.

• Radiologists: Conduct and interpret neuroimaging studies, including MRI and PET scans crucial for diagnosis and monitoring.

• Nurses: Administer infusions, monitor for infusion reactions, and provide frontline patient support.

• Neuropsychologists: Evaluate cognitive function over time using standardized assessments.

• Pharmacists: Ensure proper drug handling, monitor for drug interactions, and counsel on pharmacovigilance.

• Social Workers/Counselors: Address emotional, financial, and social support needs of patients and caregivers.

• Geriatricians and Primary Care Providers: Manage comorbid conditions and provide holistic care.

1.2 Training and Coordination

All team members must undergo comprehensive training on the pharmacodynamics, expected benefits, and risk profile of anti-amyloid agents. Familiarity with symptom monitoring tools and standardized imaging protocols is essential. Interdisciplinary communication, through case conferences and shared electronic health records, is vital for the seamless coordination of care. Clinical pathways should be developed to streamline referrals, testing, and follow-up.

Section 2: Patient Selection and Eligibility

2.1 Diagnostic Criteria

Not all individuals with Alzheimer’s disease are suitable candidates for anti-amyloid therapies. Selection criteria typically include:

• Clinical diagnosis of mild cognitive impairment (MCI) due to AD or mild AD dementia, confirmed using internationally accepted criteria such as NIA-AA.

• Evidence of amyloid-beta pathology demonstrated through positron emission tomography (PET) imaging or cerebrospinal fluid (CSF) biomarkers.

• Adequate functional reserve and ability to comply with long-term treatment and monitoring protocols.

2.2 Exclusion Criteria

Therapies are contraindicated in patients with:

• Moderate to severe AD dementia.

• Significant comorbid neurodegenerative or cerebrovascular disease.

• Prior intracranial hemorrhage or extensive white matter disease.

• Contraindications to MRI (e.g., pacemakers, metallic implants).

2.3 Shared Decision-Making

A patient-centered approach is crucial. Engage patients and families in transparent conversations about the expected course of disease, treatment benefits, and potential risks, especially amyloid-related imaging abnormalities (ARIA). Use decision aids and translated materials when appropriate to support informed consent (Sperling et al., 2021).

Section 3: Initiation of Therapy

3.1 Pre-Treatment Assessments

Before initiating therapy, conduct the following:

• Baseline MRI scan to detect microhemorrhages and establish ARIA status.

• APOE genotyping, as individuals with one or more APOE4 alleles face increased risk of ARIA.

• Comprehensive baseline neurocognitive testing and laboratory evaluation.

• Screening for cardiovascular and renal function to assess treatment suitability.

3.2 Treatment Administration

• Therapies are administered via intravenous infusions, often on a biweekly or monthly schedule, depending on the agent.

• Infusions should take place in a controlled environment with emergency protocols available.

• Monitor vital signs and symptoms during and after each infusion to identify hypersensitivity or other reactions.

3.3 Initial Follow-Up

• Repeat MRI scans are recommended at 3-month intervals for the first year to monitor for ARIA.

• Quarterly clinical visits to assess cognition, daily function, and adverse effects.

• Update care plans based on patient response and imaging results.

Section 4: Monitoring and Managing Side Effects

4.1 Amyloid-Related Imaging Abnormalities (ARIA)

ARIA represents the most significant safety concern with these therapies.

• ARIA-E (edema/effusion) and ARIA-H (hemorrhage) may present with headache, nausea, confusion, or be asymptomatic.

• Regular MRI surveillance is essential, particularly in the first 12 months of therapy.

• Management strategies include pausing therapy, reducing dosage, or symptomatic treatment. Severe ARIA may necessitate permanent discontinuation (Salloway et al., 2022).

4.2 Infusion Reactions

• Infusion-related events such as fever, chills, nausea, or skin rash can occur.

• Preventive strategies include pre-infusion medications (e.g., antihistamines, acetaminophen).

• Staff should be trained in anaphylaxis management and adverse event reporting protocols.

Section 5: Patient and Family Education

5.1 Communicating Expectations

Educating patients and caregivers is vital to maintaining adherence and emotional well-being.

• Emphasize that these therapies slow, but do not halt or reverse, disease progression.

• Clarify the timeline for clinical effects, which may take months to observe.

• Prepare families for the need for regular imaging, clinic visits, and possible therapy interruptions.

5.2 Cultural Sensitivity

Tailor educational efforts to the cultural, linguistic, and literacy levels of each population. Collaborate with local organizations and community leaders to bridge knowledge gaps and dispel misconceptions. For global practices, provide translations, use pictograms, and consider audiovisual tools.

Section 6: Global Considerations and Health System Readiness

6.1 Accessibility and Cost

In many regions, especially LMICs, access is constrained by costs related to drug acquisition, diagnostics (e.g., PET scans), and infusion infrastructure. Strategies to improve access include:

• Government and NGO partnerships for subsidy programs.

• Inclusion in national essential medicines lists.

• Training programs to build local capacity.

6.2 Regulatory Approvals and Local Adaptation

• Confirm that the therapy is approved by national regulatory agencies such as the EMA, FDA, PMDA, or WHO PQ.

• Adapt protocols to align with local medical practice norms, resource availability, and reimbursement policies.

• Collaborate with policymakers to integrate therapies into broader national dementia strategies.

Conclusion

The integration of anti-amyloid therapies into clinical practice represents a critical step forward in Alzheimer’s disease management. However, their use requires thoughtful implementation, rigorous monitoring, and patient-centered care. Through multidisciplinary collaboration, clear communication, and international cooperation, healthcare providers can ensure that these promising therapies are used to their full potential across diverse populations and healthcare systems.

References

Salloway, S., Chalkias, S., Barkhof, F., Burkett, P., Barakos, J., Purcell, D., ... & Budd Haeberlein, S. (2022). Amyloid-related imaging abnormalities in 2 phase 3 studies evaluating aducanumab in patients with early Alzheimer disease. JAMA Neurology, 79(1), 13-21. https://doi.org/10.1001/jamaneurol.2021.4161

Sperling, R. A., Jack, C. R., Black, S. E., Frosch, M. P., Greenberg, S. M., Hyman, B. T., ... & Carrillo, M. C. (2021). Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer's Association Research Roundtable Workgroup. Alzheimer's & Dementia, 17(5), 754-766. https://doi.org/10.1002/alz.12243

van Dyck, C. H., Swanson, C. J., Aisen, P., Bateman, R. J., Chen, C., Gee, M., ... & Mintun, M. A. (2022). Lecanemab in early Alzheimer’s disease. New England Journal of Medicine, 388(1), 9-21. https://doi.org/10.1056/NEJMoa2212948