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Key Clinical Summary: Implementing Anti-Amyloid Therapy & Managing Amyloid-Related Imaging Abnormalities (ARIA) in Early Alzheimer’s Disease

This is a summary of the sessions by Tammie Benzinger, MD and Brad Dickerson, MD which you can find here:

  1. Individualizing Treatment Decisions in Early Alzheimer’s Disease
  2. Detecting and Classifying Early ARIA (ARIA-E and ARIA-H)
  3. Applying Evidence-Based ARIA Management Protocols
  4. Multidisciplinary ARIA Response Protocols

Before participating, please read our CME and disclosure information which can be found in all of the links above.

This program is supported by an independent education grant from Lilly. This online education program has been designed for healthcare professionals globally excluding the UK.

1. Individualizing Treatment Decisions in Early Alzheimer’s Disease (LO1)

Early Alzheimer’s disease (AD) treatment requires balancing patient/caregiver goals, eligibility criteria, and ARIA risk.

Key steps in individualized decision-making:

  1. Confirm syndrome and etiology: Mild cognitive impairment or mild dementia with AD-consistent biomarkers (CSF Aβ/tau or amyloid PET).
  2. Assess comorbidities, medications, MRI tolerance, and social context to determine treatment candidacy and feasibility.
  3. Discuss benefits realistically: Anti-amyloid therapies slow cognitive decline (approx. 25–35% at 18 months); they do not improve cognition.
  4. Clarify risks and logistics: Infusion reactions (commonly mild), ARIA risk (APOE genotype-dependent), travel to infusion center, MRI burden, and long-term monitoring expectations.
  5. Shared decision-making (SDM): Encourage caregiver involvement, validate concerns, ensure capacity for informed consent, and set expectations regarding potential discontinuation if safety thresholds are reached.

2. Detecting and Classifying Early ARIA (ARIA-E and ARIA-H) (LO2)

ARIA detection relies on consistent MRI protocols, symptom vigilance, and clear radiological classification.

Recognizing ARIA-E (edema/effusion):

  • Appears as FLAIR hyperintensity, often in posterior cortical regions.
  • Severity is defined by size and number of lesions (mild, moderate, severe).
  • Often asymptomatic; symptoms—when present—include headache, confusion, and visual change.

Recognizing ARIA-H (microhemorrhages/superficial siderosis):

  • Microhemorrhages visible on GRE T2* or SWI; SWI is more sensitive, sometimes revealing additional lesions missed on GRE. 3T scanners are more sensitive than 1.5T scanners.
  • Radiologic severity may escalate quickly when superficial siderosis is present.
  • Often asymptomatic, especially if occurring in isolation; ARIA-H commonly co-occurs with ARIA-E and symptoms—when present—are typically those listed under ARIA-E

Symptomatic ARIA vs infusion reaction differentiation:

  • Timing matters: Infusion reactions occur immediately, often within minutes to hours after the first infusion(s); ARIA symptoms, if present, usually arise days to weeks after infusions.
  • MRI is normal in infusion reactions, abnormal in ARIA.

3. Applying Evidence-Based ARIA Management Protocols (LO3)

Management integrates ARIA radiologic grade plus symptom severity.

General Principles:

Mild ARIA-E/H:

  • If asymptomatic: often continue dosing with increased MRI frequency.
  • If symptomatic: hold dosing, monitor until resolution.

Moderate ARIA-E or any symptomatic ARIA-H:

  • Suspend dosing, initiate monthly MRIs until resolution.

Severe ARIA, extensive siderosis, or macrohemorrhage (>10 mm):

  • Discontinue therapy permanently per AUR examples discussed.

MRI cadence:

  • Baseline → early-treatment surveillance (first 6 months highest risk) → monthly MRI until radiographic resolution after any ARIA event.
  • Critical note from the webinar: ARIA can worsen even after dosing stops, so MRI follow-up must not be skipped.

4. Multidisciplinary ARIA Response Protocols (LO4)

Safe implementation requires integrated workflows

Essential components:

  • Urgent radiology-to-neurology communication:

    • Radiologists must verbally report to the treating provider new ARIA as a critical finding; reporting must quantify ARIA lesions and compare to baseline. Neurologist must talk with patient/care partner to determine whether the patient is symptomatic and whether in-person assessment is warranted.

  • Pre-infusion symptom screening:

    • Nursing teams should use a structured checklist to screen for symptoms prior to each infusion (headache, confusion, gait change, vision symptoms, seizure activity, focal deficits).

  • Electronic Medical Record (EMR) alerts:

    • Clearly flag patients on anti-amyloid therapy; include contraindicated medications (e.g., anticoagulants).

Emergency department readiness:

  • ARIA can mimic stroke; ED must recognize risk and avoid inappropriate thrombolysis.

Clear escalation pathway:

  • Symptom → urgent MRI → radiologist and neurologist review → treatment pause/continuation decisions using AUR-aligned algorithms.

Key Takeaways for Clinical Practice

  • Anti-amyloid therapy requires structured patient selection, transparent SDM, and clear explanation of realistic benefits vs risks.
  • Routine, protocolized MRI is essential—most ARIA is asymptomatic and detected only radiographically.
  • ARIA can evolve even when treatment is paused; monthly MRI follow-up is mandatory until resolution.
  • Most patients will not experience symptomatic ARIA, but multidisciplinary preparedness is crucial to prevent rare but serious complications.
  • Clear, standardized **MDT workflows **(radiology → neurology → infusion → ED) dramatically improve safety and align with the ARIA Care Pathways program design.