Amyloid-Related Imaging Abnormalities in Anti-Amyloid Therapy

A practical radiology review of Amyloid-Related Imaging Abnormalities in Anti-Amyloid Therapy, focused on imaging findings, differential diagnosis, reporting points, and high-yield teaching pearls.

• in Alzheimer Disease treated with anti-Aβ monoclonal antibodies

Big Picture

• Anti-amyloid monoclonal antibodies (MABs) (aducanumab, lecanemab, etc.) ↓ amyloid plaques
• Main imaging complication = ARIA
• MRI = only modality to diagnose & monitor ARIA → radiologist is
• What is ARIA?
• Two main types

ARIA-E (Edema / Effusion)

• Vasogenic edema ± sulcal effusion
• Due to ↑ vascular permeability & inflammation
• More common, usually transient & reversible

ARIA-H (Hemorrhage)

• Microhemorrhages
• Cortical superficial siderosis
• Less common, potentially irreversible, may stop therapy
• Pathophysiology (Think CAA!)
• Aβ deposited in vessel walls → fragile vessels
• Anti-Aβ therapy clears plaques → leaky vessels
• Mechanism overlaps with cerebral amyloid angiopathy (CAA)
• Imaging of ARIA ≈ CAA-RI → history of MAB use differentiates

Risk Factors for ARIA

• Higher dose / early titration phase
• APOE-ε4 carrier (strongest genetic risk)
• Pretreatment microhemorrhages / siderosis
• ⏱ Most ARIA occurs within first 3–6 months
• MRI Protocol (ICARE-AD)
• Mandatory sequences
• 3D FLAIR → ARIA-E (key sequence!)
• T2 GRE or SWI → ARIA-H
• DWI → rule out infarct (ARIA-E = vasogenic, ↑ADC)

Timing

• Baseline (pretreatment)
• Before 7th & 12th infusions
• Every 6–12 months (↑ frequency if APOE-ε4)

Imaging Features of ARIA-E

• Cortical–subcortical FLAIR hyperintensity
• Mild gyral swelling, no mass-like enhancement
• ↑ ADC (vasogenic edema)

Common locations

• Occipital lobes (most common)
• Frontoparietal
• Can mimic PRES

Grading (by size)

• Mild: <5 cm (single site)
• Moderate: 5–10 cm or multifocal
• Severe: >10 cm

Imaging Features of ARIA-H

• Microhemorrhages (<1 cm) on GRE/SWI
• Superficial siderosis (curvilinear cortical signal loss)
• Lobar/peripheral distribution (CAA-like)

Grading (by number)

• Mild: ≤4 new microbleeds
• Moderate: 5–9
• Severe: ≥10 → permanent therapy stop

Differential Diagnosis Pitfalls

• PRES (clinical context!)
• Subacute infarct (DWI restriction in ARIA-E)
• CAA-RI (no MAB history)
• SAH, meningitis, oxygen-related sulcal FLAIR
• Coil/shading artifacts

Rule of thumb

• New edema or sulcal FLAIR in a patient on MAB = ARIA until proven otherwise
• Management: Why Radiologists Matter
• Treatment decisions depend on radiologic grading
• Many asymptomatic patients continue therapy
• ⏸ Temporary hold common for ARIA-E
• Severe ARIA-H → permanent discontinuation

Take-Home Messages

• MRI surveillance is essential in anti-amyloid therapy
• ARIA-E = common, early, reversible
• ARIA-H = less common, but more serious
• Accurate counting & sizing = critical
• Close neurology–radiology collaboration required