What is the role of steroids in treating amyloid-related imaging abnormality (ARIA)?

Steroids for Treatment of Amyloid-Related Imaging Abnormality (ARIA)

Steroids are recommended for symptomatic ARIA cases, particularly when patients present with significant clinical symptoms or severe radiographic findings, as they can lead to resolution of symptoms and reduction in ARIA-E lesion volume. 1

Understanding ARIA

ARIA is a common adverse effect observed in patients receiving amyloid-modifying therapies for Alzheimer's disease. It presents in two main forms:

• ARIA-E: Vasogenic edema in brain parenchyma or sulcal effusions in the leptomeninges/sulci 2
• ARIA-H: Hemosiderin deposits presenting as microhemorrhages or superficial siderosis 2

Risk Factors for ARIA

Several factors increase the risk of developing ARIA:

• APOE ε4 carrier status (highest risk in homozygous carriers: 33% vs. 4.3% in non-carriers) 3, 4
• Higher doses of amyloid-modifying therapies 4
• Early treatment phase (risk decreases later in treatment) 2
• Presence of pre-existing microhemorrhages 5

Clinical Presentation

ARIA can present with varying clinical manifestations:

• Approximately 60% of cases are asymptomatic and detected only on routine MRI monitoring 3
• When symptomatic, patients may experience:
  • Headache 4
  • Confusion 4
  • Visual disturbances 4
  • Dizziness 5
  • Seizures (in severe cases) 5

Treatment Approach for ARIA

For Asymptomatic ARIA-E

• Continued monitoring with monthly MRI is recommended 5
• Treatment with the amyloid-modifying agent may be continued with caution 2

For Symptomatic ARIA-E

• Temporary suspension of the amyloid-modifying treatment 2
• Corticosteroid therapy should be considered, particularly for:
  • Moderate to severe symptoms 5
  • Extensive radiographic findings 5
  • Cases with clinical deterioration despite treatment suspension 6

Evidence for Steroid Efficacy

• Corticosteroids lead to short-term improvement in ARIA-related symptoms, with significant reduction in modified Rankin Scale scores (2.6 ± 1.4 vs. 1.6 ± 1.5; p = 0.01) 1
• Steroids significantly reduce T2/FLAIR lesion volume (78.1 ± 52.2 cm³ vs. 30 ± 30.9 cm³, p < 0.01) 1
• In CAA-related inflammation, which shares pathophysiological similarities with ARIA, inflammatory findings reverse following steroid treatment 4
• Case reports document successful use of methylprednisolone for clinical/imaging worsening in ARIA 6

Pathophysiological Basis for Steroid Treatment

The rationale for steroid use in ARIA is based on its pathophysiology:

• ARIA may involve a focal inflammatory component affecting both parenchyma and vasculature 4
• CAA-related inflammation, which shares features with ARIA, demonstrates white matter pathology with inflammatory response to vascular amyloid deposits 4
• Although CSF findings in ARIA cases are not consistently inflammatory, focal amyloid-related vascular inflammation may play a role in some cases 4

Monitoring and Management Protocol

1. Obtain baseline MRI before initiating amyloid-modifying therapy 5
2. Monitor with MRI at regular intervals, especially before dose escalations 5
3. For symptomatic ARIA or significant radiographic findings:
   • Temporarily suspend amyloid-modifying treatment 2
   • Consider methylprednisolone (dosing based on severity) 6, 1
   • Monitor with follow-up MRI to assess response 5
   • Consider anticonvulsants if seizures are present 5

Important Caveats

• Limited systematic data exists on specific treatments for ARIA 2
• Most ARIA cases resolve spontaneously without specific treatment 2
• Patients with concurrent use of anticoagulants or antithrombotics have increased risk of brain hemorrhage and require more careful monitoring 3
• ARIA-H (microhemorrhages) often persists even after ARIA-E resolves 6