MRI Brain Features Contraindicated for Lecanemab in Early Alzheimer's Disease
Several MRI brain features are absolute contraindications for lecanemab therapy in early Alzheimer's disease, including intraparenchymal macrohemorrhages >10 mm in diameter, 4 or more microhemorrhages <10 mm in diameter, superficial siderosis, evidence of vasogenic edema, significant white matter hyperintensities, multiple lacunar infarcts, and major vascular territory infarcts. 1, 2
Absolute Contraindications on MRI
- Intraparenchymal macrohemorrhages >10 mm in diameter - These indicate significant vascular fragility and substantially increase the risk of treatment-related hemorrhage 1, 2
- Four or more microhemorrhages <10 mm in diameter - Multiple microhemorrhages suggest underlying cerebral amyloid angiopathy that increases ARIA risk 1, 2
- Superficial siderosis - Indicates previous hemorrhage into subarachnoid space and high risk for recurrent bleeding 1, 2
- Evidence of vasogenic edema - Pre-existing edema may be exacerbated by anti-amyloid therapy 1
- Significant white matter hyperintensities - Suggest chronic small vessel disease that increases risk of complications 1, 2
- Multiple lacunar infarcts - Indicate significant cerebrovascular disease that increases risk of ARIA 1, 2
- Major vascular territory infarcts - Large infarcts suggest significant vascular compromise 1
Amyloid-Related Imaging Abnormalities (ARIA)
ARIA is the predominant neurologic complication associated with anti-amyloid monoclonal antibody therapy, presenting in two forms:
- ARIA-E (edema/effusion) - Detected in 12.6% of patients receiving lecanemab in the CLARITY AD phase 3 trial 1, 3
- ARIA-H (hemorrhage) - Incidence ranging from 15% to 20% in clinical trials 1, 3
ARIA-E presents as:
- Parenchymal edema with increased T2 signal and potential mass effect 1
- Sulcal "effusions" with non-suppression of sulcal CSF signal on T2 FLAIR images 1
ARIA-H manifests as:
Additional Exclusionary Findings
- Evidence of cerebral amyloid angiopathy-related inflammation (CAA-ri) or amyloid beta-related angiitis (ABRA) - These conditions have imaging findings that overlap with ARIA 1
- Parenchymal contusions - Indicate previous trauma and potential vascular fragility 1
- Encephalomalacia - Areas of brain tissue loss that may complicate assessment of treatment effects 1
- Aneurysms and vascular malformations - Increase risk of hemorrhage 1
- CNS infection - Active infection may complicate treatment 1
- Brain tumors (other than meningiomata or arachnoid cysts) - May confound assessment of treatment effects 1
MRI Monitoring Requirements
- Pre-treatment MRI must be obtained within 12 months of initiating therapy 1, 4
- Mandatory MRI sequences include DWI, T2 FLAIR, and T2* GRE or SWI 1
- Regular monitoring during therapy before the 5th, 7th, and 14th infusions 1, 4
- Additional MRI if clinical signs/symptoms of ARIA develop 1
Risk Stratification
- APOE ε4 carrier status increases risk of ARIA, particularly in homozygotes 3, 4
- Concurrent anticoagulant or tissue plasminogen activator therapy significantly increases risk of macrohemorrhage 3, 4
Clinical Implications
- Detection of ARIA may require modification of therapy, including temporary or permanent cessation 1
- Management depends on clinical symptoms and MRI grading severity 1
- Some cases may require corticosteroids or antiepileptic treatment 5
Pitfalls to Avoid
- Inadequate MRI sequences - Ensure T2* GRE or SWI sequences are included to detect microhemorrhages 1
- Missing subtle ARIA findings - Consider 3T MRI for greater sensitivity in detecting hemorrhagic abnormalities 6
- Overlooking differential diagnoses - ARIA-E can be confused with posterior reversible encephalopathy syndrome, multifocal leukoencephalopathy, or meningitis 1
- Failure to recognize ARIA-H - Can be confused with hypertensive microhemorrhages, CAA, or diffuse axonal injury 1