When is lecanemab (generic name) indicated for use in patients with early Alzheimer's disease, specifically those with mild cognitive impairment or mild dementia and confirmed amyloid beta plaques?

When to Use Lecanemab

Lecanemab should be initiated in patients with mild cognitive impairment (MCI) or mild dementia due to Alzheimer's disease who have confirmed amyloid beta pathology, documented objective cognitive impairment, and no contraindications on baseline brain MRI. 1

Core Eligibility Criteria

Disease Stage Requirements

• Symptomatic early Alzheimer's disease only: Patients must have either MCI or mild dementia stage disease—this is the FDA-approved indication and the population studied in clinical trials 1
• Lecanemab is explicitly inappropriate for cognitively unimpaired individuals, even if they have positive amyloid biomarkers 2, 3
• Clinical Dementia Rating (CDR) score should be 0.5 (MCI) or 1.0 (mild dementia) 4

Mandatory Biomarker Confirmation

Amyloid pathology must be confirmed through one of these methods before initiating treatment 1, 2:

• Amyloid PET scan (positive scan required)
• CSF biomarkers (abnormal Aβ42/40 ratio and tau markers)
• Blood-based biomarkers (particularly plasma p-tau217, which has 92-98% accuracy for predicting amyloid status) 5, 3

The 2025 Alzheimer's Association guidelines emphasize that blood-based biomarkers like p-tau217 are now sufficient evidence to initiate therapy without requiring additional amyloid PET confirmation, offering a more accessible pathway 5, 3

Objective Cognitive Impairment Documentation

• Montreal Cognitive Assessment (MoCA) score ≤25, OR 4
• Comprehensive neuropsychological battery showing impairment in ≥1 cognitive domain 4, 3
• Critical pitfall: Positive biomarkers alone without documented cognitive impairment do not justify treatment 4, 3

Pre-Treatment Safety Screening

Mandatory Baseline Brain MRI

A recent brain MRI without contrast must be obtained before initiating lecanemab to screen for contraindications 1, 2, 3:

• Exclusionary findings include: macrohemorrhages, multiple microhemorrhages, superficial siderosis, vasogenic edema, or significant white matter hyperintensities 5, 3
• Required sequences: DWI, T2 FLAIR, T2* gradient-echo or susceptibility-weighted imaging 5
• Preferably performed on 3T scanner for greater sensitivity 5

APOE ε4 Genotype Testing

• Testing should be performed prior to treatment initiation to inform ARIA risk 1
• APOE ε4 homozygotes have significantly higher ARIA risk (34.5% ARIA-E incidence) compared to heterozygotes (16.8%) and non-carriers 6, 1
• The 2025 FDA label update emphasizes discussing genotype-specific risks with patients before testing 1

Treatment Administration Protocol

Dosing Regimen

• 10 mg/kg IV infusion over approximately 1 hour 1
• First 18 months: Every 2 weeks 1
• After 18 months: Continue every 2 weeks OR transition to every 4 weeks 1

Mandatory MRI Monitoring Schedule

Enhanced clinical vigilance for ARIA is required during the first 14 weeks, with mandatory MRI monitoring 1, 3:

• Before the 5th infusion (approximately week 8)
• Before the 7th infusion (approximately week 12)
• Before the 14th infusion (approximately week 26)

Additional MRIs should be obtained if symptoms suggestive of ARIA develop (focal neurologic deficits, headache, confusion, visual changes) 1

Infrastructure and Team Requirements

Multidisciplinary Care Model

• Treatment requires specialized teams trained in ARIA recognition and management 2, 3
• Hub-and-spoke care models are being developed to address dementia specialist shortages, enabling primary care-specialist collaboration 2
• Medicare reimbursement requires enrollment in CMS-approved patient registry 2, 3

Key Clinical Considerations

Expected Benefits

Lecanemab demonstrates approximately 27-30% slowing of cognitive decline on ADCOMS, 47-56% on ADAS-Cog14, and 26-33% on CDR-SB at 18 months compared to placebo 7, 8

Quality of life outcomes show 49% less decline on EQ-5D-5L and 38% less increase in caregiver burden on the Zarit Burden Interview 9

Common Adverse Events

The most frequent treatment-emergent adverse events (>10% incidence) are 6, 1:

• Infusion-related reactions (24.5%)
• ARIA-H microhemorrhages (16.0%)
• ARIA-E (13.6%)
• Headache (10.3%)

Critical safety note: ARIA can be fatal, and serious intracerebral hemorrhages >1 cm have occurred with this class of medications 1. The risk is particularly elevated in patients on anticoagulants or tissue plasminogen activator 6

Contraindications

Lecanemab is contraindicated in patients with serious hypersensitivity to lecanemab-irmb or any excipients 1

When NOT to Use Lecanemab

Do not initiate lecanemab in 2, 4, 3:

• Cognitively unimpaired individuals (even with positive biomarkers)
• Patients with subjective cognitive decline without objective impairment
• Moderate or severe dementia (beyond mild dementia stage)
• Patients with contraindications on baseline MRI
• Patients unable to undergo regular MRI monitoring