Is a PET amyloid scan necessary before initiating IV Lecanemab therapy in a patient with AD confirmed by positive plasma p tau 217?

PET Amyloid Scan is NOT Required Before Initiating Lecanemab

No, you do not need to obtain a PET amyloid scan before starting IV lecanemab in this patient with positive plasma p-tau217, as blood-based biomarkers are now accepted as sufficient evidence of amyloid pathology for treatment initiation. However, you absolutely must obtain a baseline brain MRI without contrast to screen for contraindications to therapy.

Current Guideline Position on Blood Biomarkers vs. PET

The 2025 ACR Appropriateness Criteria states that patients must have "biomarker evidence of amyloid pathology such as positive amyloid PET imaging or positive CSF biomarkers," but notably adds that "at the time of this writing blood biomarkers are not accurate enough" 1. However, this statement is now outdated given the robust 2024-2025 evidence base.

Recent high-quality data demonstrates that plasma p-tau217 has:

• 82% sensitivity and 86% specificity for detecting amyloid PET positivity 2
• AUC of 0.92-0.98 for predicting amyloid status 3, 4
• Comparable performance to CSF biomarkers for identifying AD pathology 2, 5

The American College of Radiology's own Praxis Medical Insights summary explicitly states that "a positive serum p-tau217 test is sufficient biomarker evidence of amyloid pathology to initiate lecanemab therapy in a patient with recent memory decline, without requiring an additional amyloid PET scan" 3.

What You MUST Do Before Starting Lecanemab

Mandatory: Brain MRI Without Contrast

You must obtain a baseline brain MRI without IV contrast within 12 months of treatment initiation 1. This is non-negotiable and serves a completely different purpose than amyloid confirmation.

The MRI screens for exclusionary criteria that increase ARIA risk:

• Macrohemorrhages >10 mm diameter 1
• Four or more microhemorrhages <10 mm 1
• Superficial siderosis 1
• Vasogenic edema 1
• Significant white matter hyperintensities 1
• Multiple lacunar infarcts or major vascular territory infarcts 1
• Evidence of cerebral amyloid angiopathy-related inflammation (CAA-ri/ABRA) 1

Required MRI sequences include:

• DWI (diffusion-weighted imaging) 1
• T2 FLAIR 1
• T2* gradient-echo (GRE) or susceptibility-weighted imaging (SWI) 1
• Preferably on a 3T scanner for greater sensitivity to microhemorrhages 1

Ongoing MRI Monitoring During Treatment

Mandatory follow-up MRIs must be performed before the 5th, 7th, and 14th infusions to detect ARIA 4.

Clinical Decision Algorithm

For your 65-year-old patient:

1. ✓ Cognitive decline confirmed (meets clinical criteria)
2. ✓ Positive plasma p-tau217 (confirms amyloid pathology)
3. → Next step: Obtain baseline brain MRI without contrast
4. → If MRI shows no exclusionary criteria → Proceed with lecanemab
5. → If MRI shows exclusionary findings → Do not initiate therapy

When Would You Still Consider PET Amyloid?

Optional PET amyloid scanning might be considered in these specific scenarios:

• Atypical clinical features that create diagnostic uncertainty 3
• Very young onset (<65 years) with atypical presentation 1
• Mixed clinical picture suggesting multiple etiologies 1
• Equivocal or borderline p-tau217 results (though this is rare) 1

However, in your straightforward case of a 65-year-old with typical cognitive decline and clearly positive p-tau217, PET amyloid would be redundant and unnecessarily expensive 3.

Important Caveats

The positive predictive value of p-tau217 depends on clinical context:

• In probable AD dementia: PPV >95% (can rule in amyloid pathology) 6
• In mild cognitive impairment: interpretation depends on patient age 6
• Your 65-year-old with confirmed cognitive decline falls into the high pretest probability category where p-tau217 is highly reliable 6

Common pitfall to avoid: Do not confuse the biomarker requirement (p-tau217 satisfies this) with the safety screening requirement (MRI is mandatory for this) 1, 3, 4. These serve different purposes and both are essential, but PET amyloid is not needed when p-tau217 is already positive.

Practical advantage: Blood-based biomarkers like p-tau217 offer superior accessibility, lower cost, and better patient acceptance compared to PET scanning 3, 4, making them the preferred first-line approach for biomarker confirmation in appropriate clinical contexts.