Real-world Outcomes of Amyloid-clearing Therapies in a Memory Clinic Cohort
Ahlanna Olson1, Jae Gardella2, Michael Lin3, Anna Nordvig2, Blake Gershon2, Divya Yadav4, Samantha Keil2, Silky Pahlajani4, Joseph Osborne5, Joshua Lantos5, Sandra Castellanos5, Gloria Chiang5, Miran Salgado5, Moath Hamed6, Jana Ivanidze5, Sonja Blum5
1Neurology, Weill Cornell Medical College, 2Weill Cornell Medical College, 3Weill-Cornell/NY Presbyterian Memory Disorders Unit, 4Weill-Cornell Medicine, 5Weill Cornell, 6NYP Brooklyn Methodist
Objective:
To assess ARIA incidence, amyloid clearance and clinical outcomes in a real-world cohort of patients with Alzheimer disease (AD) undergoing amyloid-targeted therapy (ATT) in a memory clinic.
Background:
ATT with Lecanemab and Donanemab has recently received FDA approval for AD. We assessed the relationship between cognitive measures, APOE4 status, amyloid-related imaging abnormalities (ARIA), and amyloid clearance with ATT.
Design/Methods:
A retrospective analysis of 108 patients with biomarker-confirmed AD undergoing treatment with Lecanemab (≥12 months) or Donanemab (≥6 months) was performed. 19% of patients had AD confirmed via CSF (Aβ42, tau) and 81% via amyloid PET. Associations among ARIA, APOE4 status, amyloid clearance, and clinical outcomes were evaluated using nonparametric t-tests and Spearman correlation analyses. Twenty-three patients had baseline and follow-up amyloid PET imaging (Florbetaben). Ten patients had baseline CSF and follow-up amyloid PET imaging (Florbetaben). Cognitive measures included MMSE or MoCA. All scores were converted to MMSE utilizing previously published methods.
Results:
78.3% of patients had robust amyloid clearance > 57 CL. Cognitive scores remained stable across the entire treatment cohort, with no significant difference between pre-treatment and follow-up MMSE scores. ∆MMSE scores from baseline were significantly lower in patients who had diffuse amyloid burden in their follow-up imaging compared to those who achieved complete clearance of < 20 centiloid (CL) or BAPL1 (p = 0.041). ARIA occurred in 18.5% of patients, 2.7% were symptomatic. There was a moderate positive correlation between ARIA occurrence and complete clearance (p =0.022, phi =0.398). APOE4 carriers comprised 48.9% of patients (38 heterozygous, 6 homozygous).
Conclusions:
Amyloid-clearing therapies demonstrated robust amyloid clearance and overall clinical stability. Our findings support the safety and feasibility of ATTs in routine clinical care.
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