Real-world Outcomes of Amyloid-clearing Therapies in a Memory Clinic Cohort (P1-12.004)

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. ΔMMSE 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. Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff. Disclosure: Ms. Olson has nothing to disclose. Mr. Gardella has nothing to disclose. Dr. Lin has nothing to disclose. The institution of Dr. Nordvig has received research support from National Institute on Aging. Dr. Nordvig has received publishing royalties from a publication relating to health care. Dr. Gershon has nothing to disclose. Dr. Yadav has nothing to disclose. Dr. Keil has nothing to disclose. Dr. Pahlajani has nothing to disclose. Joseph Osborne has nothing to disclose. Dr. Lantos has nothing to disclose. The institution of Ms. Huicochea Castellanos has received research support from Pcf. Gloria Chiang has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Life Molecular Imaging. Gloria Chiang has received personal compensation in the range of $0-$499 for serving as a Consultant for Alnylam. The institution of Gloria Chiang has received research support from Minoryx Therapeutics. The institution of Gloria Chiang has received research support from National Institutes of Health. Gloria Chiang has received personal compensation in the range of $5,000-$9,999 for serving as a speaker with Efficient CME. Gloria Chiang has received personal compensation in the range of $500-$4,999 for serving as a speaker with PeerView. Dr. Salgado has nothing to disclose. Dr. Hamed has nothing to disclose. Author has nothing to discloseDr. Blum has nothing to disclose.