PET-guided Assessment of Amyloid Clearance and Outcomes in a Real-World Cohort of Patients with Alzheimer Disease undergoing Anti-Amyloid Therapy.
| Publication Type | Academic Article |
| Authors | Ivanidze J, Gardella J, Olson A, Sun S, Thomas C, Wong O, Intorcia B, Moirano J, Tanavde V, Gershon B, Pahlajani S, Roytman M, Nordvig A, Lin M, Hamed M, Alport A, Salgado M, Keil S, O'Dwyer E, Lantos J, Huicochea Castellanos S, Ebani E, Agee M, Fink M, Osborne J, Chiang G, Blum S |
| Journal | AJNR Am J Neuroradiol |
| Date Published | 04/29/2026 |
| ISSN | 1936-959X |
| Abstract | BACKGROUND AND PURPOSE: Beta-amyloid (Aβ)-PET is central to confirming Alzheimer disease (AD) before treatment with anti-amyloid monoclonal antibody therapies (AAT), however its role in treatment response monitoring in routine clinical practice remains unclear. This study aimed to evaluate longitudinal Aβ-PET changes following AAT and their association with clinical and safety outcomes in a real-world cohort. MATERIALS AND METHODS: We conducted a retrospective single-center study of patients with mild cognitive impairment (MCI) or mild dementia due to AD who underwent Aβ-PET before and after treatment with AAT (lecanemab or donanemab). Aβ-PET scans were assessed using visual interpretation and quantitative measures including Centiloid level (CL) and regional Z-scores. Treatment-related amyloid clearance (TRAC) was determined based on magnitude of CL changes (ΔCL). Associations between Aβ-PET changes and baseline Fazekas score, amyloid-related imaging abnormalities (ARIA) and APOE-ε4 carrier status were examined. Associations between ΔCL and cognitive performance from baseline to post-AAT as assessed per Mini-Mental State Examination (ΔMMSE) were examined using multivariable linear regression models incorporating baseline CL and adjusting APOE-ε4 status and occurrence of ARIA. Region-specific multivariable analyses evaluated associations between regional Z-score changes and ΔMMSE. RESULTS: Thirty-two patients met inclusion criteria (lecanemab, N=15; donanemab, N=17). Significant Aβ reduction was observed across the cohort (median ΔCL 59.11; p < 0.001) as well as within each treatment group. Most patients meeting TRAC criteria achieved full or partial TRAC (26/29, 89.7%). Baseline Aβ burden, as well as cognitive outcomes, did not differ significantly across TRAC categories (p = 0.25). ΔCL was not significantly associated with APOE-ε4 status or ARIA occurrence. In adjusted analyses, greater global CL reduction was associated with greater MMSE improvement, particularly at lower baseline burden. Region-specific analyses demonstrated marked, highly significant decrease in Z-scores across all regions. CONCLUSIONS: Longitudinal Aβ-PET demonstrated substantial Aβ clearance following AAT in routine clinical practice. Aβ reduction was not significantly associated with baseline Aβ burden, ARIA, APOE-ε4 status. In adjusted analyses, greater Aβ reduction was associated with greater MMSE improvement. Our findings support Aβ-PET as a sensitive biomarker of biological treatment effect, while highlighting the complexity of linking Aβ clearance to short-term cognitive outcomes. |
| DOI | 10.3174/ajnr.A9387 |
| PubMed ID | 42055956 |