Cerebral Hyperperfusion with Lecanemab in Alzheimer's Disease Assessed by Amyloid PET and Arterial Spin Labeling

INTRODUCTION/OBJECTIVE: Alzheimer's Disease (AD) is characterized by cognitive decline, amyloid-β deposition, and decreased Cerebral Blood Flow (CBF). Lecanemab, a monoclonal antibody targeting amyloid-β, slows cognitive decline in AD; however, its effects on CBF remain unclear. This study aimed to characterize CBF changes following lecanemab treatment and their association with baseline amyloid burden. METHODS: Thirty patients with AD treated with lecanemab were analyzed retrospectively. Baseline amyloid deposition was quantified using the Centiloid scale, and patients were stratified into low, middle, and high groups. CBF was analyzed at baseline and at 8, 12, and 26 weeks using arterial spin labeling (ASL). Monoclonal antibody-triggered cerebral hyperperfusion (MATCH) was defined as a >20% CBF increase at week 8. RESULTS: Seven patients were MATCH-positive (median CBF: 133.5% [125.5-167.8] of baseline). All MATCH-positive patients exhibited a decrease in CBF at week 12 compared to week 8. MATCH occurred in 6 of 10 patients in the middle Centiloid group. The low Centiloid group showed stable CBF, while the high Centiloid group showed a decreasing trend. The MATCHpositive group showed a significant deterioration in Instrumental Activities of Daily Living scores. DISCUSSION: A transient CBF increase was closely associated with the middle Centiloid group. These CBF responses, including MATCH, may reflect amyloid removal, hyperperfusion, amyloidrelated imaging abnormalities, or immune responses. CONCLUSIONS: CBF changes differed according to baseline amyloid burden. Understanding these therapy-related CBF changes is crucial for elucidating AD pathology, and ASL provides a practical, non-invasive method for longitudinal CBF monitoring in routine clinical practice.