Antiamyloid Therapy and Cerebral Blood Flow Changes on MRI: A Potential Longitudinal Biomarker of Treatment Response?

Amyloid-targeting therapy has recently become widely available in the United States for the treatment of patients with symptomatic mild Alzheimer disease (AD). At present, there are no biomarkers that have been clinically validated to assess treatment response in routine clinical practice; longitudinal amyloid PET could play a role but is not cost-effective. This report presents a case series of 6 patients with AD, whose amyloid positivity was confirmed by PET or CSF biomarkers, who underwent baseline and longitudinal arterial spin-labeling MR imaging (ASL-MR) as part of Food and Drug Administration-mandated, clinical standard-of-care, noncontrast MR monitoring to assess for amyloid-related imaging abnormalities (ARIA). We and others have previously reported that ASL-MR can screen for neurodegenerative disease as a proxy for FDG-PET and can be easily added on as a cost-effective, repeatable method to monitor post therapy changes. This series highlights varied CBF changes in response to lecanemab therapy. For instance, Cases 1, 3, and 5 showed increased CBF after multiple infusions, with subjective cognitive improvement in Case 1 and improved MoCA scores in Case 3. Case 2 showed improved CBF initially before the fifth infusion, but this returned to baseline in the subsequent study, with no cognitive improvement over the course of therapy. Cases 4 and 6 have demonstrated no substantial changes in regional CBF thus far on therapy, with cognitive decline in Case 4. This case series underscores the potential utility of ASL-MR as an adjunct sequence to current imaging protocols to monitor treatment response to antiamyloid therapy.