Anti-amyloid therapy and cerebral blood flow changes on Magnetic Resonance Imaging: a potential longitudinal biomarker of treatment response?

ABSTRACT

Amyloid-targeting therapy has recently become widely available in the U.S. for the treatment of patients with symptomatic mild Alzheimer’s disease (AD). At present, there are no biomarkers that have been clinical 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 six patients with AD, whose amyloid positivity was confirmed by PET or CSF biomarkers, who underwent baseline and longitudinal arterial spin-labeling magnetic resonance imaging (ASL-MR) as part of FDA-mandated, clinical standard-of-care, non-contrast 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 cerebral blood flow (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 5^th infusion, but this returned to baseline on the subsequent study, with no cognitive improvement over the course of therapy. Cases 4 and 6 have demonstrated no significant 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 anti-amyloid therapy.

ABBREVIATIONS: ASL-MR= arterial spin-labeling magnetic resonance imaging; MRI= magnetic resonance imaging; CBF= cerebral blood flow; AD= Alzheimer’s disease; PET= positron emission tomography; CSF= cerebrospinal fluid; FDG= fluorodeoxyglucose.