Longitudinal patterns of regional cerebral blood flow during anti-amyloid therapy in mild cognitive impairment: a pilot ASL MRI case series

Abstract

Introduction The neurovascular effects of anti-amyloid therapy remain incompletely understood. Arterial spin labeling (ASL) MRI enables non-invasive quantification of regional cerebral blood flow (rCBF) and may provide insight into perfusion patterns observed over the treatment period. Methods This pilot observational case series included participants with MCI or very early Alzheimer’s disease undergoing anti-amyloid therapy (lecanemab), who underwent longitudinal pseudo-continuous ASL MRI at baseline and predefined follow-up timepoints. Regional rCBF was quantified across predefined cortical and subcortical regions of interest. A comparison group of amyloid-positive participants with MCI who did not receive anti-amyloid therapy underwent baseline ASL MRI. Vascular and metabolic risk factors, including white matter hyperintensity burden and biochemical parameters, were assessed to characterize potential confounding influences. Results Within the treated group, increased rCBF was observed at early follow-up in several frontal, sensorimotor, and subcortical regions. No statistically significant longitudinal changes were detected at intermediate follow-up. At later follow-up, increased rCBF was observed in the cerebellar cortex, while decreased rCBF was observed in bilateral medial temporal regions. Vascular and metabolic risk profiles, including WMH burden, were broadly comparable between groups. Discussion The observed rCBF trajectories demonstrate region-specific and time-dependent perfusion changes over the treatment period. Given the small sample size, absence of longitudinal imaging in the control group, and residual vascular confounding, these findings should be interpreted cautiously as exploratory and hypothesis-generating rather than evidence of treatment efficacy.