Lecanemab Reduces Neuropsychiatric Symptoms and Related Regional Brain Amyloid Load in Early Alzheimer's Disease: A Preliminary Prospective Study

Aim This prospective study examined whether lecanemab was associated with changes in neuropsychiatric symptoms (NPS) and investigated their associations with cerebral amyloid burden in patients with early‐stage Alzheimer's disease (AD). Methods Fourteen eligible participants underwent amyloid positron emission tomography, magnetic resonance imaging, and neuropsychological assessments at baseline and following 6 months of lecanemab treatment. Neuropsychological assessments included the Clinical Dementia Rating, Mini‐Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Hamilton Depression Rating Scale, Hamilton Anxiety Scale (HAMA), and Neuropsychiatric Inventory (NPI). Results MMSE and MoCA remained stable, while amyloid burden decreased after 6 months of treatment ( p < 0.05). HAMA, total NPI score, and NPI sub‐scores for psychosis, hyperactivity, and apathy were also decreased ( p < 0.05). Improvements in NPS were associated with lower amyloid burden in the hippocampus, amygdala, thalamus, inferior frontal gyrus (IFG), and anterior cingulate gyrus. These clinical improvements were associated with increased fractal dimension in the middle cingulate cortex and decreased sulcal depth in the IFG. Conclusions These findings suggest that, in early AD, lecanemab treatment may be associated with benefits beyond cognitive stabilization, including possible improvement in NPS, which may relate to amyloid clearance and structural changes in relevant brain regions.