Reductions in neuropsychiatric symptoms after lecanemab treatment and their associations with imaging markers of β-amyloid clearance

BACKGROUND: Anti-amyloid-β (Aβ) therapies can slow cognitive decline and reduce cerebral amyloid burden in Alzheimer's disease (AD). Neuropsychiatric symptoms (NPS) are highly prevalent across the disease course and substantially contribute to disability and caregiver burden. However, whether Aβ clearance translates into improvements in NPS remains unclear. METHOD: We enrolled 144 individuals with AD-related mild cognitive impairment or AD dementia who received intravenous lecanemab infusions. Standardized clinical rating scales, including the Neuropsychiatric Inventory, and amyloid PET were assessed at baseline (V0), 6 months (V1), and 12 months (V2). Longitudinal changes in clinical function and amyloid burden were analyzed. RESULTS: Lecanemab treatment was associated with robust reductions in amyloid PET biomarkers and significant short-term reductions in NPS scores in patients who completed follow-up. Longitudinal analyses showed that reductions in total NPI scores were significantly associated with amyloid-β clearance in the insular cortex. Reductions in the hyperactivity subsyndrome were associated with amyloid reduction across a broader network, including the frontal and temporal lobes, striatum, and insular cortex. CONCLUSIONS: In this real-world cohort, lecanemab was associated with short-term reductions in NPS. Changes in NPS severity were linked to regional amyloid-β clearance.