Lecanemab for posterior cortical atrophy: Two contrasting cases

This study aimed to evaluate the clinical implications, limitations, and potential risks of lecanemab treatment for posterior cortical atrophy (PCA) by conducting a comparative analysis of two cases.

We retrospectively analyzed two patients with biomarker-confirmed PCA-pure who met the eligibility criteria for lecanemab. Clinical history, neuropsychological profiles, imaging findings, and treatment outcomes for more than 1 year were comprehensively reviewed.

At treatment initiation, Patients 1 and 2 were one year post-onset and five years post-onset, respectively, with comparable baseline Mini-Mental State Examination (25-26) and Clinical Dementia Rating (0.5) scores. Patient 1, who exhibited prominent agraphia with left-dominant parieto-occipital atrophy, began lecanemab early and maintained stable daily functioning despite a gradual decline in reading, figure copying, and visual cancelation tasks. Patient 2, with right-dominant posterior atrophy and more severe visuospatial deficits, including simultanagnosia and prosopagnosia, developed parkinsonism and hallucinations after treatment initiation, followed by rapid functional decline, possibly due to mixed pathology, ultimately leading to treatment discontinuation. Patient 1 reported high treatment satisfaction, whereas Patient 2 expressed regret.

These cases raise concerns regarding the direct application of treatment eligibility criteria developed for typical Alzheimer's disease to PCA. Clinical decision-making in PCA requires visual cognition-specific assessments that are less vulnerable to floor effects and tailored to phenotypic heterogeneity and hemispheric lateralization. Coexisting pathologies may influence the treatment response and complicate the interpretation of outcomes. A tailored, multimodal approach that integrates longitudinal neuropsychological assessments with advanced imaging is essential to ensure appropriate use of disease-modifying therapies for PCA.