Longitudinal changes in DTI‐ALPS and choroid plexus volume relative to CSF biomarkers during lecanemab treatment in mild cognitive impairment: A pilot study

BACKGROUND Lecanemab improves cerebrospinal fluid (CSF) biomarkers, but whether magnetic resonance imaging (MRI) proxies of CSF–interstitial fluid (ISF) exchange improve is unknown. METHODS This was a single‐center prospective pilot ( n = 8). The ALPS index was derived from diffusion tensor image analysis along the perivascular space (DTI‐ALPS), and intracranial volume (ICV)–normalized choroid plexus (ChP) volume was segmented with FreeSurfer Sequence Adaptive Multimodal SEGmentation (SAMSEG). Baseline changes were tested with Wilcoxon signed‐rank tests with Benjamini–Hochberg false discovery rate (FDR) control within prespecified MRI, CSF, and cognition endpoint families. RESULTS CSF Aβ42 and Aβ42/40 increased and tau phosphorylated at threonine 181 (p‐tau181) decreased at 6 and 12 months (all q < 0.05); cognition showed no FDR‐significant change. The ALPS index showed a downward tendency (9‐month q = 0.010), and ChP/ICV increased at 6–12 months (all q = 0.010). DISCUSSION The ALPS index and ChP volume may be insufficient as stand‐alone surrogate endpoints over 12 months. These findings suggest exploring complementary strategies targeting CSF–ISF exchange and clearance pathways and warrant larger controlled longitudinal studies. CLINICAL TRIAL REGISTRATION INFORMATION Not applicable (observational study).