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).