One night of closed-loop auditory stimulation during sleep enhances memory consolidation in patients with Alzheimer's Disease
Lopez-Larraz, E.; Oriol, D.; Fierro, G.; Jubera-Garcia, E.; Klinzing, J. G.; Sierra-Torralba, M.; Horna-Prat, E.; Escolano, C.; Sutil-Jimenez, J.; Rojas, F.; Montesano, L.; Moreno Loscertales, C.; Pinol, G.; Pascual-Leone, A.; Marta Moreno, E.; Munoz-Farjas, E.; Minguez, J.
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INTRODUCTION: Sleep-dependent memory consolidation is impaired early in Alzheimer's disease (AD). Closed-loop auditory stimulation (CLAS) of sleep slow oscillations enhances memory consolidation in healthy individuals, but its efficacy in AD remains unknown. METHODS: We conducted a randomized, double-blind, placebo-controlled crossover trial in 37 patients with biomarker-confirmed early symptomatic AD and an amnestic clinical phenotype. We assessed the effect of one night of CLAS, compared with one night of sham stimulation, on declarative memory retention, sleep electrophysiology, and sleep architecture. RESULTS: CLAS significantly improved overnight word-pair consolidation (Cohen's dz = 0.42, p = 0.04), enhanced stimulation-evoked slow-wave and fast spindle activity, and preserved sleep architecture and subjective sleep quality. DISCUSSION: This study provides the first demonstration that CLAS modulates sleep electrophysiology and improves overnight memory consolidation in patients with biomarker-confirmed AD. Further studies need to address the sustainability of such effects with multi-night interventions for a clinically meaningful intervention.
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