Preserved wake-dependent cortical excitability dynamics predict cognitive fitness beyond age-related brain alterations

Abstract

Age-related cognitive decline arises from alterations in brain integrity as well as in sleep-wake regulation. Here, we investigated whether preserved sleep-wake regulation of cortical function during wakefulness could represent a positive factor for cognitive fitness in aging, independently of early age-related changes in brain structure. We quantified cortical excitability dynamics during prolonged wakefulness as a sensitive marker of age-related alteration in sleep-wake regulation in 60 healthy older individuals (50-69y; 42 women). Brain structural integrity was assessed with amyloid-beta- and tau-PET, and with MRI. Participants’ cognition was extensively investigated. We show that individuals with preserved cortical excitability dynamics exhibit better cognitive performance, particularly in the executive domain, which is essential to successful cognitive aging. Critically, this association remained significant after accounting for brain integrity measures. Preserved dynamics of basic brain function during wakefulness could be essential to cognitive fitness in aging, independently from age-related brain structural modifications that can ultimately lead to dementia.