Preventing cognitive decline using portable, non‐invasive sleep enhancement.

Abstract Background Recently, disturbed slow wave sleep (SWS) has been identified as an early, modifiable risk factor for dementia. SWS is crucial for memory and metabolic clearance functions, and lack of SWS causes these important functions to suffer, which in turn worsens cognitive decline. A vicious cycle forms between cognitive decline and loss of SWS. Improving SWS could be a way to break this cycle by providing the much‐needed opportunity for the brain to recuperate and ameliorate cognitive decline. We aim to enhance slow wave activity in older adults using phase‐locked auditory stimulation (PLAS). Our laboratory‐based results show that the magnitude of the physiological response to PLAS predicts improvement of memory functions and metabolic clearance. However, larger, long‐term studies in an ecologically valid setting are needed to assess the efficacy of PLAS for the improvement of sleep, memory, and metabolic clearance with the goal of preventing cognitive decline. Laboratory‐based studies quickly become economically and logistically unfeasible to achieve this goal. Method We propose a blinded, sham‐controlled cross‐over study utilizing home‐use devices to study the effect of PLAS on memory functions in 60 older adults with MCI or SCD. Participants will undergo verum‐ and sham‐PLAS in the comfort of their own home across a 12‐week study period. Cognitive performance will be assessed using engaging “serious games”, and blood will be sampled before‐ and after each experimental period to test levels of dementia‐related biomarkers (amyloid beta, pTau181 and 217, GFAP and NfL) and their response to PLAS. Result We expect PLAS to enhance sleep, which will lead to down‐stream effects on memory performance and metabolic clearance. Using a novel approach allowing brain‐age estimation from sleep‐electrophysiology, we hypothesize to see a “rejuvenating” effect of PLAS, restoring an electrophysiological profile typically seen in younger brains. Conclusion This study could pave the way for PLAS‐capable home‐use devices as an affordable, non‐invasive tool to combat cognitive decline, and could lead to novel preventative applications for memory clinics, relieving their clinical burden and improving public health.