This randomised, double-blind, placebo-controlled trial (n=60) will assess whether an intranasal dexmedetomidine-esketamine combination improves sleep quality and cognitive function in older adults aged 60 years and above with mild-to-moderate cognitive impairment and comorbid sleep disorder. The main aim is to evaluate change in Pittsburgh Sleep Quality Index (PSQI) score 1 month after the intervention. Participants will receive either the dexmedetomidine-esketamine nasal spray, calculated at approximately 0.4 μg/kg of dexmedetomidine plus 0.2 mg/kg of esketamine, or an equal volume of 0.9% normal saline placebo. Administration uses a customised nasal spray device with alternating nostrils every 5 minutes until the target dose is reached, given twice a week for 4 consecutive weeks (8 sessions in total). Safety monitoring during treatment includes ECG, blood pressure, blood oxygen levels and consciousness, and sleep will be recorded by actigraphy on treatment nights, with face-to-face follow-up at 1, 2 and 3 months after treatment to assess sleep, cognition, mood and activities of daily living.
Sleep is crucial for maintaining brain function and clearing metabolic waste products (such as proteins associated with Alzheimer's disease) from the brain.
Continuous sleep disturbances may hinder this clearance process, thereby worsening cognitive impairment. This study aims to preliminarily explore whether a nasal spray combining dexmedetomidine and esketamine can safely and effectively improve sleep quality and cognitive function in older adults with mild-to-moderate cognitive impairment and comorbid sleep disorders.
The study plans to enroll 60 older adults (aged 60 and older) who experience both sleep disorders and mild-to-moderate cognitive impairment. Participants will be randomly assigned to one of two groups: half will receive the dexmedetomidine-esketamine combination nasal spray, and the other half will receive an equal volume of saline nasal spray (as a placebo). Both groups will receive the nasal spray twice a week for 4 consecutive weeks (8 treatments in total).
During each treatment session, a professional medical team will closely monitor participants' electrocardiogram (ECG), blood pressure, blood oxygen levels, and consciousness to ensure their safety. Additionally, participants will wear an actigraphy on the night of each treatment to objectively record their sleep patterns. Researchers will also conduct face-to-face follow-up visits at 1, 2, and 3 months after the treatment period ends to comprehensively evaluate improvements in sleep quality, cognitive function, mood, and activities of daily living. We hope this study will provide new treatment insights and options for improving the sleep and cognitive health of these patients.
Participants in this arm will receive the intranasal dexmedetomidine-esketamine combination. The dosage is calculated based on body weight (approximately 0.4 μg/kg of dexmedetomidine and 0.2 mg/kg of esketamine). It is administered via a customized nasal spray device, alternating between both nostrils, every 5 minutes until the target dose is reached. This intervention is administered twice a week for 4 consecutive weeks (8 sessions in total).
Participants in this arm will receive an equal volume of normal saline as a placebo. The placebo is administered via the identical customized nasal spray device, following the exact same alternating nostril procedure, volume, and frequency as the intervention group (twice a week for 4 consecutive weeks, 8 sessions in total).