Intranasal Dexmedetomidine-esketamine on Sleep and Cognition in Older Adults With Mild-to-moderate Cognitive Impairment

You may qualify if

• Aged ≥ 60 years.
• Meeting the clinical diagnostic criteria for Alzheimer's disease, with mild cognitive impairment (MoCA score 18-25) or moderate cognitive impairment (MoCA score 10-17) due to Alzheimer's disease.
• Comorbid with sleep disorders (Pittsburgh Sleep Quality Index [PSQI] score ≥ 7).
• Signed informed consent.

You're excluded if

• Cognitive impairment/dementia due to other causes (e.g., vascular dementia, frontotemporal dementia, Parkinson's disease dementia).
• Unsuitable for intranasal administration due to nasal cavity diseases (e.g., rhinitis, nasal polyps, or nasal congestion of any cause).
• Inability to communicate due to visual, auditory, language, or other reasons, or Mini-Mental State Examination (MMSE) score ≤ 9 or MoCA score ≤ 9.
• History of schizophrenia, epilepsy, or Parkinson's disease, or confirmed diagnosis of glaucoma, hyperthyroidism, pheochromocytoma, or myasthenia gravis.
• Confirmed diagnosis of restless legs syndrome or sleep apnea, or judged to be at high risk of moderate-to-severe sleep apnea according to STOP-Bang score, or Body Mass Index (BMI) > 30 kg/m2.
• History of stroke or transient ischemic attack within 12 months prior to enrollment, confirmed intracranial aneurysm, or elevated intracranial pressure from any cause.
• Uncontrolled hypertension (e.g., hypertensive crisis or systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg prior to enrollment), myocardial infarction, unstable angina, revascularization surgery within 12 months prior to enrollment, or NYHA class III.
• Sick sinus syndrome, severe sinus bradycardia (heart rate \< 50 beats/min), atrioventricular block above degree II without a pacemaker, corrected QT interval (Fridericia-corrected QTcF) ≥ 450 ms, or other severe arrhythmias (e.g., frequent premature ventricular contractions).
• Uncontrolled diabetes (e.g., HbA1c > 9%, diabetic ketosis, hyperglycemic coma, or hypoglycemia).
• Severe hepatic dysfunction (Child-Pugh Class C), renal dysfunction (eGFR ≤ 30 ml/min/1.73m2), respiratory insufficiency (SpO2 \< 93% on room air), or other severe diseases (e.g., frailty with inability to walk independently, advanced-stage tumors).
• Alcohol or drug dependence (manifested as strong cravings, uncontrolled use, and withdrawal symptoms upon cessation), or use of contraindicated medications.
• Major surgery under general anesthesia within 12 weeks prior to enrollment, or planned surgery within 12 weeks.
• Allergy to dexmedetomidine and/or esketamine.
• Participation in other interventional clinical studies.
• Any other conditions deemed unsuitable for study inclusion by the investigator.

The sponsor's own eligibility wording, lightly reformatted. The study team makes the final eligibility decision — worth discussing with your doctor.

Eligibility criteria as of 2026-06-01