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

NCT07610343 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 2026-0208
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with cognitive decline are frequently comorbid with sleep disorders which may in turn aggravate cognitive decline. Sedative dose dexmedetomidine improved sleep quality but incresed bradycardia and hypotension; low dose dexmedetomidine produce less side effects, but the sleep promoting effects are relatively weak. Low dose esketamine also has sleep-promoting effects but may produce neuropsychiatric side effects. Both dexmedetomidine and esketamine are approved for intranasal administration. We suppose that intranasal administration of dexmedetomidine-esketamine combination may improve sleep quality and therefore cognitive function in older ptients with Alzheimer's disease cognitive impairment and sleep disorders.

Conditions

Cognitive Impairment; Older Adults; Sleep Disorders; Dexmedetomidine; Esketamine

Keywords

Older Adults; Cognitive Impairment; Sleep Disorders; Dexmedetomidine; Esketamine

Outcome Measures

Primary Outcomes (1)

• Change in Pittsburgh Sleep Quality Index (PSQI) score from baseline to 1 month

  Sleep quality will be assessed with the Pittsburgh Sleep Quality Index (PSQI) . This is a self-report questionnaire including 7 components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Each component is scored from 0 to 3; the global score ranges from 0 to 21, with higher scores indicating worse sleep quality.

  Up to day 29 post-intervention initiation

Secondary Outcomes (2)

• Changes in Montreal Cognitive Assessment (MoCA) score from baseline to 1, 2, and 3 months

  Up to days 29, 57, and 85 post-intervention initiation

• Changes in Pittsburgh Sleep Quality Index (PSQI) score from baseline to 2 and 3 months

  Up to days 57 and 85 post-intervention initiation

Other Outcomes (4)

• Objective sleep parameters assessed by actigraphy

  During the night after each intervention (days 1, 4, 8, 11, 15, 18, 22, and 25)

• Subjective sleep quality assessed by Numeric Rating Scale (NRS)

  The morning following each intervention (days 2, 5, 9, 12, 16, 19, 23, and 26)

• Change in Patient Health Questionnaire-9 (PHQ-9) score from baseline to 1, 2, and 3 months

  Up to days 29, 57, and 85 post-intervention initiation

Study Arms (2)

Intervention group

EXPERIMENTAL

Participants in this arm will receive intranasal administration of dexmedetomidine-esketamine combination. The dosage will be calculated based on body weight (approximately 0.4 μg/kg of dexmedetomidine and 0.2 mg/kg of esketamine). The mixture of study drugs will be administered via a nasal spray device, alternating between the two nostrils every 5 minutes, until the target dose is reached. The combination will be administered twice a week for 4 consecutive weeks (8 sessions in total).

Drug: Dexmedetomidine-esketamine combination

Placebo group

PLACEBO COMPARATOR

Participants in this arm will receive intranasal administration of placebo (normal sline). The dosage (volume) will be calculated based on body weight in the same way as that in the intervention group. The placebo (normal saline) will be administered via a nasal spray device, alternating between the two nostrils every 5 minutes, until the target dose is reached. The placebo will be administered twice a week for 4 consecutive weeks (8 sessions in total).

Drug: Placebo

Interventions

Dexmedetomidine-esketamine combination DRUG

The dosage will be calculated based on body weight (approximately 0.4 μg/kg of dexmedetomidine and 0.2 mg/kg of esketamine). The mixture of study drugs will be administered via a nasal spray device, alternating between the two nostrils every 5 minutes, until the target dose is reached. The combination will be administered twice a week for 4 consecutive weeks (8 sessions in total).

Intervention group

Placebo DRUG

The dosage (volume) will be calculated based on body weight in the same way as that in the intervention group. The placebo (normal saline) will be administered via a nasal spray device, alternating between the two nostrils every 5 minutes, until the target dose is reached. The placebo will be administered twice a week for 4 consecutive weeks (8 sessions in total).

Also known as: Normal saline

Placebo group

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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 may not qualify 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.

Sponsors & Collaborators

• Peking University First Hospital: lead

Study Sites (1)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Related Publications (54)

• Austin PC. An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies. Multivariate Behav Res. 2011 May;46(3):399-424. doi: 10.1080/00273171.2011.568786. Epub 2011 Jun 8.

  PMID: 21818162 BACKGROUND

• Zisapel N, Nir T. Determination of the minimal clinically significant difference on a patient visual analog sleep quality scale. J Sleep Res. 2003 Dec;12(4):291-8. doi: 10.1046/j.0962-1105.2003.00365.x.

  PMID: 14633240 BACKGROUND

• Martin S, Chandran A, Zografos L, Zlateva G. Evaluation of the impact of fibromyalgia on patients' sleep and the content validity of two sleep scales. Health Qual Life Outcomes. 2009 Jul 10;7:64. doi: 10.1186/1477-7525-7-64.

  PMID: 19591683 BACKGROUND

• Rodrigues NB, McIntyre RS, Lipsitz O, Lee Y, Cha DS, Shekotikhina M, Vinberg M, Gill H, Subramaniapillai M, Kratiuk K, Lin K, Ho R, Mansur RB, Rosenblat JD. A simplified 6-Item clinician administered dissociative symptom scale (CADSS-6) for monitoring dissociative effects of sub-anesthetic ketamine infusions. J Affect Disord. 2021 Mar 1;282:160-164. doi: 10.1016/j.jad.2020.12.119. Epub 2020 Dec 29.

  PMID: 33418362 BACKGROUND

• Podsiadlo D, Richardson S. The timed "Up & Go": a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc. 1991 Feb;39(2):142-8. doi: 10.1111/j.1532-5415.1991.tb01616.x.

  PMID: 1991946 BACKGROUND

• Chernik DA, Gillings D, Laine H, Hendler J, Silver JM, Davidson AB, Schwam EM, Siegel JL. Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: study with intravenous midazolam. J Clin Psychopharmacol. 1990 Aug;10(4):244-51.

  PMID: 2286697 BACKGROUND

• Ding Y, Wang Z, Huang J, Yi Y, Wu Z. Esketamine Optimized the Efficacy of Dexmedetomidine in Treating Sleep Disorders with Comorbid Depression. Neuropsychiatr Dis Treat. 2025 Jul 12;21:1409-1423. doi: 10.2147/NDT.S530265. eCollection 2025.

  PMID: 40673111 BACKGROUND

• Wu J, Liu X, Ye C, Hu J, Ma D, Wang E. Intranasal dexmedetomidine improves postoperative sleep quality in older patients with chronic insomnia: a randomized double-blind controlled trial. Front Pharmacol. 2023 Nov 16;14:1223746. doi: 10.3389/fphar.2023.1223746. eCollection 2023.

  PMID: 38034987 BACKGROUND

• Popova V, Daly EJ, Trivedi M, Cooper K, Lane R, Lim P, Mazzucco C, Hough D, Thase ME, Shelton RC, Molero P, Vieta E, Bajbouj M, Manji H, Drevets WC, Singh JB. Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study. Am J Psychiatry. 2019 Jun 1;176(6):428-438. doi: 10.1176/appi.ajp.2019.19020172. Epub 2019 May 21.

  PMID: 31109201 BACKGROUND

• Lucey BP, Bateman RJ. Amyloid-beta diurnal pattern: possible role of sleep in Alzheimer's disease pathogenesis. Neurobiol Aging. 2014 Sep;35 Suppl 2:S29-34. doi: 10.1016/j.neurobiolaging.2014.03.035. Epub 2014 May 15.

  PMID: 24910393 BACKGROUND

• Mendelsohn AR, Larrick JW. Sleep facilitates clearance of metabolites from the brain: glymphatic function in aging and neurodegenerative diseases. Rejuvenation Res. 2013 Dec;16(6):518-23. doi: 10.1089/rej.2013.1530.

  PMID: 24199995 BACKGROUND

• Zhang Y, Cui F, Ma JH, Wang DX. Mini-dose esketamine-dexmedetomidine combination to supplement analgesia for patients after scoliosis correction surgery: a double-blind randomised trial. Br J Anaesth. 2023 Aug;131(2):385-396. doi: 10.1016/j.bja.2023.05.001. Epub 2023 Jun 9.

  PMID: 37302963 BACKGROUND

• Lu X, Tang L, Lan H, Li C, Lin H. A Comparison of Intranasal Dexmedetomidine, Esketamine or a Dexmedetomidine-Esketamine Combination for Induction of Anaesthesia in Children: A Randomized Controlled Double-Blind Trial. Front Pharmacol. 2022 Jan 27;12:808930. doi: 10.3389/fphar.2021.808930. eCollection 2021.

  PMID: 35185548 BACKGROUND

• Lee KH, Lee SJ, Park JH, Kim SH, Lee H, Oh DS, Kim YH, Park YH, Kim H, Lee SE. Analgesia for spinal anesthesia positioning in elderly patients with proximal femoral fractures: Dexmedetomidine-ketamine versus dexmedetomidine-fentanyl. Medicine (Baltimore). 2020 May;99(20):e20001. doi: 10.1097/MD.0000000000020001.

  PMID: 32443302 BACKGROUND

• Bornemann-Cimenti H, Wejbora M, Michaeli K, Edler A, Sandner-Kiesling A. The effects of minimal-dose versus low-dose S-ketamine on opioid consumption, hyperalgesia, and postoperative delirium: a triple-blinded, randomized, active- and placebo-controlled clinical trial. Minerva Anestesiol. 2016 Oct;82(10):1069-1076. Epub 2016 Jun 21.

  PMID: 27327855 BACKGROUND

• Ionescu DF, Fu DJ, Qiu X, Lane R, Lim P, Kasper S, Hough D, Drevets WC, Manji H, Canuso CM. Esketamine Nasal Spray for Rapid Reduction of Depressive Symptoms in Patients With Major Depressive Disorder Who Have Active Suicide Ideation With Intent: Results of a Phase 3, Double-Blind, Randomized Study (ASPIRE II). Int J Neuropsychopharmacol. 2021 Jan 20;24(1):22-31. doi: 10.1093/ijnp/pyaa068.

  PMID: 32861217 BACKGROUND

• Persson J, Hasselstrom J, Maurset A, Oye I, Svensson JO, Almqvist O, Scheinin H, Gustafsson LL, Almqvist O. Pharmacokinetics and non-analgesic effects of S- and R-ketamines in healthy volunteers with normal and reduced metabolic capacity. Eur J Clin Pharmacol. 2002 Feb;57(12):869-75. doi: 10.1007/s002280100353.

  PMID: 11936706 BACKGROUND

• Segmiller F, Ruther T, Linhardt A, Padberg F, Berger M, Pogarell O, Moller HJ, Kohler C, Schule C. Repeated S-ketamine infusions in therapy resistant depression: a case series. J Clin Pharmacol. 2013 Sep;53(9):996-8. doi: 10.1002/jcph.122. Epub 2013 Jul 24. No abstract available.

  PMID: 23893490 BACKGROUND

• Canuso CM, Singh JB, Fedgchin M, Alphs L, Lane R, Lim P, Pinter C, Hough D, Sanacora G, Manji H, Drevets WC. Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study. Am J Psychiatry. 2018 Jul 1;175(7):620-630. doi: 10.1176/appi.ajp.2018.17060720. Epub 2018 Apr 16.

  PMID: 29656663 BACKGROUND

• Bartova L, Papageorgiou K, Milenkovic I, Dold M, Weidenauer A, Willeit M, Winkler D, Kasper S. Rapid antidepressant effect of S-ketamine in schizophrenia. Eur Neuropsychopharmacol. 2018 Aug;28(8):980-982. doi: 10.1016/j.euroneuro.2018.05.007. Epub 2018 Jul 2.

  PMID: 30041987 BACKGROUND

• Newport DJ, Carpenter LL, McDonald WM, Potash JB, Tohen M, Nemeroff CB; APA Council of Research Task Force on Novel Biomarkers and Treatments. Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression. Am J Psychiatry. 2015 Oct;172(10):950-66. doi: 10.1176/appi.ajp.2015.15040465.

  PMID: 26423481 BACKGROUND

• Kishimoto T, Chawla JM, Hagi K, Zarate CA, Kane JM, Bauer M, Correll CU. Single-dose infusion ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories. Psychol Med. 2016 May;46(7):1459-72. doi: 10.1017/S0033291716000064. Epub 2016 Feb 12.

  PMID: 26867988 BACKGROUND

• Abdallah CG, Adams TG, Kelmendi B, Esterlis I, Sanacora G, Krystal JH. KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID-ACTING ANTIDEPRESSANTS. Depress Anxiety. 2016 Aug;33(8):689-97. doi: 10.1002/da.22501. Epub 2016 Apr 6.

  PMID: 27062302 BACKGROUND

• Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4. doi: 10.1016/s0006-3223(99)00230-9.

  PMID: 10686270 BACKGROUND

• Duncan WC Jr, Ballard ED, Zarate CA. Ketamine-Induced Glutamatergic Mechanisms of Sleep and Wakefulness: Insights for Developing Novel Treatments for Disturbed Sleep and Mood. Handb Exp Pharmacol. 2019;253:337-358. doi: 10.1007/164_2017_51.

  PMID: 28939975 BACKGROUND

• Song B, Zhu J. A Novel Application of Ketamine for Improving Perioperative Sleep Disturbances. Nat Sci Sleep. 2021 Dec 25;13:2251-2266. doi: 10.2147/NSS.S341161. eCollection 2021.

  PMID: 34992482 BACKGROUND

• Koncz S, Papp N, Pothorszki D, Bagdy G. (S)-Ketamine but Not (R)-Ketamine Shows Acute Effects on Depression-Like Behavior and Sleep-Wake Architecture in Rats. Int J Neuropsychopharmacol. 2023 Sep 25;26(9):618-626. doi: 10.1093/ijnp/pyad050.

  PMID: 37578355 BACKGROUND

• Feinberg I, Campbell IG. Ketamine administration during waking increases delta EEG intensity in rat sleep. Neuropsychopharmacology. 1993 Aug;9(1):41-8. doi: 10.1038/npp.1993.41.

  PMID: 8397722 BACKGROUND

• Wolff K, Winstock AR. Ketamine : from medicine to misuse. CNS Drugs. 2006;20(3):199-218. doi: 10.2165/00023210-200620030-00003.

  PMID: 16529526 BACKGROUND

• Barrett W, Buxhoeveden M, Dhillon S. Ketamine: a versatile tool for anesthesia and analgesia. Curr Opin Anaesthesiol. 2020 Oct;33(5):633-638. doi: 10.1097/ACO.0000000000000916.

  PMID: 32826629 BACKGROUND

• Uusalo P, Seppanen SM, Jarvisalo MJ. Feasibility of Intranasal Dexmedetomidine in Treatment of Postoperative Restlessness, Agitation, and Pain in Geriatric Orthopedic Patients. Drugs Aging. 2021 May;38(5):441-450. doi: 10.1007/s40266-021-00846-6. Epub 2021 Mar 16.

  PMID: 33728561 BACKGROUND

• Jun JH, Kim KN, Kim JY, Song SM. The effects of intranasal dexmedetomidine premedication in children: a systematic review and meta-analysis. Can J Anaesth. 2017 Sep;64(9):947-961. doi: 10.1007/s12630-017-0917-x. Epub 2017 Jun 21.

  PMID: 28639236 BACKGROUND

• Li A, Yuen VM, Goulay-Dufay S, Sheng Y, Standing JF, Kwok PCL, Leung MKM, Leung AS, Wong ICK, Irwin MG. Pharmacokinetic and pharmacodynamic study of intranasal and intravenous dexmedetomidine. Br J Anaesth. 2018 May;120(5):960-968. doi: 10.1016/j.bja.2017.11.100. Epub 2018 Feb 2.

  PMID: 29661413 BACKGROUND

• Sun YM, Zhu SN, Zhang C, Li SL, Wang DX. Effect of low-dose dexmedetomidine on sleep quality in postoperative patients with mechanical ventilation in the intensive care unit: A pilot randomized trial. Front Med (Lausanne). 2022 Aug 31;9:931084. doi: 10.3389/fmed.2022.931084. eCollection 2022.

  PMID: 36117973 BACKGROUND

• Skrobik Y, Duprey MS, Hill NS, Devlin JW. Low-Dose Nocturnal Dexmedetomidine Prevents ICU Delirium. A Randomized, Placebo-controlled Trial. Am J Respir Crit Care Med. 2018 May 1;197(9):1147-1156. doi: 10.1164/rccm.201710-1995OC.

  PMID: 29498534 BACKGROUND

• Zhang DF, Su X, Meng ZT, Li HL, Wang DX, Xue-Ying Li, Maze M, Ma D. Impact of Dexmedetomidine on Long-term Outcomes After Noncardiac Surgery in Elderly: 3-Year Follow-up of a Randomized Controlled Trial. Ann Surg. 2019 Aug;270(2):356-363. doi: 10.1097/SLA.0000000000002801.

  PMID: 29742525 BACKGROUND

• Su X, Meng ZT, Wu XH, Cui F, Li HL, Wang DX, Zhu X, Zhu SN, Maze M, Ma D. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet. 2016 Oct 15;388(10054):1893-1902. doi: 10.1016/S0140-6736(16)30580-3. Epub 2016 Aug 16.

  PMID: 27542303 BACKGROUND

• Wu XH, Cui F, Zhang C, Meng ZT, Wang DX, Ma J, Wang GF, Zhu SN, Ma D. Low-dose Dexmedetomidine Improves Sleep Quality Pattern in Elderly Patients after Noncardiac Surgery in the Intensive Care Unit: A Pilot Randomized Controlled Trial. Anesthesiology. 2016 Nov;125(5):979-991. doi: 10.1097/ALN.0000000000001325.

  PMID: 27571256 BACKGROUND

• Shehabi Y, Howe BD, Bellomo R, Arabi YM, Bailey M, Bass FE, Bin Kadiman S, McArthur CJ, Murray L, Reade MC, Seppelt IM, Takala J, Wise MP, Webb SA; ANZICS Clinical Trials Group and the SPICE III Investigators. Early Sedation with Dexmedetomidine in Critically Ill Patients. N Engl J Med. 2019 Jun 27;380(26):2506-2517. doi: 10.1056/NEJMoa1904710. Epub 2019 May 19.

  PMID: 31112380 BACKGROUND

• Turan A, Duncan A, Leung S, Karimi N, Fang J, Mao G, Hargrave J, Gillinov M, Trombetta C, Ayad S, Hassan M, Feider A, Howard-Quijano K, Ruetzler K, Sessler DI; DECADE Study Group. Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial. Lancet. 2020 Jul 18;396(10245):177-185. doi: 10.1016/S0140-6736(20)30631-0.

  PMID: 32682483 BACKGROUND

• Alexopoulou C, Kondili E, Diamantaki E, Psarologakis C, Kokkini S, Bolaki M, Georgopoulos D. Effects of dexmedetomidine on sleep quality in critically ill patients: a pilot study. Anesthesiology. 2014 Oct;121(4):801-7. doi: 10.1097/ALN.0000000000000361.

  PMID: 24988068 BACKGROUND

• Nelson LE, Lu J, Guo T, Saper CB, Franks NP, Maze M. The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology. 2003 Feb;98(2):428-36. doi: 10.1097/00000542-200302000-00024.

  PMID: 12552203 BACKGROUND

• Weerink MAS, Struys MMRF, Hannivoort LN, Barends CRM, Absalom AR, Colin P. Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine. Clin Pharmacokinet. 2017 Aug;56(8):893-913. doi: 10.1007/s40262-017-0507-7.

  PMID: 28105598 BACKGROUND

• Bubu OM, Brannick M, Mortimer J, Umasabor-Bubu O, Sebastiao YV, Wen Y, Schwartz S, Borenstein AR, Wu Y, Morgan D, Anderson WM. Sleep, Cognitive impairment, and Alzheimer's disease: A Systematic Review and Meta-Analysis. Sleep. 2017 Jan 1;40(1). doi: 10.1093/sleep/zsw032.

  PMID: 28364458 BACKGROUND

• Korostovtseva L, Bochkarev M, Sviryaev Y. Sleep and Cardiovascular Risk. Sleep Med Clin. 2021 Sep;16(3):485-497. doi: 10.1016/j.jsmc.2021.05.001. Epub 2021 Jun 25.

  PMID: 34325825 BACKGROUND

• Mogavero MP, DelRosso LM, Fanfulla F, Bruni O, Ferri R. Sleep disorders and cancer: State of the art and future perspectives. Sleep Med Rev. 2021 Apr;56:101409. doi: 10.1016/j.smrv.2020.101409. Epub 2020 Nov 28.

  PMID: 33333427 BACKGROUND

• Yaffe K, Falvey CM, Hoang T. Connections between sleep and cognition in older adults. Lancet Neurol. 2014 Oct;13(10):1017-28. doi: 10.1016/S1474-4422(14)70172-3.

  PMID: 25231524 BACKGROUND

• Yu J, Rawtaer I, Fam J, Jiang MJ, Feng L, Kua EH, Mahendran R. Sleep correlates of depression and anxiety in an elderly Asian population. Psychogeriatrics. 2016 May;16(3):191-5. doi: 10.1111/psyg.12138. Epub 2015 Jul 16.

  PMID: 26179204 BACKGROUND

• Irwin MR. Sleep and inflammation: partners in sickness and in health. Nat Rev Immunol. 2019 Nov;19(11):702-715. doi: 10.1038/s41577-019-0190-z.

  PMID: 31289370 BACKGROUND

• Ratner V, Gao Y, Lee H, Elkin R, Nedergaard M, Benveniste H, Tannenbaum A. Cerebrospinal and interstitial fluid transport via the glymphatic pathway modeled by optimal mass transport. Neuroimage. 2017 May 15;152:530-537. doi: 10.1016/j.neuroimage.2017.03.021. Epub 2017 Mar 18.

  PMID: 28323163 BACKGROUND

• Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, O'Donnell J, Christensen DJ, Nicholson C, Iliff JJ, Takano T, Deane R, Nedergaard M. Sleep drives metabolite clearance from the adult brain. Science. 2013 Oct 18;342(6156):373-7. doi: 10.1126/science.1241224.

  PMID: 24136970 BACKGROUND

• McCleery J, Sharpley AL. Pharmacotherapies for sleep disturbances in dementia. Cochrane Database Syst Rev. 2020 Nov 15;11(11):CD009178. doi: 10.1002/14651858.CD009178.pub4.

  PMID: 33189083 BACKGROUND

• Siegel JM. Sleep viewed as a state of adaptive inactivity. Nat Rev Neurosci. 2009 Oct;10(10):747-53. doi: 10.1038/nrn2697. Epub 2009 Aug 5.

  PMID: 19654581 BACKGROUND

• Beata BK, Wojciech J, Johannes K, Piotr L, Barbara M. Alzheimer's Disease-Biochemical and Psychological Background for Diagnosis and Treatment. Int J Mol Sci. 2023 Jan 5;24(2):1059. doi: 10.3390/ijms24021059.

  PMID: 36674580 BACKGROUND

MeSH Terms

Conditions

Cognitive Dysfunction; Sleep Wake Disorders

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Dong-Xin Wang, MD, PhD

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dong-Xin Wang, MD, PhD

CONTACT

010-83572784; wangdongxin@hotmail.com

Jia-Hui Ma, PhD

CONTACT

010-83575085; mjh@bjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician, Professor

Study Record Dates

• First Submitted: May 20, 2026
• First Posted: May 27, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: June 1, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)