Abstract Details

Title Comparative Effects of Pharmacologic Interventions on Subjective and Functional Sleep-Wake Outcomes in Alzheimer’s Disease: A Network Meta-Analysis of Randomized Controlled Trials

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P3 - Poster Session 3 (5:00 PM-6:00 PM)

Poster/Presentation
Number 13-009

Objective To assess pharmacologic effects on subjective and functional sleep-wake parameters in Alzheimer’s disease using polysomnography and actigraphy

Background Sleep-wake disturbances are common in Alzheimer’s disease(AD) which worsens cognition and function. Pharmacologic guidance based on subjective outcomes remains limited. Evaluation with polysomnography and actigraphy enables comparative efficacy assessment across drug classes in AD.

Design/Methods We performed a systematic review and meta-analysis following PRISMA guidelines. Suitable studies were identified through a comprehensive search performed across major databases up to September 2025. Data were analyzed using R (version 4.5.1) in RStudio, with the packages netmeta, gemtc, BUGSnet, and bnma. Both frequentist and Bayesian methods were employed to indirectly measure the efficacy using random models.

Results Eleven RCTs encompassing 8 distinct pharmacologic interventions were analyzed. For total nocturnal sleep time, melatonin 2.5mg demonstrated superior efficacy with SUCRA ranking of 79.2%, followed by melatonin 10mg (61.6%) and melatonin 5mg (57.2%), while placebo ranked lowest (32.0%). Pittsburgh Sleep Quality Index analysis revealed that melatonin 2mg achieved the highest SUCRA ranking (66.0%) with mean difference -0.38 [-2.32; 1.56], compared to galantamine 24mg (25.0%) with MD 0.15 [0.05; 0.25] versus placebo. For daytime sleep regulation, orexin receptor antagonists (lemborexant) showed promising effects, with lemborexant 10mg demonstrating MD 76.58 [-7.64; 160.80]. Daytime activity count analysis showed melatonin interventions had variable effects, with placebo achieving the highest SUCRA ranking (77.0%), suggesting preservation of daytime wakefulness. Ratio of daytime to nighttime sleep favored melatonin 2.5mg (MD -0.25 [-0.62; 0.12]) and melatonin 10mg (MD -0.17 [-0.54; 0.20]).

Conclusions Melatonin consistently improved nocturnal sleep and circadian rhythm on subjective measures, with dose-dependent ranking advantages across networks. Dual orexin receptor antagonists showed promising sleep maintenance signals but needed confirmation for daytime effects and longer-term outcomes, while galantamine offered minimal sleep benefit. These network-based hierarchies enable targeted pharmacotherapy and elevate restorative sleep in AD.

Authors/Disclosures
Shrideavi Murugan, MBBS PRESENTER	Miss Murugan has nothing to disclose.
Gurunathan Srinivasan	Mr. Srinivasan has nothing to disclose.
Tejaswin Mariappan, MBBS	Mr. Mariappan has nothing to disclose.
Noorul Hidhaya S, MBBS	Miss S has nothing to disclose.
Haran Srinivasan Saravanan, MBBS	Mr. Saravanan has nothing to disclose.
Praveen Nandha Kumar Pitchan Velammal, MBBS	Dr. Pitchan Velammal has nothing to disclose.
Javed Ahamed Cumbum Syed, MBBS	Mr. Cumbum Syed has nothing to disclose.

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