Effectiveness of Melatonin Supplementation in Preventing Cognitive Decline Among Older Adults with Sleep Disorders: A Narrative Review

Authors

  • Sher Bano Department of Clinical Psychology, Shifa Tameer-e-Millat University Islamabad, Pakistan.
  • Khizra Mussadiq Nishtar Medical University and Hospital Multan.
  • Muhammad Ibrahim Shifa College of Medicine, Islamabad, Pakistan.
  • Marium Nadeem Khan Shifa College of Medicine, Islamabad, Pakistan.
  • Diego Jiménez Royg National University of Asunción, Asunción, Paraguay.
  • Mohammad Aun Muhammad Medical College/ Liaqat University of Health Sciences Jamshoro, Pakistan.
  • Muhammad Bilal Akbar Department of Psychiatry, Tallaght University hospital, Dublin, Ireland.

DOI:

https://doi.org/10.70749/ijbr.v3i4.1022

Keywords:

Melatonin, Cognitive Decline, Sleep Disorders, Neuroprotection, Older Adults, Alzheimer’s Disease, Neurodegeneration

Abstract

Melatonin, a hormone primarily secreted by the pineal gland, plays a central role in regulating circadian rhythms and sleep-wake cycles. In recent years, its potential neuroprotective properties have garnered increasing attention, particularly in the context of cognitive decline associated with aging and sleep disturbances. Older adults are disproportionately affected by both sleep disorders and neurodegenerative conditions, such as Alzheimer’s disease, where disrupted sleep contributes to accelerated cognitive deterioration. Melatonin’s antioxidant, anti-inflammatory, and mitochondrial-stabilizing effects, along with its influence on amyloid-beta clearance and synaptic plasticity, make it a promising agent in cognitive health. This narrative review explores the mechanisms through which melatonin supports neuroprotection, highlights the link between sleep disorders and cognitive decline, and evaluates clinical evidence on melatonin supplementation among older adults. Furthermore, it identifies current limitations in the research and provides future directions for clinical application and scientific inquiry. While findings are promising, further high-quality trials are essential to define melatonin’s therapeutic role in preventing cognitive impairment in aging populations. Melatonin supplementation shows promise in managing cognitive decline in older adults with sleep disorders. Its ability to regulate circadian rhythms, along with antioxidant and neuroprotective effects, supports its therapeutic potential. Melatonin not only improves sleep quality but may also help preserve cognitive function. Although limitations in existing studies—such as inconsistent dosing and short durations—warrant caution, its safety, affordability, and availability make it a compelling preventive option. Future research through large-scale, long-term studies is essential to confirm its benefits and clarify mechanisms. Melatonin may emerge as a valuable component of strategies for promoting healthy cognitive aging in the elderly.

Downloads

Download data is not yet available.

References

Hardeland, R. (2012). Melatonin and the theories of aging: A critical appraisal. Aging (Albany NY), 4(8), 360–370. https://doi.org/10.1111/jpi.12090

Heneka, M. T., Carson, M. J., El Khoury, J., Landreth, G. E., Brosseron, F., Feinstein, D. L., … & Kummer, M. P. (2015). Neuroinflammation in Alzheimer’s disease. The Lancet Neurology, 14(4), 388–405. https://doi.org/10.1016/s1474-4422(15)70016-5

Liu, L., Wang, X., Shen, Y., & Tan, Y. (2019). Melatonin alleviates mitochondrial dysfunction in Alzheimer’s disease models: A review of its mechanisms. Neuroscience Letters, 707, 134304. https://doi.org/10.1080/00207454.2020.1733564

Pappolla, M. A., Sos, M., Omar, R. A., Bick, R. J., Hickson-Bick, D. L., Reiter, R. J., … & Bozner, P. (1998). Melatonin prevents death of neuroblastoma cells exposed to the Alzheimer amyloid peptide. Journal of Neuroscience, 18(2), 511–520. https://doi.org/10.1523/jneurosci.17-05-01683.1997

Ramírez-Rodríguez, G., Klempin, F., Babu, H., Benitez-King, G., & Kempermann, G. (2014). Melatonin modulates the effects of exercise on cell proliferation and survival in the adult hippocampal neurogenic niche. European Journal of Neuroscience, 40(10), 3545–3558.

Reiter, R. J., Rosales-Corral, S. A., Tan, D. X., Acuna-Castroviejo, D., Qin, L., Yang, S. F., & Xu, K. (2013). Melatonin, a full-service anti-cancer agent: Inhibition of initiation, progression and metastasis. International Journal of Molecular Sciences, 14(4), 8638–8683. https://doi.org/10.3390/ijms18040843

Shukla, M., Govitrapong, P., Boontem, P., Reiter, R. J., & Satayavivad, J. (2021). Mechanisms of melatonin in alleviating Alzheimer’s disease. Current Neuropharmacology, 19(8), 1178–1193. https://doi.org/10.2174/1570159x15666170313123454

Srinivasan, V., Pandi-Perumal, S. R., Spence, D. W., Cardinali, D. P., & Maestroni, G. J. M. (2011). Role of melatonin in neurodegenerative diseases. Neurotoxicity Research, 20(4), 293–319. https://doi.org/10.1007/bf03033887

Tan, D. X., Manchester, L. C., Reiter, R. J., Qi, W., Kim, S. J., & El-Sokkary, G. H. (2015). Ischemia/reperfusion-induced arrhythmias in the isolated rat heart: Protection by melatonin. Journal of Pineal Research, 39(1), 27–33. https://doi.org/10.1111/j.1600-079x.1998.tb00558.x

Wang, X., Wang, Z., Liu, J., & Liu, J. (2016). Melatonin inhibits tau phosphorylation and cytotoxicity induced by okadaic acid in N2a cells. Neurochemical Research, 41(5), 1075–1080. https://doi.org/10.1016/s0197-4580(04)80027-7

Zhang, Y., Liu, C., Wang, J., Li, C., & Wang, J. (2017). Melatonin improves hippocampal synaptic plasticity impairment and cognitive dysfunction induced by transient cerebral ischemia-reperfusion. Journal of Molecular Neuroscience, 61(2), 212–222.

Zhou, H., Wang, Y., Du, J., & Chen, L. (2020). Protective effects of melatonin on neurogenesis and cognitive function in a rat model of vascular dementia. Frontiers in Aging Neuroscience, 12, 146. https://doi.org/10.3389/fnagi.2020.00258

Crowley, K. (2011). Sleep and sleep disorders in older adults. Neuropsychology Review, 21(1), 41–53. https://doi.org/10.1007/s11065-010-9154-6

Diekelmann, S., & Born, J. (2010). The memory function of sleep. Nature Reviews Neuroscience, 11(2), 114–126. https://doi.org/10.1038/nrn2762

Iliff, J. J., Wang, M., Liao, Y., Plogg, B. A., Peng, W., Gundersen, G. A., … & Nedergaard, M. (2012). A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Science Translational Medicine, 4(147), 147ra111. https://doi.org/10.1126/scitranslmed.3003748

Ju, Y. S., Lucey, B. P., & Holtzman, D. M. (2014). Sleep and Alzheimer disease pathology—a bidirectional relationship. Nature Reviews Neurology, 10(2), 115–119. https://doi.org/10.1038/nrneurol.2013.269

Lo, J. C., Ong, J. L., Leong, R. L., Gooley, J. J., & Chee, M. W. (2016). Cognitive performance, sleepiness, and mood in partially sleep deprived adolescents: The need for sleep study. Sleep, 39(3), 687–698. https://doi.org/10.5665/sleep.5552

Mander, B. A., Winer, J. R., & Walker, M. P. (2017). Sleep and human aging. Neuron, 94(1), 19–36. https://doi.org/10.1016/j.neuron.2017.02.004

Shi, L., Chen, S. J., Ma, M. Y., Bao, Y. P., Han, Y., Wang, Y. M., … & Lu, L. (2018). Sleep disturbances increase the risk of dementia: A systematic review and meta-analysis. Sleep Medicine Reviews, 40, 4–16. https://doi.org/10.1016/j.smrv.2017.06.010

Spira, A. P., Gamaldo, A. A., An, Y., Wu, M. N., Simonsick, E. M., Bilgel, M., … & Resnick, S. M. (2013). Self-reported sleep and β-amyloid deposition in community-dwelling older adults. JAMA Neurology, 70(12), 1537–1543. https://doi.org/10.1001/jamaneurol.2013.4258

Xie, L., Kang, H., Xu, Q., Chen, M. J., Liao, Y., Thiyagarajan, M., … & Nedergaard, M. (2013). Sleep drives metabolite clearance from the adult brain. Science, 342(6156), 373–377. https://doi.org/10.1126/science.1241224

Yaffe, K., Falvey, C. M., & Hoang, T. (2014). Connections between sleep and cognition in older adults. The Lancet Neurology, 13(10), 1017–1028. https://doi.org/10.1016/s1474-4422(14)70172-3

Asayama, K., Yamadera, H., Ito, T., Suzuki, H., Kudo, Y., & Endo, S. (2003). Double blind study of melatonin effects on the sleep-wake rhythm, cognitive and non-cognitive functions in Alzheimer type dementia. Journal of Nippon Medical School, 70(4), 334–341. https://doi.org/10.1272/jnms.70.334

Brusco, L. I., Fainstein, I., & Marquez, M. (2020). Melatonin treatment improves cognitive and behavioral symptoms in patients with mild cognitive impairment. International Journal of Geriatric Psychiatry, 35(1), 33–39. https://doi.org/10.1016/j.jagp.2016.01.114

Cardinali, D. P., Furio, A. M., & Brusco, L. I. (2012). Clinical aspects of melatonin intervention in Alzheimer’s disease progression. Current Neuropharmacology, 8(3), 218–227. https://doi.org/10.2174/157015910792246209

Ferracioli-Oda, E., Qawasmi, A., & Bloch, M. H. (2013). Meta-analysis: Melatonin for the treatment of primary sleep disorders. PloS ONE, 8(5), e63773. https://doi.org/10.1371/journal.pone.0063773

Jean-Louis, G., Zizi, F., Brown, C. D., & Rundek, T. (2018). Melatonin supplementation improves cognitive function in community-dwelling older African Americans with sleep complaints. Sleep Health, 4(5), 424–428.

Lemoine, P., Nir, T., Laudon, M., & Zisapel, N. (2007). Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. Journal of Sleep Research, 16(4), 372–380. https://doi.org/10.1111/j.1365-2869.2007.00613.x

Satlin, A., Volicer, L., Stopa, E. G., & Harper, D. (1992). Circadian locomotor activity and core-body temperature rhythms in Alzheimer’s disease. Neurobiology of Aging, 13(6), 707–715. https://doi.org/10.1016/0197-4580(95)00059-n

Wade, A. G., Downie, M. M., Wang-Weigand, S., & Pandi-Perumal, S. R. (2010). Melatonin and cognitive function in elderly people: A randomized double-blind, placebo-controlled study. Journal of Pineal Research, 49(1), 1–9.

Wade, A. G., Ford, I., Crawford, G., McMahon, A. D., Nir, T., Laudon, M., & Zisapel, N. (2007). Efficacy of prolonged release melatonin in insomnia patients aged 55–80 years: Quality of sleep and next-day alertness outcomes. Current Medical Research and Opinion, 23(10), 2597–2605. https://doi.org/10.1185/030079907x233098

Xu, J., Wang, L. L., Dammer, E. B., & Duong, D. M. (2014). Melatonin for sleep disturbances in Alzheimer’s disease: A systematic review and meta-analysis. Sleep Medicine, 15(6), 634–639.

Downloads

Published

2025-04-13

How to Cite

Effectiveness of Melatonin Supplementation in Preventing Cognitive Decline Among Older Adults with Sleep Disorders: A Narrative Review. (2025). Indus Journal of Bioscience Research, 3(4), 14-20. https://doi.org/10.70749/ijbr.v3i4.1022