Melatonin in Alzheimer’s Disease: Literature Review and Therapeutic Trials

Issue title: Therapeutic Trials in Alzheimer’s Disease: Where Are We Now?

Guest editors: Paula I. Moreira, Jesus Avila, Daniela Galimberti, Miguel A. Pappolla, Germán Plascencia-Villa, Aaron A. Sorensen, Xiongwei Zhu and George Perry

Article type: Review Article

Authors: Steinbach, Marilyn J.^{a; b} | Denburg, Natalie L.^{b; *}

Affiliations: [a] Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA, USA | [b] Department of Neurology, Division of Cognitive Neuroscience, University of Iowa Carver College of Medicine, Iowa City, IA, USA

Correspondence: [*] Correspondence to: Natalie Denburg, PhD, Department of Neurology, Division of Cognitive Neuroscience, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA. E-mail: natalie-denburg@uiowa.edu.

Abstract: There are currently no effective treatments to prevent, halt, or reverse Alzheimer’s disease (AD), the most common cause of dementia in older adults. Melatonin, a relatively harmless over-the-counter supplement, may offer some benefits to patients with AD. Melatonin is known for its sleep-enhancing properties, but research shows that it may provide other advantages as well, such as antioxidant and anti-amyloidogenic properties. Clinical trials for melatonin use in AD have mixed results but, overall, show modest benefits. However, it is difficult to interpret clinical research in this area as there is little standardization to guide the administration and study of melatonin. This review covers basic biology and clinical research on melatonin in AD focusing on prominent hypotheses of pathophysiology of neurodegeneration and cognitive decline in AD (i.e., amyloid and tau hypotheses, antioxidant and anti-inflammation, insulin resistance and glucose homeostasis, the cholinergic hypothesis, sleep regulation, and the hypothalamic-pituitary-adrenal axis and cortisol). This is followed by a discussion on pending clinical trials, considerations for future research protocols, and open questions in the field.

Keywords: Aging, Alzheimer’s disease, circadian rhythm, clinical trials, dementia, melatonin, sleep

DOI: 10.3233/JAD-230760

Journal: Journal of Alzheimer's Disease, vol. 101, no. s1, pp. S193-S204, 2024