Melatonin Biomarkers and Delirium in Older Adults: A Systematic Review of Observational Studies
Abstract
Melatonin biomarkers and delirium in older adults: A systematic review of observational studies
Introduction
Delirium, a severe clinical syndrome characterised by acute disturbances in attention, awareness and cognition, affects approximately 20–50% of older adults in hospital care. Melatonin, a key regulator of circadian rhythms, has been proposed as a potential biomarker for delirium due to its role in sleep–wake regulation. However, evidence regarding the association between melatonin secretion and delirium remains inconsistent. This systematic review synthesised evidence on the association between melatonin biomarkers and delirium in older adults.
Methods
Six databases (MEDLINE, Embase, PsycINFO, CINAHL Plus, Scopus, and Web of Science) were systematically searched up to 1 June 2026 to identify observational studies assessing melatonin biomarkers and delirium in older adults (aged ≥60 years). Findings were synthesised narratively.
Results
Eleven observational studies involving 1,782 participants were included (32.0% with delirium). Eight studies measured melatonin concentrations in biological samples (serum, plasma, saliva, urine and cerebrospinal fluid), while three investigated genetic variants of the melatonin receptor gene MTNR1B. Most were prospective cohort studies conducted in surgical or intensive care settings. Six of the eight biomarker studies reported altered melatonin secretion or disrupted circadian rhythms in patients with delirium, although findings were heterogeneous, with several studies reporting lower melatonin concentrations while others found no association or higher postoperative levels. Genetic findings were limited and inconsistent. Heterogeneity in study populations, biological sample type, timing of melatonin measurement and delirium assessment methods limited direct comparison across studies or meta-analyses.
Conclusion
Current evidence suggests that altered melatonin regulation may be associated with delirium in older adults. However, methodological heterogeneity and inconsistent findings limit firm conclusions. Further large, prospective studies using standardised melatonin measurement and delirium assessment are needed to determine the utility of melatonin as a biomarker for delirium.