International Journal of Molecular Medical Science 2025, Vol.15 http://medscipublisher.com/index.php/ijmms © 2025 MedSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved. -
International Journal of Molecular Medical Science 2025, Vol.15 http://medscipublisher.com/index.php/ijmms © 2025 MedSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved. MedSci Publisher is an international Open Access publisher specializing in disease therapy, clinical pharmacology, clinical biochemistry, vaccines, immunology, microbiology at the publishing platform that is operated by Sophia Publishing Group (SPG), founded in British Columbia of Canada. Publisher MedSci Publisher Editedby Editorial Team of International Journal of Molecular Medical Science Email: edit@ijmms.medscipublisher.com Website: http://medscipublisher.com/index.php/ijmms Address: 11388 Stevenston Hwy, PO Box 96016, Richmond, V7A 5J5, British Columbia Canada International Journal of Molecular Medical Science (ISSN 1927-6656) is an open access, peer reviewed journal published online by MedSci Publisher. The journal publishes scientific articles like original research articles, case reports, review articles, editorials, short communications and correspondence of the high quality pertinent to all aspects of human biology, pathophysiology and molecular medical science, including genomics, transcriptomics, proteomics, metabolomics of disease therapy, clinical pharmacology, clinical biochemistry, vaccines, immunology, microbiology, epidemiology, aging, cancer biology, infectious diseases, neurological diseases and myopathies, stem cells and regenerative medicine, vascular and cardiovascular biology, as well as the important implications for human health and clinical practice research. All the articles published in International Journal of Molecular Medical Science are Open Access, and are distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. MedSci Publisher uses CrossCheck service to identify academic plagiarism through the world’s leading plagiarism prevention tool, iParadigms, and to protect the original authors’ copyrights.
International Journal of Molecular Medical Science (online), 2025, Vol. 15, No. 4 ISSN 1927-6656 http://medscipublisher.com/index.php/ijmms © 2025 MedSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved. Latest Content Effect of Nursing-Based Sleep Management on Melatonin and Cortisol Levels in Geriatric Dementia Patients MinLi International Journal of Molecular Medical Science, 2025, Vol. 15, No. 4, 155-164 Clinical and Immunological Factors Affecting Vaccine Efficacy in Frail Older Adults Hua Xu, Manman Li International Journal of Molecular Medical Science, 2025, Vol. 15, No. 4, 165-174 The Changes in Blood Exosomal miRNA Profiles and Disease Progression in Alzheimer’s Disease Patients Qiyan Lou, Xiaoying Xu International Journal of Molecular Medical Science, 2025, Vol. 15, No. 4, 175-184 The Effect of Vitamin D Supplementation on Fracture Risk in the Elderly: A Meta-Analysis Sufu Lü, Jianhui Li International Journal of Molecular Medical Science, 2025, Vol. 15, No. 4, 185-194 Role of Early Hemostasis Nursing and Coagulation Monitoring in Multiple Trauma Cases Jiahui Zhu International Journal of Molecular Medical Science, 2025, Vol. 15, No. 4, 195-204
International Journal of Molecular Medical Science, 2025, Vol.15, No.4, 155-164 http://medscipublisher.com/index.php/ijmms 155 Research Insight Open Access Effect of Nursing-Based Sleep Management on Melatonin and Cortisol Levels in Geriatric Dementia Patients MinLi The First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, 310009, Zhejiang, China Corresponding email: limin@qq.com International Journal of Molecular Medical Science, 2025, Vol.15, No.4 doi: 10.5376/ijmms.2025.15.0016 Received: 10 May, 2025 Accepted: 23 Jun., 2025 Published: 10 Jul., 2025 Copyright © 2025 Li, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Li M., 2025, Effect of nursing-based sleep management on melatonin and cortisol levels in geriatric dementia patients, International Journal of Molecular Medical Science, 15(4): 155-164 (doi: 10.5376/ijmms.2025.15.0016) Abstract This study explored the impact of nurse-led sleep care on melatonin and cortisol in patients with Alzheimer's disease, including creating a quieter environment, adjusting daily routines and lifestyles, and using simple relaxation methods. Studies show that these practices can help people sleep more soundly at night, increase nighttime melatonin, lower cortisol, help adjust the biological clock, and make the hypothalamic-pituitary-adrenal (HPA) axis function more stable. However, due to the small sample size, inconsistent intervention practices, and insufficient long-term follow-up, the results of each study are not completely consistent. Future research should include a larger population, conduct randomized trials in multiple centers, evaluate the effects through various methods, and formulate standardized nursing plans. Only in this way can the conclusion be repeatedly verified and applied in clinical practice. This study aims to integrate evidence-based sleep care into the daily care of dementia patients, providing a promising drug-free approach to improve physiological regulation and patient health. Keywords Dementia; Sleep management; Melatonin; Cortisol; Nursing interventions 1 Introduction Dementia is a common brain-degenerative disease in older adults and is often linked with serious sleep problems such as insomnia, broken sleep, and changes in the normal sleep-wake cycle. These sleep issues can speed up memory loss, increase behavioral problems like agitation and sundowning, and lower the quality of life for both patients and their caregivers (Morales-Delgado et al., 2018). The high rate of sleep problems in dementia shows the importance of finding effective care methods to manage both thinking-related and other symptoms (Cohen-Mansfield et al., 2000; Xu et al., 2015). Melatonin is a hormone produced by the pineal gland in darkness and helps set the body’s daily rhythm and start sleep. Its production drops with age and is often lower in older adults, especially those with dementia (Cohen-Mansfield et al., 2000). Melatonin affects sleep quality, helps protect brain health, and may influence the development of Alzheimer’s disease. Cortisol, a glucocorticoid hormone, regulates the stress response and follows a daily cycle that aligns with sleep-wake patterns. When melatonin and cortisol become unbalanced, sleep structure is harmed and neuropsychiatric symptoms in dementia can worsen (Li et al., 2020). This study will explore how nursing-based sleep care methods-such as improving the environment, using behavioral approaches, and giving sleep-promoting drugs like melatonin-can help improve sleep quality and reduce behavior problems in people with Alzheimer’s disease. Current clinical research shows that adding melatonin can extend total sleep time, raise sleep efficiency, and lessen restlessness and sundowning, though its effect on improving cognitive function is still limited. These care measures can increase patients’ life satisfaction, ease the workload for caregivers, and help maintain a less restrictive care setting. However, more studies are needed to understand how these methods affect hormone markers like melatonin and cortisol, and clinical care plans should be improved to make the interventions more effective and practical. 2 Characteristics of Sleep Disorders in Elderly Dementia Patients 2.1 Changes in sleep architecture and circadian rhythm disturbances Sleep patterns in older adults with dementia change clearly: slow- wave and REM sleep are reduced, sleep
International Journal of Molecular Medical Science, 2025, Vol.15, No.4, 155-164 http://medscipublisher.com/index.php/ijmms 156 becomes more broken, and waking up at night is common. These changes are stronger than in healthy older people, showing the effect of brain degeneration on areas that control sleep (Wennberg et al., 2017; Mou et al., 2024). Problems with the body clock are also frequent, with irregular sleep-wake times, weaker daily rhythms, and sometimes a flipped day-night schedule. These clock problems relate to dementia progression and the damage in key clock centers, including the suprachiasmatic nucleus and other time- keeping systems (Okawa et al., 1991; Bombois et al., 2010). These sleep and clock problems are not only effects of dementia; they may also help trigger it and speed it up. Studies suggest that insomnia and sleep- disordered breathing raise the chance of later dementia, pointing to a two- way link between sleep and thinking decline (Shi et al., 2017; Wennberg et al., 2017; Kitamura et al., 2020; Ferini-Strambi, 2022). Therefore, finding and treating these issues is important for both prevention and day- to- day care in the elderly. 2.2 Major clinical manifestations and commonly used assessment methods for sleep disorders Many older people with dementia have sleep problems, including insomnia, feeling sleepy in the day, breathing trouble during sleep (such as obstructive sleep apnea), restless legs, and REM sleep behavior disorder. In daily life, this may show up as taking a long time to fall asleep, waking often at night, wandering, becoming restless or upset, and taking extra daytime naps (Porter et al., 2015; Wennberg et al., 2017). Of these issues, insomnia and sleep apnea are the most commonly diagnosed (Bombois et al., 2010; Tallavajhula, 2024). Sleep problems are examined through what people say and device detection. Questionnaires filled out by patients or caregivers are widely used, but they may not notice the severity of the problem. More accurate data can be collected through activity recorders and polysomnography recorders, which can observe sleep efficiency, the duration of sleep, and how sleep is interrupted. It is recommended to conduct a comprehensive inspection using these tools (Okawa et al., 1991; Bombois et al., 2010). It is important to detect problems early because sleep problems are often overlooked in daily care (Higami et al., 2022). 2.3 Negative effects of sleep disorders on cognition, mood, and daily functioning In dementia, sleep problems are tied to faster decline in thinking, including worse memory, attention, and executive skills. Poor sleep can also make mood and behavior symptoms worse-such as depression, irritability, and confusion-lowering quality of life (Vitiello and Borson, 2001). Beyond thinking, sleep troubles raise the chance of agitation and wandering, which can cause injuries and add to caregiver load (Bombois et al., 2010; Porter et al., 2015; Wennberg et al., 2017). Daily life is also affected: people have more trouble with basic tasks and keeping independence. Long- lasting sleep problems increase caregiver stress and are a major reason for moving patients into institutions (Vitiello and Borson, 2001; Bombois et al., 2010; Porter et al., 2015). Tackling sleep issues is thus key to protecting both cognitive and functional abilities and to improving overall well- being in this vulnerable group. 3 Physiological Roles and Pathological Changes of Melatonin and Cortisol 3.1 Melatonin secretion rhythm, regulatory mechanisms, and declining trends in dementia Melatonin is a hormone mainly made by the pineal gland, and its release is strongly guided by the light–dark cycle. In normal cases, melatonin rises in the evening, peaks at night, and drops in the early morning, helping set daily rhythms and supporting falling asleep and staying asleep (Nous et al., 2021; Zhang, 2024). This daily pattern is controlled by the suprachiasmatic nucleus (SCN) in the hypothalamus, which reads light signals from the environment to match melatonin timing with the sleep-wake cycle (Lin et al., 2013). In dementia, especially Alzheimer’s disease, both the size and regularity of the melatonin rhythm are clearly reduced. Night- time melatonin is lower than in same- age healthy people, and the circadian pattern looks flattened or disrupted (Dori et al., 1994). This drop relates to aging and the degree of brain degeneration, and it contributes to the common sleep and body- clock problems seen in dementia (Lin et al., 2013; Ferrari et al., 2000; Nous et al., 2021).
International Journal of Molecular Medical Science, 2025, Vol.15, No.4, 155-164 http://medscipublisher.com/index.php/ijmms 157 3.2 Cortisol’s role in stress regulation and abnormal levels in dementia patients Cortisol is a glucocorticoid released by the adrenal cortex that is central to the stress response and metabolic control. Its release follows a day–night pattern, reaching a high point in the early morning and then declining over the day, which helps maintain internal balance and supports alertness while awake (Dori et al., 1994; Ferrari et al., 2000). The hypothalamic- pituitary- adrenal (HPA) axis keeps this rhythm tightly regulated, and disruption can affect many body systems. In dementia, particularly Alzheimer’s disease, cortisol control is often impaired. Older patients commonly show higher evening and night cortisol, a smaller day-night swing, and weaker feedback sensitivity of the HPA axis. These changes become more obvious with increasing age and cognitive loss, and they are linked to more neuropsychiatric symptoms, sleep problems, and faster neurodegeneration (Dori et al., 1994; Ferrari et al., 2000; Cho et al., 2023). 3.3 Interactions between the two in circadian rhythm regulation and their impact on neurodegeneration Melatonin and cortisol act in opposite ways to shape circadian rhythms and the sleep–wake cycle. In the evening, melatonin goes up as cortisol goes down to support sleep onset, while in the morning, rising cortisol and falling melatonin help promote wakefulness (Dori et al., 1994; Ferrari et al., 2000; Lin et al., 2013). This coordinated balance is key for strong daily rhythms and normal sleep structure. In dementia, the regularity of these two important hormones is disrupted, which weakens the management of the body's internal clock, resulting in poorer sleep, behavioral changes and faster decline in thinking (Dori et al., 1994). These abnormal hormonal changes, associated with more cell damage, brain inflammation and fewer new brain cells, all accelerate the degeneration of the brain. Observing these changes and making adjustments when possible may help alleviate sleep disturbances and behavioral problems in patients with dementia (Ferrari et al., 2000; Lin et al., 2013; Sarena et al., 2022; Cho et al., 2023). 4 Sleep Management Methods Based on Nursing 4.1 Improve the environment: light, noise, temperature and humidity Making the place of care more comfortable is an important part of helping sleep in care. Reducing surrounding noise, minimizing distractions at night, and adjusting light (such as using dimmer lights or eye masks at night) can help the elderly, including those with dementia, sleep better (Figure 1) (Bellon et al., 2020; Ashghab et al., 2024; Hweidi et al., 2024). A good environment also includes maintaining the room temperature and humidity at a comfortable level, as well as the regulations of the ward that patients should not be moved at night to ensure quiet time (Bellon et al., 2022; Ashghab et al., 2024; Mendonça et al., 2024). Figure 1 Categories and subcategories of sleep-enhancing nursing interventions in hospital wards (Adopted from Mendonça et al., 2024)
International Journal of Molecular Medical Science, 2025, Vol.15, No.4, 155-164 http://medscipublisher.com/index.php/ijmms 158 The best effect will be achieved by integrating these environmental changes into daily life and routine care. Research shows that integrating these changes with employee training and a clear step-by-step approach can reduce sleep disturbances and make nights more peaceful (Ashghab et al., 2024). Even so, the results may vary from person to person and are also related to how well the plan is executed, so continuous checks and minor adjustments are needed (Ritmala-Castren et al., 2021; Bellon et al., 2022; Mendonça et al., 2024) 4.2 Adjustments to activities and schedules Ensuring that patients with dementia have something to do during the day and a regular life is the key point for nurses to carry out sleep care. Fixing bedtime and wake-up times, encouraging daytime exercise and social interaction, and teaching simple sleep hygiene can help calibrate the biological clock and improve sleep (Alfonsi et al., 2021; Mendonça et al., 2024). Gentle exercise or group activities can also reduce daytime naps and promote better sleep at night (Wilfling et al., 2025). Practical advice for patients and caregivers includes: reducing caffeine and alcohol intake, maintaining consistent bedtime habits, and engaging in quiet and relaxing activities before sleep. The best results are achieved when these practices are in line with personal preferences and abilities and are continuously followed up and encouraged by nurses (Alfonsi et al., 2021; Mendonça et al., 2024). The coordination of day shifts and night shifts helps maintain these patterns and brings long-term benefits (Wilfling et al., 2025). 4.3 Relaxation methods and personalized care Non-pharmaceutical soothing methods-such as listening to music, smelling scents or gentle touching - are increasingly being used by Alzheimer's patients to help them sleep better. These methods can reduce anxiety, making people more relaxed and easier to fall asleep. Studies have also found that both total sleep duration and sleep quality have improved (Bellon et al., 2022; Al-Hammouri and Rababah, 2024; Asharhab et al., 2024). Music and aromatherapy are simple and easy to perform, and patients are often willing to accept them. Better results can be achieved by formulating personalized care plans based on each person's sleep habits, preferences and needs. The plan can adjust the schedule, choose the relaxation method preferred by the patient, or invite family members to participate and support (Alfonsi et al., 2021). The key to success lies in regular assessment, close collaboration with patients and caregivers, and flexible adjustment as circumstances change (Rintala-Castren et al., 2021; Mendonça et al., 2024; Wilfling et al., 2025). 5 The Effects of Nursing Sleep Management on Melatonin and Cortisol Levels 5.1 Current research status at home and abroad and differences in intervention models Recent work in China and other countries has paid closer attention to how nurse-led sleep care affects hormones such as melatonin and cortisol. Studies have tested several care models, including body-clock-focused nursing, multi-part non-drug programs, and targeted environmental or behavior changes. Although many projects were carried out in hospitals and intensive care units, more research is now aimed at older adults and people with dementia, who often have marked sleep problems (Guo et al., 2016; Pelin and Sert, 2025). Intervention plans vary across studies. Some focus on improving the environment and keeping the body clock on track, while others combine behavior changes, education, and relaxation methods. Research abroad often uses multi-component programs that blend supportive nursing, fixed daily schedules, and changes to the surroundings. Local work may prefer single-focus or routine-based care. These differences often reflect the health system, cultural habits, and available resources in each place (Guo et al., 2016; Pelin and Sert, 2025). 5.2 Main results and significance of changes in melatonin and cortisol Some studies suggest that nurse-led sleep care may have a positive effect on melatonin and cortisol, but the results may vary among different populations and with different approaches. Studies have found that comprehensive non-pharmaceutical care for the elderly can increase nocturnal melatonin and reduce cortisol, thereby improving sleep, reducing confusion and making recovery more stable (Guo et al., 2016). In the biological clock-focused care, both the group receiving care and the group not receiving care experienced an increase in melatonin and a
International Journal of Molecular Medical Science, 2025, Vol.15, No.4, 155-164 http://medscipublisher.com/index.php/ijmms 159 decrease in cortisol. However, the differences between the two groups were sometimes not large enough to reach statistical significance. This indicates that larger environmental or institutional factors may also be at play (Figure 2) (Pelin and Sert, 2025). Figure 2 Pre-test and post-test cortisol levels, melatonin levels in the intervention and the control groups (Adopted from Pelin and Sert, 2025) These hormonal changes are crucial because they are related to better sleep, less anxiety, and a lower risk of mental confusion or surgical problems. More melatonin and less cortisol mean a more stable biological clock, deeper and more helpful sleep, as well as better mental and behavioral states-these benefits are particularly important for the elderly and dementia patients (Guo et al., 2016; Pelin and Sert, 2025). 5.3 Possible mechanisms The helpful effects of nursing sleep care on melatonin and cortisol may work through restoring the body’s circadian rhythms. Care plans that match activities to the natural light-dark cycle and reduce night interruptions can reset the body’s own timing for releasing melatonin and cortisol, leading to steadier sleep-wake patterns . This timing balance is important for keeping hormones stable and easing brain-related symptoms in at-risk patients (Guo et al., 2016; Pelin and Sert, 2025). Better sleep care may also support the hypothalamic-pituitary-adrenal (HPA) axis, lowering stress-driven cortisol rises and protecting overall hormone health By calming the HPA axis and boosting melatonin, such care may reduce brain inflammation and oxidative stress, which could help slow brain decline and raise life quality for elderly dementia patients (Guo et al., 2016). 6 Research Limitations and Challenges 6.1 The sample size is small and there are significant differences in research designs Current research on sleep care, especially those targeting patients with Alzheimer's disease, shares a common problem: many trials have very few participants. Many sleep care studies are preliminary or feasibility studies with a small number of participants, resulting in insufficient statistical power and limiting the generalization of conclusions to larger populations (Daniel et al., 2024; Gale et al., 2025). Small sample sizes also increase the risk of result bias, making it more difficult to detect those minor but meaningful changes in melatonin and cortisol.
International Journal of Molecular Medical Science, 2025, Vol.15, No.4, 155-164 http://medscipublisher.com/index.php/ijmms 160 There are also significant differences in research design. These studies differ in terms of research subjects, care methods, measurement results and the length of follow-up time. These differences make it difficult to compare the research results or combine them for analysis (Tahmasian et al., 2021; Nsamme et al., 2023). This diversity may lead to inconsistent results and also makes it more difficult to develop clear and uniform sleep care guidelines for dementia (Tahmasian et al., 2021; Gale et al., 2025). 6.2 Lack of unified nursing methods and assessment tools Another challenge is the lack of unified rules for providing and measuring care. Many studies employ unique or location-specific protocols, which vary in content, intensity and duration (Mendonça et al., 2019; Gale et al., 2025). Without a unified approach, it is difficult to repeat research, compare results, or determine which part of the intervention measures is most helpful for sleep and hormone control. There is no unified conclusion on the best indicators for judging sleep and hormonal changes at present. Some studies employ objective tools, such as polysomnography or activity recorders; Some studies also rely on questionnaires or reports from nursing staff. The above-mentioned practices each have their limitations. The differences among different assessment tools make it more difficult to interpret and compare the research results (Crivello et al., 2019; Mendonça et al., 2019; Zhang et al., 2024). 6.3 Lack of long-term tracking and multi-center data Most studies on nursing-based sleep care are short-term, with little or no long-term follow-up. As a result, we do not know whether gains in melatonin and cortisol last, or how they affect thinking and daily function over time in dementia (Tahmasian et al., 2021; Daniel et al., 2024). Without longer tracking, it is also unclear when care plans should be updated. Large-scale, cross-center studies are still scarce. Much of the evidence comes from a single institution within a certain culture or medical system, which limits the applicability of the research conclusions in other regions (Tahmasian et al., 2021; Zhang et al., 2024). Larger-scale multi-center projects need to be carried out, a unified process should be adopted to confirm the results, and more reliable, evidence-based guidelines should be developed for sleep care in patients with Alzheimer's disease. 7 Future Research Directions and Practical Significance 7.1 Conduct large-scale, multi-site, long-term group comparative studies Future research should focus on conducting large-scale, multi-site, and long-follow-up randomized controlled trials (RCTS) to more clearly assess the impact of nurse-led sleep care on melatonin and cortisol in patients with Alzheimer's disease. Such a design can address the shortcomings of small sample and single-point studies, making the results more reliable and easier to generalize to different populations and care scenarios (Song et al., 2021; Daniel et al., 2024). Multi-site projects can also incorporate participants from different backgrounds and health conditions, which is important for formulating more widely applicable guiding principles. It is necessary to observe for a long time whether the improvements in sleep, hormone levels and thinking ability can be maintained. Long-term research can clarify whether the changes in melatonin and cortisol are persistent and whether they can bring stable benefits to thinking ability, mood and daily activities. Such a plan can also identify the potential delayed effects or long-term impacts of care and help develop better dementia management methods (Song et al., 2021; Daniel et al., 2024). 7.2 Use multimodal detection methods Applying multimodal detection-combining objective sleep monitoring (such as actigraphy and polysomnography) with regular hormone testing-can give a more complete view of intervention effects. Advances in wearable and digital technology now make it possible to track sleep and circadian rhythms continuously and without discomfort, allowing for more accurate and personalized evaluations (Perez-Pozuelo et al., 2020; Song et al., 2021). This can help explain the link between behavioral care, sleep patterns, and hormone changes.
International Journal of Molecular Medical Science, 2025, Vol.15, No.4, 155-164 http://medscipublisher.com/index.php/ijmms 161 Tracking sleep and hormone levels together helps link better sleep to bodily changes, which strengthens the evidence. This kind of data can also catch small effects that surveys might miss and supports creating personalized care plans using real-time information (Perez-Pozuelo et al., 2020; Song et al., 2021). 7.3 Establish a unified care program and enhance family and community assistance Formulating a clear and scientific sleep care plan is of great significance for achieving stable and effective care results in various regions. Unified steps can make research easier to repeat, results more convenient to compare, and promote experience exchange and sharing among medical institutions (Daniel et al., 2024; Gale et al., 2025). At the same time, these plans should retain a certain degree of flexibility to meet the needs of each patient, but still follow the key principles proven by research. It is equally important to enhance the assistance from families and communities, as dementia care is mostly carried out outside hospitals and at home. Teaching family members some methods to involve them in planning and follow-up work can help maintain a regular sleep schedule and improve the patient's condition (Gale et al., 2025). The projects and resources of the community can also complement the deficiencies of family care, help address problems early, and support a more comprehensive approach to dealing with sleep disturbances in Alzheimer's patients. 8 Concluding Remarks Nurse-guided sleep care can help dementia patients sleep better, reduce sleep troubles and improve overall well-being. Adjusting the environment, adopting simple behavioral methods and providing tailor-made care for patients are now regarded as important parts of comprehensive care for dementia patients in nursing homes and hospitals. Melatonin and cortisol are responsible for regulating the body's clock and stress response, and may be useful signals for measuring the effectiveness of sleep care. Although there is not much research evidence on their changes, improved sleep may be related to more stable melatonin and cortisol patterns, which in turn are associated with the improvement of thinking and behavior in patients with dementia. Using these signals can make the assessment more accurate and also support the formulation of personalized care plans. Scientific nursing is a key part of comprehensive care for dementia. It is patient-centered and meets both physical and emotional needs in a non-pharmaceutical way. To achieve better results, it is necessary for multi-disciplinary teams to collaborate, continuously train personnel, and make adjustments based on the special requirements of dementia care. As research progresses, incorporating sleep care into daily routines is of great significance for enhancing the quality of life and health of this key group. Acknowledgments I extend my sincere thanks to Mrs Fang for his feedback on the initial draft of this study. Conflict of Interest Disclosure The author affirms that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. Reference Alfonsi V., Scarpelli S., Gorgoni M., Pazzaglia M., Giannini A., and De Gennaro L., 2021, Sleep-related problems in night shift nurses: towards an individualized interventional practice, Frontiers in Human Neuroscience, 15: 644570. https://doi.org/10.3389/fnhum.2021.644570 Al-Hammouri M., and Rababah J., 2024, A brief mindfulness-based intervention sleep quality sleep duration and fatigue among nurses: a randomized controlled trial, Journal of Clinical Psychology, 80(7): 1504-1514. https://doi.org/10.1002/jclp.23677 Ashghab A., Vahedian-Azimi A., Vafadar Z., Mollahadi M., and Sepandi M., 2024, Nursing interventions to improve the sleep quality of hospitalized patients: a systematic review and meta-analysis, Intensive Care Research, 4(1): 55-71. https://doi.org/10.1007/s44231-024-00056-9 Bombois S., Derambure P., Pasquier F., and Monaca C., 2010, Sleep disorders in aging and dementia, The Journal of Nutrition Health and Aging, 14: 212-217. https://doi.org/10.1007/S12603-010-0052-7
International Journal of Molecular Medical Science, 2025, Vol.15, No.4, 155-164 http://medscipublisher.com/index.php/ijmms 162 Bellon F., Beti-Abad A., Pastells-Peiró R., Casado-Ramírez E., Moreno-Casbas M., Gea-Sánchez M., and Abad-Corpa E., 2022, Effects of nursing interventions to improve inpatients' sleep in intensive and non-intensive care units: findings from an umbrella review, Journal of Clinical Nursing, 32(9-10): 1963-1978. https://doi.org/10.1111/jocn.16251 Bellon F., Mora-Noya V., Pastells-Peiró R., Abad-Corpa E., Gea-Sánchez M., and Moreno-Casbas M., 2020, The efficacy of nursing interventions on sleep quality in hospitalized patients: a systematic review of randomized controlled trials, International Journal of Nursing Studies, 115: 103855. https://doi.org/10.1016/j.ijnurstu.2020.103855 Cho E., Lee H., Shin J., Kim S., Heo S., Park H., and Seok J., 2023, Salivary cortisol and melatonin sleep and behavioral patterns in older adults living with dementia, Nursing Research, 73: E11-E20. https://doi.org/10.1097/NNR.0000000000000709 Cohen-Mansfield J., Garfinkel D., and Lipson S., 2000, Melatonin for treatment of sundowning in elderly persons with dementia-a preliminary study, Archives of Gerontology and Geriatrics, 31(1): 65-76. https://doi.org/10.1016/S0167-4943(00)00068-6 Crivello A., Barsocchi P., Girolami M., and Palumbo F., 2019, The meaning of sleep quality: a survey of available technologies, IEEE Access, 7: 167374-167390. https://doi.org/10.1109/ACCESS.2019.2953835 Daniel L., Catarozoli C., Crabtree V., Bridgeman M., Van Litsenburg R., and Irestorm E., 2024, Sleep interventions in pediatric oncology: A systematic review of the evidence, Pediatric Blood and Cancer, 71(10): e31202. https://doi.org/10.1002/pbc.31202 Dori D., Casale G., Solerte S., Fioravanti M., Migliorati G., Cuzzoni G., and Ferrari E., 1994, Chrono-neuroendocrinological aspects of physiological aging and senile dementia, Chronobiologia, 21(1-2): 121-126. Ferini-Strambi L., 2022, Sleep disorders and increased risk of dementia., European Journal of Neurology, 29: 3484-3485. https://doi.org/10.1111/ene.15562 Ferrari E., Arcaini A., Gornati R., Pelanconi L., Cravello L., Fioravanti M., Solerte S., and Magri F., 2000, Pineal and pituitary-adrenocortical function in physiological aging and in senile dementia, Experimental Gerontology, 35: 1239-1250. https://doi.org/10.1016/S0531-5565(00)00160-1 Gale E., Manrai R., Caddick L., Murray A., Whalley H., Smith D., and Gardani M., 2025, Co-production in sleep research: a scoping review of current practices and future directions, Journal of Sleep Research, 9: e14476. https://doi.org/10.1111/jsr.14476 Guo Y., Sun L., Li L., Jia P., Zhang J., Jiang H., and Jiang W., 2016, Impact of multicomponent nonpharmacologic interventions on perioperative cortisol and melatonin levels and postoperative delirium in elderly oral cancer patients, Archives of Gerontology and Geriatrics, 62: 112-117. https://doi.org/10.1016/j.archger.2015.10.009 Higami Y., Takeya Y., Takemura Y., Oguro R., Katsuma K., Matsukawa N., Rakugi H., and Kamide K., 2022, Sleep disturbance in elderly patients with dementia at home and the factors associated with its identification: an observational study, Nihon Ronen igakkai zasshi, Japanese Journal of Geriatrics, 59(2): 200-208. https://doi.org/10.3143/geriatrics.59.200 Hweidi I., Jebreel O., Alhawatmeh H., Jarrah M., Abu-Awwad A., and Hweidi M., 2024, Nursing-based sleep promotion intervention effectiveness for post cardiac surgery patients: systematic review, Journal of Clinical Nursing, 33(12): 4528-4542. https://doi.org/10.1111/jocn.17442 Kitamura T., Miyazaki S., Sulaiman H., Akaike R., Ito Y., and Suzuki H., 2020, Insomnia and obstructive sleep apnea as potential triggers of dementia: is personalized prediction and prevention of the pathological cascade applicable?, EPMA Journal, 11: 355-365. https://doi.org/10.1007/s13167-020-00219-w Li Y., Zhang J., Wan J., Liu A., and Sun J., 2020, Melatonin regulates Aβ production/clearance balance and Aβ neurotoxicity: A potential therapeutic molecule for Alzheimer's disease, Biomedicine and Pharmacotherapy, 132: 110887. https://doi.org/10.1016/j.biopha.2020.110887 Lin L., Huang Q., Yang S., Chu J., Wang J., and Tian Q., 2013, Melatonin in Alzheimer's disease, International Journal of Molecular Sciences, 14: 14575-14593. https://doi.org/10.3390/ijms140714575 Mendonça F., Mostafa S., Morgado-Dias F., Ravelo-García A., and Penzel T., 2019, A review of approaches for sleep quality analysis, IEEE Access, 7: 24527-24546. https://doi.org/10.1109/ACCESS.2019.2900345 Mendonça S., Martins D., Durão C., Teixeira J., and Da Silva Rafael Henriques H., 2024, Sleep-enhancing nursing interventions in hospital wards: a systematic review, International Nursing Review, 72(1): e13062. https://doi.org/10.1111/inr.13062 Morales R., Álvarez G., Lemarroy C., Treviño D., Jaime A., Maldonado E., and Martinez R., 2017, Effect of melatonin over sleep quality in older adults with mild to moderate dementia, Innovation in Aging, 1(suppl_1): 487. https://doi.org/10.1093/GERONI/IGX004.1730 Mou L., Wu L., Fu X.Y., Wang B., Wang X., and Xiao X.J., 2024 The role of genetic factors in dementia, International Journal of Molecular Medical Science, 14(6): 355-368.
International Journal of Molecular Medical Science, 2025, Vol.15, No.4, 155-164 http://medscipublisher.com/index.php/ijmms 163 Morales-Delgado R., Cámara-Lemarroy C., Salinas-Martínez R., Gámez-Treviño D., Arredondo-Jaime A., Hernández-Maldonado E., and Guajardo-Álvarez G., 2018, A randomized placebo-controlled trial evaluating the effect of melatonin on sleep quality in patients with mild-moderate dementia, European Geriatric Medicine, 9: 449-454. https://doi.org/10.1007/s41999-018-0068-9 Németh D., Gerbier E., Born J., Rickard T., Diekelmann S., Fogel S., Genzel L., Prehn-Kristensen A., Payne J., Dresler M., Simor P., Mazza S., Hoedlmoser K., Ruby P., Spencer R., Albouy G., Vékony T., Schabus M., and Janacsek K., 2023, Optimizing the methodology of human sleep and memory research, Nature Reviews Psychology, 3(2): 123-137. https://doi.org/10.1038/s44159-023-00262-0 Nous A., Engelborghs S., and Smolders I., 2021, Melatonin levels in the Alzheimer's disease continuum: a systematic review, Alzheimer's Research and Therapy, 13(1): 52. https://doi.org/10.1186/s13195-021-00788-6 Okawa M., Mishima K., Hishikawa Y., Hozumi S., Hori H., and Takahashi K., 1991, Circadian rhythm disorders in sleep-waking and body temperature in elderly patients with dementia and their treatment, Sleep, 14(6): 478-485. https://doi.org/10.1093/SLEEP/14.6.478 Pelin M., and Sert H., 2025, The effect of nursing care provided to coronary intensive care patients according to their circadian rhythms on sleep quality pain anxiety and delirium: a randomised controlled trial, BMC Nursing, 24(1): 1-4. https://doi.org/10.1186/s12912-025-02793-8 Perez-Pozuelo I., Zhai B., Palotti J., Mall R., Aupetit M., García-Gómez J., Taheri S., Guan Y., and Fernández-Luque L., 2020, The future of sleep health: a data-driven revolution in sleep science and medicine, NPJ Digital Medicine, 3: 42. https://doi.org/10.1038/s41746-020-0244-4 Porter V., Buxton W., and Avidan A., 2015, Sleep cognition and dementia, Current Psychiatry Reports, 17: 1-11. https://doi.org/10.1007/s11920-015-0631-8 Ritmala-Castren M., Salanterä S., Holm A., Heino M., Lundgrén-Laine H., and Koivunen M., 2021, Sleep improvement intervention and its effect on patients' sleep on the ward, Journal of Clinical Nursing, 31(1-2): 275-282. https://doi.org/10.1111/jocn.15906 Sarena P., Sharma A., Urmera M., Tambuwala M., Aljabali A., Chellappan D., Dua K., Taliyan R., and Goyal R., 2022, Chronic light-distorted glutamate-cortisol signaling behavioral and histological markers and induced oxidative stress and dementia: an amelioration by melatonin, ACS Chemical Neuroscience, 13(11): 1604-1614. https://doi.org/10.1021/acschemneuro.1c00531 Shi L., Chen S., Ma M., Bao Y., Han Y., Wang Y., Shi J., Vitiello M., and Lu L., 2017, 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 Song Y., Campbell L., and Moore R., 2021, Future directions for sleep and cognition research in at-risk older adults, International Psychogeriatrics, 33: 655-658. https://doi.org/10.1017/S1041610220003828 Tahmasian M., Aleman A., Andreassen O., Arab Z., Baillet M., Benedetti F., Bresser T., Bright J., Chee M., Chylinski D., Cheng W., Deantoni M., Dresler M., Eickhoff S., Eickhoff C., Elvsåshagen T., Feng J., Foster-Dingley J., Ganjgahi H., Grabe H., Groenewold N., Ho T., Hong S., Houenou J., Irungu B., Jahanshad N., Khazaie H., Kim H., Koshmanova E., Kocevska D., Kochunov P., Lakbila-Kamal O., Leerssen J., Li M., Luik A., Muto V., Narbutas J., Nilsonne G., O'Callaghan V., Olsen A., Osorio R., Poletti S., Poudel G., Reesen J., Reneman L., Reyt M., Riemann D., Rosenzweig I., Rostampour M., Saberi A., Schiel J., Schmidt C., Schrantee A., Sciberras E., Silk T., Sim K., Smevik H., Soares J., Spiegelhalder K., Stein D., Talwar P., Tamm S., Teresi G., Valk S., Van Someren E., Vandewalle G., Van Egroo M., Völzke H., Walter M., Wassing R., Weber F., Weihs A., Westlye L., Wright M., Wu M., Zak N., and Zarei M., 2021, ENIGMA-sleep: challenges opportunities and the road map, Journal of Sleep Research, 30(6): e13347. https://doi.org/10.1111/jsr.13347 Tallavajhula S., 2024, 0745 Prevalence of sleep disorders in dementia patients- a demographic analysis, Sleep, 47(Issue Supplement_1): A319. https://doi.org/10.1093/sleep/zsae067.0745 Vitiello M., and Borson S., 2001, Sleep disturbances in patients with Alzheimer’s disease, CNS Drugs, 15: 777-796. https://doi.org/10.2165/00023210-200115100-00004 Wennberg A., Wu M., Rosenberg P., and Spira A., 2017, Sleep disturbance cognitive decline and dementia: a review, Seminars in Neurology, 37: 395-406. https://doi.org/10.1055/s-0037-1604351 Wilfling D., Kühn A., Lüth F., Berg A., Klatt T., Meyer G., Dörner J., Halek M., Köpke S., Dichter M., and Möhler R., 2025, Process evaluation of an intervention to reduce sleep problems in people living with dementia in nursing homes: a mixed-methods study, Age and Ageing, 54(3): afaf051. https://doi.org/10.1093/ageing/afaf051 Xu J., Wang L., Dammer E., Li C., Xu G., Chen S., and Wang G., 2015, Melatonin for sleep disorders and cognition in dementia, American Journal of Alzheimer's Disease and Other Dementias, 30: 439-447. https://doi.org/10.1177/1533317514568005 Zhang Y., Kim M., Prerau M., Mobley D., Rueschman M., Sparks K., Tully M., Purcell S., and Redline S., 2024, The national sleep research resource: making data findable accessible interoperable reusable and promoting sleep science, Sleep, 47(7): zsae088. https://doi.org/10.1093/sleep/zsae088
International Journal of Molecular Medical Science, 2025, Vol.15, No.4, 155-164 http://medscipublisher.com/index.php/ijmms 164 Zhang J., 2024, A comparative study: revealing the prevalence of dementia among the homeless population, International Journal of Molecular Medical Science, 14(2): 48-54. https://doi.org/10.5376/ijccr.2024.14.0006
International Journal of Molecular Medical Science, 2025, Vol.15, No.4, 165-174 http://medscipublisher.com/index.php/ijmms 165 Research Insight Open Access Clinical and Immunological Factors Affecting Vaccine Efficacy in Frail Older Adults Hua Xu, Manman Li Hainan Institute of Biotechnology, Haikou, 570206, Hainan, China Corresponding author: manman.li@hibio.org International Journal of Molecular Medical Science, 2025, Vol.15, No.4 doi: 10.5376/ijmms.2025.15.0017 Received: 19 May, 2025 Accepted: 09 Jul., 2025 Published: 20 Jul., 2025 Copyright © 2025 Xu and Li, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Xu H., and Li M., 2025, Clinical and immunological factors affecting vaccine efficacy in frail older adults, International Journal of Molecular Medical Science, 15(4): 165-174 (doi: 10.5376/ijmms.2025.15.0017) Abstract This study explores the physical and immune reasons why elderly people with weak constitutions and frequent illnesses have poor responses after vaccination. Physical weakness is a common health problem encountered by the elderly. It interacts with the aging of the immune system, jointly weakening the body's humoral and cellular immune responses to vaccines. This leads to a smaller increase in antibodies, a slower response, and a shorter protection period after vaccination. Physical reasons include whether the nutrition is good or not, whether the metabolism is normal or not, whether there is a long-term illness, whether multiple medications are taken at the same time, and the lifestyle and daily activity ability, etc. All of these will alter the efficacy of vaccines by influencing the function of the immune system. From the perspective of the immune system, the main issue is the decline in T cell capacity, the weakening of antibodies produced by B cells, and the combined effect of long-term mild inflammation in the body and some factors that suppress the immune system. This article also explores methods to enhance the efficacy of vaccines, such as improving the vaccine formula and booster shots, conducting immunomodulatory treatment, and adjusting the timing of injections and the arrangement of booster shots. In the future, accurate immunization tests, large-scale trials conducted in collaboration with multiple hospitals, research on the immune system and overall analysis methods should be carried out to predict and improve vaccine responses and promote personalized vaccination plans. Keywords Frailty; Immunosenescence; Vaccine efficacy; Inflammaging; Personalized vaccination 1 Introduction Nowadays, there are more and more elderly people in the world, and the proportion of people aged 65 and above in the total population is getting larger and larger. This demographic change has brought about significant public health problems, as the elderly are more prone to infectious diseases such as influenza, pneumonia, shingles and COVID-19. Compared with young people, they are at a higher risk of getting sick, dying and leaving long-term disabilities. The physical changes brought about by aging, having other diseases and deteriorating body functions can make infections more severe. Therefore, formulating effective preventive measures, especially vaccination, is the key to making the elderly healthier and reducing their medical burden (Wagner and Weinberger, 2020; Cadar et al., 2023; Incalzi et al., 2023). Frailty is a common condition among the elderly, characterized by a decline in physical reserve capacity and greater sensitivity to stress, such as infections. It is different from simply getting older, which means poorer health outcomes, greater chances of hospitalization and a higher risk of death. In terms of immunity, physical weakness is increasingly regarded as a key factor influencing immune function It often aggravates "immunosenescence"-the phenomenon where the body's first line of defense (innate immunity) and specific defense (adaptive immunity) capabilities decline with age (Cadar et al., 2023). Elderly people with weak constitutions usually produce fewer antibodies after vaccination, and the response of immune cells also weakens, leading to a decline in the protective effect of the vaccine and an increased risk of infection and complications (Ridda et al., 2009; Semelka et al., 2023). Physical weakness, long-term illness and immune system problems interact with each other, forming a cycle of "susceptibility to illness", which poses a challenge to traditional vaccination strategies (Yao et al., 2011; Wagner and Weinberger, 2020; Incalzi et al., 2023).
International Journal of Molecular Medical Science, 2025, Vol.15, No.4, 165-174 http://medscipublisher.com/index.php/ijmms 166 This study will explore how clinical factors and the state of the immune system (immune factors) affect the vaccine efficacy of physically weak elderly people. By studying the effects of physical faltering, "immune system aging", and related physical and disease factors, this review aims to identify any gaps in our knowledge and provide useful strategic information for improving the vaccine response of this vulnerable population. Understanding these factors is of great significance for designing targeted vaccination methods, improving health outcomes, and guiding future research and policies targeting the global aging population. 2 Physical Weakness and an Aging Immune System 2.1 What is physical weakness, how to diagnose it and how common it is Physical weakness is a common and complex condition among the elderly, mainly manifested as reduced strength, easy fatigue and poor physical functions. This makes it more difficult for the body to resist stress like infection and also reduces the body's response to treatment. It is different from simple aging, which makes the elderly more prone to disability, hospitalization and even death. One of the common methods for judging physical frailty is the "Fried Frailty Criterion", which mainly examines whether there is unexpected weight loss, frequent fatigue, reduced grip strength, slower walking and less physical activity. Another commonly used tool is the "frailties Index", which calculates how many health problems a person has (Moehling et al., 2020). In terms of the incidence rate, the older one gets, the more likely their body is to become weak. This situation is very common among people over 65 years old. Studies have found that a weakened body accelerates the aging of the immune system, making the body less responsive to infections and vaccines. Although physical weakness is often closely related to aging, not all elderly people will experience this. Scientists are still studying its impact on people's ability to produce antibodies after vaccination. Some studies have found that in frail elderly people, the activity of some genes that control the growth of immune cells, energy use and antiviral signaling has changed, and the response of immune cells has also slowed down (Moehling et al., 2020). 2.2 The main manifestations of immune system aging Immune system aging refers to the weakening and alteration of the immune system as one ages, which affects the body's first line of defense (innate immunity) and the defense line specifically against certain pathogens (adaptive immunity). On the first line of defense, aging leads to a decline in the ability of neutrophils, monocytes, dendritic cells and natural killer cells, resulting in their poor ability to recognize pathogens, consume pathogens and signal. The characteristic of the specialized defense part is that the number of T cells and B cells capable of recognizing new bacteria decreases, while the number of T cells that remember old bacteria and are aging increases. The antibodies produced by the body and the attack ability of T cells both weaken, making it more difficult for the body to deal with new bacteria (Crooke et al., 2019; Oh et al., 2019; Pereira et al., 2020; Aiello et al., 2022). A clear sign of an aging immune system is that the body remains in a mild state of inflammation for a long time, which is called "inflammation". This persistent mild inflammation is due to the body producing more substances that promote inflammation. It is associated with poor vaccination efficacy and a higher risk of infection (Oh et al., 2019; Pereira et al., 2020; Aiello et al., 2022). These changes in the immune system interact with the aging physical environment, making the immune condition of the elderly more complex. 2.3 Physical weakness and an aging immune system jointly reduce the efficacy of vaccines Physical weakness and an aging immune system can interact with each other, jointly reducing the protective effect of vaccines on the elderly. Physical weakness will accelerate the aging of the immune system, making both humoral immunity (antibodies) and cellular immunity (direct attack by immune cells) weaker. Research shows that in physically weak elderly people, the activities of some genes that control immune cell division, energy metabolism and interferon signaling pathways have changed. At the same time, T cells are more prone to "fatigue", and the number of oxidative stress markers in the body has also increased. These changes may not be detectable by simple antibody level tests. These changes have led to a slower, weaker response to vaccines or a shorter protection period for them, making them more susceptible to infection (Moehling et al., 2020; Pereira et al., 2020).
RkJQdWJsaXNoZXIy MjQ4ODYzNA==