Improved sleep quality in older adults with insomnia reduces biomarkers of disease risk: Pilot results from a randomized controlled comparative efficacy trial
Introduction
Insomnia symptoms are characterized as impairments in sleep quantity and/or quality that can result from difficulties in falling or staying asleep, frequent arousals, and/or obtaining restorative sleep (CDC, 2011, Colten and Altevogt, 2006, Motivala, 2011). Insufficient sleep and poor sleep quality have been linked to disease risk and mortality (CDC, 2011, Vgontzas et al., 2010, Suzuki et al., 2009, Kojima et al., 2000, Cappuccio et al., 2010, Rod et al., 2014). Not getting enough quality sleep causes repeated disruptions to multiple regulatory systems including metabolic, cardiovascular, and immune (McEwen, 2006, Redline and Foody, 2011, Chen et al., 2014). This is particularly salient in older adults, where the risk for disease and death is elevated, with as many as half of adults over 65 years old reporting insomnia symptoms (Ohayon, 2002). Sleep is a modifiable behavior with established behavioral treatments that improve sleep quality (Irwin et al., 2006, Irwin et al., 2008). Although disturbed sleep has been associated with increased risk for disease and death, it is not clear whether treating sleep problems would reduce laboratory markers of disease risk, particularly among those with elevated levels of such risk markers. Further research is needed to determine whether the treatment of sleep disturbances, such as insomnia, has the potential to aid in the prevention of disease.
There are a number of pathways through which sleep problems likely contribute to poorer health. Among them, inadequate sleep has been associated with adverse effects on levels of glucose, lipids, inflammation, and blood pressure (Motivala, 2011, McEwen, 2006, Chen et al., 2014, Redwine, 2000, Gottlieb et al., 2006, Spiegel et al., 2005, Palagini et al., 2013, Van Cauter et al., 2007, Ju and Choi, 2013, Mullington et al., 2009). Inadequate and fragmented sleep disrupts the normal diurnal rhythm across regulatory systems and interferes with the restorative nature of sleep (McEwen, 2006, Robles and Carroll, 2011). Although each system is important in understanding disease risk, recent work has found that higher multisystem biological risk (a combination of biomarkers representing cardiovascular, metabolic, immune, nervous, and endocrine systems) is a stronger predictor of morbidity and mortality outcomes as compared to the predictive role of each biologic system alone (Gruenewald et al., 2006, Gruenewald et al., 2009, Karlamangla et al., 2006, Seeman et al., 1997, Seeman et al., 2001, Seeman et al., 2010). Hence, this work is grounded in the hypothesis that the pathway to disease is a dynamic interface between multiple biologic systems that influence the whole and may not be fully captured when measuring individual components. Importantly, multisystem biological risk has been linked to sleep, with shorter sleep duration and poor sleep quality associated with an elevated multisystem risk (Chen et al., 2014, Carroll et al., 2013).
An unanswered question is whether treating sleep disturbances such as insomnia in individuals with elevated markers of disease risk can then reduce such levels, with implications for disease. Cognitive behavioral therapy (CBT) is an effective treatment for insomnia in young and older adults (Irwin et al., 2006, Morin et al., 1999, Morin et al., 2006, Morin et al., 2009, Epstein et al., 2012, Sivertsen et al., 2006) Tai Chi Chih (TCC) has also been proposed as an alternative treatment, with evidence that it improves sleep quality in older adults (Irwin et al., 2007, Irwin et al., 2008, Irwin et al., 2014, Nguyen and Kruse, 2012, Irwin and Olmstead, 2012). With the exception of our initial findings showing decreases in C-reactive protein following the successful treatment of insomnia (Irwin et al., 2014), we know of no published trials examining the efficacy of an RCT for insomnia in older adults on biomarkers of diabetes and cardiovascular disease risk. An observed reduction in risk via changes in clinical laboratory biomarkers that traditionally signal risk (e.g., LDL cholesterol, hemoglobin A1c, CRP) following the successful improvement of sleep quality would suggest that the treatment of sleep problems among individuals showing initially elevated risk might be included as part of a disease prevention strategy. Following our initial analyses showing that CBT and TCC are efficacious at improving sleep quality in older adults (Irwin et al., 2014), we report on the efficacy of this RCT to reduce multisystem biological risk among individuals classified as higher risk at the beginning of the trial based on several key clinical laboratory biomarkers indicative of disease risk.
Section snippets
Study design
Methods of the study design and intervention modalities have been reported previously (Irwin et al., 2014). Briefly, after obtaining UCLA institutional review board approval, subjects were recruited from the surrounding Los Angeles community through advertisements. Following eligibility screening, older adults were invited to participate in the RCT, which was conducted from the period of April 2006 through August 2011. Each participated in 120 minutes of group class time weekly for 4-months,
Results
Of the 294 who underwent the baseline assessment, a total of 207 participants met further eligibility criteria and 123 agreed to participate. These subjects completed the entire baseline, agreed to participate in the clinical trial, and were randomly assigned to treatment (Fig. 1 CONSORT). Of these 123 participants, 109 subjects had biomarker data and are included in this secondary analysis. Treatment groups were similar in demographics (Table 1). Data on completers and non-completers has been
Discussion
The present paper presents the first randomized controlled trial in older adults with insomnia that examines the efficacy of the treatment on reducing multisystem biological markers of disease risk among subjects who begin the trial with elevated risk. We report that high risk insomnia subjects who experienced improvements in sleep quality showed reduced biological risk. In addition, among these individuals who exhibit elevated risk at the beginning of the treatment trial, both CBT and TCC
Financial disclosure
None.
All authors have contributed to the design, analyses, and writing of the manuscript and have consented to publication.
Role of the funding source
The following supported the conduct of the research and/or preparation of the article, but had no involvement in the study design, collection, analysis, or interpretation of the data, or in the writing of the report or decision to submit the article for publication. Grant R01 AG026364 from the National Institute of Aging; NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant number UL1TR000124. Other grant support to JEC from the National Institute of Aging K01-AG044462
Conflict of interest statement
No known conflicts of interest for JEC, RO, RS, GM, PN, RB, & MRI. TES served on an advisory board for a NIH funded National Health and Aging Trends study and received an honoraria. She also received honoraria for giving a keynote speech at the University of Alabama, Birmingham Health Disparities conference.
Acknowledgements
We thank all the study participants for their involvement in this research project. Institutional Review Board approval was obtained from the University of California, Los Angeles.
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