This review discusses existing and developing state-of-the-art noninvasive methods for quantifying the effects of integrative medicine (IM) in aging populations. The medical conditions of elderly patients are often more complex than those of younger adults, making the multifaceted approach of IM particularly suitable for aging populations. However, because IM interventions are multidimensional, it has been difficult to examine their effectiveness and mechanisms of action. Optimal assessment of IM intervention effects in the elderly should include a multifaceted approach, utilizing advanced analytic methods to integrate psychological, behavioral, physiological, and biomolecular measures of a patient's response to IM treatment. Research is presented describing methods for collecting and analyzing psychological data; wearable unobtrusive devices for monitoring heart rate variability, activity and other behavioral responses in real time; immunochemical methods for noninvasive molecular biomarker analysis, and considerations and analytical approaches for the integration of these measures. The combination of methods and devices presented in this review will provide new approaches for evaluating the effects of IM interventions in real-life ambulatory settings of older adults, and will extend the concept of mobile health to the domains of IM and healthy aging.

1.
National Institute on Aging, National Institutes of Health, US Department of Health and Human Services, World Health Organization: Global health and aging. 2011. http://www.who.int/ageing/publications/global_health.pdf.
2.
Centers for Disease Control and Prevention, AARP, American Medical Association: Promoting Preventive Services for Adults 50-64: Community and Clinical Partnerships. Atlanta, National Association of Chronic Disease Directors, 2009.
3.
Rakel D, Weil A: Philosophy of integrative medicine; in Rakel D (ed): Integrative Medicine, ed 3. Philadelphia, Elsevier Science, 2012, pp 2-11.
4.
Maizes V, Rakel D, Niemiec C: Integrative medicine and patient-centered care. Explore (NY) 2009;5:277-289.
5.
Ornish D, Lin J, Chan JM, Epel E, Kemp C, Weidner G, et al: Effect of comprehensive lifestyle changes on telomerase activity and telomere length in men with biopsy-proven low-risk prostate cancer: 5-year follow-up of a descriptive pilot study. Lancet Oncol 2013;14:1112-1120.
6.
Papanikolaou Y, Brooks J, Reider C, Fulgoni VL III: US adults are not meeting recommended levels for fish and omega-3 fatty acid intake: results of an analysis using observational data from NHANES 2003-2008. Nutr J 2014;13:31.
7.
Centers for Disease Control and Prevention: Prevalence of regular physical activity among adults - United States, 2001 and 2005. Atlanta, 2007. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5646a1.htm.
8.
Barnes PM, Powell-Griner E, McFann K, Nahin RL: Complementary and alternative medicine use among adults: United States, 2002. Semin Integr Med 2004;2:54-71.
9.
Kristoffersen AE, Fønnebø V, Norheim AJ: Use of complementary and alternative medicine among patients: classification criteria determine level of use. J Altern Complement Med 2008;14:911-919.
10.
Nahin RL, Pecha M, Welmerink DB, Sink K, DeKosky ST, Fitzpatrick AL, et al: Concomitant use of prescription drugs and dietary supplements in ambulatory elderly people. J Am Geriatr Soc 2009;57:1197-1205.
11.
Irwin MR, Olmstead R, Oxman MN: Augmenting immune responses to varicella zoster virus in older adults: a randomized, controlled trial of Tai Chi. J Am Geriatr Soc 2007;55:511-517.
12.
Toosizadeh N, Lei H, Schwenk M, Sherman SJ, Sternberg E, Mohler J, et al: Does integrative medicine enhance balance in aging adults? Proof of concept for the benefit of electroacupuncture therapy in Parkinson's disease. Gerontology 2015;61:3-14.
13.
Liu Y, Liu JP, Xia Y: Chinese herbal medicines for treating osteoporosis. Cochrane Database Syst Rev 2014;3:CD005467.
14.
Leong M, Smith TJ, Rowland-Seymour A: Complementary and integrative medicine for older adults in palliative care. Clin Geriatr Med 2015;31:177-191.
15.
Cnossen R, Heetderks W, Kumar S, Nilsen W, Pettigrew R, Patrick K, et al: Data collection and mobile technologies. National Institutes of Health Precision Medicine Initiative, 2015. http://www.nih.gov/precisionmedicine/whitepapers/Data-Collection-Mobile-Technologies.pdf.
16.
Skeath P, Norris S, Katheria V, White J, Baker K, Handel D, et al: The nature of life-transforming changes among cancer survivors. Qual Health Res 2013;23:1155-1167.
17.
Smith A: 46% of American Adults Are Smartphone Owners: Smartphone Users Now Outnumber Users of More Basic Mobile Phones within the National Adult Population. Washington, Pew Research Center, 2012.
18.
Hektner JM, Schmidt JA, Csikszentmihalyi M (eds): Experience Sampling Method: Measuring the Quality of Everyday Life. Thousand Oaks, Sage Publications, 2007.
19.
Conner TS, Tennen H, Fleeson W, Barrett LF: Experience sampling methods: a modern idiographic approach to personality research. Soc Personal Psychol Compass 2009;3:292-313.
20.
Murphy SL, Smith DM, Clauw DJ, Alexander NB: The impact of momentary pain and fatigue on physical activity in women with osteoarthritis. Arthritis Care Res 2008;59:849-856.
21.
Runyan JD, Steenbergh TA, Bainbridge C, Daugherty DA, Oke L, Fry BN: A smartphone ecological momentary assessment/intervention ‘app' for collecting real-time data and promoting self-awareness. PLoS One 2013;8:e71325.
22.
Curran PJ, Obeidat K, Losardo D: Twelve frequently asked questions about growth curve modeling. J Cogn Dev 2010;11:121-136.
23.
Garland AF, Bickman L, Chorpita BF: Change what? Identifying quality improvement targets by investigating usual mental health care. Adm Policy Ment Health 2010;37:15-26.
24.
Garland EL, Geschwind N, Peeters F, Wichers M: Mindfulness training promotes upward spirals of positive affect and cognition: multilevel and autoregressive latent trajectory modeling analyses. Front Psychol 2015;6:15.
25.
Thayer JF, Sternberg EM: Neural aspects of immunomodulation: focus on the vagus nerve. Brain Behav Immun 2010;24:1223-1228.
26.
Thayer JF, Sternberg E: Beyond heart rate variability: vagal regulation of allostatic systems. Ann NY Acad Sci 2006;1088:361-372.
27.
Peng CK, Henry IC, Mietus JE, Hausdorff JM, Khalsa G, Benson H, et al: Heart rate dynamics during three forms of meditation. Int J Cardiol 2004;95:19-27.
28.
Thayer JF, Loerbroks A, Sternberg EM: Inflammation and cardiorespiratory control: the role of the vagus nerve. Respir Physiol Neurobiol 2011;178:387-394.
29.
De Meersman RE, Stein PK: Vagal modulation and aging. Biol Psychol 2007;74:165-173.
30.
Tsuji H, Venditti FJ, Manders ES, Evans JC, Larson MG, Feldman CL, et al: Reduced heart rate variability and mortality risk in an elderly cohort. The Framingham Heart Study. Circulation 1994;90:878-883.
31.
Hunt BE, Farquhar WB, Taylor JA: Does reduced vascular stiffening fully explain preserved cardiovagal baroreflex function in older, physically active men? Circulation 2001;103:2424-2427.
32.
Parvaneh S, Grewal GS, Grewal E, Menzies RA, Talal TK, Armstrong DG, et al: Stressing the dressing: assessing stress during wound care in real-time using wearable sensors. Wound Med 2014;4:21-26.
33.
Schwenk M, Mohler J, Wendel C, D'Huyvetter K, Fain M, Taylor-Piliae R, et al: Wearable sensor-based in-home assessment of gait, balance, and physical activity for discrimination of frailty status: baseline results of the Arizona frailty cohort study. Gerontology 2015;61:258-267.
34.
Schwenk M, Howe C, Saleh A, Mohler J, Grewal G, Armstrong D, et al: Frailty and technology: a systematic review of gait analysis in those with frailty. Gerontology 2014;60:79-89.
35.
Parvaneh S, Howe CL, Toosizadeh N, Honarvar B, Slepian MJ, Fain M, et al: Regulation of cardiac autonomic nervous system control across frailty statuses: a systematic review. Gerontology 2015, Epub ahead of print.
36.
Stein PK, Domitrovich PP, Hui N, Rautaharju P, Gottdiener J: Sometimes higher heart rate variability is not better heart rate variability: results of graphical and nonlinear analyses. J Cardiovasc Electrophysiol 2005;16:954-959.
37.
Parvaneh S, Grewal G, Menzies R, Talal T, Armstrong D, Sternberg E, et al: Diabetic foot ulcers: how stressed are patients during clinical visits? J Altern Complement Med 2014;20:A149.
38.
Najafi B, Armstrong DG, Mohler J: Novel wearable technology for assessing spontaneous daily physical activity and risk of falling in older adults with diabetes. J Diabetes Sci Technol 2013;7:1147-1160.
39.
Maijó M, Clements SJ, Ivory K, Nicoletti C, Carding SR: Nutrition, diet and immunosenescence. Mech Ageing Dev 2014;136-137:116-128.
40.
Bauer ME, Jeckel CMM, Luz C: The role of stress factors during aging of the immune system. Ann NY Acad Sci 2009;1153:139-152.
41.
Rohleder N, Nater UM: Determinants of salivary α-amylase in humans and methodological considerations. Psychoneuroendocrinology 2009;34:469-485.
42.
Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD, et al: Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci USA 2004;101:17312-17315.
43.
Kirschbaum C, Hellhammer DH: Salivary cortisol in psychoneuroendocrine research: recent developments and applications. Psychoneuroendocrinology 1994;19:313-333.
44.
American Society for Clinical Laboratory Science: Role of the Clinical Laboratory in Response to an Expanding Geriatric Population. McLean, ASCLS, 2012. http://www.ascls.org/position-papers/187-expanding-geriatric-population/149-expanding-geriatric-population (accessed August 14, 2015).
45.
Cizza G, Marques AH, Eskandari F, Christie IC, Torvik S, Silverman MN, et al: Elevated neuroimmune biomarkers in sweat patches and plasma of premenopausal women with major depressive disorder in remission: the POWER study. Biol Psychiatry 2008;64:907-911.
46.
Marques AH, Silverman MN, Sternberg EM: Evaluation of stress systems by applying noninvasive methodologies: measurements of neuroimmune biomarkers in the sweat, heart rate variability and salivary cortisol. Neuroimmunomodulation 2010;17:205-208.
47.
Jia M, Belyavskaya E, Deuster P, Sternberg EM: Development of a sensitive microarray immunoassay for the quantitative analysis of neuropeptide Y. Anal Chem 2012;84:6508-6514.
48.
Marques-Deak A, Cizza G, Eskandari F, Torvik S, Christie IC, Sternberg EM, et al: Measurement of cytokines in sweat patches and plasma in healthy women: validation in a controlled study. J Immunol Methods 2006;315:99-109.
49.
Grass J, Kirschbaum C, Miller R, Gao W, Steudte-Schmiedgen S, Stalder T: Sweat-inducing physiological challenges do not result in acute changes in hair cortisol concentrations. Psychoneuroendocrinology 2015;53:108-116.
50.
Moreira N: UMass patch would spot stressed-out soldiers. Boston Globe, 2014. https://www.bostonglobe.com/business/2014/08/03/umass-scientists-working-patch-that-measures-stress/X7MEkIZDz3Mwalb1NY3PNL/story.html (accessed August 4, 2014).
51.
Brosschot JF, Thayer JF: Heart rate response is longer after negative emotions than after positive emotions. Int J Psychophysiol 2003;50:181-187.
52.
Jacob RG, Thayer JF, Manuck SB, Muldoon MF, Tamres LK, Williams DM, et al: Ambulatory blood pressure responses and the circumplex model of mood: a 4-day study. Psychosom Med 1999;61:319-333.
53.
Loerbroks A, Schilling O, Haxsen V, Jarczok MN, Thayer JF, Fischer JE: The fruits of one's labor: effort-reward imbalance but not job strain is related to heart rate variability across the day in 35-44-year-old workers. J Psychosom Res 2010;69:151-159.
54.
Saul JP: Beat-to-beat variations of heart rate reflect modulation of cardiac autonomic outflow. Physiology 1990;5:32-37.
55.
Weber CS, Thayer JF, Rudat M, Wirtz PH, Zimmermann-Viehoff F, Thomas A, et al: Low vagal tone is associated with impaired post stress recovery of cardiovascular, endocrine, and immune markers. Eur J Appl Physiol 2010;109:201-211.
56.
Looser RR, Metzenthin P, Helfricht S, Kudielka BM, Loerbroks A, Thayer JF, et al: Cortisol is significantly correlated with cardiovascular responses during high levels of stress in critical care personnel. Psychosom Med 2010;72:281-289.
57.
Pieper S, Brosschot JF, van der Leeden R, Thayer JF: Prolonged cardiac effects of momentary assessed stressful events and worry episodes. Psychosom Med 2010;72:570-577.
58.
Fox S, Duggan M: Health Online 2013. Washington, Pew Research Center, 2013.
59.
Fox S, Duggan M: Mobile Health 2012. Washington, Pew Research Center, 2012.
60.
Centers for Disease Control and Prevention: Healthy aging data portfolio. http://nccd.cdc.gov/DPH_Aging/Location/LocationSummary.aspx?national=801 (accessed August 31, 2015).
61.
National Council on Aging: Fact sheet: healthy aging. https://www.ncoa.org/resources/fact-sheet-healthy-aging/ (accessed August 31, 2015).
62.
Mellone S, Tacconi C, Schwickert L, Klenk J, Becker C, Chiari L: Smartphone-based solutions for fall detection and prevention: the FARSEEING approach. Z Gerontol Geriatr 2012;45:722-727.
63.
Kwan A: Using Mobile Health Technologies for Healthier Aging. Pfizer, mHealth Alliance, United Nations Foundation, 2012.
64.
Lane RD, Wang M, Allen JB: Real-time vagal monitoring and vagal intervention. US Patent No 62/064,943. 2014.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.