Aging Clinical and Experimental Research

, Volume 30, Issue 2, pp 119–132 | Cite as

Impact of caregiving for older people and pro-inflammatory biomarkers among caregivers: a systematic review

  • Florence PotierEmail author
  • Jean-Marie Degryse
  • Marie de Saint-Hubert



Evidence suggests that providing care for an older loved one may present a risk to the health of the caregiver. To understand the link between the psychosocial stress of caregiving and damage to the health of caregivers, numerous studies have assessed the presence of inflammatory biomarkers among caregivers. These biomarkers are measured to understand the relationships between the social stress of caregiving and the health of caregivers.


To provide a complete summary of the current literature regarding the most clinically relevant pro-inflammatory biomarkers associated with caregiving.


We searched articles in MEDLINE and EMBASE from January 1980 to 30 April 2016 for all studies that assessed biomarkers (cortisol, interleukin-6 and c-reactive protein) among caregivers of community-dwelling older persons. The quality of the selected studies was assessed by two reviewers using the STROBE or CONSORT checklist.


Twenty-four studies were included. Most of the studies were cross-sectional and focused on dementia caregiving. Increases in biomarkers were associated with problems such as disturbed sleep, burden or pain and caregiving characteristics, including daily stressors and the duration of caregiving. Cognitive-behavioural therapy and participation in leisure activities were associated with significantly lower levels of cortisol and IL-6, respectively.


We found little evidence concerning the association between caregiving status and biomarkers of stress and inflammation. We discuss potential sources of bias and suggest some directions for further research. This stress model can be expanded by taking into account the positive aspects of caregiving and the potential resources of caregivers.


Caregiving Biomarkers Inflammation Chronic stress Allostatic load 


Compliance with ethical standards


Fond d’innovation sociale “Germaine Tillion”, Wallonie. The funding source was not involved in this review.

Conflict of interest

The author(s) declare that they have no competing interests.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study formal consent is not required.

Supplementary material

40520_2017_765_MOESM1_ESM.pdf (191 kb)
Appendix 1. Concept of allostasis to understand the health consequences of caregiving stress. In response to a stressful stimulus, the main mediators of allostasis are released and support the adaptation. The response depends on the nature of the stimulus and on characteristics of the individual. Allostasis defines health as a state of responsiveness and optimal fluctuation to adapt to the demands of the environment. If the stressful situation remains, the consumption of resources is needed to reach a new state of balance; this price is called the “allostatic load”. (PDF 190 KB)
40520_2017_765_MOESM2_ESM.docx (14 kb)
Appendix 2. Search strategy (DOCX 14 KB)
40520_2017_765_MOESM3_ESM.docx (17 kb)
Appendix 3. Qualification of the articles with the STROBE statement tool. Numbers 1 to 22 correspond to the criteria of the STROBE statement tool. “+” means present, “-“ means not present and “?” means unclear. The quality of reporting is heterogeneous, with scores between 13 and 23/23. Several items were missing in a majority of the studies: presentation of the study design, description of potential sources of bias and explanation about the study size. (DOCX 16 KB)
40520_2017_765_MOESM4_ESM.docx (14 kb)
Appendix 4. Qualification of the articles with the CONSORT statement tool. Numbers 1 to 25 correspond to the criteria of the CONSORT statement tool. “+” means present, “-“ means not present, “?” means unclear and “NA” means non-applicable. (DOCX 13 KB)


  1. 1.
    Institute TNAfCNatAPP (2015) CaregivingintheUS_Final-ReportGoogle Scholar
  2. 2.
    Murray J, Schneider J, Banerjee S et al (1999) EUROCARE: a cross-national study of co-resident spouse carers for people with Alzheimer’s disease: II–A qualitative analysis of the experience of caregiving. Int J Geriatr Psychiatry 14:662–667CrossRefPubMedGoogle Scholar
  3. 3.
    Yaffe K, Fox P, Newcomer R et al (2002) Patient and caregiver characteristics and nursing home placement in patients with dementia. JAMA 287:2090–2097CrossRefPubMedGoogle Scholar
  4. 4.
    Vitaliano PP, Zhang J, Scanlan JM (2003) Is caregiving hazardous to one’s physical health? A meta-analysis. Psychol Bull 129:946–972. doi: 10.1037/0033-2909.129.6.946 CrossRefPubMedGoogle Scholar
  5. 5.
    Pinquart M, Sorensen S (2003) Differences between caregivers and noncaregivers in psychological health and physical health: a meta-analysis. Psychol Aging 18:250–267CrossRefPubMedGoogle Scholar
  6. 6.
    Van Durme T, Macq J, Jeanmart C et al (2012) Tools for measuring the impact of informal caregiving of the elderly: a literature review. Int J Nurs Stud 49:490–504. doi: 10.1016/j.ijnurstu.2011.10.011 CrossRefPubMedGoogle Scholar
  7. 7.
    Mosquera I, Vergara I, Larranaga I et al (2016) Measuring the impact of informal elderly caregiving: a systematic review of tools. Qual Life Res Int J Qual Life Asp Treat Care Rehabil 25:1059–1092. doi: 10.1007/s11136-015-1159-4 CrossRefGoogle Scholar
  8. 8.
    Shaw WS, Patterson TL, Ziegler MG et al (1999) Accelerated risk of hypertensive blood pressure recordings among Alzheimer caregivers. J Psychosom Res 46:215–227CrossRefPubMedGoogle Scholar
  9. 9.
    Lee S, Colditz GA, Berkman LF et al (2003) Caregiving and risk of coronary heart disease in US women: a prospective study. Am J Prev Med 24:113–119CrossRefPubMedGoogle Scholar
  10. 10.
    McEwen BS (2003) Mood disorders and allostatic load. Biol Psychiatry 54:200–207CrossRefPubMedGoogle Scholar
  11. 11.
    Maggio M, Guralnik JM, Longo DL et al (2006) Interleukin-6 in aging and chronic disease: a magnificent pathway. J Gerontol Ser A Biol Sci Med Sci 61:575–584CrossRefGoogle Scholar
  12. 12.
    Adriaensen W, Mathei C, van Pottelbergh G et al (2014) Significance of serum immune markers in identification of global functional impairment in the oldest old: cross-sectional results from the BELFRAIL study. Age 36:457–467. doi: 10.1007/s11357-013-9558-3 CrossRefPubMedGoogle Scholar
  13. 13.
    Adriaensen W, Mathei C, Vaes B et al (2014) Interleukin-6 predicts short-term global functional decline in the oldest old: results from the BELFRAIL study. Age 36:9723. doi: 10.1007/s11357-014-9723-3 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Kraemer HC, Stice E, Kazdin A et al (2001) How do risk factors work together? Mediators, moderators, and independent, overlapping, and proxy risk factors. Am J Psychiatry 158:848–856. doi: 10.1176/appi.ajp.158.6.848 CrossRefPubMedGoogle Scholar
  15. 15.
    Damjanovic AK, Yang Y, Glaser R et al (2007) Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer’s disease patients. J Immunol (Baltimore, MD: 1950) 179:4249–4254CrossRefGoogle Scholar
  16. 16.
    Mills PJ, Yu H, Ziegler MG et al (1999) Vulnerable caregivers of patients with Alzheimer’s disease have a deficit in circulating CD62L-T lymphocytes. Psychosom Med 61:168–174CrossRefPubMedGoogle Scholar
  17. 17.
    von Kanel R, Mausbach BT, Dimsdale JE et al (2010) Problem behavior of dementia patients predicts low-grade hypercoagulability in spousal caregivers. J Gerontol Ser A Biol Sci Med Sci 65:1004–1011. doi: 10.1093/gerona/glq073 CrossRefGoogle Scholar
  18. 18.
    von Elm E, Altman DG, Egger M et al (2007) The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. PLoS Med 4:e296. doi: 10.1371/journal.pmed.0040296 CrossRefGoogle Scholar
  19. 19.
    Schulz KF, Altman DG, Moher D (2010) CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. BMC Med 8:18. doi: 10.1186/1741-7015-8-18 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Hernan MA, Hernandez-Diaz S, Werler MM et al (2002) Causal knowledge as a prerequisite for confounding evaluation: an application to birth defects epidemiology. Am J Epidemiol 155:176–184CrossRefPubMedGoogle Scholar
  21. 21.
    Aboulafia-Brakha T, Suchecki D, Gouveia-Paulino F et al (2014) Cognitive-behavioural group therapy improves a psychophysiological marker of stress in caregivers of patients with Alzheimer’s disease. Aging Ment Health 18:801–808. doi: 10.1080/13607863.2014.880406 CrossRefPubMedGoogle Scholar
  22. 22.
    Cacioppo JT, Burleson MH, Poehlmann KM et al (2000) Autonomic and neuroendocrine responses to mild psychological stressors: effects of chronic stress on older women. Ann Behav Med Publ Soc Behav Med 22:140–148CrossRefGoogle Scholar
  23. 23.
    Clark MC, Nicholas JM, Wassira LN et al (2013) Psychosocial and biological indicators of depression in the caregiving population. Biol Res Nurs 15:112–121. doi: 10.1177/1099800411414872 CrossRefPubMedGoogle Scholar
  24. 24.
    Davis LL, Weaver M, Zamrini E et al (2004) Biopsychological markers of distress in informal caregivers. Biol Res Nurs 6:90–99. doi: 10.1177/1099800404267353 CrossRefPubMedGoogle Scholar
  25. 25.
    Fonareva I, Amen AM, Zajdel DP et al (2011) Assessing sleep architecture in dementia caregivers at home using an ambulatory polysomnographic system. J Geriatr Psychiatry Neurol 24:50–59. doi: 10.1177/0891988710397548 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Gouin JP, Glaser R, Malarkey WB et al (2012) Chronic stress, daily stressors, and circulating inflammatory markers. Health Psychol 31:264–268CrossRefPubMedGoogle Scholar
  27. 27.
    Leggett AN, Liu Y, Klein LC et al (2015) Sleep duration and the cortisol awakening response in dementia caregivers utilizing adult day services. Health Psychol Off J Div Health Psychol Am Psychol Assoc. doi: 10.1037/hea0000276 Google Scholar
  28. 28.
    Lutgendorf SK, Garand L, Buckwalter KC et al (1999) Life stress, mood disturbance, and elevated interleukin-6 in healthy older women. J Gerontol Ser A Biol Sci Med Sci 54:M434–M439CrossRefGoogle Scholar
  29. 29.
    Oken BS, Fonareva I, Haas M et al (2010) Pilot controlled trial of mindfulness meditation and education for dementia caregivers. J Altern Complement Med 16:1031–1038. doi: 10.1089/acm.2009.0733 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Okun ML, Reynolds CF 3rd, Buysse DJ et al (2011) Sleep variability, health-related practices, and inflammatory markers in a community dwelling sample of older adults. Psychosom Med 73:142–150. doi: 10.1097/PSY.0b013e3182020d08 CrossRefPubMedGoogle Scholar
  31. 31.
    Segerstrom SC, Schipper LJ, Greenberg RN (2008) Caregiving, repetitive thought, and immune response to vaccination in older adults. Brain Behav Immun 22:744–752. doi: 10.1016/j.bbi.2007.11.004 CrossRefPubMedGoogle Scholar
  32. 32.
    Vitaliano P, Echeverria D, Shelkey M et al (2007) A cognitive psychophysiological model to predict functional decline in chronically stressed older adults. J Clin Psychol Med Settings 14:177–190. doi: 10.1007/s10880-007-9071-x CrossRefGoogle Scholar
  33. 33.
    Graham JE, Robles TF, Kiecolt-Glaser JK et al (2006) Hostility and pain are related to inflammation in older adults. Brain Behav Immun 20:389–400. doi: 10.1016/j.bbi.2005.11.002 CrossRefPubMedGoogle Scholar
  34. 34.
    Kiecolt-Glaser JK, Glaser R, Gravenstein S et al (1996) Chronic stress alters the immune response to influenza virus vaccine in older adults. Proc Natl Acad Sci USA 93:3043–3047CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Kiecolt-Glaser JK, Preacher KJ et al (2003) Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proc Natl Acad Sci USA 100:9090–9095. doi: 10.1073/pnas.1531903100 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Mausbach BT, von Kanel R, Roepke SK et al (2011) Self-efficacy buffers the relationship between dementia caregiving stress and circulating concentrations of the proinflammatory cytokine interleukin-6. Am J Geriatric Psychiatry Off J Am Assoc Geriatric Psychiatry 19:64–71. doi: 10.1097/JGP.0b013e3181df4498 CrossRefGoogle Scholar
  37. 37.
    Mills PJ, Ancoli-Israel S, Känel Rv et al (2009) Effects of gender and dementia severity on Alzheimer’s disease caregivers’ sleep and biomarkers of coagulation and inflammation. Brain Behav Immun 23:605–610. doi: 10.1016/j.bbi.2008.09.014 CrossRefPubMedGoogle Scholar
  38. 38.
    Moore RC, Chattillion EA, Ceglowski J et al (2013) A randomized clinical trial of behavioral activation (BA) therapy for improving psychological and physical health in dementia caregivers: results of the pleasant events program (PEP). Behav Res Ther 51:623–632. doi: 10.1016/j.brat.2013.07.005 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Von Känel R, Dimsdale JE, Ancoli-Israel S et al (2006) Poor sleep is associated with higher plasma proinflammatory cytokine interleukin-6 and procoagulant marker fibrin D-dimer in older caregivers of people with Alzheimer’s disease. J Am Geriatr Soc 54:431–437. doi: 10.1111/j.1532-5415.2005.00642.x CrossRefGoogle Scholar
  40. 40.
    Von Känel R, Dimsdale JE, Mills PJ et al (2006) Effect of Alzheimer caregiving stress and age on frailty markers interleukin-6, C-reactive protein, and D-dimer. J Gerontol Ser A Biol Sci Med Sci 61:963–969CrossRefGoogle Scholar
  41. 41.
    von Kanel R, Ancoli-Israel S, Dimsdale JE et al (2010) Sleep and biomarkers of atherosclerosis in elderly Alzheimer caregivers and controls. Gerontology 56:41–50. doi: 10.1159/000264654 CrossRefGoogle Scholar
  42. 42.
    Von Känel R, Mausbach BT, Dimsdale JE et al (2012) Ways of coping and biomarkers of an increased atherothrombotic cardiovascular disease risk in elderly individuals. Cardiovasc Psychiatry Nerol. doi: 10.1155/2012/875876 Google Scholar
  43. 43.
    Von Känel R, Mills PJ, Mausbach BT et al (2012) Effect of Alzheimer caregiving on circulating levels of C-reactive protein and other biomarkers relevant to cardiovascular disease risk: a longitudinal study. Gerontology 58:354–365. doi: 10.1159/000334219 CrossRefGoogle Scholar
  44. 44.
    von Kanel R, Mausbach BT, Mills PJ et al (2014) Longitudinal relationship of low leisure satisfaction but not depressive symptoms with systemic low-grade inflammation in dementia caregivers. J Gerontol Ser B Psychol Sci Soc Sci 69:397–407. doi: 10.1093/geronb/gbt020 CrossRefGoogle Scholar
  45. 45.
    Boeckxstaens P, Vaes B, De Sutter A et al (2016) A high sense of coherence as protection against adverse health outcomes in patients aged 80 years and older. Ann Fam Med 14:337–343. doi: 10.1370/afm.1950 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Alexandraki K, Piperi C, Kalofoutis C et al (2006) Inflammatory process in type 2 diabetes: the role of cytokines. Ann N Y Acad Sci 1084:89–117. doi: 10.1196/annals.1372.039 CrossRefPubMedGoogle Scholar
  47. 47.
    Vasan RS, Sullivan LM, Roubenoff R et al (2003) Inflammatory markers and risk of heart failure in elderly subjects without prior myocardial infarction: the Framingham Heart Study. Circulation 107:1486–1491CrossRefPubMedGoogle Scholar
  48. 48.
    Gouin JP, Hantsoo L, Kiecolt-Glaser JK (2008) Immune dysregulation and chronic stress among older adults: a review. Neuroimmunomodulation 15:251–259. doi: 10.1159/000156468 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Capistrant BD, Moon JR, Berkman LF et al (2012) Current and long-term spousal caregiving and onset of cardiovascular disease. J Epidemiol Community Health 66:951–956. doi: 10.1136/jech-2011-200040 CrossRefPubMedGoogle Scholar
  50. 50.
    Fredman L, Daly MP (1993) Physicians and family caregivers: a model for partnership. JAMA 270:1426–1427CrossRefPubMedGoogle Scholar
  51. 51.
    Biomarkers Definitions Working Group Bethesda M (2001) Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 69:89–95. doi: 10.1067/mcp.2001.113989 CrossRefGoogle Scholar
  52. 52.
    Hansel A, Hong S, Camara RJ et al (2010) Inflammation as a psychophysiological biomarker in chronic psychosocial stress. Neurosci Biobehav Rev 35:115–121. doi: 10.1016/j.neubiorev.2009.12.012 CrossRefPubMedGoogle Scholar
  53. 53.
    Allen AP, Curran EA, Duggan A et al (2016) A systematic review of the psychobiological burden of informal caregiving for patients with dementia: focus on cognitive and biological markers of chronic stress. Neurosci Biobehav Rev. doi: 10.1016/j.neubiorev.2016.12.006 Google Scholar
  54. 54.
    von Kanel R, Dimsdale JE, Adler KA et al (2005) Exaggerated plasma fibrin formation (D-dimer) in elderly Alzheimer caregivers as compared to noncaregiving controls. Gerontology 51:7–13. doi: 10.1159/000081428 CrossRefGoogle Scholar
  55. 55.
    Mausbach BT, Ancoli-Israel S, von Kanel R et al (2006) Sleep disturbance, norepinephrine, and D-dimer are all related in elderly caregivers of people with Alzheimer disease. Sleep 29:1347–1352CrossRefPubMedGoogle Scholar
  56. 56.
    Mausbach BT, von Kanel R, Aschbacher K et al (2007) Spousal caregivers of patients with Alzheimer’s disease show longitudinal increases in plasma level of tissue-type plasminogen activator antigen. Psychosom Med 69:816–822. doi: 10.1097/PSY.0b013e318157d461 CrossRefPubMedGoogle Scholar
  57. 57.
    Aschbacher K, Patterson TL, von Kanel R et al (2005) Coping processes and hemostatic reactivity to acute stress in dementia caregivers. Psychosom Med 67:964–971. doi: 10.1097/01.psy.0000188458.85597.bc CrossRefPubMedGoogle Scholar
  58. 58.
    Cole SW, Hawkley LC, Arevalo JM et al (2007) Social regulation of gene expression in human leukocytes. Genome Biol 8:R189. doi: 10.1186/gb-2007-8-9-r189 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.Department of GeriatricsCentre Hospitalier Universitaire Université Catholique de Louvain NamurNamurBelgium
  2. 2.Institute of Health and SocietyUniversité Catholique de LouvainBrusselsBelgium
  3. 3.Department of Public Health and Primary CareKatholieke Universiteit LeuvenLeuvenBelgium

Personalised recommendations