Chronic stress in elderly carers of dementia patients and antibody response to influenza vaccination
Abstract
Background There are many reports of psychological morbidity in spousal carers of patients with dementia. The consequences of this increased stress on the immune system are unclear. We investigated whether antibody responses to influenza vaccination differed between carers and a control group, and the relation of the antibody response to the hypothalamic-pituitary-adrenal (HPA) axis.Methods 50 spousal carers of dementia patients, median age 73 years (IQR 66-77), and 67 controls (68 years [66-71]) of similar socioeconomic status were enrolled. Anxiety and depression were measured by the Savage Aged Personality Screening Scale and stress by the Global Measure of Perceived Stress scale. Principal-component analysis was used to yield a summary score of emotional distress from these two scales. Salivary cortisol concentrations were measured over a single day at three times (0800-1000, 1100-1300, and 2000-2200). Participants received a trivalent influenza vaccine and IgG antibody titres to each strain were measured on days 0, 7, 14, and 28.Findings Mean scores of emotional distress were significantly higher in carers at each time point than in controls (all p<0.0003). Mean (SD) salivary cortisol concentrations, calculated as area under the curve (AUC), were higher in carers than controls at all three assessments (6 months 16.0 [8.0] vs 11.2 [4.4], p=0.0001; respectively). Eight (16%) of 50 carers and 26 (39%) of 67 controls had a four-fold increase in at least one of the IgG titres (p=0.007). There was an inverse relation between AUC cortisol and IgG antibody titre to the Nanchang strain that was significant on day 14 (r=-0.216, p=0.039).Interpretation Elderly carers of spouses with dementia have increased activation of the hypothalamic-pituitary-adrenal axis and a poor antibody response to influenza vaccine. Carers may be more vulnerable to infectious disease than the population of a similar age.
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Compared with noncaregivers, caregivers have poorer immune responses to influenza virus and pneumococcal pneumonia vaccines.
“they have poorer immune responses to influenza virus and pneumococcal pneumonia vaccines (2-4)”
From Chronic stress and age-related increases in the proinflammatory cytokine IL-6. (2003) · cites this paper as [4]
Caregiving is a risk factor for health.
“A growing body of evidence has implicated caregiving as a risk factor for health.”
From Chronic stress and age-related increases in the proinflammatory cytokine IL-6. (2003) · cites this paper as [4]
Negative emotions contribute to greater risk for infection, prolonged infection, and delayed wound healing.
“negative emotions contribute to greater risk for infection, prolonged infection, and delayed wound healing (1-5)”
From Chronic stress and age-related increases in the proinflammatory cytokine IL-6. (2003) · cites this paper as [4]
Caregivers report more infectious illness episodes and have poorer immune responses to influenza virus and pneumococcal pneumonia vaccines than noncaregivers.
“caregivers report more infectious illness episodes, and they have poorer immune responses to influenza virus and pneumococcal pneumonia vaccines than noncaregivers (1-4).”
From Chronic stress and age-related increases in the proinflammatory cytokine IL-6. (2003) · cites this paper as [4]
Cites
A Global Measure of Perceived Stress
Cohen, S., Kamarck, T., & Mermelstein, R. (1983) · Journal of Health and Social Behavior · doi:10.2307/2136404 · Cited by 32,807 · see citing works
Chronic stress alters the immune response to influenza virus vaccine in older adults.
Kiecolt-Glaser, J. K., Glaser, R., Gravenstein, S., Malarkey, W. B., & Sheridan, J. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.7.3043 · Cited by 789 · see citing works
Kirschbaum, C., Prussner, J. C., Stone, A. A., Federenko, I., Gaab, J., Lintz, D., Schommer, N., & Hellhammer, D. H. (1995) · Psychosomatic Medicine · doi:10.1097/00006842-199509000-00009 · Cited by 666 · see citing works
Chronic stress and immunity in family caregivers of Alzheimerʼs disease victims.
Kiecolt‐Glaser, J. K., Glaser, R., Shuttleworth, E. C., Dyer, C. S., Ogrocki, P. K., & Speicher, C. E. (1987) · Psychosomatic Medicine · doi:10.1097/00006842-198709000-00008 · Cited by 484 · see citing works
Urinary Cortisol Levels, Cellular Immunocompetency, and Loneliness in Psychiatric Inpatients
Kiecolt‐Glaser, J. K., Ricker, D. M., George, J. M., Messick, G., Speicher, C. E., Garner, W. L., & Glaser, R. (1984) · Psychosomatic Medicine · doi:10.1097/00006842-198401000-00004 · Cited by 322 · see citing works
Psychosocial Modulation of Cytokine-Induced Natural Killer Cell Activity in Older Adults
Esterling, B. A., Kiecolt‐Glaser, J. K., & Glaser, R. (1996) · Psychosomatic Medicine · doi:10.1097/00006842-199605000-00010 · Cited by 188 · see citing works
Plasma cortisol and natural killer cell activity during bereavement
Irwin, M. R., Daniels, M. L., Risch, S. C., Bloom, E. T., & Weiner, H. (1988) · Biological Psychiatry · doi:10.1016/0006-3223(88)90272-7 · Cited by 177 · see citing works
Ironson, G. H., Friedman, A. L., Klimas, N. G., Antoni, M. H., FLETCHER, M. A., LaPerriere, A. R., Simoneau, J., & Schneiderman, N. (1994) · International Journal of Behavioral Medicine · doi:10.1207/s15327558ijbm0101_6 · Cited by 168 · see citing works
Endocrine Responses to Stressful Psychological Events
Rose, R. M. (1980) · Psychiatric Clinics of North America · doi:10.1016/s0193-953x(18)30965-1 · Cited by 155 · see citing works
Chronic stress alters the immune response to influenza virus vaccine in older adults
Kiecolt-Graser, J. (1996) · Medical Entomology and Zoology · Cited by 151 · see citing works
Glaser, R., Pearl, D. K., Kiecolt‐Glaser, J. K., & Malarkey, W. B. (1994) · Psychoneuroendocrinology · doi:10.1016/0306-4530(94)90023-x · Cited by 147 · see citing works
Convergence between the Daily Stress Inventory and endocrine measures of stress.
Brantley, P. J., Dietz, L. S., McKnight, G. T., Jones, G. N., & Tulley, R. T. (1988) · Journal of Consulting and Clinical Psychology · doi:10.1037/0022-006x.56.4.549 · Cited by 127 · see citing works
Shimada, M., Takahashi, K., Ohkawa, T., Segawa, M., & Higurashi, M. (2008) · Hormone Research · doi:10.1159/000184628 · Cited by 101 · see citing works
Irwin, M. R., Hauger, R. L., Patterson, T. L., Semple, S. J., Ziegler, M. G., & Grant, I. (1997) · Annals of Behavioral Medicine · doi:10.1007/bf02883324 · Cited by 88 · see citing works
Understanding Stress in Informal Caregiving
Braithwaite, V. A. (1996) · Research on Aging · doi:10.1177/0164027596182001 · Cited by 64 · see citing works
Characterization of the Immune Response to Trivalent Influenza Vaccine in Elderly Men
Levine, M., Beattie, B. L., McLean, D. M., et al. (1987) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1987.tb04335.x · Cited by 61 · see citing works
Stress-associated modulation of proto-oncogene expression in human peripheral blood leukocytes.
Glaser, R., Lafuse, W. P., Bonneau, R. H., Atkinson, C., & al, E. (1993) · Behavioral Neuroscience · doi:10.1037//0735-7044.107.3.525 · Cited by 41 · see citing works
Stress-associated modulation of proto-oncogene expression in human peripheral blood leukocytes.
Glaser, R., Lafuse, W. P., Bonneau, R. H., et al. (1993) · Behavioral Neuroscience · doi:10.1037/0735-7044.107.3.525 · Cited by 31 · see citing works
Greater emotional distress is associated with accelerated CD4+ cell decline in HIV infection
Vedhara, K., Nott, K. H., Bradbeer, C. S., Davidson, E., Ong, E. L. C., Snow, M., Palmer, D., & Nayagam, A. T. (1997) · Journal of Psychosomatic Research · doi:10.1016/s0022-3999(96)00351-0 · Cited by 29 · see citing works
Self-citationWaltrowicz, W., Ames, D. J., McKenzie, S., & Flicker, L. A. (1996) · Australian Journal on Ageing · doi:10.1111/j.1741-6612.1996.tb00007.x · Cited by 22 · see citing works
Comparing Patterns of Stress in Daily Experiences of Elderly Caregivers and Noncaregivers
Wallsten, S. M. (1993) · The International Journal of Aging and Human Development · doi:10.2190/fb4j-mndk-ynth-3xjp · Cited by 19 · see citing works
Caring for an older spouse with a psychiatric illness
Murray, J., Manela, M., Shuttleworth, A., et al. (1997) · Aging & Mental Health · doi:10.1080/13607869757155 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
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Psychological stress and the human immune system: a meta-analytic study of 30 Years of inquiry
Segerstrom, S. C., & Miller, G. E. (2004) · Psychological Bulletin · doi:10.1037/0033-2909.130.4.601 · Cited by 3,334 · see citing works
Miller, G. E., Chen, E., & Zhou, E. S. (2007) · Psychological Bulletin · doi:10.1037/0033-2909.133.1.25 · Cited by 2,467 · see citing works
Marriage and health: His and hers
Kiecolt-Glaser, J. K., & Newton, T. L. (2001) · Psychological Bulletin · doi:10.1037//0033-2909.127.4.472 · Cited by 2,460 · see citing works
Stress-induced immune dysfunction: implications for health
Glaser, R., & Kiecolt-Glaser, J. K. (2005) · Nature Reviews Immunology · doi:10.1038/nri1571 · Cited by 2,190 · see citing works
Is caregiving hazardous to one’s physical health? A meta-analysis
Vitaliano, P. P., Zhang, J., & Scanlan, J. M. (2003) · Psychological Bulletin · doi:10.1037/0033-2909.129.6.946 · Cited by 1,734 · see citing works
Family caregivers of people with dementia
Brodaty, H., & Donkin, M. (2009) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2009.11.2/hbrodaty · Cited by 1,644 · see citing works
Chronic stress and age-related increases in the proinflammatory cytokine IL-6.
Kiecolt-Glaser, J. K., Preacher, K. J., MacCallum, R. C., Atkinson, C., Malarkey, W. B., & Glaser, R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1531903100 · Cited by 1,220 · see citing works
Emotions, morbidity, and mortality: new perspectives from psychoneuroimmunology.
Kiecolt-Glaser, J. K., McGuire, L., Robles, T. F., & Glaser, R. (2002) · Annual Review of Psychology · doi:10.1146/annurev.psych.53.100901.135217 · Cited by 1,176 · see citing works
Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens
Sternberg, E. M. (2006) · Nature Reviews Immunology · doi:10.1038/nri1810 · Cited by 1,064 · see citing works
How stress influences the immune response
Padgett, D. A., & Glaser, R. (2003) · Trends in Immunology · doi:10.1016/s1471-4906(03)00173-x · Cited by 1,059 · see citing works
Stress and Health: A Review of Psychobiological Processes
O'Connor, D. B., Thayer, J. F., & Vedhara, K. (2021) · Annual Review of Psychology · doi:10.1146/annurev-psych-062520-122331 · Cited by 948 · see citing works
Self-citationThe physiology of marriage: pathways to health.
Robles, T. F., & Kiecolt-Glaser, J. K. (2003) · Physiology & Behavior · doi:10.1016/s0031-9384(03)00160-4 · Cited by 748 · see citing works
Depressive disorders and immunity: 20 years of progress and discovery
Irwin, M. R., & Miller, A. H. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.01.010 · Cited by 676 · see citing works
Psychoneuroimmunology: psychological influences on immune function and health
Kiecolt-Glaser, J. K., McGuire, L., Robles, T. F., & Glaser, R. (2002) · Journal of Consulting and Clinical Psychology · doi:10.1037/0022-006x.70.3.537 · Cited by 686 · see citing works
Socioeconomic Status Is Associated With Stress Hormones
Cohen, S., Doyle, W. J., & Baum, A. (2006) · Psychosomatic Medicine · doi:10.1097/01.psy.0000221236.37158.b9 · Cited by 639 · see citing works
Loneliness, social network size, and immune response to influenza vaccination in college freshmen
Pressman, S. D., Cohen, S., Miller, G. E., Barkin, A., Rabin, B. S., & Treanor, J. J. (2005) · Health Psychology · doi:10.1037/0278-6133.24.3.297 · Cited by 608 · see citing works
Miller, G., Chen, E., & Cole, S. W. (2009) · Annual Review of Psychology · doi:10.1146/annurev.psych.60.110707.163551 · Cited by 591 · see citing works
Depression and immune function
Kiecolt-Glaser, J. K., & Glaser, R. (2002) · Journal of Psychosomatic Research · doi:10.1016/s0022-3999(02)00309-4 · Cited by 571 · see citing works
Caring for a relative with dementia: family caregiver burden
Papastavrou, E., Kalokerinou, A., Papacostas, S. S., Tsangari, H., & Sourtzi, P. (2007) · Journal of Advanced Nursing · doi:10.1111/j.1365-2648.2007.04250.x · Cited by 540 · see citing works
Stress, age, and immune function: toward a lifespan approach
Graham, J. E., Christian, L. M., & Kiecolt-Glaser, J. K. (2006) · Journal of Behavioral Medicine · doi:10.1007/s10865-006-9057-4 · Cited by 329 · see citing works
Acute stress, memory, attention and cortisol
Vedhara, K., Hyde, J., Gilchrist, I. D., Tytherleigh, M., & Plummer, S. (2000) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(00)00008-1 · Cited by 313 · see citing works
Self-citationChronic Stress Modulates the Immune Response to a Pneumococcal Pneumonia Vaccine
Glaser, R., Sheridan, J., Malarkey, W. B., MacCallum, R. C., & Kiecolt-Glaser, J. K. (2000) · Psychosomatic Medicine · doi:10.1097/00006842-200011000-00010 · Cited by 295 · see citing works
The role of psychobiological pathways in socio-economic inequalities in cardiovascular disease risk
Steptoe, A. (2002) · European Heart Journal · doi:10.1053/euhj.2001.2611 · Cited by 274 · see citing works
Rohleder, N., Marin, T. J., Ma, R., & Miller, G. E. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.18.7435 · Cited by 252 · see citing works
Allen, A. P., Curran, E. A., Duggan, Á., Cryan, J. F., Chorcoráin, A. N., Dinan, T. G., Molloy, D. W., Kearney, P. M., & Clarke, G. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.12.006 · Cited by 244 · see citing works
Diurnal cortisol decline is related to coronary calcification: CARDIA study
Matthews, K., Schwartz, J., Cohen, S., & Seeman, T. (2006) · Psychosomatic Medicine · doi:10.1097/01.psy.0000244071.42939.0e · Cited by 240 · see citing works
Knowles, S. R., Nelson, E. A., & Palombo, E. A. (2008) · Biological Psychology · doi:10.1016/j.biopsycho.2007.09.010 · Cited by 192 · see citing works
Psychoneuroimmunology of depression: clinical implications
Irwin, M. (2002) · Brain, Behavior, and Immunity · doi:10.1006/brbi.2001.0654 · Cited by 160 · see citing works
Glaser, R. (2005) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2004.06.003 · Cited by 158 · see citing works
Coping and adjustment in caregivers: a systematic review
Hawken, T., Turner-Cobb, J., & Barnett, J. (2018) · Health Psychology Open · doi:10.1177/2055102918810659 · Cited by 128 · see citing works
Behavioral problems in dementia patients and salivary cortisol patterns in caregivers
de Vugt, M. E., Nicolson, N. A., Aalten, P., Lousberg, R., Jolle, J., & Verhey, F. R. J. (2005) · The Journal of Neuropsychiatry and Clinical Neurosciences · doi:10.1176/jnp.17.2.201 · Cited by 136 · see citing works
Vitlic, A., Lord, J. M., & Phillips, A. C. (2014) · AGE · doi:10.1007/s11357-014-9631-6 · Cited by 123 · see citing works
Enhanced Th17 phenotype in individuals with generalized anxiety disorder
Vieira, M. M. M., Ferreira, T. B., Pacheco, P. A. F., Barros, P. O., Almeida, C. R. M., Araújo-Lima, C. F., Silva-Filho, R. G., Hygino, J., Andrade, R. M., Linhares, U. C., et al. (2010) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2010.07.018 · Cited by 118 · see citing works
Neural regulation of bone and bone marrow
Maryanovich, M., Takeishi, S., & Frenette, P. S. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a031344 · Cited by 114 · see citing works
Utilizing a wristband sensor to measure the stress level for people with dementia
Kikhia, B., Stavropoulos, T., Andreadis, S., Karvonen, N., Kompatsiaris, I., Sävenstedt, S., Pijl, M., & Melander, C. (2016) · Sensors · doi:10.3390/s16121989 · Cited by 89 · see citing works
Wingo, A. P., & Gibson, G. (2015) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2014.09.016 · Cited by 59 · see citing works
Derhovanessian, E., & Pawelec, G. (2012) · Microbial Biotechnology · doi:10.1111/j.1751-7915.2011.00283.x · Cited by 51 · see citing works
The effects of an anticipated challenge on diurnal cortisol secretion
Wetherell, M. A., Lovell, B., & Smith, M. A. (2015) · Stress · doi:10.3109/10253890.2014.993967 · Cited by 50 · see citing works
Neuroticism, cognitive ability, and the metabolic syndrome: The Vietnam Experience Study
Phillips, A. C., Batty, G. D., Weiss, A., Deary, I., Gale, C. R., Thomas, G. N., & Carroll, D. (2010) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2010.01.016 · Cited by 45 · see citing works
Review: Brain—immune communication psychoneuroimmunology of multiple sclerosis
Kern, S., & Ziemssen, T. (2008) · Multiple Sclerosis Journal · doi:10.1177/1352458507079657 · Cited by 45 · see citing works
Li, J., Cowden, L. G., King, J. D., Briles, D. A., Schroeder, H. W., Stevens, A. B., Perry, R. T., Chen, Z., Simmons, M. S., Wiener, H. W., et al. (2007) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3180cc2c61 · Cited by 40 · see citing works
Influenza Virus-Specific Immunological Memory Is Enhanced by Repeated Social Defeat
Mays, J. W., Bailey, M. T., Hunzeker, J. T., Powell, N. D., Papenfuss, T., Karlsson, E. A., Padgett, D. A., & Sheridan, J. F. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0900183 · Cited by 37 · see citing works
On race, human variation, and who gets and dies of sepsis
Brinkworth, J. F., & Shaw, J. G. (2022) · American Journal of Biological Anthropology · doi:10.1002/ajpa.24527 · Cited by 9 · see citing works
- Authors
- Vedhara, K., Cox, N. K., Wilcock, G. K., Perks, P., Hunt, M., Anderson, S., Lightman, S. L., & Shanks, N. M.
- Affiliations
- University of Bristol (GB)
- Frenchay Hospital (GB)
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 1999-02
- Volume
- 353
- Issue
- 9153
- Pages
- 627-631
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W1974857283
- Cited by
- 496
- References
- 22
- Citations by year
- 2026: 10 · 2025: 1 · 2024: 7 · 2023: 6 · 2022: 16 · 2021: 15 · 2020: 15 · 2019: 12 · 2018: 12 · 2017: 14 · 2016: 13 · 2015: 16 · 2014: 27 · 2013: 19 · 2012: 26
- FWCI
- 9.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Health Professions › Pharmacy › Nursing care and research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- chronic stress, dementia caregivers, spousal caregivers, influenza vaccination, antibody response, salivary cortisol, hypothalamic-pituitary-adrenal axis, emotional distress, anxiety, depression, immune function, elderly caregivers
- MeSH terms
- Aged, Analysis of Variance, Antibodies, Viral, Anxiety, Chronic Disease, Dementia, Depression, Female, Follow-Up Studies, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Immunoglobulin G, Influenza Vaccines, Male, Influenza A virus, Influenza B virus, Pituitary-Adrenal System, Saliva, Social Class, Stress, Physiological, Stress, Psychological, Caregivers, Spouses, Area Under Curve
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