Elsevier

The Lancet

Volume 353, Issue 9153, 20 February 1999, Pages 627-631
The Lancet

Articles
Chronic stress in elderly carers of dementia patients and antibody response to influenza vaccination

https://doi.org/10.1016/S0140-6736(98)06098-XGet rights and content

Summary

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-pituary-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.

Introduction

The task of caring for a significant other with a dementing illness is arduous and prolonged.1 Furthermore, the care of people with dementia is generally by partners who are themselves elderly and often ill-prepared for the physical and emotional demands placed on them.2 There are many reports of increased psychological morbidity in carers which, according to some investigators, may persist for up to 2 years after the partner is taken into full-time care.3, 4

The consequences on the immune system of this increased stress have been investigated but both the existence of immune impairments and the significance of the specific deficits are controversial.5, 6, 7 Impairments in T-cell proliferation in response to mitogens, shift in T-cell subpopulations, and reductions in natural killer cell in vitro provide little information about the clinical significance of the observed immune alterations. To know whether chronic stress increases vulnerability to disease in the elderly, the immune assessment must be both specific and involve exposure to a clinically relevant in vivo antigenic challenge.

Kiecolt-Glaser and colleagues8 found that spousal carers of dementia patients had a poorer antibody response to influenza vaccination than non-carers matched for age and sex. Other workers have suggested that neuroendocrine mechanisms may account for the inverse relation between stress and immunity.9, 10, 11

Bereaved women have reduced natural-killer-cell activity and increased plasma cortisol concentrations.12 Similarly, psychiatric inpatients who described themselves as more distressed and isolated had higher concentrations of urinary cortisol which were associated with poorer proliferative responses of T cells to the mitogen phytohaemagglutinin and reduced natural-killer-cell activity.9

We investigated the immune response to influenza vaccine and the activity of the hypothalamic-pituitary-adrenal (HPA) axis in spousal carers of dementia patients and non-carers. We hypothesised that spousal carers of dementia patients would have poorer antibody responses to influenza vaccine and persistently elevated concentrations of cortisol in the 6 months before vaccination compared with controls.

Section snippets

Patients

This investigation was approved by the ethics committee of the United Bristol Healthcare Trust and the Frenchay NHS Trust. All participants gave informed written consent. 50 spousal carers (24 men) of patients with dementia were recruited from the Bristol Memory Disorders Clinic where their partners had attended. The inclusion criteria were: a partner with a diagnosis of dementia; they were the primary carer; and that they cared for their partners at home and reported no other caregiving

Results

The characteristics of the participants and their known disorders are shown in table 1. All participants were Caucasian. Mean (SD) scores of emotional distress were significantly higher in carers than controls at each time point in the 6 months before vaccination: at 0 months 0·43 (1·09) vs −0·31 (0·81); at 3 months 0·47 (1·00) vs −0·33 (0·86); and, at 6 months 0·39 (1·06) vs −0·29 (0·85), all p<0·0003.

Similarly, mean AUC values for cortisol were significantly higher in carers at each time

Discussion

We found increased levels of distress in carers of spouses with dementia compared with controls. This increased distress was also associated with significantly raised concentrations of cortisol. Furthermore, the chronic activation of the HPA axis was associated with significantly impaired antibody responses to influenza vaccination. The proportion of carers who were able to generate a four-fold increase in antibody titre to at least one of the vaccine components was substantially lower than

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