As a healthy man or woman grows older, caring for an elderly spouse with Alzheimer's disease or other dementias may itself bring on disease.

Immunologist and medical geneticist Ronald Glaser, at Ohio State University in Columbus, finds it "startling" that "stress and depression can permanently alter the responsiveness of the immune system."

"I think," Glaser observed, "that the significance of this finding is that individuals who are older and taking care of a person over a long period of time, like an Alzheimer's disease or stroke patient, have to be aware and try to take steps to do things about it. For example exercising, trying to get more sleep, avoiding smoking, not overeating, and trying to network. People who lose their social network," Glaser explained, "that's not good. They need to try to keep contact with their friends and their family. Those are things they can do to help deal with that risky stress."

Glaser is senior author of a paper in the current Proceedings of the National Academy of Sciences (PNAS) released online June 31, 2003. Its title: "Chronic stress and age-related increases in the pro-inflammatory cytokine IL-6." Its lead author is research psychiatrist Janice Kiecolt-Glaser.

"The finding or message of this PNAS article," Glaser told BioWorld Today, "is that chronic stress in older individuals can have major health consequences, and actually make your immune system age faster than it ordinarily would with advancing age. We saw that within three years after the chronic stress ceases, it doesn't look as if the immune system can recover if you're older."

Of all the cytokines set loose by the body's immune defenses, Glaser explained, "Interleukin-6 is a prime enforcer. It overproduces with age, and is a specific risk factor in the spectrum that runs from cardiovascular disease to Type II diabetes, arthritis, osteoporosis, frailty, certain cancers, periodontal disease to functional decline and other age-related conditions."

Six-Year Study Samples Frozen Blood In Mates

Glaser and his co-authors embarked on a six-year research project - part of a 12-year program - plotting IL-6 blood levels in older men and women who were caring for a spouse with dementia. "We found that the caregivers' rate of increase in IL-6 was about four times larger than that of the control group," Kiecolt-Glaser noted. "This could have important implications for morbidity and mortality. It is key evidence," she continued, "for one pathway through which chronic stress may pose potent health consequences in older people. It may well accelerate the rise of a host of age-related diseases, as well as deaths."

She pointed out that "in addition, former caregivers continued to have higher IL-6 rates for up to three years after the impaired spouse had died."

"Such changes in caregivers," Kiecolt-Glaser observed, "are not simply an artifact of bereavement. This indicated that the adverse health effects continued past the cessation of the stressful situation. As our paper suggested, caregiving and other chronic stressors may accelerate normal age-related increases in the risk of serious health problems, by prematurely aging the immune response."

Rather than follow their living patients year by year, the investigators sampled six years' worth of frozen blood plasma samples all at once. They monitored the health status of 119 caregivers of chronic patients and compared them to a control group of 106 who had no caregiving role. The controls were matched for age, general health and socioeconomic status. The combined 223 subjects ranged in age from 55 to 89, with a mean 70.58 years.

Self-Reported Loneliness One Toll On Caregivers

Prior to the six-year sample collection phase, each of the study participants completed a series of psychological surveys to gauge their perceived levels of stress, depression, self-reported loneliness and other negative emotions. At the start of this phase of the 12-year longitudinal caregivers' study, nearly a quarter of the spouses had already died. During the six years of the study, another 50 spouses died. Earlier work by Glaser's group showed that a person's stress levels can have a detrimental effect on how efficiently certain vaccines immunize, that high stress levels can markedly slow wound healing and exacerbate infections, and that even short-term stressful events, such as arguments and test taking, could weaken the subject's immune status, and promote highly harmful IL-6 output.

Their study also provided some preliminary data showing that African-American participants had higher levels of IL-6 than non-African Americans. "African-Americans seem to have higher levels of IL-6 in both the control group and the active cohorts than the Caucasians," Glaser proffered. "Presumably," he speculated, "there might be a genetic component to that. We don't know, but it could be one explanation."

Glaser's advice to at-risk African-Americans repeats his prior prescription: exercise, sleep, food in moderation, no smoking and social networking. "All the same things, because they all affect IL-6 levels," he commented. "They should apply to any individual from any racial or other background."

As for "biotechies," he volunteered, "One thing that researchers in biotech might think about is for pharmaceutical companies to develop new ways of lowering IL-6 levels and other inflammatory cytokines. Such new compounds could be taken prophylactically," Glaser concluded, "by people who are at high risk in their advancing years of IL-6-elicited age-related diseases."