Deborah Brauser

March 25, 2011

March 25, 2011 (San Antonio, Texas) — Marital history may predict the development of both dementia and Alzheimer's disease (AD), new research suggests.

In a sample study of almost 4000 elderly participants, investigators found that those who never remarried after being widowed had an 83% higher risk of developing dementia and a more than 2-fold higher risk of developing AD than did the reference group, made up of those still on their first marriage.

The results were presented here at the American Association for Geriatric Psychiatry (AAGP) 2011 Annual Meeting.

"We found that the lowest risk for dementia was among those who were long-time married and remained married throughout this long-term memory study," co-investigator Maria C. Norton, PhD, from the Department of Family, Consumer, and Human Development at Utah State University in Logan, told Medscape Medical News

Dr. Maria C. Norton

"Apparently, these were good marriages with less stress. But almost tied with them were those who were married, divorced, and then did not remarry. Presumably, a large proportion of those had unhappy marriages, ended it, and then moved on with their lives and were happy with a new beginning without the stressors they had been dealing with back then," explained Dr. Norton.

She said that in contrast to these groups, where their status was a conscious decision on the part of the participants, it makes sense that the highest risk was found in the widowed and never remarried group where they had no choice in the matter.

"This left the remaining spouse to have to cope alone, which was usually not something they expected to have to deal with. There was also probably more chronic grieving going on, which explains why they never remarried."

Although it is too early to say that these specific marital patterns will definitely increase dementia risk or that there is a cause-effect association, "we did see a more rapid incidence in dementia among the widowed left alone," said Dr. Norton.

"So clinicians should be mindful that besides being at a higher risk for depression and other declines in health, it may be that the cognitive capacity of this group may also rapidly decline."

Assessing Lifelong Patterns

Psychosocial stress "has been linked with adverse health outcomes such as depression, anxiety, cardiovascular disease, and cognitive impairment," the researchers note.

Although a few past studies have looked at the relationship between marital changes and dementias, "only limited time points" in marital status were assessed.

Therefore, the current study "examines lifelong pattern of marital history and dementia-free survival … spanning 10 years of follow-up," write the investigators.

They evaluated data on 3971 initially nondemented older adults (56.7% female; mean age at baseline, 75 years) from the Cache County Memory Study linked with demographic information from the Utah Population Database. All participants were divided into the following subgroups:

  • Married once, divorced, never remarried;

  • Married once, widowed, never remarried;

  • Multiple marriages with divorce but not widowhood;

  • Multiple marriages with widowhood but never divorce;

  • Multiple marriages with both widowhood and divorce; and

  • Never married.

The reference group consisted of those who had married once and were never divorced or widowed.

"Our hypothesis was that some of these marital patterns would probably be correlated to higher stress levels — not just one-time stress but chronic stress," said Dr. Norton.

"That's where the biological mechanism comes in: that chronic exposure to these glucocorticoid stress hormones in the brain can cause increased neuronal cell death and higher risk for Alzheimer's."

Robust Risks for Widowhood

Results showed that the study participants who married once, were widowed, and then never remarried were at a significantly higher risk of developing dementia compared to the reference group (hazard ratio [HR], 1.83; P < .001), as well as a higher risk for AD (HR, 2.17; P < .001).

There was also a significantly higher risk for dementia development in those who had married multiple times and were widowed at least once — without ever having undergone a divorce — compared to the reference group (HR, 1.44; P = .03).

All of these findings "were robust to adjustment for gender, education level, and presence of any apolipoprotein e4 allele (all P < .005), but not age," write the investigators.

Dr. Norton reported that the never-married and multiple marriages ending in divorce groups were in "the middle of the pack" for dementia risk.

"Overall, I'd say these are really preliminary findings for the association with dementia risk and there is much more work to be done. For example, we would like to look at whether the stage within the life course makes a difference, such as being widowed at age 30 versus at age 80," she said.

"We'd also like to see if individuals who have a history of depression may be a subgroup that is more vulnerable for these risks. So we're going to continue to investigate so that we can better understand some of the contextual factors."

Dr. Norton also pointed out that in Utah, the number of offspring "ranges from 0 to 15 members." So the investigators would like to assess whether large families vs smaller ones contribute to higher or lower stress in terms of a social support network, "that would presumably be there to buffer" these marital transitions.

In a study reported on last year by Medscape Medical News , the investigative team found a 6-fold higher risk for dementia in people who have a spouse with dementia.

"This current study fits into a larger body of research that has looked at other types of psychosocial stressors and their association with this higher risk. Again, more work is needed, but it seems that those who are coping with stress in a much more positive, problem-focused way are the ones who have negligible dementia," said Dr. Norton.

More Evidence Stress Plays a Role

Meryl Butters, PhD, agreed, telling Medscape Medical News, "this is another illustration of the way stressors can contribute to people being at risk for developing AD."

Dr. Butters, who was not involved with this study, is an associate professor of psychiatry at the University of Pittsburgh School of Medicine in Pennsylvania and has conducted research on the ways depression might increase AD risk.

"This study is saying that people who have an abrupt change in marital status experience more stress. There's a whole hypothesis that says stress dysregulates the HPA [hypothalamic-pituitary-adrenal] axis and leads to increased levels of cortisol/glucocorticoids, which damages the hippocampus and makes people more vulnerable to Alzheimer's disease."

She said that although this mechanism wasn't specifically examined in this study, the findings were interesting.

"Widowhood is very stressful, and there is probably some overlap with depression and even anxiety, which is also associated with an increase in glucocorticoids. It's the same mechanism at work and might bring Alzheimer's on faster."

Dr. Butters noted that there also may be elements of complicated grief, "which is not the same as depression" in some of these participants — diagnoses that are currently being debated for the upcoming fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

"The bottom line is although we have ideas about what might cause AD, right now we really don't know what they are. I am happy to hear that the investigators are next going to look at the age when widowhood happened to see if that can help shed some light on this topic," she concluded.

The study was funded by the National Institute on Aging. Dr. Norton and Dr. Butters disclosed no relevant financial relationships.

American Association for Geriatric Psychiatry (AAGP) 2011 Annual Meeting. Abstract EI-4. Presented March 19, 2011.

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