Published on: December 10, 2020
by Women’s Brain Health Initiative:
Women are affected by Alzheimer’s disease and other forms of dementia in much larger numbers than men. Approximately two-thirds of Canadians and Americans living with dementia are women.
Why are women disproportionately affected? Partly, it is because women tend to live longer than men, and age is the strongest-known risk factor for developing dementia. However, age alone does not account for the sex differences in dementia. One of the potential contributing factors that may help explain the disparity is sex differences in stress response.
Numerous animal and human studies have shown that both females and males are adversely affected by prolonged stress-induced release of hormones such as cortisol. When cortisol levels remain high for long periods of time (i.e. from “chronic” stress), parts of the brain shrink, overall brain weight decreases, and learning and memory are negatively impacted. Short-term or “acute” stress has also been shown to impair brain function.
Age plays a role in physiological stress response for both sexes, but more so for women.
A meta-analysis conducted by Dr. Christian Otte and colleagues compiled data from 45 studies and found that older participants (mean age 69 years) showed a larger cortisol response to challenge (i.e. a type of stressor) compared with younger participants (mean age 28 years). However, the effect of age on cortisol response was found to be significantly stronger in women – three times higher than in men. These findings were published in 2005 in Psychoneuroendocrinology.
Stress also appears to affect memory performance of women and men differently as they age.
One study – conducted by Dr. Mercedes Almela and colleagues, published in 2010 in Stress – examined the short-term effects of acute stress on memory in an experimental situation. Sixteen women and 16 men between the ages of 54 and 72 years were exposed to a social stress test and a control condition, followed by memory testing. The researchers found that only the female participants experienced an acute negative impact on memory performance in response to stress.
Research conducted by Dr. Cynthia Munro and colleagues – published in 2019 in International Journal of Geriatric Psychiatry – suggests that there are also differences between the sexes when it comes to the impact of stressful life experiences and the long-term impact on memory. The researchers analyzed data from over 900 Baltimore adults who were participating in the U.S. National Institute of Mental Health’s Epidemiologic Catchment Area Study. The participants met with the researchers four times: once when enrolling in the study in 1981, and then at follow-up assessments in 1982, between 1993 and 1996, and between 2003 and 2004.
During the third visit, the participants were asked if they had experienced a traumatic or stressful event recently (namely, in the past year) or in the more distant past (namely, between 1981 and one year ago, which the researchers referred to as “remote” stress/trauma). Participants also completed the Mini-Mental State Examination (MMSE) and a word-list memory test. At the fourth visit, they were tested again and the results from the third and fourth visits were compared.
The MMSE is a standardized questionnaire used widely to assess overall cognitive impairment. The word-list memory test involved having participants recall 20 words that had been spoken aloud, immediately after hearing them and then again 20 minutes later. Then, the participants were asked to identify those same 20 words from among 40 words on a written list.
There was no association found between changes in MMSE score and stressful or traumatic events occurring at any time in either sex. However, some interesting findings emerged from the word-list memory testing. A greater number of recent stressful life experiences reported at the third visit was linked with greater verbal memory decline by the fourth visit in women only. Earlier (remote) stressors were not linked to memory decline in women or men.
These findings suggest that women are more cognitively vulnerable to stressful life events than men as they age, and that the timing of stressors may be important, explained Dr. Munro, lead researcher on the study and Associate Professor of Psychiatry and Behavioral Sciences at Johns Hopkins University School of Medicine. “It looks like stressors that happen in midlife may be taking a bigger toll on women’s cognition in later life than earlier stressors.”
Interestingly, traumatic experiences were not associated with cognitive decline in either women or men, suggesting that ongoing stress may have more of a negative effect on brain functioning than the occurrence of a traumatic event. This finding is perhaps not as surprising as it might at first seem. A healthy response to stress causes a brief increase in stress hormones, but then the levels return to normal quickly. Sometimes, though, a person’s body gets stuck in “stress mode,” and there is a sustained hormone response.
Not everyone who experiences a traumatic event gets stuck in stress mode. Other studies have found that individuals who develop post-traumatic stress disorder (PTSD) have a higher risk of developing dementia than those who experience trauma but do not develop PTSD, suggesting that it is one’s response to stressful events that matters more than the occurrence of such events.
Another study – conducted by Dr. Lena Johansson and colleagues – also found that midlife stressors are linked with long-term negative cognitive impact on women. This research involved 800 women in Sweden who were studied over a 38-year period, from midlife to late life. This study revealed that the presence of common psychosocial stressors (such as divorce, widowhood, or work problems) at baseline was linked with higher incidence of dementia later in life. These findings, published in 2013 in BMJ Open, suggest that common stressors experienced in midlife may have severe and long-lasting physiological and psychological consequences for women.
The good news is that the negative cognitive consequences of stressful experiences may not be inevitable. Yes, women appear to be more vulnerable than men to the effects of midlife stress on their brain function, but how they handle stressors may help to decrease the effects, said Dr. Munro. “Of course, decreasing the amount of stress would be ideal, but is not always possible. However, everyone can practice stress-management techniques such as exercise, yoga, and meditation to help their bodies respond in a healthy way to unavoidable stressors, possibly decreasing their risk of cognitive decline with age.”
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