Is Midlife Stress the Cause of Dementia in Aging Women?

A study points to midlife stress as a cause of dementia in older women.

Posted Aug 23, 2019

Alzheimer’s disease (AD) is an irreversible and progressive neurological disease that eventually makes sufferers unable to live independently. One of the cardinal symptoms of AD is memory loss and eventually complete cognitive decline. It is unfortunately not an uncommon disease, half of adults aged 85 and over have AD. It is ranked as the sixth leading cause of death in the United States, and others have ranked it even higher (1). AD is the most common cause of dementia in older people.

Causes of dementia are numerous, some are known and many are unknown. Stress has been shown to increase the likelihood of dementia. Early traumatic events are associated with higher risk of dementia (2). In a retrospective study, patients encountered a greater number of stressful events prior to the onset of dementia compared to those who did not develop dementia (3). It is not necessarily trauma that is related to the increased risk! Individuals who suffer from PTSD are at a higher risk of dementia than those who experienced trauma but did not develop PTSD (4).

Why stress? A part of the stress response is the release of hormones such as cortisol. Prolonged and/or excessive amounts of cortisol damage the hippocampus. This area is heavily involved in long term memory and its damage is related to Alzheimer's Disease. Thus, it is not surprising that stress increases the risk of dementia as we age.

Interestingly, women are at an increased risk for dementia. One explanation has to do with sex differences in the stress response. I.e. women physiologically react differently to stress than men. And these differences place stressed women at a higher risk for dementia as they age (5).

Aging and cortisol’s deleterious effects on the brain are much more intimately related in women than in men. In other words, aging women are more vulnerable to the adverse cognitive effects of stress than aging men. In one study investigating the effects of acute stress on memory in older adults (aged 54-72 years), researchers reported memory decline after stressors only in women and not in men (6).

A recent study based on the Baltimore Epidemiologic Catchment Area study shed some light on the relationship between stress, sex, aging and risk for dementia. Wave 1 of the study was in 1981, wave 2 in 1982, wave 3 between 1993 and 1996, and wave 4 between 2003-2004. At wave 3, participants were questioned to reveal specific traumatic and stressful life events within the last year (recent events) or earlier than that dating back to 1981 (remote events) (7). Examples of specific traumatic events were combat, rape, accident, combat, or natural disaster. Examples of stressful life events were divorce, separation, death of a spouse, retirement or loss of a job.

At waves 3 and 4, researchers collected cognitive assessments and memory tests. These assessments included measures of memory, attention, and visuospatial ability. Researchers were interested in the relationships between interview responses from wave 3 and performance in wave 4 for elderly men and women.

The findings were somewhat surprising. They found an association between recently occurring stressful life events collected at wave 3 and greater memory decline 11 years later only in women and not in men. Earlier (remote) stressors were not related to cognitive decline in men or women. Strangely, traumatic events reported at wave 3 were not associated with later cognitive decline in men or women. It seems like chronic stress may have a greater impact on cognitive functions than a short term traumatic incident.

A closer examination points to the importance of the timing of stressor. It seems like life stressors encountered in midlife are more harmful to women and selectively increase their risk for dementia. The study showed that recent stressors when women were aged 47 to 48 years on average and not earlier (remote) stressors were associated with cognitive decline. In other words, it may be that midlife stress is most lethal to women.

Why are women more vulnerable to stress’s effects on cognition as they age? There are no definite answers. It may be that men and women perceive similar stressors differently. Sex hormones interact with stress hormones. These complex interactions may predispose women under stress particularly in midlife to cognitive decline. Regardless of what the answer is, one thing is clear from these findings: middle-aged women should take stress seriously. Stress prevention and management during midlife may significantly reduce the risk of dementia in women.

References

1.  https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet

2. Whalley, L. J., Staff, R. T., Murray, A. D., Deary, I. J. & Starr, J. M. (2013). Genetic and environmental factors in late onset dementia: possible role for early parental death. Int J Geriatr Psychiatry, 28(1), 75‐81.

3. Charles E., Bouby‐Serieys, V., Thomas, P. & Clement, J. P. (2006). Links between life events, trauma and dementia; an open study including 565 patients with dementia. Encéphale, 32(5 Pt 1), 746‐752.

4. Qureshi, S. U., Kimbrell, T., Pyne, J. M., et al. Greater prevalence and incidence of dementia in older veterans with posttraumatic stress disorder. (2010). J Am Geriatr Soc., 58(9 ), 1627‐163.

5. Zandi, P. P., Carlson, M. C., Plassman, B. L., et al. (2002). Hormone replacement therapy and incidence of Alzheimer disease in older women: The Cache County study. JAMA, 288(17), 2123‐2129.

6. Almela, M., Hidalgo, V., Villada, C., Espín, L., Gómez‐Amor, J. & Salvador, A. (2011). The impact of cortisol reactivity to acute stress on memory: sex differences in middle‐aged people. Stress, 14(2), 117‐127.

7. Munro, C. A., Wennber, A. M., Bienko, N., Eaton, W. W., Lyketsos, C. G. & Spira, A. (2018). International Journal of Geriatric Psychiatry, 34, 1008-1017.

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