Stressful life events, such as the death of a loved one or divorce, put a person at greater risk of developing dementia in later life, a recent study has found. But only if the stressful event happened in childhood or midlife.
The study, published in Annals of Neurology, included 1,290 people at increased risk of developing Alzheimer’s disease. The researchers looked at 18 stressful life events and when in people’s lives they happened.
They took spinal fluid samples of a subset of the group (393) to look for abnormal proteins – called amyloid and tau – that are associated with Alzheimer’s. They also looked for signs of brain inflammation, which is thought to contribute to the disease, and examined grey matter volume. Grey matter is crucial for thinking and processing information and tends to reduce in people with Alzheimer’s.
Although the researchers found that stressful life events in childhood and midlife were associated with “biological markers” of Alzheimer’s (abnormal amyloid and tau), they found no association between stressful life events and reductions in grey matter.
The presence of markers of Alzheimer’s disease could indicate that childhood and midlife are periods where the effects of stress in terms of chemicals and responses in the brain are particularly strong. Childhood is a time of significant brain development, and researchers think that stress at this time can have long-lasting effects including increasing the risk of Alzheimer’s.
Midlife is the time when Alzheimer’s biomarkers start to accrue in the brain, so this could be why this is a vulnerable time, too.
Total stressful life events were also associated with amyloid biomarkers, brain inflammation and decreased grey matter, but only in those with a history of psychiatric disorders.
This could be because those with psychiatric disorders are more susceptible to negative effects of stress. Or it could be that those who experience certain stressful life events are more likely to have had a psychiatric disorder. Either way, there is potentially increased risk for those who experience both. Total stressful life events were not linked to markers of Alzheimer’s for everyone.
The researchers also looked at the differences between men and women in the relationships between stressful life events and biomarkers of Alzheimer’s. Total stressful life events were associated with reduced grey matter in women, but not men. In contrast, total stressful life events were associated with tau biomarkers in men but not women.
These differences could be related to differences in how men and women respond to stress. Men and women respond differently both psychologically and biologically. For example, while men are likely to engage in a fight-or-flight response to stress, women have been shown to have a “tend and befriend response” – tending children and relying on social networks.
These results suggest there are certain periods or conditions that increase the effects of stressful life events on developing brain changes related to Alzheimer’s disease – at least in those at a greater risk of the disease.
The study provides a large enough sample to be able to consider stressful events at different times of life and also differences between groups, such as gender. Identifying those at greater risk early could make prevention a possibility through early interventions, such as lifestyle changes.
There are some limitations to the findings. The researchers relied on people to recall what and when stressful events happened – sometimes many years later. There is also no measure of how stressful people found these events. Some people might be affected differently by stressful events than others.
Also, we cannot be sure who developed Alzheimer’s symptoms. The study only reports early physical markers of the disease, not diagnosis.
Unfortunately, we cannot ensure that no one is exposed to stressful life events, but we can focus on how we can reduce the negative effects of these experiences. This could be done in a variety of ways.
One option is to help those who experience stressful life events develop coping strategies, such as exercise, meditation or seeking help from a therapist.
The other option is to consider how lifestyle factors that are related to a reduced risk of developing dementia can help to reduce the effect of unavoidable stressful events, perhaps even many years later.
Continuing to build profiles of the different experiences that are related to negative brain changes could help to identify who would benefit most from interventions or even early treatments. The new generation of amyloid-removing drugs – such as lecanemab and donanemab – are most effective early in the disease process.
Continuing this work to understand the associations between stressful life events and the development of dementia will help to find effective ways to intervene early, and possibly even reduce the number of people who develop dementia.
Carol Opdebeeck has previously received funding from the UK Research and Innovation (UKRI) Healthy Ageing Challenge.
