Stressful life events can negatively impact brain health. Specifically, grief over the loss of a partner has been linked to alterations in biological processes associated with Alzheimer’s disease, while unemployment and financial loss have been associated with structural differences in the brain. These are the main conclusions of a study conducted by the Barcelona Institute for Global Health (ISGlobal), a centre promoted by ”la Caixa” Foundation, and the Barcelonaβeta Brain Research Centre (BBRC), a research centre of the Pasqual Maragall Foundation. The results, which highlight differences in the brain’s response to stressful events according to gender and educational level, have been published in the journal Neurology.
Led by Eider Arenaza-Urquijo, an ISGlobal researcher, the study involved 1,200 people from the ALFA (ALzheimer’s and FAmilies) cohort at the BBRC, which is promoted by ”la Caixa” Foundation. The participants were individuals without cognitive impairment, most of whom had a family history of Alzheimer’s disease. “Using magnetic resonance imaging, we studied the differences in grey matter volume in the brain and analysed Alzheimer’s disease biomarkers in the cerebrospinal fluid, such as beta-amyloid protein,” explains Eleni Palpatzis, a pre-doctoral researcher at ISGlobal and first author of the study.
The impact of grief and economics on the brain
In Alzheimer’s disease, changes in the brain—such as alterations in the levels of certain proteins—can occur years before the first symptoms appear. For example, a lower ratio of amyloid beta 42/40 is observed; this ratio compares the concentrations of two forms of the protein. Since amyloid beta 42 is more likely to aggregate in the brain, a decrease in this ratio in the cerebrospinal fluid usually reflects greater amyloid beta deposition in brain tissue, making it an important early indicator of Alzheimer’s disease. Higher levels of phosphorylated tau, which causes neuronal damage, and neurogranin, which increases when connections between neurons are lost, are also found.
The death of a partner was associated with changes in these biomarkers: a lower amyloid beta 42/40 ratio (an effect that was more pronounced in men), and higher levels of phosphorylated tau and neurogranin (effects that were more pronounced in women). All of these effects were more pronounced in people with lower levels of education.
Conversely, unemployment and economic losses were associated with a lower grey matter volume in key brain regions responsible for emotional and cognitive regulation. Gender differences were also evident in these effects; unemployment affected men’s brains more, while economic losses had a greater structural impact on women’s brains.
The role of inequality in Alzheimer’s
A previous study by the same group already showed that exposure to stressful life events in middle age can increase vulnerability to Alzheimer’s disease. However, the prevalence and impact of stressful life events varies according to certain social determinants, such as gender and education; women and people with lower levels of education experience more stressful life events, and it is also in these groups that the prevalence of Alzheimer’s is most prevalent. The research showed that different stressful situations affect men and women differently.
“Men seem to be more negatively affected by the loss of a partner (which affects amyloid-related proteins) and unemployment (which reduces grey matter). This may be because men tend to have fewer close relationships, making the loss of a partner more isolating, so the loss of a partner is more isolating for them, and because unemployment carries a greater social stigma for men,” explains Eider Arenaza-Urquijo, ISGlobal researcher and senior author of the study.
“On the other hand, women seem more vulnerable to financial difficulties, which affect grey matter volume. This could be related to the fact that women have historically had less financial security, and that they tend to report higher levels of economic concern, which negatively impacts their overall mental well-being,” adds the researcher.
Reference: Palpatzis E, Akinci M, Garcia-Prat M, et al. Grief and economic stressors by sex, gender, and education: associations with Alzheimer disease–related outcomes. Neurology. 2025;104(8). doi: 10.1212/wnl.0000000000213377
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