Stressful Life Events Linked to Increased Risk of Alzheimer’s Disease
Summary
Researchers have discovered a strong correlation between midlife stress and childhood trauma to an increased risk of Alzheimer’s disease and neuroinflammation. A study conducted with 1,290 volunteers found that stressful life events, particularly during midlife, were associated with higher levels of β-amyloid protein, a key factor in Alzheimer’s development. Furthermore, childhood stress was found to be linked to neuroinflammation in later life.
Notably, the study also revealed sex-specific effects, indicating that stress leads to amyloid protein accumulation in men while causing brain atrophy in women. These findings shed light on the profound and potentially diverse impact of stress on brain health, underscoring the need for further research into stress’s role in neurodegenerative diseases.
Key Facts
- Stressful life events during midlife and childhood are significantly linked to an increased risk of Alzheimer’s disease and neuroinflammation, respectively.
- The study highlights sex differences in stress’s impact, with men showing higher amyloid buildup and women experiencing greater brain atrophy as a result of stress.
- Individuals with a history of psychiatric disease may be more vulnerable to the adverse effects of stress on brain health, showing higher levels of Alzheimer’s-related proteins and neuroinflammation.
Stressful Life Events and Alzheimer’s Disease
A study published in the Annals of Neurology provides evidence connecting stressful life events in midlife and childhood to the risk of developing Alzheimer’s disease and neuroinflammation, respectively. The Barcelona Institute for Global Health (ISGlobal), in collaboration with the Barcelonaβeta Brain Research Center (BBRC), led the research.
Stressful life events refer to situations in which objective external threats activate behavioral and psychological responses, such as the death of a loved one, unemployment, or illness. Accumulating evidence suggests that stress could be associated with an increased risk of dementia and cognitive decline.
To evaluate the influence of accumulated stressful life events on the development of Alzheimer’s-related pathologies in older age, the research team enlisted the participation of 1,290 cognitively unimpaired volunteers from the ALFA cohort in Barcelona. All the individuals had a direct family history of Alzheimer’s disease and were supported by the “la Caixa” Foundation.
The volunteers underwent interviews to assess the number of stressful life events they had experienced. The researchers also performed lumbar punctures and magnetic resonance imaging (MRI) to analyze different biomarkers associated with Alzheimer’s disease.
Midlife: A Vulnerable Period
Statistical analyses of the data revealed that accumulating stressful events during midlife was associated with higher levels of β-amyloid (Aβ) protein, a key player in the development of Alzheimer’s disease. This suggests that midlife may be a vulnerable period wherein psychological stress could have long-lasting effects on brain health, according to Eleni Palpatzis, a researcher from ISGlobal and the study’s first author.
Childhood Stress and Neuroinflammation
The research team discovered that higher levels of stressful experiences in childhood were linked to an increased risk of developing neuroinflammation in later life. Inflammation is known to be a key molecular response in neurodegenerative diseases, and these findings align with emerging evidence suggesting that childhood trauma contributes to enhanced inflammation in adulthood.
Sex Differences in the Impact of Stressors
The accumulation of stressful life events throughout a person’s life was associated with increased levels of β-amyloid (Aβ) protein in men but with reduced volumes of gray matter in women. These observations indicate that stress may have sex-specific effects on the brain. Eider Arenaza-Urquijo, a researcher from ISGlobal and the study’s last author, states, “Our results suggest that the mechanisms through which life stressors affect brain health in men and women are different: amyloid protein accumulation in men and brain atrophy in women.”
Stronger Effects in People with a Psychiatric History
Additionally, the authors found that stressful life events in individuals with a history of psychiatric disease were associated with higher levels of Aβ and tau proteins, increased neuroinflammation, and lower volumes of gray matter. This suggests that this particular group may be more susceptible to the effects of stressful life events, potentially due to impaired stress-coping abilities and increased vulnerability.
While this study supports the idea that stress plays a significant role in the development of Alzheimer’s disease and offers initial insights into the mechanisms behind this effect, further research is required to validate these findings. Eider Arenaza-Urquijo emphasizes the need for replication and validation of the study’s initial findings.
About the Research
This research, conducted by the Barcelona Institute for Global Health (ISGlobal) in collaboration with the Barcelonaβeta Brain Research Center (BBRC), investigates the association between accumulated stressful life events and Alzheimer’s pathology, neuroinflammation, and brain structure in cognitively unimpaired individuals at increased risk of Alzheimer’s disease.
Original Research
For more information, please refer to the original research paper “Lifetime Stressful Events Associated with Alzheimer’s Pathologies, Neuroinflammation and Brain Structure in a Risk-Enriched Cohort” published in the Annals of Neurology.
Abstract
Objective
Alongside the recognized effects of stress on brain structure and inflammatory processes, mounting evidence suggests a role of chronic stress in the pathogenesis of Alzheimer’s disease (AD). This study investigates the association between accumulated stressful life events (SLEs) and AD pathologies, neuroinflammation, and gray matter (GM) volume among cognitively unimpaired (CU) individuals at heightened risk of AD.
Methods
This cross-sectional cohort study involved 1,290 CU participants (aged 48–77) from the ALFA cohort. SLEs were evaluated, and participants underwent lumbar puncture (n=393) and/or structural magnetic resonance imaging (n=1,234) assessments. Multiple regression analyses were employed to examine the associations of total SLEs with cerebrospinal fluid (1) phosphorylated (p)-tau181 and Aβ1–42/1–40 ratio; (2) interleukin 6 (IL-6); and (3) GM volumes voxel-wise. Additionally, stratified and interaction analyses were conducted to assess sex and history of psychiatric disease, and associations were explored with SLEs during specific life periods.
Results
Within the entire sample, childhood and midlife SLEs were associated with AD pathophysiology and neuroinflammation, while no association was found with total SLEs. Participants with a history of psychiatric disease and SLEs exhibited higher levels of p-tau181 and IL-6. Participants with a history of psychiatric disease and men showed lower Aβ1–42/1–40 with higher SLEs. Women with a history of psychiatric disease displayed reduced GM volumes in somatic regions, while men exhibited such a reduction in prefrontal and limbic regions.
Interpretation
No evidence was found to support the association between total SLEs and AD pathophysiology, neuroinflammation, or atrophy pathways. Instead, the associations appeared contingent on events occurring during early and midlife and were influenced by sex and history of psychiatric disease.
