Alzheimer’s risk associated with stressful life events during childhood and midlife, study finds

Alzheimer’s disease, a leading cause of dementia, currently affects around 50 million people worldwide, a number expected to triple by 2050. A recent study published in the journal Annals of Neurology explores the relationship between stressful life events and the risk of developing Alzheimer’s disease, focusing on how the timing and nature of these stressors might influence the onset of the disease. The study reveals that not all stressful events have the same impact, with midlife or childhood stressors showing a stronger association with Alzheimer’s risk factors than accumulated stress during childhood. course of a life.

Previous research has identified various psychological factors such as depression, anxiety, and chronic stress as potential risk factors for Alzheimer’s disease. These factors can activate biological responses that may predispose individuals to disease.

The new study aimed to further this understanding by specifically focusing on the role of stressful life events and their impact on Alzheimer’s disease biomarkers, brain inflammation and brain structure. This was particularly relevant as previous studies focused primarily on neuropsychiatric symptoms rather than the broader category of life stressors.

Stressful life events are incidents that significantly disrupt an individual’s usual routine, requiring considerable psychological and emotional adjustment. These events can range from personal losses, such as the death of a loved one, to major life changes such as divorce, job loss, or serious health problems.

For their study, the researchers used a well-established cohort from the ALFA (ALzheimer’s and FAmilies) study. This longitudinal project involves a large group of 2,743 participants with cognitive impairment who are at increased risk of developing Alzheimer’s disease, primarily due to the diagnosis of at least one parent with the disease.

Participants underwent a series of assessments including clinical interviews to gather detailed health and lifestyle information, cognitive tests to assess mental function, blood tests for genetic analysis (genotyping) and punctures. lumbar muscles to collect cerebrospinal fluid (CSF). This fluid was analyzed for key Alzheimer’s disease biomarkers, such as phosphorylated-tau (p-tau) and amyloid-beta (Aβ) ratios, which are proteins associated with Alzheimer’s disease pathology. Alzheimer’s. Additionally, magnetic resonance imaging (MRI) scans were performed to assess brain structure, focusing on gray matter volume.

To specifically measure exposure to stressful life events, researchers conducted semi-structured interviews using a predefined list of 18 life events known to potentially require significant psychological adjustment. Participants were asked if they had experienced these events at any time in their lives, the number of occurrences, and their age at the time of these events. This method allowed the researchers to build a comprehensive profile of each participant’s stress exposure at different stages of life.

The total number of stressful events experienced over a person’s lifetime is not uniformly associated with increased risk for Alzheimer’s disease biomarkers, neuroinflammation, or changes in brain structure typically indicative of progression of Alzheimer’s disease.

However, the analysis revealed more nuanced associations when considering the timing of these stressors and certain demographic factors. Specifically, stressors occurring during childhood and midlife were more strongly correlated with indicators of Alzheimer’s disease risk.

For example, childhood stress was linked to increased levels of neuroinflammation, as measured by elevated levels of interleukin 6 (IL-6), a pro-inflammatory cytokine associated with various diseases, including Alzheimer’s disease. This suggests that early life stress may trigger long-term inflammatory responses that may contribute to the development of Alzheimer’s disease later in life.

On the other hand, stressful life events experienced during midlife have shown a link with changes in Alzheimer’s disease biomarkers, such as beta-amyloid (Aβ) ratios. Beta-amyloid plaques are one of the hallmark pathologies of Alzheimer’s disease and their accumulation can begin years before the appearance of clinical symptoms. The study results suggest that stressors during this critical period of life may influence early pathological processes associated with Alzheimer’s disease, particularly the accumulation of these damaging proteins.

“We know that midlife is a time when Alzheimer’s disease pathologies begin to accumulate. It is possible that these years represent a vulnerable period where psychological stress can have a lasting impact on brain health,” said Eleni Palpatzis, a researcher at the Barcelona Institute for Global Health and first author of the study.

Researchers also found that the effects of accumulated stressful events over the lifespan differ between men and women when it comes to Alzheimer’s risk factors. Specifically, in men, a higher number of stressful life events was linked to increased levels of amyloid beta (Aβ) protein. In contrast, in women, a greater number of stressful events correlated with reduced gray matter volumes in the brain, suggesting that the impact of stress may vary significantly by gender.

People with a history of psychiatric disorders appeared particularly vulnerable to the effects of stressful life events. In this group, increased stress was associated with higher levels of amyloid beta (Aβ) and tau proteins. Additionally, these individuals had lower gray matter volumes.

“Our study reinforces the idea that stress may play an important role in the development of Alzheimer’s disease and provides initial evidence regarding the mechanisms behind this effect, but additional research is needed to replicate and “validate our initial results,” said Eider Arenaza-Urquijo, the study’s lead author.

Although the study provides valuable information, it has limitations. Relying on participants’ recollection of stressful events can introduce bias, and measuring stress does not take into account the personal importance or severity of the events. Additionally, the study population was largely homogeneous (primarily Caucasian Whites), which may limit the generalizability of the results to other ethnic groups.

The research opens several avenues for future research, suggesting the need for more nuanced studies that take into account the type and perceived severity of stressors. It also highlights the potential for early interventions that could target specific periods of life to reduce the risk of Alzheimer’s disease.

“Our results demonstrate moderate support that, in certain contexts, (stressful life events) can have a lasting impact on brain health through (Alzheimer’s disease), neuroinflammation and of atrophy decades after exposure to (stressful life events)… Future research is needed to refine the identification of risk profiles that would benefit most from these types of interventions,” the researchers concluded.

The study titled “Lifetime Stressful Events Associated with Alzheimer’s Pathologies, Neuroinflammation, and Brain Structure in a Risk-Enriched Cohort” was authored by Eleni Palpatzis, Muge Akinci, Pablo Aguilar-Dominguez, Marina Garcia-Prat , Kaj Blennow, Henrik Zetterberg, Margherita Carboni. , Gwendlyn Kollmorgen, Norbert Wild, Karine Fauria, Carles Falcon, Juan Domingo Gispert, Marc Suárez-Calvet, Oriol Grau-Rivera, Gonzalo Sánchez-Benavides, Eider M. Arenaza-Urquijo and the ALFA study.