Chronic Stress & Alzheimer's Disease

Exposure to chronic stress creates a higher risk of developing Alzheimer’s disease (AD).  AD causes a progressive decline in cognition, language capacity, and physical ability, and eventually results in death.  A growing body of research indicates that chronic stress, which is long-term and involves long-lasting activation of the HPA axis, contributes to the cognitive decline and neurodegeneration seen in the brains of people with AD. 

The fight-or-flight stress response is activated via the hypothalamic-pituitary-adrenal (HPA) axis.  The HPA axis is the stress response pathway between the brain and the adrenal glands where stress hormones are released.  The HPA axis is designed to help the body focus resources to deal with short term challenges.  It is not designed to be chronically activated, routinely releasing stress hormones into the body and brain.

The amygdala in the emotional brain is the first to detect stressful stimuli.  The stress response signals travel in the brain from the amygdala to the hypothalamus to the pituitary glands, which then signal the adrenal glands above the kidneys to release adrenalin and glucocorticoids, which are stress hormones.  They main glucocorticoid is cortisol.  The HPA axis regulates the release of cortisol.

A recent literature review of research on the connection between chronic stress and AD demonstrates that dysregulation of the HPA axis and increased levels of cortisol are routinely found in the brains of AD patients.  The exact mechanics of how the HPA axis becomes impaired are unknown.  The article cites studies that demonstrate that impairment of the HPA axis is also associated with depression and PTSD. 

The HPA axis prepares the body to deal with physical or psychological threats.  Repeated activation of the stress response system during chronic stress causes it to become maladaptive and creates a higher risk of depression and AD.  This literature review makes a strong argument for controlling stress to reduce risk of depression and AD. 

Takeaway: Controlling stress is likely to lower the risk of developing Alzheimer’s disease.

Source

Ayeisha Milligan Armstrong, et al., Chronic Stress and Alzheimer's Disease: The Interplay between the Hypothalamic–Pituitary–Adrenal Axis, Genetics and Microglia, Biological Reviews, Cambridge Philosophical Society, May, 2021, https://onlinelibrary.wiley.com/doi/10.1111/brv.12750.