By Urja Vohra, Fall 2024.

Imagine the human brain as a bustling metropolis, where neurons communicate like citizens in constant interaction. But what happens when this city is besieged by an unrelenting storm—chronic stress—that gradually erodes its infrastructure? It sounds like the setup for a sci-fi dystopia, but it’s the reality faced by millions diagnosed with Alzheimer’s Disease. The twist? Emerging research now suggests a striking new perspective: what if Alzheimer’s isn’t merely a “disease,” but a consequence of prolonged stress—an overload that slowly wears down the brain’s ability to function, leaving behind a tangled mess of memory loss and cognitive decline?

FIGURE I: Contrast between the brains of a healthy individual and an Alzheimer’s patient. [1]

This idea could change everything. Alzheimer’s affects more than 55 million people worldwide, yet traditional treatments barely slow its devastating effects. [2] But what if chronic stress—a force that shapes our daily lives—plays a far greater role in cognitive decline than we ever realized? Mounting evidence suggests that prolonged stress may accelerate brain aging, weaken neural resilience, and even trigger the very processes that lead to Alzheimer’s. We may be closer than ever to uncovering a crucial link, with cortisol and the brain’s stress response at the core of the mystery. Could rethinking Alzheimer’s through the lens of stress lead to a breakthrough in prevention and treatment? Let’s dive into what we know, what remains unanswered, and the mounting clues that could reshape our understanding of this complex disease.

 

FIGURE II: Results from the voxel-wise multiple regression analysis between stress coping ability and tau-PET adjusted by sex, age, and education. [3]

In the provided figure, the toll of chronic stress on the brain is undeniable. The scans glow with reds and yellows, marking areas where toxic tau proteins have accumulated. Normally, tau helps keep brain cells stable, but under prolonged stress, it twists into tangled clumps, choking off communication between neurons. The damage is most severe in the temporal and prefrontal cortices—the very regions that control memory, decision-making, and emotions. [4]

The scatter plot  in Figure II tells an even darker story. It charts stress resilience (BRS scores) -where resilience is defined as the ability to adapt and recover from stressful or challenging life experiences-against tau buildup (SUVR values), and the trend is clear: the less resilient a person is to stress, the more damage their brain endures. Those who struggle with stress show higher tau accumulation, a sign that their brains may be breaking down faster, inching closer to Alzheimer’s.

This image tells a chilling story: stress isn’t just exhausting—it may be actively rewiring the brain for neurodegeneration. And if stress is fueling the same biological changes that lead to Alzheimer’s, what does that mean for the millions of young people experiencing chronic stress every day?

At the center of this slow destruction is cortisol, the body’s primary stress hormone. Meant to help us survive immediate threats, cortisol floods the brain during stressful moments, sharpening focus and increasing alertness. But when the stress never stops, neither does the cortisol. The research reveals a disturbing reality: prolonged exposure to cortisol actively shrinks the hippocampus, the brain’s memory and learning center. The very regions—the prefrontal cortex and hippocampus— shown in the PET scans in Figure IIare the first to suffer under relentless stress. [5]

Who is the most stressed to digress? Students. Studies show that over 60% of young people experience chronic stress daily. [6] The pressure to excel academically, build careers, and meet impossible expectations keeps their cortisol levels perpetually elevated as seen in FIGURE III with teens depicting the highest percentage. If stress-induced cortisol is actively dismantling the brain’s ability to form and retain memories, how much are we really learning? If a person in their twenties is already experiencing heightened cortisol levels, what will their brain look like at forty? 

FIGURE III: Percentage of individuals worldwide reporting moderate to severe symptoms of stress, depression, and anxiety in 2022, by age group. [7]

Cortisol isn’t the only culprit. Chronic stress also ignites inflammation, an immune response that, when left unchecked, becomes a slow, silent killer. According to research, stress triggers the release of pro-inflammatory cytokines, molecules that break down the blood-brain barrier, which is the selective protective layer which separates blood in the circulatory system from the brain tissues. [8] This leaves neurons vulnerable to toxins and harmful proteins like amyloid-beta and tau, which leads to an inflamed brain that struggles to repair itself, accelerating the onset of cognitive decline. [9]

FIGURE IV: A PET scan of an inflamed brain. [10]

At the same time, emotional and mental distress  fuels oxidative stress, the brain’s version of rusting from the inside out. Findings from several studies reveal that prolonged stress weakens the brain’s natural defense mechanisms, making neurons more susceptible to free radicals, which are unstable molecules that have unpaired valence electrons. These molecules damage cell structure and function. [11] When combined with inflammation and cortisol overload, the brain is caught in a relentless cycle of destruction.

If chronic stress can butcher brain health this significantly, what does that mean for a generation raised under constant pressure? The same stress that drives students to overwork and overachieve may also be the force that erodes their cognitive future. We are setting young minds up for burnout, or something far worse. The research suggests that this isn’t just about mental exhaustion—it’s a biological risk factor for neurodegeneration.

But the scatter plot also offers a glimmer of hope. Individuals with higher resilience scores had lower tau accumulation, meaning resilience could be a shield against neurodegeneration (Figure II). According to a study done by Cherie Strikwerda-Brown et al, it has been shown that Mindfulness is associated with less amyloid, tau, and cognitive decline in individuals at risk for Alzheimer’s disease. [12] If we start prioritizing stress management, mindfulness, and mental well-being as essential parts of education and work culture, we could change the trajectory of brain health for future generations.

The evidence is clear: chronic stress is not just a short-term burden—it is a long-term threat to cognitive health. If we continue to glorify constant productivity, competition, and perfection, we are not just creating a stressed generation—we are also creating a generation predestined for cognitive decline. The question now is: will we recognize the danger before it’s too late?

 

 

[1] Mullin, Melissa. “Diabetes of the Brain: Are You at Risk?” Mind Body Harmony Medicine, October 18, 2023. https://thehealthymelissa.com/diabetes-of-the-brain-are-you-at-risk/?v=34f435c6b599.

[2] Alzheimer’s Disease International. Dementia Statistics. Alzheimer’s Disease International. https://www.alzint.org/about/dementia-facts-figures/dementia-statistics/.

[3] Urquijo, E.M.A., Przybelski, S.A. and Machulda, M.M. (no date) Better stress coping associated with lower tau in amyloid …, Better stress coping associated with lower tau in amyloid-positive cognitively unimpaired older adults. Available at: https://www.neurology.org/doi/10.1212/WNL.0000000000008979 (Accessed: 03 February 2025).

[4] Professional, C.C. medical (2024) Cerebral cortex: What it is, Function & Location, Cleveland Clinic. Available at: https://my.clevelandclinic.org/health/articles/23073-cerebral-cortex (Accessed: 02 February 2025).

[5] Ávila-Villanueva M, Gómez-Ramírez J, Maestú F, Venero C, Ávila J, Fernández-Blázquez MA. The Role of Chronic Stress as a Trigger for the Alzheimer Disease Continuum. Front Aging Neurosci. 2020 Oct 22;12:561504. doi: 10.3389/fnagi.2020.561504. PMID: 33192456; PMCID: PMC7642953.

[6] Transformingeducation.org (2025) Student stress statistics [2024 update], Transforming Education for People. Available at: https://transformingeducation.org/student-stress-statistics/ (Accessed: 02 February 2025).

[7] AXA. (2023). Percentage of individuals worldwide reporting moderate to severe symptoms of stress, depression, and anxiety in 2022, by age group. Statista. Statista Inc.. Accessed: February 03, 2025. https://www.statista.com/statistics/1400861/percentage-of-individuals-reporting-symptoms-of-stress-depression-anxiety-by-age-group-worldwide/

[8] Cleveland Clinic. The blood-brain barrier: Out with the bad, in with the good. Cleveland Clinic. https://my.clevelandclinic.org/health/body/24931-blood-brain-barrier-bbb.

[9] Wallensten, J., Ljunggren, G., Nager, A. et al. Stress, depression, and risk of dementia – a cohort study in the total population between 18 and 65 years old in Region Stockholm. Alz Res Therapy 15, 161 (2023). https://doi.org/10.1186/s13195-023-01308-4

[10] Pet reveals inflammatory cycle in the brain (2021a) Imaging Technology News. Available at: https://www.itnonline.com/content/pet-reveals-inflammatory-cycle-brain (Accessed: 02 February 2025).

[11] Justice, Nicholas J. “The relationship between stress and Alzheimer’s disease.” Neurobiology of stress vol. 8 127-133. 21 Apr. 2018, doi:10.1016/j.ynstr.2018.04.002

[12] Strikwerda-Brown, Cherie et al. “Trait Mindfulness Is Associated With Less Amyloid, Tau, and Cognitive Decline in Individuals at Risk for Alzheimer’s Disease.” Biological psychiatry global open science vol. 3,1 130-138. 17 Jan. 2022, doi:10.1016/j.bpsgos.2022.01.001