Cortisol, Stress, and Distress: Why We Must Stay Within What We Actually Study

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In July 2026, Ng and colleagues published a JAMA Network Open article titled “Salivary Cortisol and Cognitive Decline and Alzheimer Disease in Older Adults.” Their cohort study of nearly 4,000 Black and White older adults reported that diurnal salivary cortisol indices—especially higher cumulative exposure (mean cortisol, AUCg) and altered variability—are associated with cognitive performance and longitudinal cognitive decline. They conclude that salivary cortisol “may capture early, modifiable stress physiology associated with cognitive aging” and describe it as “an early, physiologically relevant, and modifiable biomarker associated with stress-related neurocognitive aging.” 

The data on cortisol and cognition are valuable. The way the authors speak about “stress-related” aging, however, raises a critical question: what did the study actually measure, and what did it not?

What the JAMA Study Did Measure

The paper did several important things well. 

  • It collected salivary cortisol at waking, afternoon, and bedtime, and derived multiple indices:

    • Coefficient of variation (intraday variability),

    • Mean cortisol,

    • AUCg (total daily output),

    • Diurnal slope,

    • AUCi (change relative to baseline).

  • It linked these indices to:

    • Baseline global cognition,

    • Cognitive decline over approximately 11 years,

    • Incident Alzheimer disease in a clinically adjudicated subsample.

  • It showed that:

    • Medium–high intraday variability was associated with better cognition and slower decline.

    • The highest quintile of mean cortisol and AUCg was associated with faster cognitive decline.

    • Black participants had lower cumulative cortisol but blunted diurnal rhythms and faster cognitive decline. 

In short, the study robustly associates cortisol patterning with cognitive outcomes in a large, racially diverse community cohort.

What the Study Did Not Measure

Equally important is what the study did not measure. 

  • It did not assess perceived stress, psychological distress, anxiety, or depressive symptoms.

  • It did not directly quantify stress exposures in daily life, such as trauma history, chronic work strain, family-level stress systems, or institutional unpredictability.

  • It did not distinguish between:

    • normal physiological stress (adaptive regulation), and

    • distress (a deviation from healthy stress regulation, with sustained overactivation, sleep disruption, and rigid defensive coping).

The authors themselves note that “perceived stress was not assessed alongside cortisol” and that this joint evaluation is an important direction for future research. That acknowledgment is crucial, because it means that stress and distress are not empirical variables in this study—only cortisol is. 

Stress, Distress, and the Role of Habitats

In physiology, stress is a normal, essential adaptive process. It is the coordinated reaction that allows an organism to respond to change, mobilize energy, learn, and survive. Without physiological stress responses, human life would not be viable; we could not respond to danger, effort, or novelty.

Distress, by contrast, is a deviation from healthy stress regulation. It arises when stress systems are chronically driven into rigid, high-cost configurations—overactivation, exhaustion, or loss of flexible recovery. In our work on Stress Systems Across Time, we argue that stress and distress are shaped by habits and habitats: families, organizations, communities, and political ecologies that continuously educate nervous systems through routines, predictability, feedback, and background load. Stress is normal; distress is what happens when environments become “anti-ecological” and force the organism into permanent defensive mode.[ 

From this perspective, cortisol is one component of humoral regulation and HPA-axis activity. Altered cortisol can reflect distress, but it can also reflect adaptive responses to ecological demands. Without measuring stress or distress directly, we cannot know which is which.

Why Language Must Stay Within What Was Studied

This brings us to the central point of this blog article:

If a study does not measure stress or distress, it should not claim to be studying “stress-related” anything.

Ng et al. present strong evidence that diurnal cortisol patterns are associated with cognitive decline. That is fully supported by their data. But when they describe cortisol as a biomarker of “stress-related neurocognitive aging,” they step beyond what was measured. Stress—and especially distress—remains an inferred construct, not a studied variable. A more precise framing would be:

  • “Diurnal salivary cortisol patterns, reflecting HPA-axis regulation, are associated with cognitive decline in older adults.”

  • “Cortisol is an early biomarker of HPA-axis dysregulation associated with cognitive aging.”

These statements stay strictly within the frame of what was actually studied: cortisol, its diurnal patterning, and cognition. They do not assume that cortisol patterns automatically equal “stress” or “distress” without evidence.

Why Over-Claiming Matters

Some might see this as a small semantic issue, but it has practical consequences.

When cortisol is described as a biomarker of “stress-related neurocognitive aging” without stress being measured, readers may:

  • Pathologize normal stress physiology, which is necessary for healthy life.

  • Assume that any altered cortisol is evidence of “stress-related harm,” rather than one piece of a complex regulatory system.

  • Direct interventions toward “reducing stress” in general, instead of restoring healthy stress regulation and addressing true distress in specific habitats.

In clinical and public discourse, “stress” often carries a negative, purely harmful connotation. If we do not distinguish physiological stress (essential) from distress (harmful), we risk confusing adaptation with pathology. In research, the remedy is simple: only call “stress-related” those findings that measure stress or distress directly.

Conclusion

Ng et al. have contributed important data on salivary cortisol and cognitive decline in older adults and shown racial differences in diurnal cortisol patterning. Their results support the view that HPA-axis regulation, as reflected in diurnal cortisol, is linked to neurocognitive aging. 

My critique is modest but fundamental: claims must stay within what has been studied. When stress or distress is not measured, it is more accurate to speak of cortisol as a biomarker of HPA-axis activity and humoral regulation associated with cognition, rather than as a biomarker of “stress-related” aging.

Physiological stress is a key factor of healthy human life. Without it, regulation would not be physiological at all. Distress is the deviation we must document, not assume. 

Mykola Iabluchanskyi 

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