An analysis of data from the Chicago Health and Aging Project suggests that daily fluctuations in salivary cortisol may help predict cognitive decline in older adults. The study found that those with medium to high intraday cortisol variability started with higher cognitive functioning and experienced slower decline, while the highest average cortisol levels were linked to faster cognitive deterioration. The research was published in JAMA Network Open.
As people age, cognitive function can deteriorate, with memory, processing speed, attention and executive function common areas of decline. Chronic stress is thought to contribute to this process by repeatedly activating the body’s stress regulation system, the hypothalamic-pituitary-adrenal axis, and by altering cortisol regulation itself.
Cortisol can influence brain regions central to memory and higher-order thinking, notably the hippocampus and prefrontal cortex. Persistently elevated or dysregulated cortisol has therefore attracted attention as a potential contributor to poorer cognitive performance and an increased risk of neurodegenerative disease.
Beyond cortisol, other bodily processes such as inflammation, metabolic health and vascular function may shape cognitive aging. Because many of these factors are potentially modifiable, researchers increasingly view age-related cognitive decline within the broader scope of dementia prevention.
Study author Ted K. S. Ng and colleagues tested daily variations in salivary cortisol in a large, ethnically diverse group of older adults over an 11-year follow-up. Saliva was chosen because it measures physiologically active “free” cortisol and avoids the acute stress of blood draws. The researchers examined links between these cortisol patterns and cognition, Alzheimer’s disease incidence and cognitive decline over time.
The analysis used data from CHAP, a population-based longitudinal study of aging and Alzheimer’s disease among community-dwelling older adults on Chicago’s South Side. CHAP data were collected in three-year cycles starting in 1993, with later waves through 2012.
From 3,895 participants who provided saliva samples suitable for cortisol assessment, the researchers constructed multiple indices of daily HPA axis activity. The hypothalamic-pituitary-adrenal axis governs the body’s stress response and cortisol secretion, and its daily patterning can reveal nuanced information about stress regulation.
The participants also underwent in-home cognitive assessments at three-year intervals, with clinical evaluations for a subset of participants to determine Alzheimer’s disease status. These evaluations were conducted by a neurologist who did not know participants’ cognitive scores.
In the results, middle to high intraday cortisol variability was associated with higher cognitive functioning at baseline and slower cognitive decline. Those with the highest intraday variability began with strong cognitive performance but did not exhibit a slower trajectory over time. Participants with the highest average cortisol levels tended to show faster cognitive decline and started with the lowest cognitive scores.
Additionally, individuals whose cortisol remained relatively high across the day, or who showed large overall changes in cortisol across the day, tended to have lower cognitive scores at baseline than those with the lowest values on these measures.
The associations did not depend on race. Nevertheless, Black participants tended to have lower cortisol levels, smaller daily changes and lower intraday variability in cortisol levels.
“In this cohort study of Black and White older adults, altered diurnal [daily] cortisol patterning was associated with faster cognitive decline but not short-term AD risk. These findings support salivary cortisol as a potential early biomarker of neurocognitive aging,” the study authors concluded.
The study highlights cortisol’s potential as a biomarker of cognitive health in later life. It did not assess participants’ perceived stress, so it remains unclear whether the observed cortisol variations primarily reflect environmental stressors, intrinsic physiological differences, or other bodily changes.
The paper, “Salivary Cortisol and Cognitive Decline and Alzheimer Disease in Older Adults,” was authored by Ted K. S. Ng, Todd Beck, Yashwanth Sudhini, Robert S. Wilson, Denis A. Evans and Kumar B. Rajan.
