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An analysis of the Chicago Health and Aging Project data found that cortisol level variations may be used to predict cognitive decline in older adults. Longitudinally, individuals with medium to high cortisol intraday variability showed slower cognitive decline whereas individuals with the highest average cortisol levels tended to show faster cognitive decline. The paper was published in JAMA Network Open.
As people grow older, their mental functioning gradually worsens. This is called age-related cognitive decline. Changes are typically seen in memory, processing speed, attention, and executive functioning, although the extent of decline varies considerably between individuals. Chronic stress may contribute to this process by repeatedly activating the hypothalamic-pituitary-adrenal axis (the neural mechanism responsible for reactions to stress) and altering the regulation of the stress hormone cortisol.
Cortisol can influence brain regions that are especially important for memory and higher-order cognition, including the hippocampus and prefrontal cortex. Persistently elevated or dysregulated cortisol has therefore been investigated as a possible contributor to poorer cognitive functioning and greater risk of neurodegenerative disease.
Aside from cortisol, other systemic processes, such as inflammation, metabolic dysfunction, and vascular health, may also affect the course of cognitive aging. Because many of the factors shaping these processes are potentially modifiable, age-related cognitive decline is increasingly studied within the broader field of dementia prevention.
Study author Ted K. S. Ng and his colleagues explored daily variations in salivary cortisol in a large and racially diverse group of older adults over an 11-year follow-up period. They chose to test saliva because it specifically measures physiologically active “free” cortisol and avoids the acute stress response caused by needle pricks during blood draws. They examined the associations between these variations and participants’ cognition, Alzheimer’s disease occurrence, and cognitive decline over time.
The study used data from the Chicago Health and Aging Project (CHAP). CHAP is an established population-based longitudinal study of aging and Alzheimer’s disease among community-dwelling older adults on the South Side of Chicago in four Chicago neighborhoods with substantial proportions of Black and White older adults. CHAP data were collected in three-year cycles, starting in 1993, and with later data collection waves conducted up to 2012.
Data used in this analysis came from 3,895 participants who provided saliva samples for the study. To be included in the analysis, they needed to have provided saliva that allowed at least one valid cortisol level assessment. Participants’ average age was 77 years. Sixty-four percent of them were women, and 64 percent were Black. Eighty-three percent of these participants provided three valid saliva samples.
From the cortisol level data derived from saliva samples (cortisol levels from three collection time points), multiple indices of daily variations in hypothalamic-pituitary-adrenal axis (HPA axis) activity were created. The HPA axis is a hormone-regulating system linking the hypothalamus, pituitary gland, and adrenal glands that controls the body’s stress response, including cortisol secretion. Its activity level reflects how strongly the body’s stress-regulation system is operating. Daily variations in its activity can provide much more nuanced information.
The participants also completed in-home interviews at three-year intervals that assessed their cognitive functioning. Additionally, clinical evaluations of a smaller group of participants explored whether they were developing Alzheimer’s disease. This was done by a neurologist who was not informed about participants’ cognitive assessment scores.
The results showed that participants with middle to high intraday variability in cortisol levels—meaning how much their cortisol levels fluctuated over the course of a single day—had higher cognitive functioning at the start of the study and slower cognitive decline. Participants with the highest intraday variability in cortisol levels also tended to have better cognitive functioning at the start but did not show slower decline. Participants with the highest average cortisol levels tended to show faster cognitive decline compared to those with the lowest levels. Their cognitive function scores at the start of the study tended to be the lowest. People whose cortisol levels stayed relatively high across the day instead of dropping normally, and people who showed the largest overall change in cortisol across the day, had lower cognitive scores at the start of the study than those with the lowest values on these patterns.
These associations did not depend on the race of participants. However, Black participants tended to have lower cortisol levels, smaller daily change, 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 [Alzheimer’s disease] risk. These findings support salivary cortisol as a potential early biomarker of neurocognitive aging,” the study authors concluded.
The study sheds light on the utility of cortisol as a biomarker of cognitive health in older adults. However, the study did not assess the stress levels participants perceived, so it remains unknown how much the variations in cortisol levels reflect reactions to environmental stressors and how much they reflect intrinsic physiological differences or changes in the biochemistry of the body.
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.
