Hormone by the hour: what cortisol in saliva says about brain aging

Cortisol is often referred to as a stress hormone and is evaluated based on the result of a single analysis. However, not only the level of the brain can be important for brain function, but also how it changes throughout the day. Researchers from the United States studied saliva samples from almost 3.9 thousand elderly people and found a link between certain cortisol levels and a subsequent decrease in memory and thinking test results. At the same time, it was not possible to predict Alzheimer's disease from them. The article "Izvestia" describes exactly what changes scientists have noticed, whether such an analysis can be used for personal forecasting, and what the study says about stress.

Why measure cortisol several times a day

Cortisol is involved in regulating metabolism and helps the body respond to stress. Its release follows a circadian rhythm: the hormone level changes after waking up and throughout the day. Therefore, two samples with the same result may mean different things if one is taken in the morning and the other before bedtime.

The authors of the study, published in the JAMA Network Open, decided to evaluate not only the amount of hormone at a particular moment. They were interested in the total cortisol level for the day, the differences between measurements, and the direction of changes from morning to evening. This way you can get a better understanding of the system that regulates the release of this hormone.

The researchers used data from the Chicago Health and Aging Project, a multi—year health monitoring program for Chicago's elderly residents. The main analysis included 3,895 people with an average age of 76.7 years. Almost two thirds of the participants were women.

Participants were asked to collect saliva on their own three times: immediately after waking up, in the afternoon and in the evening, before going to bed. This made it possible to measure free, biologically active cortisol and compare its values during the day. Most people provided all three samples, some provided only one or two. For calculations requiring multiple measurements, the scientists used data from participants with a sufficient number of samples.

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What was tested besides saliva analysis

The participants repeatedly completed tasks on memory, information processing speed, and general cognitive abilities. For example, they were asked to memorize and retell a short story later. The results of several tests were combined by scientists to track how the abilities of the same person changed over time.

The calculations took into account age, education, body mass index, smoking, alcohol consumption, a number of diseases and medications, as well as the presence of the APOE gene variant associated with the risk of Alzheimer's disease. This helped to check whether the association with cortisol persisted after accounting for other known differences between the participants. This approach cannot completely exclude the influence of all possible factors.

What cortisol levels were associated with memory loss?

The first indicator concerns the cumulative effect of cortisol per day. Among the participants with the highest scores, the average cognitive test score was lower at the beginning of the follow-up, and the subsequent decline was faster than for people with the lowest scores. This result was obtained both when estimating the average hormone level and when calculating its total production per day.

The second part of the study concerns the difference between morning, afternoon and evening measurements. People with moderate fluctuations in cortisol levels had slower cognitive decline than those with the least fluctuations. However, the strongest fluctuations were not as consistently associated with a slower decline.

The researchers also assessed how quickly cortisol levels decreased in the evening. This indicator was related to the results of tests performed around the same period, but did not show a link with the rate of further deterioration. Different ways to describe the circadian rhythm of the hormone, therefore, gave different results.

Is it possible to detect Alzheimer's disease by saliva?

To answer this question, the researchers separately examined 825 participants who underwent a clinical examination. During the follow-up, 92 of them were diagnosed with Alzheimer's disease. After statistical adjustments, none of the studied cortisol levels turned out to be significantly associated with the subsequent diagnosis.

This is a fundamental difference. Deterioration in memory and thinking test results is not in itself equal to Alzheimer's disease. The causes of cognitive changes may vary, and diagnosis requires a separate clinical assessment.

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At the same time, the lack of a meaningful connection in this work does not completely close the issue. For the analysis of Alzheimer's disease, the group was much smaller than the main one, and there were 92 confirmed cases. The authors admit that the observation might not have been long enough or the analysis lacked the statistical power to notice the connection, if it exists. This is an assumption for future research, not a discovered result.

Does high cortisol mean that stress is to blame?

Cortisol is associated with the body's response to stress, but its levels vary for other reasons. Moreover, in this work, the scientists did not compare saliva samples with a simultaneous assessment of how much stress the person himself felt. Therefore, it cannot be argued that participants with a certain cortisol profile necessarily experienced more or that it was the experiences that caused memory loss.

The cause-and-effect order has not been established either. Perhaps changes in cortisol regulation affect brain health. But the reverse situation or the influence of third factors cannot be completely excluded: early changes in health, sleep, and daily life can affect both the results of tests and the performance of cognitive tasks.

The study found differences in daily cortisol levels between two groups of participants identified by their self-reported race. At the same time, the association of cortisol with cognitive decline was generally similar in both groups. The authors discuss social conditions as a possible explanation for differences in hormone profiles, but the direct impact of these conditions was not measured in this work.

Is it worth taking a saliva test now "as a keepsake"

The study does not yet provide any reason to use it in this way. In most cases, the samples were collected over the course of one day: they showed differences between morning, afternoon and evening, but did not allow us to know whether the same profile persists in a person for weeks or months. It is also unknown how useful the cortisol indicator will be for a personal prognosis compared to other information about the patient's health.

In addition, the observational study did not test the treatment. It cannot be concluded that trying to lower cortisol will slow down memory loss. Such a recommendation would require work in which scientists evaluate the effects of a particular intervention.

Now the result rather provides a direction for further search.: Daily cortisol readings may help researchers better understand what body changes accompany brain aging. Before turning saliva analysis into a method of diagnosing or predicting Alzheimer's disease, a separate test of its accuracy and practical usefulness will have to be carried out.