Cortisol and the aging brainHypothalamic-pituitary-adrenal axis and cognitive performance in older people.

Résumé

One of the greatest achievements in modern society is the increase in life expectancy. This increment is so great that children born after 2011 have a one in three chance of reaching their 100th birthday, and specifically in Europe, a quarter of the population will be over 60 years of age by 2020 (European Commission, 2014). This is an important change in society that is occurring for the first time in human history and producing new challenges that need to be addressed, especially those concerning age-related health problems. In this regard, one of the main aims of new research programs, such as Horizon 2020 in Europe, is to increase the possibilities of keeping older people healthy and independent as long as possible. To do so, it is critical to understand what processes can provoke, or at least contribute to, an increase in the vulnerability of older people because this will help to develop new strategies of prevention and intervention. Conserving good cognitive functioning is especially important for the maintenance of independent life. Therefore, it is essential to identify those mechanisms that can affect cognitive performance in older people and their adaptation to the environment. Along these lines, changes in the activity of the hypothalamus-pituitary-adrenal axis (HPA-axis) have been related to changes in the cognitive performance of both young and older people, and it has become a research target that can shed light on the changes that can be observed in aging. This dissertation presents the results of a research study focused on investigating the relationship between cognitive performance and the activity of the HPA-axis in older people. The first chapter of this dissertation provides a description of the HPA-axis, its main functions and the biological samples commonly used in research to measure the hormone cortisol, the end product of this neuroendocrine axis. Additionally, this chapter explains the age-related changes that can be observed in the circadian activity of the HPA-axis and in the stress-induced cortisol response. The last part of this chapter presents a short overview of the studies that have investigated the effects of acute stress and cortisol on memory performance in young and older people, and the relationship between the basal activity of the HPA-axis and cognitive performance in older people. The second and third chapters present two studies designed to investigate the effect of acute stress on memory in older men and women. The first empirical study of this dissertation investigated the effects of the cortisol response to stress on long-term memory retrieval. In the second study, two experiments were performed to investigate the effects of acute stress on the memory span and the executive component of the working memory. The fourth chapter describes the third study, designed to investigate whether differences in the long-term endogenous cortisol exposure and in the diurnal regulation of the HPA-axis are related to inter-individual differences in the cognitive performance of older people. In this study, a new technique was used to assess cortisol levels in hair samples, making it possible to measure cortisol exposure during the three months prior to the cognitive performance assessment. The fifth chapter includes a study designed to investigate whether the cortisol awakening response, a discrete component of the diurnal HPA-axis, was related to walking speed, a commonly used measure of physical activity that has been closely related to cognitive performance in older people. Also focused on the CAR, the sixth chapter describes the fifth study. It investigated whether the CAR is different in normotensive and hypertensive older people. Additionally, the relationship between the cortisol awakening response and cognitive performance was studied in these two groups. The seventh chapter contains a general discussion, the clinical implications of the findings, study limitations, and future considerations drawn from the results of the previous empirical studies. Finally, the eighth chapter includes a summary of the main conclusions of this doctoral dissertation.