Increased Saliva Cortisol Awakening Response in Patients with Mild Cognitive Impairment

Institute of Neuroscience and Physiology, Sahlgrenska Academy, Göteborg University, Mölndal, Sweden.
Dementia and Geriatric Cognitive Disorders (Impact Factor: 3.55). 02/2007; 24(5):389-95. DOI: 10.1159/000109938
Source: PubMed


It is unknown whether HPA-axis dysfunction is present in patients with mild cognitive impairment (MCI). The aim of the present study was to investigate whether cortisol levels are elevated among patients with MCI and/or whether the individuals have adequate feedback control of their HPA axis.
27 patients with MCI and 15 healthy controls were included in the study. Saliva samplings were performed 5 times a day before intake of 0.5 mg dexamethasone, and 5 times a day after intake of dexamethasone, respectively.
Significantly higher cortisol levels were found 15 min after awakening among patients with MCI in comparison with the controls, both before and after dexamethasone administration (p<0.05). Also, the ratio between cortisol at awakening time and 15 min after awakening was lower in the patient group after dexamethasone administration (p<0.05). There were no significant differences in basal cortisol levels before or after dexamethasone between groups.
The results indicate that there is an HPA-axis disturbance, with normal basal cortisol levels and increased awakening response among patients with MCI. The dissociation between basal values and the awakening response may be of pathophysiological importance for the cognitive impairment.

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    • "Alterations in the CAR may be related to cognitive function. Increased CAR has been associated with both poorer and better behavioral performance in higher order functions such as working memory and attention-switching (Aas et al., 2011; Almela et al., 2012; Evans et al., 2012; Lind et al., 2007; Moriarty et al., 2014). The relationship between the CAR and the neurocognitive processing that underlies explicit behavior, however, remains unknown. "
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    ABSTRACT: The cortisol awakening response (CAR), a rapid increase in cortisol levels following morning awakening, is an important aspect of hypothalamic-pituitary-adrenocortical axis activity. Alterations in the CAR have been linked to a variety of mental disorders and cognitive function. However, little is known regarding the relationship between the CAR and error processing, a phenomenon that is vital for cognitive control and behavioral adaptation. Using high-temporal resolution measures of event-related potentials (ERPs) combined with behavioral assessment of error processing, we investigated whether and how the CAR is associated with two key components of error processing: error detection and subsequent behavioral adjustment. Sixty university students performed a Go/No-go task while their ERPs were recorded. Saliva samples were collected at 0, 15, 30 and 60 min after awakening on the two consecutive days following ERP data collection. The results showed that a higher CAR was associated with slowed latency of the error-related negativity (ERN) and a higher post-error miss rate. The CAR was not associated with other behavioral measures such as the false alarm rate and the post-correct miss rate. These findings suggest that high CAR is a biological factor linked to impairments of multiple steps of error processing in healthy populations, specifically, the automatic detection of error and post-error behavioral adjustment. A common underlying neural mechanism of physiological and cognitive control may be crucial for engaging in both CAR and error processing.
    Full-text · Article · Jul 2015 · Stress (Amsterdam, Netherlands)
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    • "The CAR has been examined in relation to cognitive function in a number of studies in both healthy subjects and patients with a variety of psychiatric illnesses (e.g. Lind et al., 2007; Aas et al., 2011; van der Werf-Eldering et al., 2012). Studies examining the relationship between CAR and memory performance have been largely equivocal , although a study by Almela et al. (2012) did suggest a quadratic relationship between CAR and measures of declarative memory processes in 55-to 77-year-olds. "
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    ABSTRACT: Objective The association between hypothalamic–pituitary–adrenal (HPA)-axis function and cognition has long been investigated. An inverted U-shaped relationship has been described between various measures of HPA-axis function and neuropsychological performance in animals and man. Work with glucocorticoid receptor manipulation has corroborated these findings, with particular effects observed in relation to spatial working memory (SWM). As HPA-axis dysfunction is frequently found in patients with psychiatric illness, research in this area has potential implications for the treatment of the commonly observed cognitive impairment in such disorders. Here, we present the results of a pilot study examining the relationship between cortisol awakening response (CAR) and cognitive functions known to be susceptible to HPA-axis manipulation.Methods Nineteen healthy male volunteers were recruited, and their CAR and performance in a task of SWM were assessed.ResultsA highly significant quadratic relationship was observed between the CAR and SWM error rate (R2 = 0.63, p = 0.001).Conclusion We provide novel evidence supporting the existence of an inverted U-shaped relationship between corticosteroid levels and cognitive function in humans. Copyright © 2014 John Wiley & Sons, Ltd.
    Full-text · Article · May 2014 · Human Psychopharmacology Clinical and Experimental
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    • "As there are no longitudinal studies revealing to what degree early stress induces reduced hippocampal volume , changes in serotonin receptor levels, dysfunction in the HPA-axis response results in depression, it is not yet possible to determine whether these features comprise purely risk factors or are also causal effectors of the disease. In any case, what is interesting is that both reduced hippocampal volume [196] [197], hyperresponsive HPA-axis [198], and changes in serotonin receptor levels [86] are by themselves associated with increased risk for developing AD. "
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    ABSTRACT: The existence of a high co-morbidity between Alzheimer's disease (AD) and depression has been known for a long time. More interesting though are recent studies indicating that depression and number of depressive episodes earlier in life is associated with increased risk of AD development. This suggests the existence of common neuropathological mechanisms behind depression and AD. Here we propose that the brain changes associated with depressive episodes that compromise the brain's ability to cope with stress may constitute risk factors for development of AD. Furthermore, in individuals with a genetic linkage to depression, there may be an increased vulnerability towards the initiation of a detrimental neurodegenerative cascade. The following review will deal with the various observations reported within the different neurobiological systems known to be involved and affected in depression, like serotonergic and cholinergic system, hypothalamic-pituitary-adrenal axis and brain derived neurotrophic factor, and discussed in relation to AD.
    Full-text · Article · Jan 2011 · Journal of Alzheimer's disease: JAD
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