High Cortisol and the Risk of Dementia and Alzheimer’s Disease: A Review of the Literature

Abstract

Introduction: Cortisol effects on the brain are exerted through two distinct receptors, inducing complex and even opposite effects on the cerebral structures implicated in the various cognitive functions. High cortisol may also have deleterious effects on the brain structures and contribute to neurodegeneration, in particular Alzheimer’s disease (AD), via different mechanisms. Objective: To examine the interrelationships between cortisol, cognitive impairment and AD. Methods: Review of the literature. Results: Clinical studies found that elevated cortisol was associated with poorer overall cognitive functioning, as well as with poorer episodic memory, executive functioning, language, spatial memory, processing speed, and social cognition; while in animals, glucocorticoid administration resulted in cognitive impairment and abnormal behavior. In cognitively healthy subjects, higher cortisol levels have been associated with an increased risk of cognitive decline and AD. Subjects with dementia and Mild Cognitive Impairment (MCI) due to AD have been found to have higher CSF cortisol levels than cognitively healthy controls. Elevated CSF cortisol may also be associated with a more rapid cognitive decline in MCI due to AD. Elevated cortisol levels have been also found in delirium. High cortisol may mediate the impact of stressful life events, high neuroticism, depression, sleep disturbances, as well as cardiovascular risk factors on cognitive performance, neurodegeneration, and cognitive decline. High cortisol may also exert neurotoxic effects on the hippocampus, and promote oxidative stress and amyloid β peptide toxicity. Further possible underlying mechanisms include the interactions of cortisol with inflammatory mediators, neurotransmitters, and growth factors. Conclusion: Elevated cortisol levels may exert detrimental effects on cognition and contribute to AD pathology. Further studies are needed to investigate cortisol-reducing and glucocorticoidreceptor modulating interventions to prevent cognitive decline.

Psychological stress, cognitive decline and the development of dementia in amnestic mild cognitive impairment

“…Notably, although not significant we also found a trend (p = 0.05) relationship showing an increased cortisol AUC Levels in the aMCI group compared with the control group after correction for age and gender. These findings are thus consistent with the hypothesis that high levels of cortisol may have had a damaging effect on the hippocampus and are consistent with studies suggesting a potential role of cortisol in precipitating the early development of aMCI 34 . Table 5.…”

Psychophysiological Responses in People Living with Dementia after an Art Gallery Intervention: An Exploratory Study

“…Several studies have reported associations between higher cortisol levels, decreased cognitive performance, and the pathophysiology of AD [7,38]. However, these studies measured cortisol at one-time point, and higher cortisol has also been associated with a decreased rate of cognitive decline in individuals with mild cognitive impairment [39].…”

“…Impaired mineralocorticoid receptor function is related to the aging process, inhibiting HPA-axis activity via receptors in the hippocampus. Activation of these receptors is associated with positive effects on cognitive performance, but only until glucocorticoid receptors are activated, which occurs once mineralocorticoid receptors are saturated [38]. Glucocorticoid receptor activation occurs when cortisol levels are chronically elevated and lead to detrimen-tal effects on cognitive performance, particularly in executive functioning [42], and cause alterations in hippocampal functioning [43].…”

Dual-Task Training with Cisual Stimulation Affect Cognitive and Physical Performances and Brain Wave Ratio of Patients with Alzheimer's Disease: A Randomized Controlled Trial

“…Moreover, exercise-mediated production of neurotransmitters, such as dopamine, serotonin (41), and brain-derived neurotrophic factor (42), contributes to the treatment of depression. Also, AD-induced high cortisol levels exert neurotoxic effects on the hippocampus and promote oxidative stress, leading to depression, neurodegeneration, and cognitive decline (43). On the other hand, one of the protective effects of regular exercise is lowering the serum cortisol level (44).…”