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.