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

Sami Ouanes,Julius Popp

doi:10.3389/fnagi.2019.00043

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.

Highlights

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
In a study by Cox et al (2015) elevated salivary cortisol levels at the start and at the end of a cognitive task appointment have been associated with a poorer white matter structure, i.e., greater white matter hyperintensity volume and/or elevated general factor of tract mean diffusivity. These findings suggest that aside from the “acute effects” of cortisol on cognition, chronically elevated cortisol levels likely bring about brain structural changes that may reflect long-term cognitive deficits
In a cross-sectional study examining the links between cardiovascular risk factors and amyloid β (Aβ) brain burden as determined by Pittsburgh Compound B-positron emission tomography (PiBPET), an association has been found between plasma cortisol and Aβ brain burden (Toledo et al, 2012). These findings suggest that increased cortisol may induce and/or exacerbate cerebral Alzheimer’s disease (AD) pathology by increasing Aβ brain burden, tau pathology as well as oxidative stress, which can all contribute to neurodegeneration

Summary

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 have deleterious effects on the brain structures and contribute to neurodegeneration, in particular Alzheimer’s disease (AD), via different mechanisms

Results

INTRODUCTION

STRENGTHS AND LIMITATIONS

CONCLUSION