Glucocorticoids and cognitive function: a walkthrough in endogenous and exogenous alterations

Abstract

Purpose The hypothalamic–pituitary–adrenal (HPA) axis exerts many actions on the central nervous system (CNS) aside from stress regulation. Glucocorticoids (GCs) play an important role in affecting several cognitive functions through the effects on both glucocorticoid (GR) and mineralocorticoid receptors (MR). In this review, we aim to unravel the spectrum of cognitive dysfunction secondary to derangement of circulating levels of endogenous and exogenous glucocorticoids. Methods All relevant human prospective and retrospective studies published up to 2022 in PubMed reporting information on HPA disorders, GCs, and cognition were included. Results Cognitive impairment is commonly found in GC-related disorders. The main brain areas affected are the hippocampus and pre-frontal cortex, with memory being the most affected domain. Disease duration, circadian rhythm disruption, circulating GCs levels, and unbalanced MR/GR activation are all risk factors for cognitive decline in these patients, albeit with conflicting data among different conditions. Lack of normalization of cognitive dysfunction after treatment is potentially attributable to GC-dependent structural brain alterations, which can persist even after long-term remission. Conclusion The recognition of cognitive deficits in patients with GC-related disorders is challenging, often delayed, or mistaken. Prompt recognition and treatment of underlying disease may be important to avoid a long-lasting impact on GC-sensitive areas of the brain. However, the resolution of hormonal imbalance is not always followed by complete recovery, suggesting irreversible adverse effects on the CNS, for which there are no specific treatments. Further studies are needed to find the mechanisms involved, which may eventually be targeted for treatment strategies.

Cognitive Impairment and Anxiety Are Prevalent in Kidney Transplant Recipients

“…In another, long-term study evaluating the effects of TAC therapy on cognition, brain structure, and metabolism 10 years after KT, researchers concluded that TAC may lead to cognitive decline, but not alone, and other causes may also be involved [ 22 ]. On the other hand, GCs are also known to negatively affect cognition [ 23 ]. Long-term GCs therapy may cause CI, usually characterized by deficits in memory and mental processing speed [ 23 ].…”

“…On the other hand, GCs are also known to negatively affect cognition [ 23 ]. Long-term GCs therapy may cause CI, usually characterized by deficits in memory and mental processing speed [ 23 ]. Moreover, other side effects may occur during GCs therapy, the most common of which are psychosis, mania/hypomania, depression, and anxiety [ 23 ].…”

“…Long-term GCs therapy may cause CI, usually characterized by deficits in memory and mental processing speed [ 23 ]. Moreover, other side effects may occur during GCs therapy, the most common of which are psychosis, mania/hypomania, depression, and anxiety [ 23 ]. In addition, we showed a strong positive effect of better education on cognitive performance.…”

Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the Good From the Bad?

“…In addition, there is evidence of improvement in brain atrophy following GC withdrawal ( 368-371 ). We have recently extensively reviewed elsewhere the contribution of GC on cognitive function ( 372 ).…”

Psychosocial exposome and double precarity as emergent concepts for an old story

“…induces stress. And the physiological mechanisms of stress, with suppression of pre-frontal and hippocampus activity, impairing large-band attention, learning, and memory consolidation) (De Alcubierre et al, 2023;Blankenship et al, 2019;Souza-Talarico et al, 2011), provide additional explanation, as structural correlates, of the well-established scarcity effect. However, stress is not limited to scarcity situational contexts.…”