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Sleep, Cognition and Cortisol in Addison’s Disease: A Mechanistic Relationship
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Sleep is a critical biological process, essential for cognitive well-being. Neuroscientific literature suggests there are mechanistic relations between sleep disruption and memory deficits, and that varying concentrations of cortisol may play an important role in mediating those relations. Patients with Addison's disease (AD) experience consistent and predictable periods of sub- and supra-physiological cortisol concentrations due to lifelong glucocorticoid replacement therapy, and they frequently report disrupted sleep and impaired memory. These disruptions and impairments may be related to the failure of replacement regimens to restore a normal circadian rhythm of cortisol secretion. Available data provides support for existing theoretical frameworks which postulate that in AD and other neuroendocrine, neurological, or psychiatric disorders, disrupted sleep is an important biological mechanism that underlies, at least partially, the memory impairments that patients frequently report experiencing. Given the literature linking sleep disruption and cognitive impairment in AD, future initiatives should aim to improve patients' cognitive performance (and, indeed, their overall quality of life) by prioritizing and optimizing sleep. This review summarizes the literature on sleep and cognition in AD, and the role that cortisol concentrations play in the relationship between the two.
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![Figure 3 Simulated cortisol profile for a patient [broken line] following thrice-daily hydrocortisone administration [10mg at 06:00, 5mg at 12:00 and 2.5mg at 18:00, shown as solid arrows]. The normal circadian rhythm of cortisol [solid line]. From Mah et al. (211). Weight‐related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency. Clinical Endocrinology, 61(3), 367-375.](/paper-figures/82505d8e38a2434880bf9a837463fefd/sleep-cognition-and-cortisol-in-addisons-disease-a-mechanistic-relationship-figure-3.jpg)

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“Furthermore, glucocorticoids may modulate the brain indirectly through their effects on the immune system, metabolism, sleep, other hormones, and the GM (432, 433).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [433]
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Metadata
- Authors
- Henry, M., Thomas, K. G. F., & Ross, I. L.
- Affiliations
- University of Cape Town (ZA)
- Corresponding author
- Henry, Michelle
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2021-08-27
- Volume
- 12
- Pages
- 694046-694046
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC8429905
- OpenAlex
- W3198496472
- Cited by
- 34
- References
- 292
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 9 · 2023: 7 · 2022: 4
- FWCI
- 0.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- Addison's disease, sleep disruption, cognitive impairment, memory impairment, cortisol, glucocorticoid replacement therapy, circadian rhythm, quality of life
- MeSH terms
- Addison Disease, Cognition, Humans, Hydrocortisone, Memory Disorders, Quality of Life, Risk Factors, Sleep, Signal Transduction
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