Cortisol levels during human aging predict hippocampal atrophy and memory deficits
Abstract
Elevated glucocorticoid levels produce hippocampal dysfunction and correlate with individual deficits in spatial learning in aged rats. Previously we related persistent cortisol increases to memory impairments in elderly humans studied over five years. Here we demonstrate that aged humans with significant prolonged cortisol elevations showed reduced hippocampal volume and deficits in hippocampus-dependent memory tasks compared to normal-cortisol controls. Moreover, the degree of hippocampal atrophy correlated strongly with both the degree of cortisol elevation over time and current basal cortisol levels. Therefore, basal cortisol elevation may cause hippocampal damage and impair hippocampus-dependent learning and memory in humans.
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Hypothalamus-pituitary-adrenal axis hyperactivity has been associated with hippocampal atrophy in aging and in Cushing's disease.
“Hypothalamus-pituitary-adrenal axis hyperactivity have been associated with hippocampal atrophy in aging (16) and in Cushing's disease (17).”
From Reduced glucose tolerance is associated with poor memory performance and hippocampal atrophy among normal elderly (2003) · cites this paper as [16]
The HPA axis appears to become less responsive with aging, contributing to the dysregulation of stress responses and the resultant development of cognitive decline.
“Essentially, the HPA axis appears to become less responsive with aging, contributing to the dysregulation of stress responses and the resultant development of cognitive decline (111, 112).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [111]
Older adults were found to display higher levels of circulating corticosterone at baseline that was associated with hippocampal atrophy and memory deficits.
“Indeed, older adults were found to display higher levels of circulating corticosterone at baseline that was associated with hippocampal atrophy and memory deficits (Lupien et al, 1998).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Lupien et al, 1998
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Self-citation
- Authors
- Lupien, S. J., de Leon, M., de Santi, S., Convit, A., Tarshish, C., Nair, N. P. V., Thakur, M., McEwen, B. S., Hauger, R. L., & Meaney, M. J.
- Affiliations
- Douglas Mental Health University Institute (CA)
- NYU Langone Health (US)
- Rockefeller University (US)
- University of California San Diego (US)
- Corresponding author
- Lupien, Sonia J.
- ORCID
- Venue
- Nature Neuroscience
- Published
- 1998-05
- Volume
- 1
- Issue
- 1
- Pages
- 69-73
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- DOI
- 10.1038/271
- OpenAlex
- W2141463840
- Cited by
- 1,653
- References
- 33
- Citations by year
- 2026: 54 · 2025: 22 · 2024: 42 · 2023: 46 · 2022: 46 · 2021: 70 · 2020: 82 · 2019: 50 · 2018: 51 · 2017: 64 · 2016: 77 · 2015: 71 · 2014: 74 · 2013: 67 · 2012: 69
- FWCI
- 25.47
- Type
- journal article
- Language
- en
- Update notices
- Open access
- closed
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG 09488, AG 12101, R01AG009488, R01AG013616, AG 13616)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- cortisol, glucocorticoids, aging, hippocampal atrophy, hippocampal volume, memory impairment, spatial learning, hippocampal-dependent memory, hippocampal dysfunction
- MeSH terms
- Aged, Aging, Atrophy, Forecasting, Hippocampus, Humans, Hydrocortisone, Magnetic Resonance Imaging, Memory, Memory Disorders, Organ Size
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