Cited by 1,653Stress Responses and CortisolMemory and Neural MechanismsAdrenal Hormones and Disorders

Cortisol levels during human aging predict hippocampal atrophy and memory deficits

Lupien, Sonia J., de Leon, Mony, de Santi, Susan, Convit, Antonio, Tarshish, Chaim, Nair, N. P. V., Thakur, Mira, McEwen, Bruce S. +2 more·1998·Nature Neuroscience

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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Crossref · 10.1038/271

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33 of 33 references verified0 citation errors · 0 not checkable

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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).”
  • 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).”
  • 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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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.
Venue
Nature Neuroscience
Published
1998-05
Volume
1
Issue
1
Pages
69-73
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
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
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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