Increased cortisol levels and impaired cognition in human aging: Implication for depression and dementia in later life
Abstract
Perhaps the most prominent feature of human aging is the variability in decline of intellectual processes. Although many research avenues have been used to study the origin of such an increased variability with aging, new studies show that some biological factors may be associated with normal and pathological cognitive aging. One biological parameter that came under scrutiny in the past few years is the hypothalamic-pituitary-adrenal (HPA) axis, an endocrine closed-loop system controlling the secretion of stress hormones (glucocorticoids). In this review, we summarize data obtained in both animals and humans suggesting that cumulative exposure to high levels of glucocorticoids can be particularly detrimental for the aged hippocampus, a brain structure involved in learning and memory in both animals and humans. We then analyze the implication of these data for the study of dementia and depression in later life, two disorders characterized by increased glucocorticoid secretion in a significant proportion of patients. Finally, we suggest various factors that could explain the development of glucocorticoid hypersecretion in later life.
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Previous studies have shown smaller hippocampi in depressed patients and hippocampal atrophy following stress.
“Although increased hypothalamic volume supports the notion that HPA axis hyperactivity is associated with susceptibility to chronic stress, increased hippocampal volume may appear contrary to previous studies, which have shown smaller hippocampi in depressed patients (48,49) and hippocampal atrophy following stress (8,31,50–52).”
From Neuroanatomic differences associated with stress susceptibility and resilience (2016) · cites this paper as [52]
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- Authors
- Lupien, S. J., Nair, N. P. V., Briére, S., Maheu, F., Tu, M. T., Lemay, Μ., McEwen, B. S., & Meaney, M. J.
- Affiliations
- Douglas Mental Health University Institute (CA)
- Venue
- Reviews in the Neurosciences
- Publisher
- Walter de Gruyter GmbH
- Published
- 1999-01
- Volume
- 10
- Issue
- 2
- Pages
- 117-39
- ISSN
- 0334-1763 (ISSN-L)
- 2191-0200
- OpenAlex
- W2036672386
- Cited by
- 283
- References
- 82
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 8 · 2023: 8 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 12 · 2018: 9 · 2017: 7 · 2016: 10 · 2015: 11 · 2014: 11 · 2013: 9 · 2012: 4
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Reviews in the Neurosciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council Canada
- National Institutes of Health (5r01ag009488-05)
- Fonds de Recherche du Québec - Santé
- National Institute on Aging (AG 09488)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- cortisol, glucocorticoids, aging, cognitive aging, hippocampus, hypothalamic-pituitary-adrenal axis, stress hormones, later-life depression, dementia, learning and memory
- MeSH terms
- Aging, Animals, Cognition Disorders, Dementia, Depressive Disorder, Humans, Hydrocortisone
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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