Trends in Endocrinology & Metabolism
ReviewCorticosteroids, the Aging Brain and Cognition
Section snippets
Brain Changes in Age-related Cognitive Impairment
Early detection of Alzheimer's disease is important so that preventative measures, when they exist, can be undertaken. Structural magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging of glucose utilization have found value as tools for revealing early reductions in hippocampal size and glucose utilization before a definitive diagnosis9, 10, 11, 12 (Fig. 1). Yet, not all reported changes in the aging hippocampus point inexorably to dementia.
Behavioral and neurological
Mechanisms of Plasticity and Vulnerability in the Hippocampus
Decreased hippocampal volume with aging is one of a number of conditions in which hippocampal atrophy has been reported with links to glucocorticoids or stress7. Hippocampal volume reductions can be caused by neuronal loss, but they can also be due to other structural changes that do not represent damage4, and recent evidence shows that there is reversible functional and structural plasticity in the adult hippocampus as a result of the actions of adrenal steroids (Fig. 2).
First, adrenal
Biological Basis of Individual Differences in Brain Aging
Individual differences in brain aging have been related to rising cortisol levels and may come about because of a lifelong pattern of hypothalamo–pituitary–adrenal (HPA) activity. The ‘glucocorticoid cascade hypothesis’ proposed that adrenal steroids promote progressive dysfunction of the hippocampus, not only impairing various cognitive functions carried out by this brain region but also impairing a regulatory influence of the hippocampus in the shut-off of the hormonal stress response2. This
Acute or Chronic Glucocorticoid Effects?
The presence of increased glucocorticoid levels in mild forms of cognitive impairment raises the ‘chicken-and-egg’ questions: whether hippocampal atrophy is a cause and/or a result of the raised glucocorticoids and whether the cognitive impairment accompanying these conditions is a result of the hippocampal atrophy per se, or a result of raised glucocorticoids affecting neuronal excitability, or both. Apart from its role in memory, the hippocampus is involved in the regulation of HPA activity32
Future Directions
The range of plasticity exhibited by the adult hippocampus argues against an overly pessimistic assessment of the decline of cognitive function with age and the inevitability of dementia, but there are several critical areas for future research, stemming from studies in animal models and investigations of human hippocampal function.
One important issue is the refinement of imaging methods for the human hippocampus to determine the underlying neuroanatomical basis for atrophy. Findings in animal
Conclusions
The hippocampal region of the brain is an important model system for understanding the plasticity of brain cells in relation to stress and aging. Rather than being a static and fragile brain structure, the hippocampus is dynamic and resilient, having a number of forms of structural and functional plasticity, and new information on long-term effects of early life experiences provides insights into environmental causes of individual differences in cognitive decline with age, based upon the
References (39)
Modulation of brain aging correlates by long-term alterations of adrenal steroids and neurally-active peptides
Prog. Brain Res.
(1987)Stress and the brain: a paradoxical role for adrenal steroids
- et al.
Early marker for Alzheimer's disease: the atrophic hippocampus
Lancet
(1989) Hippocampal volume losses in minimally impaired elderly
Lancet
(1995)Frequency of hippocampal formation atrophy in normal aging and Alzheimer's disease
Neurobiol. Aging
(1997)- et al.
Stress and cognitive function
Curr. Opin. Neurobiol.
(1995) - et al.
Repeated changes of dendritic morphology in the hippocampus of ground squirrels in the course of hibernation
Neuroscience
(1992) - et al.
Sex differences in dendritic atrophy of CA3 pyramidal neurons in response to chronic restraint stress
Neuroscience
(1997) - et al.
Reactivity to novelty during youth as a predictive factor of cognitive impairment in the elderly: a longitudinal study in rats
Brain Res.
(1994) Progeny of mothers drinking corticosterone during lactation has lower stress-induced corticosterone secretion and better cognitive performance
Brain Res.
(1993)
Early environmental programming hypothalamic–pituitary–adrenal responses to stress
Semin. Neurosci.
Neurocircuitry of stress: central control of the hypothalamo–pituitary–adrenocortical axis
Trends Neurosci.
The acute effects of corticosteroids on cognition: integration of animal and human model studies
Brain Res. Rev.
Stress- and treatment-induced elevations of cortisol levels associated with impaired verbal and spatial declarative memory in healthy adults
Life Sci.
Stress and the aging hippocampus
Front. Neuroendocrinol.
Cumulative impact of sustained economic hardship on physical, cognitive, psychological, and social functioning
New Engl. J. Med.
The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis
Endocr. Rev.
Protective and damaging effects of stress mediators
New Engl. J. Med.
Cited by (88)
Tau pathology mediates age effects on medial temporal lobe structure
2022, Neurobiology of AgingNeurogenesis in the damaged mammalian brain
2020, Patterning and Cell Type Specification in the Developing CNS and PNS: Comprehensive Developmental Neuroscience, Second Edition11β-Hydroxysteroid Dehydrogenases
2017, Stress: Neuroendocrinology and Neurobiology