Published: 2019-06-15

impact of psychological stress and trauma on later-life cognitive function and dementia

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands
Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; INSERM, U1061, Neuropsychiatrie, Recherche Clinique et Epidémiologique, Univ. Montpellier, Montpellier, France
Stress Trauma Post-traumatic Stress Disorder Cortisol Dementia Alzheimer’s Disease


Dementia is an increasing global issue, currently affecting an estimated 50 million people worldwide. This number
is predicted to increase to 82 million by the year 2030, due to the ageing global population. Theoretically,
preventing late-onset dementia may seem extremely difficult as the greatest risk factor, age, is unmodifiable.
However, it is estimated that a third of dementia cases could potentially be prevented or delayed by removing
or reducing modifiable risk factors. Increasing evidence suggests that chronic stress, which may arise from
experiencing a traumatic event or daily stress, may be a potential risk factor for dementia. Whilst it may not play
a vital role in causing the syndrome, stress may contribute to the progression of cognitive decline, which is the
main symptom of dementia. The primary stress hormone, cortisol, may have detrimental effects on cognitive
brain regions when its levels are elevated for long durations. Preliminary evidence suggests that stress may
have different effects on brain structure and function, depending on the individual’s age when exposed to the
stress. Stress during early and later life may lead to more permanent brain changes, which may contribute to
cognitive decline in later life. Limited evidence links chronic stress or major trauma at specific stages of the
lifespan, with cognitive decline and incidence of dementia. Whether or not an accumulation of stress across
the lifespan influences later life cognition and risk of dementia, still remains to be determined. Understanding
to what extent stressful events are risk factors for later-life cognitive decline and dementia will be crucial to the
implementation of targeted psychosocial interventions efforts.


Mental stress refers to a state of strain and pressure on cognitive processes 1. In response, the body alters its physiology in order to deal with the stressor. This innate mechanism, termed ‘eustress’, is advantageous and allows perceived threats to be dealt with immediately 2. However, the long-term exposure to these hormones can cause ‘distress’ to the individual, and can increase their risk of various physical and mental diseases. Mental stress is common and has huge social and economic impacts. A commonly experienced daily stressor in adults includes workplace stress 3. In 2002, the European Union estimated the annual economic burden of workplace stress within EU-15 countries (including the UK) to be €20 billion. In the US alone, workplace stress costs $300 billion annually, when taking into account factors such as the loss of productivity and healthcare costs 4.

Traumatic events from witnessing or being part of often life-threatening situations can also lead to chronic and severe stress which, in a small proportion of people, can clinically manifest in the form of Post-Traumatic Stress Disorder (PTSD) 5. PTSD is a chronic and highly debilitating psychiatric disorder which can manifest in different ways including flashbacks, avoidance behaviour and negative alterations in cognition. Common traumatic events in children under 18 years include sexual victimisation and witnessing violence 6. On a global level, the most common adult traumatic events include the unexpected death of a loved one and vehicle-related accidents 7. An estimated 28-90% of adults in the developed world will encounter at least one traumatic event throughout their lifetime. A recent analysis of 26 World Health Organisation World Mental Health Surveys, across 24 countries, estimated the global prevalence of PTSD to be 3.9% 8.

Both stress and traumatic events can have immediate and long-lasting negative effects on the brain and can alter the structure of regions involved in cognition 9. Indeed, there is some evidence to suggest that stress and trauma can negatively affect cognitive function, in particular when these occur at sensitive periods of the life (i.e. critical periods of brain development in childhood, and brain decline in old age) or when there is an accumulation of stress over the lifetime 10. The effects of stress and trauma on cognitive function in later life and the risk of dementia, will be the focus of this review.


Mental stress elicits a threat to the body’s natural homeostatic processes 2. In response, the body aims to restore equilibrium by neutralising this threat with a combination of physiological and behavioural responses. Collectively this is known as the “adaptive stress response”. The adaptive stress response is mainly mediated by two biological mechanisms - the Hypothalamic Pituitary Adrenal (HPA) axis and the sympathetic nervous system. Specifically, the HPA axis mediates the slow-onset stress response, whilst the sympathetic nervous system mediates the acute stress response to an immediate danger, otherwise known as the ‘fight or flight’ response 11. The mechanisms of both systems are outlined in Figure 1, and results in the release of stress mediators via the adrenal gland. The HPA axis is characterised by the release of corticotropin-releasing hormone (CRH) and vasopressin (AVP) by the paraventricular nucleus in the hypothalamus. Both hormones promote the secretion of adrenocorticotropic (ACTH) from the anterior pituitary to the systemic circulation, where it triggers the synthesis and release of the primary class of stress hormones, glucocorticoids, from the adrenal cortex. Glucocorticoids act to redistribute energy to enable the body to respond to the actual/perceived threat 12. These responses include increasing cardiovascular, respiratory, metabolic, and behavioural responses in the body. Similarly, these responses are regulated by the short-term stress response – the sympathetic nervous system. Nerve impulses from the hypothalamus are relayed to the spinal cord, and travel through pre-ganglionic fibres to the adrenal medulla 13. This results in the release of adrenaline and noradrenaline noradrenergic neurons in the adrenal medulla 13. The HPA axis and sympathetic nervous system also interact with each other to trigger the adaptive stress response. This joint action is mediated by the corticotropin-releasing hormone. This is a hormone responsible for relaying signals to neurons, which causes the release of pro-opiomelanocortin (POMC) in the arcuate nucleus of the hypothalamus 14. In turn, this inhibits the sympathetic nervous system. Similarly, noradrenergic neurons in the sympathetic nervous system can relay signals to the arcuate nucleus to regulate neurons which produce corticotropin-releasing hormone.


The adaptive stress response can be beneficial when improving personal performance to overcome short-term stressful events 2. Contrarily, distress is related to chronic stress and results when stress overuses and diminishes the integrity of the HPA axis and the sympathetic nervous system. As stress redistributes energy to certain tissues, chronic stress may deprive other tissues, leading to detrimental physiological effects. This phenomenon is known as allostatic load, or ‘wear and tear,’ and can lead to complications such as inflammation, and may also play a role in cognitive decline 15. For example, cortisol, the primary glucocorticoid of the human stress response, influences memory in a dose-dependent fashion 16. Intermediate levels of cortisol has been shown to consolidate memory in order to respond to the perceived threat. However in high levels, cortisol can have a negative effect on cognition 17.


There is some evidence that increased levels of cortisol, resulting from acute and chronic exposure to stress, are negatively associated with cognitive processes including learning and memory 16. For example, hyperactivity of the HPA system has been observed in those with self-reported memory loss 18. It has been suggested that increased cortisol may affect cognitive processes due to the abundance of glucocorticoid receptors in brain regions associated with these cognitive processes, including the hippocampus, amygdala and prefrontal cortex 19. These are also the main brain regions affected in AD and dementia.

The hippocampus has been well characterised in the stress response as it contains the greatest concentration of cortisol receptors within the brain, possibly due to its role in regulating the negative feedback mechanism of the HPA axis. Its primary role includes the formation of long-term memory through processes such as long-term potentiation 20. Studies have shown a correlation with dysregulated long-term potentiation and elevated cortisol, which may result in hippocampal atrophy and decreased cognition 21 22. Elevated cortisol and hippocampal atrophy have both also been noted in AD and dementia 23 24. Imaging studies of patients with AD show decreased levels of hippocampal grey matter (which is comprised of neuronal cell bodies) 25. The greater the severity of the disease, the more pronounced the atrophy.

These detrimental effects on the hippocampus may be explained by the Glucocorticoid Vulnerability Hypothesis 26. This hypothesis suggests that the death of hippocampal neurons occurs due to a stress-induced dendritic retraction when exposed to elevated glucocorticoid levels. Elevated glucocorticoid levels binds and downregulates to glucocorticoid receptors to activate a negative feedback system which leads to a greater release of glucocorticoids 27. An increase in glucocorticoids in turn increases extracellular glutamate levels, which can have a neurotoxic effect. Thus dendritic retraction may occur in hippocampal neurons to prevent further exposure to glutamate 26.

However, this seemingly protective mechanism has a downside as retracted dendrites may make the cell vulnerable during metabolic events (e.g. ischemia and hyperglycaemia) which can occur in the hippocampus, leading to cell death 28. Hippocampal damage is greater when such metabolic events are introduced after periods of chronic stress (when glucocorticoid levels are elevated for an extended time), than periods of acute stress 29. Conrad et al. demonstrated that rats with a history of chronic stress induced over 21 days suffered from greater hippocampal damage than rats injected once with the rodent form of cortisol-corticosterone 29. Chronic stress is of particular interest to this study as it can be assumed to result from a lifetime accumulation of stress and trauma 15. These findings suggest that older people are more likely to suffer from hippocampal damage in the face of metabolic events. In the case of no such metabolic event, cell death is avoided and the dendritic retraction is reversible once glucocorticoid levels reduce 29.

Likewise, elevated glucocorticoids also causes reversible dendritic retraction in the prefrontal cortex 30. The prefrontal cortex is involved in a wide range of processes (e.g. working memory and attention) which are required to execute goal-directed behaviour 31. Chronic stress is associated with decreased prefrontal cortex grey matter, which impairs these functions and its ability to interact with the hippocampus to regulate working memory 32. Similarly with the hippocampus, atrophy in the prefrontal cortex has also been noted in AD and dementia 33.

In addition, chronic stress decreases prefrontal cortex regulation of the amygdala, which has a role in the formation of emotional memory (when interacting with the hippocampus) 34. Unlike in the hippocampus and prefrontal cortex, elevated glucocorticoids increases activity in the basolateral amygdala and promotes dendritic growth in an irreversible manner 35. Thus this basolateral hypertrophy is likely to enhance emotional memory through an increase in synaptic connections, and contribute to the affective symptoms associated with stress (e.g. anxiety and depression) 36.


The effect of stress on brain regions involved in cognition is suspected to vary throughout the lifespan 37. It has been hypothesised that the most critical periods where the brain is most susceptible to damage by stress, is in early and later-life 10. Brain regions involved in learning/memory are extremely vulnerable to cortisol during these life periods, as it is when the brain undergoes many changes during early-life and in the ageing process 38 39.

Changes to the ageing brain mainly include the reduction of total brain volume, which decreases at a rate of 5% per decade after 40 years of age 40. This may result from neuronal cell death briefly described in “Section 3.3”. A reduction in dendritic growth and synapses has also been described during the ageing process. Several molecular mechanisms have been proposed to explain neurodegeneration in ageing. One mechanism includes a decline in levels of neurotransmitters such as dopamine 41. In addition, decreased gene expression of various components involved in the release of neurotransmitters have also been reported 42. Other mechanisms also include mitochondrial dysregulation and reactive oxygen species 43. Despite the mechanism involved for neurodegeneration, these changes could make the ageing brain particularly susceptible to damage by cortisol.

In terms of early-life, the human brain is not fully developed at birth. For example, the hippocampus undergoes rapid growth until two years of age, and more delayed growth until age 14 44. The hippocampus also undergoes the most continuous change after birth, compared to other regions 44 45. These changes include synaptic pruning and dendritic growth 46. The amygdala and prefrontal cortex also undergo similar changes during childhood. The amygdala undergoes most changes during adolescence or sexual maturation 47 48. The prefrontal cortex undergoes changes throughout early-life and fully matures at age 25 47.

The effect of stress on these brain regions may induce lasting changes in adulthood 10. Early-life stress has been shown to be associated with hippocampal atrophy in later life 49. This has been noted in studies involving PTSD, although has not been investigated for milder forms of stress. A reduction in hippocampal size is observed in adults with PTSD related to childhood maltreatment, but not observed in children with PTSD related to mistreatment 50. This suggests that trauma does not cause hippocampal damage immediately, but impairs its development over time. However, the age in which the trauma occurred can make a difference in the type of brain impairments which are accumulated in later life. For example, whilst childhood trauma showed an association with hippocampal atrophy in adulthood, trauma during adolescence showed an association with prefrontal cortex atrophy 51. Thus the effect of stress differs depending on the stage of brain development the individual is experiencing. In contrary to the prefrontal cortex and hippocampus, early-life stress is associated with increased amygdala activity 52. For example, adults raised in a negative family environment displayed greater amygdala activity and decreased cortical activity in comparison to adults raised by more nurturing families 53.

A number of animal studies also suggests that early-life stress may induce cognitive deficits in adulthood 38. Maternal deprivation is commonly used to show this link as disruptions to standard maternal care is the main source of early-life stress 54. For example, one study showed that maternally deprived rats in early life performed worse in cognitive tasks associated with the hippocampus in mid-adulthood rather than young adulthood 55. Stress induced hippocampal damage occurred over-time, with its functional effects seen in later-life. However, there are opportunities to reverse the effects of early-life stress in the rat model 56. In these models, hippocampal volume can be restored and cognitive deficits can be reversed, when introducing pharmacological intervention or social housing to maternally deprived pups 57. The possibility to reverse the effects of early-life stress has also been observed in humans, as supported by observational studies in institutionalised children 58. Children raised in nurturing households after being institutionalised performed better on cognitive tasks compared to those still being institutionalised 59.


As discussed above, elevated cortisol from chronic stress may be associated with the atrophy of brain regions such as the hippocampus and prefrontal cortex. This may lead to declined cognition and symptoms associated with dementia, as atrophy in these brain regions are also observed in AD 60. In addition, elevated cortisol levels have been shown to promote an increase in AD neuropathology and is also observed in the natural ageing process 61. The strongest evidence is observed in animal studies. In mouse models of AD and in vitro studies, elevated levels of glucocorticoids are associated with an increased expression of amyloid precursor protein and β-secretase, thus shifting the amyloid precursor protein processing towards the pathogenic, amyloidogenic pathway 62. This glucocorticoid-induced increase in the amyloidogenic pathway and hence amyloid plaques, is suggested to influence downstream tau pathology and the formation of neurofibrillary tangles 63. Further animal studies also show evidence to suggest that elevated amyloid precursor protein, amyloid plaques, and abnormal tau are linked with cognitive impairment through the process of neuronal death and synaptic dysfunction in brain areas involved in learning and memory 64. Cortisol may interact with amyloid plaques and further exacerbate cognitive impairment in learning than amyloid deposits alone, regardless of other factors 65.

These animal studies are consistent with the limited findings of studies in humans which suggest that chronic stress and elevated cortisol is associated with negative effects on both cognitive outcomes and risk of AD. This is best illustrated by two large-scaled and prospective longitudinal studies, which are most ideal to determine this association. The first study by Johansson et al. analysed a Swedish female population (n = 1415) over 35 years 66. Participants were asked to self-report frequent stress in the last 5 years at 3 time points. Diagnosis of dementia subtype by neuropsychiatric examination was also performed at each of these time points. Various potential risk factors for dementia (e.g. smoking and socioeconomic status) were adjusted for in their analyses. They found an association between self-reported frequent stress during mid-life, and an increased likelihood of both early and late onset dementia. In particular, the incidence of dementia increased according to the amount of times the participants reported stress at the three different time points. Participants who reported frequent stress at all 3 time points had a greater likelihood of developing dementia (particularly AD) than participants who reported stress at only 2 or 1 time points (HR = 2.7, 1.7, 1.1 respectively). This supports the notion that chronic stress across the lifespan may be a risk factor for dementia. However, there are some limitations to consider. Firstly, the study cannot be generalisable to the male population, despite dementia being more prevalent in the female population 67. In addition, the study focused solely on the frequency of common everyday stress and did not take into account more severe stress (e.g. arising from traumatic events). To date, there are no longitudinal studies which combine both common and severe stressors, to investigate the association between stress and incidence of dementia.

The second longitudinal study investigated morning plasma cortisol levels across a period of 6 years as a marker for chronic stress 68. This prospective cohort study (n = 416) observed cognitively normal adults over the age of 60 with preclinical AD, as identified by the presence of high levels of amyloid plaques via neuroimaging techniques. Likewise to the previous study, various potential risk factors for AD were accounted for in their analyses. Their results found that adults with preclinical AD and high plasma cortisol levels, had lower cognitive scores than adults with preclinical AD and low plasma cortisol levels, across the 6 year period. This supports the notion that chronic stress, which is related to elevated cortisol over a significant duration (6 years), is only associated with cognitive decline in the presence of AD neuropathology. This also supports animal findings that cortisol accelerates cognitive decline associated with AD 65. However, unlike the previous study, this study cannot be generalised to other types of dementia. A second limitation to this study, is that cortisol levels were only collected in the morning across the 6 year period. Cortisol levels naturally fluctuate throughout the day in order to regulate the wake-sleep cycle, with its level highest in the early morning 69. Diurnal collection of cortisol may have produced more accurate results.

The role of cortisol in AD has also been observed in post-mortem studies, which is the only method, to date, that can provide an accurate diagnosis of AD 70. One study observed significant increases in cortisol collected from cerebrospinal fluid after death, in early-onset AD patients, compared to age matched controls 71. Interestingly, this association was not observed in late-onset AD patients compared to their age matched controls. This may be due to the natural increase of cortisol, with age, even in the absence of dementia, and may explain the normal decline in cognition in the elderly 72. The HPA axis naturally increases in activity with age 73. Several studies indicate that diurnal cortisol levels are significantly higher in older adults 17. Cortisol may facilitate cognitive decline in the normal ageing process, as neuroimaging studies indicate similar changes to the brain in AD and ageing 74. In ageing, there is grey matter reduction in the hippocampus and prefrontal cortex, with the majority comprising of prefrontal cortex atrophy 74. In addition, a reduction in synaptic density has been noted in structures associated with cognition. These changes to brain structures are present in both the normal ageing process, and in early-onset AD which is independent of old age 75. Thus, these findings suggest that cortisol facilitates cognitive decline in both situations.

Further human evidence linking stress with dementia and cognitive decline, include studies of PTSD populations. As mentioned earlier, PTSD is a disease characterised by chronic stress. In a large-scaled retrospective cohort study of 181,093 US veterans over 55 years, veterans diagnosed with PTSD were found to be more than twice as likely to develop dementia, than veterans without PTSD 76. However it is important to note that PTSD is a unique, clinically significant condition that is diagnosed according to a set criteria 77. These findings may not be directly applicable to either chronic or acute stress in the absence of a clinical PTSD diagnosis. However, due to the similar physiological responses in PTSD and chronic stress, they may be more applicable to chronic than acute stress 78. In addition, both PTSD and dementia observe similar structural changes to the brain such as hippocampal and prefrontal cortex atrophy 79. It is not yet determined if structural changes in both diseases are due to common risk factors. This study adjusted for some known risk factors e.g. low education levels. However, as there are further risk factors yet to be identified in both PTSD and dementia, an unconfounded causal link cannot be accurately established.

Similar associations between trauma and dementia have been observed in the Aboriginal Australian population, which have reported both higher exposure to stressful events (especially childhood trauma), and higher rates of dementia 80. A cross-sectional study by Radford et al. surveyed 336 Aboriginal and Torres Strait Islander participants aged 60-92 years regarding the frequency of their childhood trauma, using a validated childhood trauma questionnaire. All-cause dementia and AD were both diagnosed clinically, in adherence with the National Institute on Aging-Alzheimer’s Association criteria 81. Higher frequencies of childhood trauma were associated with an increased risk of all-cause dementia (OR = 1.70, 95% CI 1.14-2.54) and AD (OR = 1.77, 1.08-2.91) 80. These findings suggest that early-life trauma may contribute to dementia in later-life. This may be due to the vulnerability of the developing brain to cortisol, which may lead to lasting changes (as discussed in Section 3.4). However, the strongest evidence would ideally be derived from larger-scaled and prospective longitudinal studies following participants from childhood to adulthood. Due to time and financial constraints, such studies may not be feasible. Current longitudinal prospective cohort studies recruiting in mid-adulthood are likely to have too few participants with the development of dementia at present. Furthermore, longitudinal prospective cohort studies tend to focus on chronic diseases which are of high burden at the initiation of the cohort and as dementia is a relatively new burden. Finally, the effects of stress on health is a relatively new concept, and therefore longitudinal prospective cohort studies that undertook recruitment 15 years ago are unlikely to have a measure at baseline. These factors contribute to the lack of evidence regarding stress as a risk factor for dementia. No studies to date have investigated if not only early-life trauma, but the accumulation of stress and trauma across the lifespan, is associated with later-life dementia and cognitive decline.


There is an accumulation of evidence which links chronic stress or major trauma at specific stages of the lifespan with impairments in cognitive function. However whether or not an accumulation of stress over the lifetime influences later life cognition and the dementia risk (as well as the age of onset), remains to be determined.

Understanding to what extent stressful events are risk factors for later-life cognitive decline and dementia, as well as potentially modifiable factors which can help reduce this risk, will be crucial to the implementation of psychosocial interventions targeted on an individual basis (given a person’s place of residence, social support and family networks). Delaying the onset and/or progression of dementia or helping an individual to maintain independence as long as possible, will be beneficial to the individual, their family, carers and the wider community.

Figures and tables

Figure 1.Short-term and long-term stress response. Shows the mechanisms of the short-term stress response mediated by the sympathetic nervous system, and the long-term stress response mediated by the HPA axis. Both responses are regulated by the hypothalamus, and result in the release of stress mediators by the adrenal gland. The adrenal cortex releases glucocorticoids in the HPA axis pathway, whilst the adrenal medulla releases adrenaline and noradrenaline via the sympathetic nervous system.


  1. Sandi C. Stress and cognition. Wires Cognitive Science. 2013; 4:245-61.
  2. Szabo S, Yoshida M, Filakovszky J. “Stress” is 80 years old: from hans selye original paper in 1936 to recent advances in GI ulceration. Curr Pharmaceut Design. 2017; 23:4029-41.
  3. Schneiderman N, Ironson G, Siegel SD. Stress and health: psychological, behavioral, and biological determinants. Ann Rev Clin Psychol. 2005; 1:607-28.
  4. Limm H, Angerer P, Heinmueller M. Self-perceived stress reactivity is an indicator of psychosocial impairment at the workplace. BMC Public Health. 2010; 10:252.
  5. Sherin JE, Nemeroff CB. Post-traumatic stress disorder: the neurobiological impact of psychological trauma. Dialogues Clin Neurosci. 2011; 13:263-78.
  6. Saunders BE, Adams ZW. Epidemiology of traumatic experiences in childhood. Child Adolesc Psych Clinics North Am. 2014; 23:167-84.
  7. Benjet C, Bromet E, Karam EG. The epidemiology of traumatic event exposure worldwide: results from the World Mental Health Survey Consortium. Psychol Med. 2016; 46:327-43.
  8. Koenen KC, Ratanatharathorn A, Ng L. Posttraumatic stress disorder in the World Mental Health Surveys. Psychol Med. 2017; 47:2260-74.
  9. McEwen BS, Bowles NP, Gray JD. Mechanisms of stress in the brain. Nature Neurosci. 2015; 18:1353-63.
  10. Lupien SJ, McEwen BS, Gunnar MR. Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nature Rev Neurosci. 2009; 10:434-45.
  11. Goldstein DS. Adrenal responses to stress. Cell Mol Neurobiol. 2010; 30:1433-40.
  12. Herman JP. Neural control of chronic stress adaptation. Front Behav Neurosci. 2013; 7:61.
  13. Won E, Kim Y-K. Stress, the autonomic nervous system, and the immune-kynurenine pathway in the etiology of depression. Curr Neuropharmacol. 2016; 14:665-73.
  14. Herman JP, McKlveen JM, Ghosal S. Regulation of the hypothalamic-pituitary-adrenocortical stress response. Comprehens Physiol. 2016; 6:603-21.
  15. Maestripieri D, Hoffman CL. Chronic stress, allostatic load, and aging in nonhuman primates. Develop Psychopathol. 2011; 23:1187-95.
  16. Tatomir A, Micu C, Crivii C. The impact of stress and glucocorticoids on memory. Clujul Medical. 2014; 87:3-6.
  17. Beluche I, Carriere I, Ritchie K. A prospective study of diurnal cortisol and cognitive function in community-dwelling elderly people. Psychol Med. 2010; 40:1039-49.
  18. Wolf OT, Dziobek I, McHugh P. Subjective memory complaints in aging are associated with elevated cortisol levels. Neurobiol Aging. 2005; 26:1357-63.
  19. Lupien SJ, Maheu F, Tu M. The effects of stress and stress hormones on human cognition: implications for the field of brain and cognition. Brain Cogn. 2007; 65:209-37.
  20. Anand KS, Dhikav V. Hippocampus in health and disease: an overview. Ann Indian Acad Neurol. 2012; 15:239-46.
  21. Pavlides C, Nivon LG, McEwen BS. Effects of chronic stress on hippocampal long-term potentiation. Hippocampus. 2002; 12:245-57.
  22. Alfarez DN, Joels M, Krugers HJ. Chronic unpredictable stress impairs long-term potentiation in rat hippocampal CA1 area and dentate gyrus in vitro. Eur J Neurosci. 2003; 17:1928-34.
  23. Csernansky JG, Dong H, Fagan AM. Plasma cortisol and progression of dementia in DAT subjects. Am J Psychiatry. 2006; 163:2164-9.
  24. Henneman WJ, Sluimer JD, Barnes J. Hippocampal atrophy rates in Alzheimer disease: added value over whole brain volume measures. Neurology. 2009; 72:999-1007.
  25. Schuff N, Woerner N, Boreta L. MRI of hippocampal volume loss in early Alzheimer’s disease in relation to ApoE genotype and biomarkers. Brain. 2009; 132:1067-77.
  26. Conrad CD. Chronic stress-induced hippocampal vulnerability: the glucocorticoid vulnerability hypothesis. Rev Neurosci. 2008; 19:395-411.
  27. Herman JP, McKlveen JM, Solomon MB. Neural regulation of the stress response: glucocorticoid feedback mechanisms. Braz J Medical Biolog Res. 2012; 45:292-8.
  28. Tombaugh GC, Yang SH, Swanson RA. Glucocorticoids exacerbate hypoxic and hypoglycemic hippocampal injury in vitro: biochemical correlates and a role for astrocytes. J Neurochemistry. 1992; 59:137-46.
  29. Conrad CD, Jackson JL, Wise LS. Chronic stress enhances ibotenic acid-induced damage selectively within the hippocampal CA3 region of male, but not female rats. Neuroscience. 2004; 125:759-67.
  30. Radley JJ, Rocher AB, Janssen WGM. Reversibility of apical dendritic retraction in the rat medial prefrontal cortex following repeated stress. Experim Neurology. 2005; 196:199-203.
  31. Rossi AF, Pessoa L, Desimone R. The prefrontal cortex and the executive control of attention. Experim Brain Res. 2009; 192:489-97.
  32. Rauch SL, Shin LM, Segal E. Selectively reduced regional cortical volumes in post-traumatic stress disorder. Neuroreport. 2003; 14:913-6.
  33. Hornberger M, Yew B, Gilardoni S. Ventromedial-frontopolar prefrontal cortex atrophy correlates with insight loss in frontotemporal dementia and Alzheimer’s disease. Human Brain Mapping. 2014; 35:616-26.
  34. McEwen BS, Nasca C, Gray JD. Stress effects on neuronal structure: hippocampus, amygdala, and prefrontal cortex. Neuropsychopharmacology. 2016; 41:3-23.
  35. Vyas A, Pillai AG, Chattarji S. Recovery after chronic stress fails to reverse amygdaloid neuronal hypertrophy and enhanced anxiety-like behavior. Neuroscience. 2004; 128:667-73.
  36. Morey RA, Gold AL, LaBar KS. Amygdala volume changes with post-traumatic stress disorder in a large case-controlled veteran group. Arch Gen Psychiatry. 2012; 69:1169-78.
  37. Soares JM, Marques P, Magalhães R. Brain structure across the lifespan: the influence of stress and mood. Front Aging Neurosci. 2014; 6:330.
  38. Chen Y, Baram TZ. Toward understanding how early-life stress reprograms cognitive and emotional brain networks. Neuropsychopharmacology. 2016; 41:197-206.
  39. Walhovd KB, Krogsrud SK, Amlien IK. Neurodevelopmental origins of lifespan changes in brain and cognition. Proceedings of the National Academy of Sciences of the United States of America. 2016; 113:9357-62.
  40. Svennerholm L, Bostrom K, Jungbjer B. Changes in weight and compositions of major membrane components of human brain during the span of adult human life of Swedes. Acta Neuropathologica. 1997; 94:345-52.
  41. Mukherjee J, Christian BT, Dunigan KA. Brain imaging of 18F-fallypride in normal volunteers: blood analysis, distribution, test-retest studies, and preliminary assessment of sensitivity to aging effects on dopamine D-2/D-3 receptors. Synapse (New York, NY). 2002; 46:170-88.
  42. Toescu EC, Verkhratsky A, Landfield PW. Ca2+ regulation and gene expression in normal brain aging. Trends Neurosci. 2004; 27:614-20.
  43. Melov S. Modeling mitochondrial function in aging neurons. Trends Neurosci. 2004; 27:601-6.
  44. Thompson DK, Omizzolo C, Adamson C. Longitudinal growth and morphology of the hippocampus through childhood: impact of prematurity and implications for memory and learning. Human Brain Mapping. 2014; 35:4129-39.
  45. Uematsu A, Matsui M, Tanaka C. Developmental trajectories of amygdala and hippocampus from infancy to early adulthood in healthy individuals. PLoS One. 2012; 7:e46970.
  46. Leuner B, Gould E. Structural plasticity and hippocampal function. Ann Rev Psychol. 2010; 61:111-C3.
  47. Arain M, Haque M, Johal L. Maturation of the adolescent brain. Neuropsych Disease Treat. 2013; 9:449-61.
  48. Casey BJ, Jones RM, Hare TA. The adolescent brain. Annals of the New York Academy of Sciences. 2008; 1124:111-26.
  49. Aust S, Stasch J, Jentschke S. Differential effects of early life stress on hippocampus and amygdala volume as a function of emotional abilities. Hippocampus. 2014; 24:1094-101.
  50. Woon FL, Hedges DW. Hippocampal and amygdala volumes in children and adults with childhood maltreatment-related posttraumatic stress disorder: a meta-analysis. Hippocampus. 2008; 18:729-36.
  51. Teicher MH, Tomoda A, Andersen SL. Neurobiological consequences of early stress and childhood maltreatment: are results from human and animal studies comparable?. Annals of the New York Academy of Sciences. 2006; 1071:313-23.
  52. Fareri DS, Tottenham N. Effects of early life stress on amygdala and striatal development. Developm Cogn Neurosci. 2016; 19:233-47.
  53. Taylor SE. Mechanisms linking early life stress to adult health outcomes. Proceedings of the National Academy of Sciences of the United States of America. 2010; 107:8507-12.
  54. Molet J, Maras PM, Avishai-Eliner S. Naturalistic rodent models of chronic early-life stress. Developm Psychobiol. 2014; 56:1675-88.
  55. Brunson KL, Kramár E, Lin B. Mechanisms of late-onset cognitive decline after early-life stress. J Neurosci. 2005; 25:9328-38.
  56. James MH, Campbell EJ, Walker FR. Exercise reverses the effects of early life stress on orexin cell reactivity in male but not female rats. Front Behav Neurosci. 2014; 8:244.
  57. Bredy TW, Zhang TY, Grant RJ. Peripubertal environmental enrichment reverses the effects of maternal care on hippocampal development and glutamate receptor subunit expression. Eur J Neurosci. 2004; 20:1355-62.
  58. Hedges DW, Woon FL. Early-life stress and cognitive outcome. Psychopharmacology. 2011; 214:121-30.
  59. Nelson CA, Zeanah CH, Fox NA. Cognitive recovery in socially deprived young children: the Bucharest Early Intervention Project. Science (New York, NY). 2007; 318:1937-40.
  60. Raji CA, Lopez OL, Kuller LH. Age, Alzheimer disease, and brain structure. Neurology. 2009; 73:1899-905.
  61. Ennis GE, An Y, Resnick SM. Long-term cortisol measures predict Alzheimer disease risk. Neurology. 2017; 88:371-8.
  62. Green KN, Billings LM, Roozendaal B. Glucocorticoids increase amyloid-β and tau pathology in a mouse model of Alzheimer’s disease. J Neurosci. 2006; 26:9047-56.
  63. Oddo S, Caccamo A, Shepherd JD. Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron. 2003; 39:409-21.
  64. Di J, Cohen LS, Corbo CP. Abnormal tau induces cognitive impairment through two different mechanisms: synaptic dysfunction and neuronal loss. Scientific Reports. 2016; 6:20833.
  65. Sayer R, Robertson D, Balfour DJK. The effect of stress on the expression of the amyloid precursor protein in rat brain. Neurosci Letters. 2008; 431:197-200.
  66. Johansson L, Guo X, Waern M. Midlife psychological stress and risk of dementia: a 35-year longitudinal population study. Brain. 2010; 133:2217-24.
  67. Podcasy JL, Epperson CN. Considering sex and gender in Alzheimer disease and other dementias. Dialogues Clin Neurosci. 2016; 18:437-46.
  68. Pietrzak RH, Laws SM, Lim YY. Plasma cortisol, brain amyloid-b and cognitive decline in preclinical Alzheimer’s disease: a 6-Year Prospective Cohort Study. Biolog Psychiatry Cogn Neurosci Neuroimaging. 2017; 2:45-52.
  69. Quabbe HJ, Gregor M, Bumke-Vogt C. Pattern of plasma cortisol during the 24-hour sleep/wake cycle in the rhesus monkey. Endocrinology. 1982; 110:1641-6.
  70. Perl DP. Neuropathology of Alzheimer’s disease. The Mount Sinai Journal of Medicine. 2010; 77:32-42.
  71. Swaab DF, Raadsheer FC, Endert E. Increased cortisol levels in aging and Alzheimer’s disease in postmortem cerebrospinal fluid. J Neuroendocrinol. 1994; 6:681-7.
  72. Wrosch C, Miller GE, Schulz R. Cortisol secretion and functional disabilities in old age: importance of using adaptive control strategies. Psychosomatic Med. 2009; 71:996-1003.
  73. Gupta D, Morley JE. Hypothalamic-pituitary-adrenal (HPA) axis and aging. Compr Physiol. 2014; 4:1495-510.
  74. Harada CN, Natelson Love MC, Triebel K. Normal cognitive aging. Clin Geriatric Med. 2013; 29:737-52.
  75. Apostolova LG, Thompson PM. Mapping progressive brain structural changes in early Alzheimer’s disease and mild cognitive impairment. Neuropsychologia. 2008; 46:1597-612.
  76. Yaffe K, Vittinghoff E, Lindquist K. Post-traumatic stress disorder and risk of dementia among U.S. veterans. Arch Gen Psychiatry. 2010; 67:608-13.
  77. Sareen J. Post-traumatic stress disorder in adults: impact, comorbidity, risk factors, and treatment. Can J Psych Revue Canadienne Psychiatrie. 2014; 59:460-7.
  78. Sherin JE, Nemeroff CB. Post-traumatic stress disorder: the neurobiological impact of psychological trauma. Dialogues Clin Neurosci. 2011; 13:263-78.
  79. Greenberg MS, Tanev K, Marin MF. Stress, PTSD, and dementia. Alzheimer’s & dementia. The journal of the Alzheimer’s Association. 2014; 10:S155-65.
  80. Radford K, Delbaere K, Draper B. Childhood stress and adversity is associated with late-life dementia in aboriginal Australians. Am J Geriatr Psychiatry. 2017; 25:1097-106.
  81. McKhann GM, Knopman DS, Chertkow H. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011; 7:263-9.


D. Nilaweera

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia

R. Freak-Poli

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands

J. Ryan

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; INSERM, U1061, Neuropsychiatrie, Recherche Clinique et Epidémiologique, Univ. Montpellier, Montpellier, France


© Società Italiana di Gerontologia e Geriatria (SIGG) , 2019

How to Cite

Nilaweera, D., Freak-Poli, R. and Ryan, J. 2019. impact of psychological stress and trauma on later-life cognitive function and dementia. JOURNAL OF GERONTOLOGY AND GERIATRICS. 67, 2 (Jun. 2019), 114-122.
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