Cerebrospinal Fluid Cortisol and Dehydroepiandrosterone Sulfate, Alzheimer’s Disease Pathology, and Cognitive Decline

Ouanes, Sami; Clark, Christopher; Richiardi, Jonas; Maréchal, Bénédicte; Lewczuk, Piotr; Kornhuber, Johannes; Kirschbaum, Clemens; Popp, Julius

doi:10.3389/fnagi.2022.892754

Cited by 15 publications

(16 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our findings suggest that the ratio of DHEAS to cortisol is one possible mechanism mediating cognitive changes in chimpanzees. In humans, a high cortisol to DHEAS ratio has been negatively correlated with hippocampal, amygdala, and insula volume in humans, and with tau and p-tau levels ( Jin et al, 2016 ; Ouanes et al, 2022 ). Although further research correlating brain volume and adrenal steroids in chimpanzees is needed to test whether this relationship is similar in chimpanzees and humans, a previous study that included the chimpanzees described in the present work found age-related loss in grey matter in brain regions associated with cognition, and old chimpanzees with greater grey matter performed better within their age category ( Mulholland et al., 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have reported that DHEAS levels are affected by acute and chronic stress due to its antagonistic action on glucocorticoids ( Kalimi et al, 1994 ; Maninger et al, 2010 ; McNelis et al, 2013 ). For this reason, recent studies that adopted the co-measurement of cortisol and DHEAS to investigate cognition and stress levels in several species, including marine mammals ( Gundlach et al, 2018 ; O’Brien et al, 2017 ), ungulates ( Almeida et al, 2008 ; Jurkovich et al, 2020 ), humans ( DeBruin et al., 2002 ; Miller et al, 1998 ; Ouanes et al, 2022 ), and nonhuman primates ( Goncharova, Vengerin & Chigarova, 2012 ; Maninger et al, 2010 ; Takeshita et al, 2014 ; Takeshita et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Age, adrenal steroids, and cognitive functioning in captive chimpanzees (Pan troglodytes)

Takeshita

Edler

Meindl

et al. 2022

PeerJ

View full text Add to dashboard Cite

Background Dehydroepiandrosterone-sulfate is the most abundant circulating androgen in humans and other catarrhines. It is involved in several biological functions, such as testosterone production, glucocorticoid antagonist actions, neurogenesis and neuroplasticty. Although the role of dehydroepiandrosterone-sulfate (DHEAS) in cognition remains elusive, the DHEAS/cortisol ratio has been positively associated with a slower cognitive age-decline and improved mood in humans. Whether this relationship is found in nonhuman primates remains unknown. Methods We measured DHEAS and cortisol levels in serum of 107 adult chimpanzees to investigate the relationship between DHEAS levels and age. A subset of 21 chimpanzees was used to test the potential associations between DHEAS, cortisol, and DHEAS/cortisol ratio in cognitive function, taking into account age, sex, and their interactions. We tested for cognitive function using the primate cognitive test battery (PCTB) and principal component analyses to categorize cognition into three components: spatial relationship tasks, tool use and social communication tasks, and auditory-visual sensory perception tasks. Results DHEAS levels, but not the DHEAS/cortisol ratio, declined with age in chimpanzees. Our analyses for spatial relationships tasks revealed a significant, positive correlation with the DHEAS/cortisol ratio. Tool use and social communication had a negative relationship with age. Our data show that the DHEAS/cortisol ratio, but not DHEAS individually, is a promising predictor of spatial cognition in chimpanzees.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Age, adrenal steroids, and cognitive functioning in captive chimpanzees (Pan troglodytes)

Takeshita

Edler

Meindl

et al. 2022

PeerJ

View full text Add to dashboard Cite

show abstract

“…We also used a battery of cognitive tests to assess the most important cognitive domains (including episodic memory, verbal fluency, executive functions, and visuospatial construction) and proxy questionnaires to evaluate basic and instrumental activities of daily living, as previously described [ 5 ]. These tools are validated and widely used in the field.…”

Section: Methodsmentioning

confidence: 99%

“…NPS have been linked to poorer quality of life and to more pronounced impairment in activities of daily living [ 1 , 4 ]. Their presence has also been associated with faster disease progression and earlier institutionalization [ 2 , 5 ]. NPS, especially irritability, agitation, sleep disturbances, anxiety, apathy, and delusion, have also been shown to increase the caregiver burden [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Persisting neuropsychiatric symptoms, Alzheimer’s disease, and cerebrospinal fluid cortisol and dehydroepiandrosterone sulfate

et al. 2022

Self Cite

View full text Add to dashboard Cite

Introduction Neuropsychiatric symptoms are important treatment targets in the management of dementia and can be present at very early clinical stages of neurodegenerative diseases. Increased cortisol has been reported in Alzheimer’s disease (AD) and has been associated with faster cognitive decline. Elevated cortisol output has been observed in relation to perceived stress, depression, and anxiety. Dehydroepiandrosterone sulfate (DHEAS) has known anti-glucocorticoid effects and may counter the effects of cortisol. Objectives We aimed to examine whether CSF cortisol and DHEAS levels were associated with (1) neuropsychiatric symptoms at baseline, (2) changes in neuropsychiatric symptoms over 3 years, and (3) whether these associations were related to or independent of AD pathology. Methods One hundred and eighteen participants on a prospective study in a memory clinic setting, including patients with cognitive impairment (n = 78), i.e., mild cognitive impairment or mild dementia, and volunteers with normal cognition (n = 40), were included. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). CSF cortisol and DHEAS, as well as CSF AD biomarkers, were obtained at baseline. Neuropsychiatric symptoms were re-assessed at follow-up visits 18 and 36 months from baseline. We constructed linear regression models to examine the links between baseline neuropsychiatric symptoms, the presence of AD pathology as indicated by CSF biomarkers, and CSF cortisol and DHEAS. We used repeated-measures mixed ANCOVA models to examine the associations between the neuropsychiatric symptoms’ changes over time, baseline CSF cortisol and DHEAS, and AD pathology. Results Higher CSF cortisol was associated with higher NPI-Q severity scores at baseline after controlling for covariates including AD pathology status (B = 0.085 [0.027; 0.144], p = 0.027; r = 0.277). In particular, higher CSF cortisol was associated with higher baseline scores of depression/dysphoria, anxiety, and apathy/indifference. Elevated CSF cortisol was also associated with more marked increase in NPI-Q scores over time regardless of AD status (p = 0.036, η2 = 0.207), but this association was no longer significant after controlling for BMI and the use of psychotropic medications. CSF DHEAS was associated neither with NPI-Q scores at baseline nor with their change over time. Cortisol did not mediate the association between baseline NPI-Q and changes in clinical dementia rating sum of boxes over 36 months. Conclusion Higher CSF cortisol may reflect or contribute to more severe neuropsychiatric symptoms at baseline, as well as more pronounced worsening over 3 years, independently of the presence of AD pathology. Our findings also suggest that interventions targeting the HPA axis may be helpful to treat neuropsychiatric symptoms in patients with dementia.

show abstract

The effect of plasma cortisol on hippocampal atrophy and clinical progression in mild cognitive impairment

White

Mauer

Lange

et al. 2023

Alz & Dem Diag Ass & Dis Mo

View full text Add to dashboard Cite

IntroductionBoth elevated cortisol and hippocampal volume have been linked to an increased risk for the development of Alzheimer's disease (AD). This longitudinal study assessed the effects of plasma cortisol on hippocampal atrophy and clinical progression rates in patients with mild cognitive impairment (MCI).MethodsPatients with amnestic MCI (n = 304) were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) based on availability of baseline plasma cortisol and hippocampal volume measures, assessed at baseline and during follow‐ups. We investigated associations between plasma cortisol, hippocampal volume, and risk of clinical progression to AD over a study period of up to 100 months (mean follow‐up time 36.8 months) using linear mixed models, Cox proportional hazards models, and Kaplan‐Meier estimators.ResultsPlasma cortisol predicted greater hippocampal atrophy, such that participants with higher cortisol showed faster decline in hippocampal volume over time (interaction: β = ‐0.15, p = 0.004). Small hippocampal volume predicted a higher risk of clinical progression to AD (haard ratio [HR] = 2.15; confidence in terval [CI], 1.64–2.80; p < 0.001). A similar effect was not found for cortisol (HR = 1.206; CI, 0.82–1.37; p = 0.670) and there was no statistical evidence for an interaction between hippocampal volume and cortisol on clinical progression (HR = 0.81; CI, 0.57–0.17; p = 0.260).DiscussionOur findings suggest that higher cortisol predicts higher hippocampal atrophy, which in turn is a risk factor for progression to AD. Regulation of the hypothalamic‐pituitary‐adrenal axis through stress‐reducing lifestyle interventions might be a protective factor against hippocampal degeneration at the prodromal stage of AD.

show abstract

Cerebrospinal Fluid Cortisol and Dehydroepiandrosterone Sulfate, Alzheimer’s Disease Pathology, and Cognitive Decline

Cited by 15 publications

References 62 publications

Age, adrenal steroids, and cognitive functioning in captive chimpanzees (Pan troglodytes)

Age, adrenal steroids, and cognitive functioning in captive chimpanzees (Pan troglodytes)

Persisting neuropsychiatric symptoms, Alzheimer’s disease, and cerebrospinal fluid cortisol and dehydroepiandrosterone sulfate

The effect of plasma cortisol on hippocampal atrophy and clinical progression in mild cognitive impairment

Contact Info

Product

Resources

About