Circulating Stress Hormones, Brain Health, and Cognition in Healthy Older Adults: Cross-Sectional Findings and Sex Differences in Age-Well

Background: Increased stress is a proposed risk factor for Alzheimer’s disease (AD). We examined cross-sectional associations between circulating stress biomarkers and multimodal measures of brain health and cognition susceptible to AD in older adults and sex-specific subgroups. Methods: Baseline da...

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Main Authors: Maxie Liebscher, Silke White, Simon Hass, Anne Chocat, Florence Mezenge, Brigitte Landeau, Marion Delarue, Oriane Hébert, Anne-Laure Turpin, Natalie L. Marchant, Gaël Chételat, Olga Klimecki, Géraldine Poisnel, Miranka Wirth, Claire André, Pierre Champetier, Léa Chauveau, Fabienne Collette, Sophie Dautricourt, Robin de Flores, Vincent De La Sayette, Harriet Demnitz-King, Séverine Fauvel, Francesca Felisatti, Victor Ferment, Eglantine Ferrand-Devouge, Julie Gonneaud, Antoine Garnier-Crussard, Anaïs Hamel, Sacha Haudry, Pierre Krolak-Salmon, Elizabeth Kuhn, Valérie Lefranc, Antoine Lutz, Valentin Ourry, Cassandre Palix, Anne Quillard, Géraldine Rauchs, Eric Salmon, Edelweiss Touron, Patrik Vuilleumier, Tim Whitfield
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Language:English
Published: Elsevier 2025-03-01
Series:Biological Psychiatry Global Open Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667174324001447
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author Maxie Liebscher
Silke White
Simon Hass
Anne Chocat
Florence Mezenge
Brigitte Landeau
Marion Delarue
Oriane Hébert
Anne-Laure Turpin
Natalie L. Marchant
Gaël Chételat
Olga Klimecki
Géraldine Poisnel
Miranka Wirth
Claire André
Pierre Champetier
Léa Chauveau
Fabienne Collette
Sophie Dautricourt
Robin de Flores
Vincent De La Sayette
Harriet Demnitz-King
Séverine Fauvel
Francesca Felisatti
Victor Ferment
Eglantine Ferrand-Devouge
Julie Gonneaud
Antoine Garnier-Crussard
Anaïs Hamel
Sacha Haudry
Pierre Krolak-Salmon
Elizabeth Kuhn
Valérie Lefranc
Antoine Lutz
Valentin Ourry
Cassandre Palix
Anne Quillard
Géraldine Rauchs
Eric Salmon
Edelweiss Touron
Patrik Vuilleumier
Tim Whitfield
author_facet Maxie Liebscher
Silke White
Simon Hass
Anne Chocat
Florence Mezenge
Brigitte Landeau
Marion Delarue
Oriane Hébert
Anne-Laure Turpin
Natalie L. Marchant
Gaël Chételat
Olga Klimecki
Géraldine Poisnel
Miranka Wirth
Claire André
Pierre Champetier
Léa Chauveau
Fabienne Collette
Sophie Dautricourt
Robin de Flores
Vincent De La Sayette
Harriet Demnitz-King
Séverine Fauvel
Francesca Felisatti
Victor Ferment
Eglantine Ferrand-Devouge
Julie Gonneaud
Antoine Garnier-Crussard
Anaïs Hamel
Sacha Haudry
Pierre Krolak-Salmon
Elizabeth Kuhn
Valérie Lefranc
Antoine Lutz
Valentin Ourry
Cassandre Palix
Anne Quillard
Géraldine Rauchs
Eric Salmon
Edelweiss Touron
Patrik Vuilleumier
Tim Whitfield
author_sort Maxie Liebscher
collection DOAJ
description Background: Increased stress is a proposed risk factor for Alzheimer’s disease (AD). We examined cross-sectional associations between circulating stress biomarkers and multimodal measures of brain health and cognition susceptible to AD in older adults and sex-specific subgroups. Methods: Baseline data from 132 cognitively unimpaired participants without depression (age, mean ± SD = 74.0 ± 4.0 years, women: n = 80) in the Age-Well trial (NCT02977819) were included. Stress hormone levels were measured in overnight fasting blood serum (cortisol, dehydroepiandrosterone sulfate) and blood plasma (epinephrine, norepinephrine) samples. AD-sensitive measures of brain health, including glucose metabolism (n = 89), cerebral perfusion, gray matter volume, amyloid deposition in a priori regions of interest, and cognitive markers were evaluated. Models were adjusted for age, sex, education, trait anxiety, and depressive symptoms. Results: Higher epinephrine levels were associated (false discovery rate–corrected p < .05) with lower glucose metabolism in the anterior cingulate cortex (β = −0.26, p = .008), posterior cingulate cortex (β = −0.32, p = .006), and precuneus (β = −0.27, p = .021) and lower perfusion in the posterior cingulate cortex (β = −0.23, p = .013). Interactions between stress hormones and sex showed (false discovery rate–corrected p < .05) that in women only, higher epinephrine was associated with larger anterior cingulate cortex volume (interaction: β = 0.32, p = .016), whereas in men only, higher cortisol was associated with lower episodic memory performance (interaction: β = 0.98, p = .012). Conclusions: The current study demonstrates the involvement of circulating stress hormones, particularly epinephrine and cortisol, in greater resilience or vulnerability of brain health and cognitive indicators of susceptibility to AD in older adults. The identification of sex-specific patterns in these associations may inform the development of more effective and tailored interventions.
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spelling doaj-art-21b5c5ca935d4f20944c00a95acebfc82025-02-06T05:13:00ZengElsevierBiological Psychiatry Global Open Science2667-17432025-03-0152100431Circulating Stress Hormones, Brain Health, and Cognition in Healthy Older Adults: Cross-Sectional Findings and Sex Differences in Age-WellMaxie Liebscher0Silke White1Simon Hass2Anne Chocat3Florence Mezenge4Brigitte Landeau5Marion Delarue6Oriane Hébert7Anne-Laure Turpin8Natalie L. Marchant9Gaël Chételat10Olga Klimecki11Géraldine Poisnel12Miranka Wirth13Claire André14Pierre Champetier15Léa Chauveau16Fabienne Collette17Sophie Dautricourt18Robin de Flores19Vincent De La Sayette20Harriet Demnitz-King21Séverine Fauvel22Francesca Felisatti23Victor Ferment24Eglantine Ferrand-Devouge25Julie Gonneaud26Antoine Garnier-Crussard27Anaïs Hamel28Sacha Haudry29Pierre Krolak-Salmon30Elizabeth Kuhn31Valérie Lefranc32Antoine Lutz33Valentin Ourry34Cassandre Palix35Anne Quillard36Géraldine Rauchs37Eric Salmon38Edelweiss Touron39Patrik Vuilleumier40Tim Whitfield41German Center for Neurodegenerative Diseases, Dresden, GermanyGerman Center for Neurodegenerative Diseases, Dresden, GermanyGerman Center for Neurodegenerative Diseases, Dresden, GermanyNormandie University, UNICAEN, French Institute of Health and Medical Research, INSERM, U1237, Physiopathology and Imaging of Neurological Disorders, NeuroPresage Team, GIP Cyceron, Caen, FranceNormandie University, UNICAEN, French Institute of Health and Medical Research, INSERM, U1237, Physiopathology and Imaging of Neurological Disorders, NeuroPresage Team, GIP Cyceron, Caen, FranceNormandie University, UNICAEN, French Institute of Health and Medical Research, INSERM, U1237, Physiopathology and Imaging of Neurological Disorders, NeuroPresage Team, GIP Cyceron, Caen, FranceNormandie University, UNICAEN, French Institute of Health and Medical Research, INSERM, U1237, Physiopathology and Imaging of Neurological Disorders, NeuroPresage Team, GIP Cyceron, Caen, FranceNormandie University, UNICAEN, French Institute of Health and Medical Research, INSERM, U1237, Physiopathology and Imaging of Neurological Disorders, NeuroPresage Team, GIP Cyceron, Caen, FranceNormandie University, UNICAEN, French Institute of Health and Medical Research, INSERM, U1237, Physiopathology and Imaging of Neurological Disorders, NeuroPresage Team, GIP Cyceron, Caen, FranceDivision of Psychiatry, University College London, London, United KingdomNormandie University, UNICAEN, French Institute of Health and Medical Research, INSERM, U1237, Physiopathology and Imaging of Neurological Disorders, NeuroPresage Team, GIP Cyceron, Caen, FranceTechnische Universität Dresden, Dresden, GermanyNormandie University, UNICAEN, French Institute of Health and Medical Research, INSERM, U1237, Physiopathology and Imaging of Neurological Disorders, NeuroPresage Team, GIP Cyceron, Caen, France; Géraldine Poisnel, Ph.D.German Center for Neurodegenerative Diseases, Dresden, Germany; Address correspondence to Miranka Wirth, Ph.D.Normandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, FranceNormandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, FranceNormandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, FranceGIGA–Cyclotron Research Centre, In Vivo Imaging and Psychology and Cognitive Neuroscience Unit, Liège University, Liège, BelgiumNormandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, France; Hospices Civils de Lyon, Lyon, FranceNormandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, FranceService de Neurologie, CHU de Caen-Normandie, Caen, FranceDivision of Psychiatry, University College London, London, United KingdomNormandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, FranceNormandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, FranceNormandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, FranceNormandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, FranceNormandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, FranceNormandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, France; Hospices Civils de Lyon, Lyon, FranceNormandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, FranceNormandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, FranceHospices Civils de Lyon, Lyon, FranceNormandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, FranceNormandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, FranceLyon Neuroscience Research Center, Institut National d la Santé et de la Recherche Médicale Unité 1028, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5292, Lyon University, Lyon, FranceNormandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, FranceNormandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, FranceNormandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, FranceNormandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, FranceGIGA–Cyclotron Research Centre, In Vivo Imaging and Psychology and Cognitive Neuroscience Unit, Liège University, Liège, BelgiumNormandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, FranceSwiss Center for Affective Sciences, Department of Medicine, University of Geneva, Geneva, SwitzerlandNormandie Université, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Caen, FranceBackground: Increased stress is a proposed risk factor for Alzheimer’s disease (AD). We examined cross-sectional associations between circulating stress biomarkers and multimodal measures of brain health and cognition susceptible to AD in older adults and sex-specific subgroups. Methods: Baseline data from 132 cognitively unimpaired participants without depression (age, mean ± SD = 74.0 ± 4.0 years, women: n = 80) in the Age-Well trial (NCT02977819) were included. Stress hormone levels were measured in overnight fasting blood serum (cortisol, dehydroepiandrosterone sulfate) and blood plasma (epinephrine, norepinephrine) samples. AD-sensitive measures of brain health, including glucose metabolism (n = 89), cerebral perfusion, gray matter volume, amyloid deposition in a priori regions of interest, and cognitive markers were evaluated. Models were adjusted for age, sex, education, trait anxiety, and depressive symptoms. Results: Higher epinephrine levels were associated (false discovery rate–corrected p < .05) with lower glucose metabolism in the anterior cingulate cortex (β = −0.26, p = .008), posterior cingulate cortex (β = −0.32, p = .006), and precuneus (β = −0.27, p = .021) and lower perfusion in the posterior cingulate cortex (β = −0.23, p = .013). Interactions between stress hormones and sex showed (false discovery rate–corrected p < .05) that in women only, higher epinephrine was associated with larger anterior cingulate cortex volume (interaction: β = 0.32, p = .016), whereas in men only, higher cortisol was associated with lower episodic memory performance (interaction: β = 0.98, p = .012). Conclusions: The current study demonstrates the involvement of circulating stress hormones, particularly epinephrine and cortisol, in greater resilience or vulnerability of brain health and cognitive indicators of susceptibility to AD in older adults. The identification of sex-specific patterns in these associations may inform the development of more effective and tailored interventions.http://www.sciencedirect.com/science/article/pii/S2667174324001447AgingAlzheimer’s diseaseHypothalamic-pituitary-adrenal (HPA)PreventionStressSympathetic-adrenal-medullary (SAM)
spellingShingle Maxie Liebscher
Silke White
Simon Hass
Anne Chocat
Florence Mezenge
Brigitte Landeau
Marion Delarue
Oriane Hébert
Anne-Laure Turpin
Natalie L. Marchant
Gaël Chételat
Olga Klimecki
Géraldine Poisnel
Miranka Wirth
Claire André
Pierre Champetier
Léa Chauveau
Fabienne Collette
Sophie Dautricourt
Robin de Flores
Vincent De La Sayette
Harriet Demnitz-King
Séverine Fauvel
Francesca Felisatti
Victor Ferment
Eglantine Ferrand-Devouge
Julie Gonneaud
Antoine Garnier-Crussard
Anaïs Hamel
Sacha Haudry
Pierre Krolak-Salmon
Elizabeth Kuhn
Valérie Lefranc
Antoine Lutz
Valentin Ourry
Cassandre Palix
Anne Quillard
Géraldine Rauchs
Eric Salmon
Edelweiss Touron
Patrik Vuilleumier
Tim Whitfield
Circulating Stress Hormones, Brain Health, and Cognition in Healthy Older Adults: Cross-Sectional Findings and Sex Differences in Age-Well
Biological Psychiatry Global Open Science
Aging
Alzheimer’s disease
Hypothalamic-pituitary-adrenal (HPA)
Prevention
Stress
Sympathetic-adrenal-medullary (SAM)
title Circulating Stress Hormones, Brain Health, and Cognition in Healthy Older Adults: Cross-Sectional Findings and Sex Differences in Age-Well
title_full Circulating Stress Hormones, Brain Health, and Cognition in Healthy Older Adults: Cross-Sectional Findings and Sex Differences in Age-Well
title_fullStr Circulating Stress Hormones, Brain Health, and Cognition in Healthy Older Adults: Cross-Sectional Findings and Sex Differences in Age-Well
title_full_unstemmed Circulating Stress Hormones, Brain Health, and Cognition in Healthy Older Adults: Cross-Sectional Findings and Sex Differences in Age-Well
title_short Circulating Stress Hormones, Brain Health, and Cognition in Healthy Older Adults: Cross-Sectional Findings and Sex Differences in Age-Well
title_sort circulating stress hormones brain health and cognition in healthy older adults cross sectional findings and sex differences in age well
topic Aging
Alzheimer’s disease
Hypothalamic-pituitary-adrenal (HPA)
Prevention
Stress
Sympathetic-adrenal-medullary (SAM)
url http://www.sciencedirect.com/science/article/pii/S2667174324001447
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