[en] [en] 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. [en] In the current study, we investigated how stress hormones are associated with indicators of brain health and cognition related to Alzheimer’s disease in older adults. We examined 132 cognitively unimpaired older participants and measured hormone levels in blood as well as several brain and cognition health markers. Our results showed that higher levels of circulating epinephrine were linked to lower glucose metabolism and cerebral perfusion in key areas affected in Alzheimer’s disease. Notably, in women only, higher levels of epinephrine were associated with greater brain volume in the anterior cingulate cortex, while in men only, higher cortisol levels were linked to poorer memory performance. These findings suggest that stress hormones may affect brain and cognitive health and that responses may differ by sex, which could guide future intervention strategies.
Disciplines :
Neurosciences & behavior
Author, co-author :
Liebscher, Maxie; German Center for Neurodegenerative Diseases, Dresden, Germany
White, Silke; German Center for Neurodegenerative Diseases, Dresden, Germany
Hass, Simon; German Center for Neurodegenerative Diseases, Dresden, Germany
Chocat, Anne; Normandie University, UNICAEN, French Institute of Health and Medical Research, INSERM, U1237, Physiopathology and Imaging of Neurological Disorders, NeuroPresage Team, GIP Cyceron, Caen, France
Mezenge, Florence; Normandie University, UNICAEN, French Institute of Health and Medical Research, INSERM, U1237, Physiopathology and Imaging of Neurological Disorders, NeuroPresage Team, GIP Cyceron, Caen, France
Landeau, Brigitte; Normandie University, UNICAEN, French Institute of Health and Medical Research, INSERM, U1237, Physiopathology and Imaging of Neurological Disorders, NeuroPresage Team, GIP Cyceron, Caen, France
Delarue, Marion; Normandie University, UNICAEN, French Institute of Health and Medical Research, INSERM, U1237, Physiopathology and Imaging of Neurological Disorders, NeuroPresage Team, GIP Cyceron, Caen, France
Hébert, Oriane; Normandie University, UNICAEN, French Institute of Health and Medical Research, INSERM, U1237, Physiopathology and Imaging of Neurological Disorders, NeuroPresage Team, GIP Cyceron, Caen, France
Turpin, Anne-Laure; Normandie University, UNICAEN, French Institute of Health and Medical Research, INSERM, U1237, Physiopathology and Imaging of Neurological Disorders, NeuroPresage Team, GIP Cyceron, Caen, France
Marchant, Natalie L; Division of Psychiatry, University College London, London, United Kingdom
Chételat, Gaël; Normandie University, UNICAEN, French Institute of Health and Medical Research, INSERM, U1237, Physiopathology and Imaging of Neurological Disorders, NeuroPresage Team, GIP Cyceron, Caen, France
Klimecki, Olga ; Université de Liège - ULiège > Département de Psychologie > Neuropsychologie de l'adulte ; Technische Universität Dresden, Dresden, Germany
Poisnel, Géraldine; Normandie University, UNICAEN, French Institute of Health and Medical Research, INSERM, U1237, Physiopathology and Imaging of Neurological Disorders, NeuroPresage Team, GIP Cyceron, Caen, France
Wirth, Miranka; German Center for Neurodegenerative Diseases, Dresden, Germany
Collette, Fabienne ; Université de Liège - ULiège > Département de Psychologie > Neuropsychologie de l'adulte ; ULiège - Université de Liège > GIGA > GIGA-CRC Human Imaging
Language :
English
Title :
Circulating Stress Hormones, Brain Health, and Cognition in Healthy Older Adults: Cross-Sectional Findings and Sex Differences in Age-Well.
The Age-Well randomized clinical trial is part of the Medit-Ageing project and is funded through the European Union's Horizon 2020 Research and Innovation Program (Grant No. 667696), Institut National de la Sant\u00E9 et de la Recherche M\u00E9dicale (INSERM), R\u00E9gion Normandie, and Fondation MMA des Entrepreneurs du Futur. GC, GP, and MW were responsible for conceptualization. AC, FM, BL, MD, OH, ALT, ML, SW, OK, GP, and MW were responsible for acquisition, methodology, or validation. ML, SW, OK, GP, and MW were responsible for writing the original draft of the article. ML, SW, SH, AC, FM, NLM, GC, OK, GP, and MW were responsible for writing, reviewing, and editing the article. ML, SW, SH, and MW were responsible for statistical analysis. GC, GP, OK, and NLM were responsible for funding acquisition. AC, BL, FM, MD, NLM, and OH were responsible for project administration. OK, GP, and MW were responsible for supervision. Other principal investigators: Vincent De La Sayette (Medit-Ageing Research Group). We thank A. Cognet, C. Gaubert, T. Jorand, M. Botton, M.Sc. A. Joret Philippe, M.Sc. S. Egret, M.Sc. P. Lacheray, M.Sc. J. Lebahar, Ph.D. L. Paly, M.Sc. C. Tomadesso, Ph.D. H Esp\u00E9rou, M.D. E. Frison, M.D. Ph.D. and the Cyceron MRI-PET staff members for their help with recruitment and data acquisition or administrative support. We acknowledge the Euclid team, the sponsor (INSERM P\u00F4le de Recherche Clinique), and all the participants of the study for their contribution. We acknowledge the Medit-Ageing Research Group. The data underlying this study are made available on request following approval by the executive committee and a formal data-sharing agreement (https://silversantestudy.eu/2020/09/25/data-sharing). The data can be mobilized, under the conditions and modalities defined in the Medit-Ageing Chartery, by any research team that belongs to an academic institution for carrying out a scientific research project related to the scientific theme of mental health and wellbeing in older people. The data may also be mobilized by nonacademic third parties, under conditions, in particular financial, which will be established by separate agreement between INSERM and said third party. Data-sharing policies described in the Medit-Ageing Charter are in compliance with the ethics approval and guidelines of our funding body. Data contain potentially identifying or sensitive patient information. To request data, please contact the data access committee via the official project website (https://silversantestudy.eu/2020/09/25/data-sharing). The R scripts that were used for the analyses for the current study are available via the Open Science Framework (https://osf.io/4vp8g/). GC, GP, OK, and NLM report support from European Union's Horizon 2020 Research and Innovation Program (Grant No. 667696). All other authors report no biomedical financial interests or potential conflicts of interest.Funding: The Age-Well randomized clinical trial is part of the Medit-Aging project and is funded through the European Union\u2019s Horizon 2020 Research and Innovation Program (grant 667696), Institut National de la Sant\u00E9 et de la Recherche M\u00E9dicale, R\u00E9gion Normandie, and Fondation MMA des Entrepreneurs du Futur.Dr. Ga\u00EBl Ch\u00E9telat reports a grant from European Union\u2019s Horizon 2020 research and innovation programme (grant 667696).
Machado, A., Herrera, A.J., de Pablos, R.M., Espinosa-Oliva, A.M., Sarmiento, M., Ayala, A., et al. Chronic stress as a risk factor for Alzheimer's disease. Rev Neurosci 25 (2014), 785–804.
Justice, N.J., The relationship between stress and Alzheimer's disease. Neurobiol Stress 8 (2018), 127–133.
Islamoska, S., Hansen, Å.M., Ishtiak-Ahmed, K., Garde, A.H., Andersen, P.K., Garde, E., et al. Stress diagnoses in midlife and risk of dementia: A register-based follow-up study. Aging Ment Health 25 (2021), 1151–1160.
Wallensten, J., Ljunggren, G., Nager, A., Wachtler, C., Bogdanovic, N., Petrovic, P., Carlsson, A.C., Stress, depression, and risk of dementia – A cohort study in the total population between 18 and 65 years old in Region Stockholm. Alzheimers Res Ther, 15, 2023, 161.
Luo, J., Beam, C.R., Gatz, M., Is stress an overlooked risk factor for dementia? A systematic review from a lifespan developmental perspective. Prev Sci 24 (2023), 936–949.
Rasmuson, S., Näsman, B., Carlström, K., Olsson, T., Increased levels of adrenocortical and gonadal hormones in mild to moderate Alzheimer's disease. Dement Geriatr Cogn Disord 13 (2002), 74–79.
Popp, J., Schaper, K., al Kölsch, H., Cvetanovska, G., Rommel, F., Klingmüller, D., et al. CSF cortisol in Alzheimer's disease and mild cognitive impairment. Neurobiol Aging 30 (2009), 498–500.
Dronse, J., Ohndorf, A., Richter, N., Bischof, G.N., Fassbender, R., Behfar, Q., et al. Serum cortisol is negatively related to hippocampal volume, brain structure, and memory performance in healthy aging and Alzheimer's disease. Front Aging Neurosci, 15, 2023, 1154112.
Martignoni, E., Petraglia, F., Costa, A., Bono, G., Genazzani, A.R., Nappi, G., Dementia of the Alzheimer type and hypothalamus-pituitary-adrenocortical axis: Changes in cerebrospinal fluid corticotropin releasing factor and plasma cortisol levels. Acta Neurol Scand 81 (1990), 452–456.
Zheng, B., Tal, R., Yang, Z., Middleton, L., Udeh-Momoh, C., Cortisol hypersecretion and the risk of Alzheimer's disease: A systematic review and meta-analysis. Ageing Res Rev, 64, 2020, 101171.
Aldred, S., Mecocci, P., Decreased dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) concentrations in plasma of Alzheimer's disease (AD) patients. Arch Gerontol Geriatr 51 (2010), e16–e18.
Henjum, K., Watne, L.O., Godang, K., Halaas, N.B., Eldholm, R.S., Blennow, K., et al. Cerebrospinal fluid catecholamines in Alzheimer's disease patients with and without biological disease. Transl Psychiatry, 12, 2022, 151.
Fitzgerald, P.J., Is elevated norepinephrine an etiological factor in some cases of Alzheimer's disease?. Curr Alzheimer Res 7 (2010), 506–516.
Pan, X., Kaminga, A.C., Jia, P., Wen, S.W., Acheampong, K., Liu, A., Catecholamines in Alzheimer's disease: A systematic review and meta-analysis. Front Aging Neurosci, 12, 2020, 184.
Engert, V., Vogel, S., Efanov, S.I., Duchesne, A., Corbo, V., Ali, N., Pruessner, J.C., Investigation into the cross-correlation of salivary cortisol and alpha-amylase responses to psychological stress. Psychoneuroendocrinology 36 (2011), 1294–1302.
Godoy, L.D., Rossignoli, M.T., Delfino-Pereira, P., Garcia-Cairasco, N., de Lima Umeoka, E.H., A comprehensive overview on stress neurobiology: Basic concepts and clinical implications. Front Behav Neurosci, 12, 2018, 127.
Maninger, N., Wolkowitz, O.M., Reus, V.I., Epel, E.S., Mellon, S.H., Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). Front Neuroendocrinol 30 (2009), 65–91.
Wurtman, R.J., Stress and the adrenocortical control of epinephrine synthesis. Metabolism 51:suppl 1 (2002), 11–14.
Wong, D.L., Tai, T.C., Wong-Faull, D.C., Claycomb, R., Meloni, E.G., Myers, K.M., et al. Epinephrine: A short- and long-term regulator of stress and development of illness: A potential new role for epinephrine in stress. Cell Mol Neurobiol 32 (2012), 737–748.
White, S., Mauer, R., Lange, C., Klimecki, O., Huijbers, W., Wirth, M., Alzheimer's Disease Neuroimaging Initiative. The effect of plasma cortisol on hippocampal atrophy and clinical progression in mild cognitive impairment. Alzheimers Dement (Amst), 15, 2023, e12463.
Lupien, S.J., de Leon, M., de Santi, S., Convit, A., Tarshish, C., Nair, N.P., et al. Cortisol levels during human aging predict hippocampal atrophy and memory deficits. Nat Neurosci 1 (1998), 69–73.
Wirth, M., Lange, C., Huijbers, W., Alzheimer's Disease Neuroimaging Initiative. Plasma cortisol is associated with cerebral hypometabolism across the Alzheimer's disease spectrum. Neurobiol Aging 84 (2019), 80–89.
Geerlings, M.I., Sigurdsson, S., Eiriksdottir, G., Garcia, M.E., Harris, T.B., Gudnason, V., Launer, L.J., Salivary cortisol, brain volumes, and cognition in community-dwelling elderly without dementia. Neurology 85 (2015), 976–983.
Lebedeva, A., Sundström, A., Lindgren, L., Stomby, A., Aarsland, D., Westman, E., et al. Longitudinal relationships among depressive symptoms, cortisol, and brain atrophy in the neocortex and the hippocampus. Acta Psychiatr Scand 137 (2018), 491–502.
Toledo, J.B., Da, X., Bhatt, P., Wolk, D.A., Arnold, S.E., Shaw, L.M., et al. Relationship between plasma analytes and SPARE-AD defined brain atrophy patterns in ADNI. PLoS One, 8, 2013, e55531.
Echouffo-Tcheugui, J.B., Conner, S.C., Himali, J.J., Maillard, P., DeCarli, C.S., Beiser, A.S., et al. Circulating cortisol and cognitive and structural brain measures: The Framingham Heart Study. Neurology 91 (2018), e1961–e1970.
Stomby, A., Boraxbekk, C.J., Lundquist, A., Nordin, A., Nilsson, L.G., Adolfsson, R., et al. Higher diurnal salivary cortisol levels are related to smaller prefrontal cortex surface area in elderly men and women. Eur J Endocrinol 175 (2016), 117–126.
Toledo, J.B., Toledo, E., Weiner, M.W., Jack, C.R. Jr., Jagust, W., Lee, V.M.Y., et al. Cardiovascular risk factors, cortisol, and amyloid-beta deposition in Alzheimer's Disease Neuroimaging Initiative. Alzheimers Dement 8 (2012), 483–489.
MacLullich, A.M.J., Ferguson, K.J., Wardlaw, J.M., Starr, J.M., Deary, I.J., Seckl, J.R., Smaller left anterior cingulate cortex volumes are associated with impaired hypothalamic-pituitary-adrenal axis regulation in healthy elderly men. J Clin Endocrinol Metab 91 (2006), 1591–1594.
Touron, E., de Flores, R., Coulbaut, L., Palix, C., Chocat, A., Kuhn, E., et al. Depressive symptoms in older adults are associated with changes in stress-related markers, functional connectivity and brain volume. Alz Res Therapy, 17, 2025, 9.
Pulopulos, M.M., Hidalgo, V., Almela, M., Puig-Perez, S., Villada, C., Salvador, A., Hair cortisol and cognitive performance in healthy older people. Psychoneuroendocrinology 44 (2014), 100–111.
Lee, B.K., Glass, T.A., Wand, G.S., McAtee, M.J., Bandeen-Roche, K., Bolla, K.I., Schwartz, B.S., Apolipoprotein E genotype, cortisol, and cognitive function in community-dwelling older adults. Am J Psychiatry 165 (2008), 1456–1464.
Lupien, S.J., McEwen, B.S., Gunnar, M.R., Heim, C., Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 10 (2009), 434–445.
Ouanes, S., Clark, C., Richiardi, J., Maréchal, B., Lewczuk, P., Kornhuber, J., et al. Cerebrospinal fluid cortisol and dehydroepiandrosterone sulfate, Alzheimer's disease pathology, and cognitive decline. Front Aging Neurosci, 14, 2022, 892754.
Pietrzak, R.H., Laws, S.M., Lim, Y.Y., Bender, S.J., Porter, T., Doecke, J., et al. Plasma cortisol, brain amyloid-β, and cognitive decline in preclinical Alzheimer's disease: A 6-year prospective cohort study. Biol Psychiatry Cogn Neurosci Neuroimaging 2 (2017), 45–52.
Valenti, G., Ferrucci, L., Lauretani, F., Ceresini, G., Bandinelli, S., Luci, M., et al. Dehydroepiandrosterone sulfate and cognitive function in the elderly: The InCHIANTI Study. J Endocrinol Invest 32 (2009), 766–772.
Wang, L.Y., Murphy, R.R., Hanscom, B., Li, G., Millard, S.P., Petrie, E.C., et al. Cerebrospinal fluid norepinephrine and cognition in subjects across the adult age span. Neurobiol Aging 34 (2013), 2287–2292.
Jacobs, H.I.L., Riphagen, J.M., Ramakers, I.H.G.B., Verhey, F.R.J., Alzheimer's disease pathology: Pathways between central norepinephrine activity, memory, and neuropsychiatric symptoms. Mol Psychiatry 26 (2021), 897–906.
Ross, J.A., McGonigle, P., Van Bockstaele, E.J., Locus coeruleus, norepinephrine and Aβ peptides in Alzheimer's disease. Neurobiol Stress 2 (2015), 73–84.
Bale, T.L., Epperson, C.N., Sex differences and stress across the lifespan. Nat Neurosci 18 (2015), 1413–1420.
Kudielka, B.M., Kirschbaum, C., Sex differences in HPA axis responses to stress: A review. Biol Psychol 69 (2005), 113–132.
Yan, Y., Dominguez, S., Fisher, D.W., Dong, H., Sex differences in chronic stress responses and Alzheimer's disease. Neurobiol Stress 8 (2018), 120–126.
Poisnel, G., Arenaza-Urquijo, E., Collette, F., Klimecki, O.M., Marchant, N.L., Wirth, M., et al. The Age-well randomized controlled trial of the MEdit-Ageing European project: Effect of meditation or foreign language training on brain and mental health in older adults. Alzheimers Dement (N Y) 4 (2018), 714–723.
Papp, K.V., Rentz, D.M., Orlovsky, I., Sperling, R.A., Mormino, E.C., Optimizing the preclinical Alzheimer's cognitive composite with semantic processing: The PACC5. Alzheimers Dement (N Y) 3 (2017), 668–677.
Demnitz-King, H., Requier, F., Whitfield, T., Schlosser, M., Gonneaud, J., Ware, C., et al. Effects of meditation training and non-native language training on cognition in older adults: A secondary analysis of a randomized clinical trial. JAMA Netw Open, 6, 2023, e2317848.
Montgomery, S.A., Asberg, M., A new depression scale designed to be sensitive to change. Br J Psychiatry 134 (1979), 382–389.
Chételat, G., Lutz, A., Klimecki, O., Frison, E., Asselineau, J., Schlosser, M., et al. Effect of an 18-month meditation training on regional brain volume and perfusion in older adults: The age-well randomized clinical trial. JAMA Neurol 79 (2022), 1165–1174.
André, C., Rehel, S., Kuhn, E., Landeau, B., Moulinet, I., Touron, E., et al. Association of sleep-disordered breathing with Alzheimer disease biomarkers in community-dwelling older adults: A secondary analysis of a randomized clinical trial. JAMA Neurol 77 (2020), 716–724.
Demnitz-King, H., Gonneaud, J., Klimecki, O.M., Chocat, A., Collette, F., Dautricourt, S., et al. Association of self-reflection, cognition, and brain health in cognitively unimpaired older adults. Neurology 99 (2022), e1422–e1431.
Klunk, W.E., Koeppe, R.A., Price, J.C., Benzinger, T.L., Devous, M.D., Jagust, W.J., et al. The Centiloid Project: Standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement 11 (2015), 1–15.e1.
Navitsky, M., Joshi, A.D., Kennedy, I., Klunk, W.E., Rowe, C.C., Wong, D.F., et al. Standardization of amyloid quantitation with florbetapir standardized uptake value ratios to the Centiloid scale. Alzheimers Dement 14 (2018), 1565–1571.
La Joie, R., Ayakta, N., Seeley, W.W., Borys, E., Boxer, A.L., DeCarli, C., et al. Multisite study of the relationships between antemortem [11C]PIB-PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology. Alzheimers Dement 15 (2019), 205–216.
Spielberger, C.D., Gorsuch, R.L., Lushene, R., Vagg, P.R., Jacobs, G.A., Manual for the State-Trait Anxiety Inventory. 1983, Consulting Psychologists Press, Palo Alto, CA.
Yesavage, J.A., Brink, T.L., Rose, T.L., Lum, O., Huang, V., Adey, M., Leirer, V.O., Development and validation of a geriatric depression screening scale: A preliminary report. J Psychiatr Res 17 (1982-1983), 37–49.
Schiepers, O.J.G., Köhler, S., Deckers, K., Irving, K., O'Donnell, C.A., van den Akker, M., et al. Lifestyle for Brain Health (LIBRA): A new model for dementia prevention. Int J Geriatr Psychiatry 33 (2018), 167–175.
Lange, C., Suppa, P., Frings, L., Brenner, W., Spies, L., Buchert, R., Optimization of statistical single subject analysis of brain FDG PET for the prognosis of mild cognitive impairment-to-Alzheimer's disease conversion. J Alzheimers Dis 49 (2016), 945–959.
Landau, S.M., Harvey, D., Madison, C.M., Koeppe, R.A., Reiman, E.M., Foster, N.L., et al. Associations between cognitive, functional, and FDG-PET measures of decline in AD and MCI. Neurobiol Aging 32 (2011), 1207–1218.
Wirth, M., Pichet Binette, A., Brunecker, P., Köbe, T., Witte, A.V., Flöel, A., Divergent regional patterns of cerebral hypoperfusion and gray matter atrophy in mild cognitive impairment patients. J Cereb Blood Flow Metab 37 (2017), 814–824.
Landau, S.M., Harvey, D., Madison, C.M., Reiman, E.M., Foster, N.L., Aisen, P.S., et al. Comparing predictors of conversion and decline in mild cognitive impairment. Neurology 75 (2010), 230–238.
Landau, S.M., Mintun, M.A., Joshi, A.D., Koeppe, R.A., Petersen, R.C., Aisen, P.S., et al. Amyloid deposition, hypometabolism, and longitudinal cognitive decline. Ann Neurol 72 (2012), 578–586.
Rodrigues, S.M., LeDoux, J.E., Sapolsky, R.M., The influence of stress hormones on fear circuitry. Annu Rev Neurosci 32 (2009), 289–313.
Langbaum, J.B.S., Chen, K., Launer, L.J., Fleisher, A.S., Lee, W., Liu, X., et al. Blood pressure is associated with higher brain amyloid burden and lower glucose metabolism in healthy late middle-age persons. Neurobiol Aging 33 (2012), 827.e11–827.e19.
Wirth, M., Gaubert, M., Köbe, T., Garnier-Crussard, A., Lange, C., Gonneaud, J., et al. Vascular health is associated with functional connectivity decline in higher-order networks of older adults. Front Integr Neurosci, 16, 2022, 847824.
Misquitta, K.A., Miles, A., Prevot, T.D., Knoch, J.K., Fee, C., Newton, D.F., et al. Reduced anterior cingulate cortex volume induced by chronic stress correlates with increased behavioral emotionality and decreased synaptic puncta density. Neuropharmacology, 190, 2021, 108562.
Ansell, E.B., Rando, K., Tuit, K., Guarnaccia, J., Sinha, R., Cumulative adversity and smaller gray matter volume in medial prefrontal, anterior cingulate, and insula regions. Biol Psychiatry 72 (2012), 57–64.
Papagni, S.A., Benetti, S., Arulanantham, S., McCrory, E., McGuire, P., Mechelli, A., Effects of stressful life events on human brain structure: A longitudinal voxel-based morphometry study. Stress 14 (2011), 227–232.
Shin, L.M., Liberzon, I., The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology 35 (2010), 169–191.
Yucel, K., McKinnon, M.C., Chahal, R., Taylor, V.H., Macdonald, K., Joffe, R., MacQueen, G.M., Anterior cingulate volumes in never-treated patients with major depressive disorder. Neuropsychopharmacology 33 (2008), 3157–3163.
Cera, N., Esposito, R., Cieri, F., Tartaro, A., Altered cingulate cortex functional connectivity in normal aging and mild cognitive impairment. Front Neurosci, 13, 2019, 857.
de Godoy, L.L., Alves, C.A.P.F., Saavedra, J.S.M., Studart-Neto, A., Nitrini, R., da Costa Leite, C., Bisdas, S., Understanding brain resilience in superagers: A systematic review. Neuroradiology 63 (2021), 663–683.
Arenaza-Urquijo, E.M., Landeau, B., La Joie, R., Mevel, K., Mézenge, F., Perrotin, A., et al. Relationships between years of education and gray matter volume, metabolism and functional connectivity in healthy elders. Neuroimage 83 (2013), 450–457.
Arenaza-Urquijo, E.M., Przybelski, S.A., Lesnick, T.L., Graff-Radford, J., Machulda, M.M., Knopman, D.S., et al. The metabolic brain signature of cognitive resilience in the 80+: Beyond Alzheimer pathologies. Brain 142 (2019), 1134–1147.
Holz, N.E., Boecker, R., Jennen-Steinmetz, C., Buchmann, A.F., Blomeyer, D., Baumeister, S., et al. Positive coping styles and perigenual ACC volume: Two related mechanisms for conferring resilience?. Soc Cogn Affect Neurosci 11 (2016), 813–820.
van Der Werff, S.J., van Den Berg, S.M., Pannekoek, J.N., Elzinga, B.M., van Der Wee, N.J., Neuroimaging resilience to stress: A review. Front Behav Neurosci, 7, 2013, 39.
Luine, V., Gomez, J., Beck, K., Bowman, R., Sex differences in chronic stress effects on cognition in rodents. Pharmacol Biochem Behav 152 (2017), 13–19.
Beck, K.D., Luine, V.N., Sex differences in behavioral and neurochemical profiles after chronic stress: Role of housing conditions. Physiol Behav 75 (2002), 661–673.
Bowman, R.E., Micik, R., Gautreaux, C., Fernandez, L., Luine, V.N., Sex-dependent changes in anxiety, memory, and monoamines following one week of stress. Physiol Behav 97 (2009), 21–29.
Wei, J., Yuen, E.Y., al Liu, W., Li, X., Zhong, P., Karatsoreos, I.N., et al. Estrogen protects against the detrimental effects of repeated stress on glutamatergic transmission and cognition. Mol Psychiatry 19 (2014), 588–598.
Bowman, R.E., Zrull, M.C., Luine, V.N., Chronic restraint stress enhances radial arm maze performance in female rats. Brain Res 904 (2001), 279–289.
Kitraki, E., Kremmyda, O., Youlatos, D., Alexis, M.N., Kittas, C., Gender-dependent alterations in corticosteroid receptor status and spatial performance following 21 days of restraint stress. Neuroscience 125 (2004), 47–55.
Ortiz, J.B., Taylor, S.B., Hoffman, A.N., Campbell, A.N., Lucas, L.R., Conrad, C.D., Sex-specific impairment and recovery of spatial learning following the end of chronic unpredictable restraint stress: Potential relevance of limbic GAD. Behav Brain Res 282 (2015), 176–184.
Paolillo, E.W., You, M., Gontrum, E., Saloner, R., Gaynor, L.S., Kramer, J.H., Casaletto, K.B., Sex differences in the relationship between perceived stress and cognitive trajectories. Am J Geriatr Psychiatry 31 (2023), 401–410.
McEwen, B.S., Neurobiological and systemic effects of chronic stress. Chronic Stress (Thousand Oaks), 1, 2017, 2470547017692328.
McEwen, B.S., Sleep deprivation as a neurobiologic and physiologic stressor: Allostasis and allostatic load. Metabolism 55:suppl 2 (2006), S20–S23.
Stalder, T., Kirschbaum, C., Analysis of cortisol in hair—State of the art and future directions. Brain Behav Immun 26 (2012), 1019–1029.
