Depressive symptoms in older adults are associated with changes in stress-related markers, functional connectivity and brain volume
Abstract Background Subclinical depressive symptoms increase the risk of developing Alzheimer’s disease (AD). The neurobiological mechanisms underlying this link may involve stress system dysfunction, notably related to the hippocampus which is particularly sensitive to AD. We aimed to investigate t...
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BMC
2025-01-01
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| Series: | Alzheimer’s Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13195-024-01643-0 |
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| author | Edelweiss Touron Robin de Flores Laurent Coulbault Cassandre Palix Anne Chocat Elizabeth Kuhn Brigitte Landeau Florence Mézenge Daniel Roquet Léa Chauveau Sacha Haudry Denis Vivien Vincent de La Sayette Natalie L. Marchant Gaël Chételat Géraldine Poisnel for the Medit-Ageing Research Group |
| author_facet | Edelweiss Touron Robin de Flores Laurent Coulbault Cassandre Palix Anne Chocat Elizabeth Kuhn Brigitte Landeau Florence Mézenge Daniel Roquet Léa Chauveau Sacha Haudry Denis Vivien Vincent de La Sayette Natalie L. Marchant Gaël Chételat Géraldine Poisnel for the Medit-Ageing Research Group |
| author_sort | Edelweiss Touron |
| collection | DOAJ |
| description | Abstract Background Subclinical depressive symptoms increase the risk of developing Alzheimer’s disease (AD). The neurobiological mechanisms underlying this link may involve stress system dysfunction, notably related to the hippocampus which is particularly sensitive to AD. We aimed to investigate the links between blood stress markers and changes in brain regions involved in the stress response in older adults with or without subclinical depressive symptoms. Methods This cross-sectional study was conducted using baseline data from the Age-Well trial. Cognitively unimpaired (CU) older adults with (DepS; n = 73) or without (NoDepS; n = 58) subclinical depressive symptoms (defined using the 15-item Geriatric Depression Scale) were included in the analyses. Blood cortisol, epinephrine and norepinephrine were measured; as well as the resting-state functional connectivity (rs-FC) between, and gray matter (GM) volume of, the hypothalamus, hippocampus and hippocampal subfields. Blood stress markers levels and neuroimaging measures were compared between groups; then regression analyses were conducted between these measures. Results DepS participants showed higher plasma epinephrine levels, which was associated with greater rs-FC between the CA1 and Subiculum hippocampal subfields and the hypothalamus. Lower GM volume in the CA1 and DG/CA2-3–4 subfields was also found in DepS. No between-group differences were observed for blood cortisol and norepinephrine. Conclusions Our findings show that subclinical depressive symptoms are associated with increased sympatho-adrenomedullary axis activity, together with lower GM volume in a hippocampal subfield (i.e., CA1) particularly sensitive to AD. While causation cannot be inferred, these results suggest that screening and treating subclinical depressive symptoms in CU older adults could reduce AD risk. Trial registration ClinicalTrials.gov Identifier: NCT02977819, Registration Date: 2016–11-25. |
| format | Article |
| id | doaj-art-5269f1a77812496187b22a0ea3a08085 |
| institution | Kabale University |
| issn | 1758-9193 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Alzheimer’s Research & Therapy |
| spelling | doaj-art-5269f1a77812496187b22a0ea3a080852025-01-12T12:10:54ZengBMCAlzheimer’s Research & Therapy1758-91932025-01-0117111410.1186/s13195-024-01643-0Depressive symptoms in older adults are associated with changes in stress-related markers, functional connectivity and brain volumeEdelweiss Touron0Robin de Flores1Laurent Coulbault2Cassandre Palix3Anne Chocat4Elizabeth Kuhn5Brigitte Landeau6Florence Mézenge7Daniel Roquet8Léa Chauveau9Sacha Haudry10Denis Vivien11Vincent de La Sayette12Natalie L. Marchant13Gaël Chételat14Géraldine Poisnel15for the Medit-Ageing Research GroupNormandie Univ, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP CyceronNormandie Univ, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP CyceronNormandie Univ, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP CyceronNormandie Univ, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP CyceronNormandie Univ, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP CyceronNormandie Univ, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP CyceronNormandie Univ, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP CyceronNormandie Univ, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP CyceronNormandie Univ, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP CyceronNormandie Univ, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP CyceronNormandie Univ, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP CyceronNormandie Univ, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP CyceronService de Neurologie, CHU de Caen-NormandieDivision of Psychiatry, University College LondonNormandie Univ, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP CyceronNormandie Univ, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP CyceronAbstract Background Subclinical depressive symptoms increase the risk of developing Alzheimer’s disease (AD). The neurobiological mechanisms underlying this link may involve stress system dysfunction, notably related to the hippocampus which is particularly sensitive to AD. We aimed to investigate the links between blood stress markers and changes in brain regions involved in the stress response in older adults with or without subclinical depressive symptoms. Methods This cross-sectional study was conducted using baseline data from the Age-Well trial. Cognitively unimpaired (CU) older adults with (DepS; n = 73) or without (NoDepS; n = 58) subclinical depressive symptoms (defined using the 15-item Geriatric Depression Scale) were included in the analyses. Blood cortisol, epinephrine and norepinephrine were measured; as well as the resting-state functional connectivity (rs-FC) between, and gray matter (GM) volume of, the hypothalamus, hippocampus and hippocampal subfields. Blood stress markers levels and neuroimaging measures were compared between groups; then regression analyses were conducted between these measures. Results DepS participants showed higher plasma epinephrine levels, which was associated with greater rs-FC between the CA1 and Subiculum hippocampal subfields and the hypothalamus. Lower GM volume in the CA1 and DG/CA2-3–4 subfields was also found in DepS. No between-group differences were observed for blood cortisol and norepinephrine. Conclusions Our findings show that subclinical depressive symptoms are associated with increased sympatho-adrenomedullary axis activity, together with lower GM volume in a hippocampal subfield (i.e., CA1) particularly sensitive to AD. While causation cannot be inferred, these results suggest that screening and treating subclinical depressive symptoms in CU older adults could reduce AD risk. Trial registration ClinicalTrials.gov Identifier: NCT02977819, Registration Date: 2016–11-25.https://doi.org/10.1186/s13195-024-01643-0Depressive symptomsAgingCortisolCatecholaminesHypothalamusHippocampal subfields |
| spellingShingle | Edelweiss Touron Robin de Flores Laurent Coulbault Cassandre Palix Anne Chocat Elizabeth Kuhn Brigitte Landeau Florence Mézenge Daniel Roquet Léa Chauveau Sacha Haudry Denis Vivien Vincent de La Sayette Natalie L. Marchant Gaël Chételat Géraldine Poisnel for the Medit-Ageing Research Group Depressive symptoms in older adults are associated with changes in stress-related markers, functional connectivity and brain volume Alzheimer’s Research & Therapy Depressive symptoms Aging Cortisol Catecholamines Hypothalamus Hippocampal subfields |
| title | Depressive symptoms in older adults are associated with changes in stress-related markers, functional connectivity and brain volume |
| title_full | Depressive symptoms in older adults are associated with changes in stress-related markers, functional connectivity and brain volume |
| title_fullStr | Depressive symptoms in older adults are associated with changes in stress-related markers, functional connectivity and brain volume |
| title_full_unstemmed | Depressive symptoms in older adults are associated with changes in stress-related markers, functional connectivity and brain volume |
| title_short | Depressive symptoms in older adults are associated with changes in stress-related markers, functional connectivity and brain volume |
| title_sort | depressive symptoms in older adults are associated with changes in stress related markers functional connectivity and brain volume |
| topic | Depressive symptoms Aging Cortisol Catecholamines Hypothalamus Hippocampal subfields |
| url | https://doi.org/10.1186/s13195-024-01643-0 |
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