Age modulates the link between stress-related neural activity and mortality

Stress-related neural activity (SNA), as measured by amygdala metabolism, has been linked in prior work to all-cause mortality and major adverse cardiovascular events. In this study, we sought to clarify SNA determinants and test whether age modifies its association with all-cause mortality. Using 2-[18 F]fluoro-2-deoxy-D-glucose positron emission tomography (<sup>18</sup>F-FDG-PET), we quantified amygdala metabolism, a surrogate for SNA, in 1,336 patients (mean age 59.4 ± 15.6 years, 37.8% women). Assessing demographic and imaging confounders, associations between SNA and mortality were evaluated in a subgroup of 960 participants with a median 5-year follow-up (IQR 3-9). Higher SNA appears independently associated with greater all-cause mortality across all age groups (HR 1.45, 95% CI 1.08-1.95; p = 0.012). The association is strongest in younger, healthier individuals (HR 7.86, 95% CI 2.92-21.21; p < 0.001) and attenuates with advancing age. Mediation analysis indicates that SNA accounts for 38.2% (95% CI 15.7%-60.7%) of the age-mortality link. Here, we find that SNA is independently associated with all-cause mortality, with effect sizes that diminish with age; if confirmed, incorporating SNA into risk models alongside conventional factors may improve mortality prediction and help identify younger adults, who appear low risk by standard criteria, for closer follow-up and preventive strategies.

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Publication Details

Journal
Nature Communications
Published
2025-11-07
DOI
https://doi.org/10.1038/s41467-025-64802-3
Primary Topic
Stress Responses and Cortisol
Type
article
Field-Weighted Citation Impact
0.00

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article

Age modulates the link between stress-related neural activity and mortality

Ahmed Haider, Cathérine Gebhard, Atanas Todorov, Valérie Treyer et al.
Nature Communications
Stress Responses and Cortisol
article

Age modulates the link between stress-related neural activity and mortality

Ahmed Haider, Cathérine Gebhard, Atanas Todorov, Valérie Treyer, Aju P. Pazhenkottil, Susan Bengs, Alexia Rossi, Caroline E. Gebhard, Philipp Antonio Kaufmann, Christoph Gräni, Ronny R. Buechel, Vera Regitz‐Zagrosek, Noemi Sablonier, Pimrapat Gebert, Isabelle Glarner, Nidaa Mikaïl, Susanne Wegener, Felix Christoph Tanner, Adriana Vinzens, Angela Portmann
article en

Abstract

Stress-related neural activity (SNA), as measured by amygdala metabolism, has been linked in prior work to all-cause mortality and major adverse cardiovascular events. In this study, we sought to clarify SNA determinants and test whether age modifies its association with all-cause mortality. Using 2-[18 F]fluoro-2-deoxy-D-glucose positron emission tomography (<sup>18</sup>F-FDG-PET), we quantified amygdala metabolism, a surrogate for SNA, in 1,336 patients (mean age 59.4 ± 15.6 years, 37.8% women). Assessing demographic and imaging confounders, associations between SNA and mortality were evaluated in a subgroup of 960 participants with a median 5-year follow-up (IQR 3-9). Higher SNA appears independently associated with greater all-cause mortality across all age groups (HR 1.45, 95% CI 1.08-1.95; p = 0.012). The association is strongest in younger, healthier individuals (HR 7.86, 95% CI 2.92-21.21; p < 0.001) and attenuates with advancing age. Mediation analysis indicates that SNA accounts for 38.2% (95% CI 15.7%-60.7%) of the age-mortality link. Here, we find that SNA is independently associated with all-cause mortality, with effect sizes that diminish with age; if confirmed, incorporating SNA into risk models alongside conventional factors may improve mortality prediction and help identify younger adults, who appear low risk by standard criteria, for closer follow-up and preventive strategies.

Nature CommunicationsVol. 16(1)
University of Bern (CH), Harvard University (US), University of Zurich (CH), University Hospital of Bern (CH), University Hospital of Basel (CH), Massachusetts General Hospital (US), Zimmer Biomet (Germany) (DE), University Hospital of Zurich (CH), Charité - Universitätsmedizin Berlin (DE)
National Science Foundation, Amgen, Novartis Foundation, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Universität Zürich, Baugarten Stiftung, EMDO Stiftung, Universitätsspital Zürich, Olga Mayenfisch Stiftung, Innosuisse - Schweizerische Agentur für Innovationsförderung, Helmut Horten Stiftung, UZH Foundation
Openalex Percentile: Top 65%
Stress Responses and Cortisol
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