Lifetime Stressful Events Associated with Alzheimer's Pathologies, Neuroinflammation and Brain Structure in a Risk Enriched Cohort
Objective Along with the known effects of stress on brain structure and inflammatory processes, increasing evidence suggest a role of chronic stress in the pathogenesis of Alzheimer's disease (AD). We investigated the association of accumulated stressful life events (SLEs) with AD pathologies,...
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| Veröffentlicht in: | Annals of neurology 2024-06, Vol.95 (6), p.1058-1068 |
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| container_title | Annals of neurology |
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| creator | Palpatzis, Eleni Akinci, Muge Aguilar‐Dominguez, Pablo Garcia‐Prat, Marina Blennow, Kaj Zetterberg, Henrik Carboni, Margherita Kollmorgen, Gwendlyn Wild, Norbert Fauria, Karine Falcon, Carles Gispert, Juan Domingo Suárez‐Calvet, Marc Grau‐Rivera, Oriol Sánchez‐Benavides, Gonzalo Arenaza‐Urquijo, Eider M. Peña‐Gómez, Cleofé Anastasi, Federica Beteta, Annabella Brugulat‐Serrat, Anna Cacciaglia, Raffaele Cumplido‐Mayoral, Irene Cañas, Alba Campo, Marta Deulofeu, Carme Cumplido, Irene Dominguez, Ruth Emilio, Maria Fuentes, Sherezade Genius, Patricia González‐Escalante, Armand Hernández, Laura Huguet, Jordi Marne, Paula Menchón, Tania Minguillon, Carolina Ortiz, Paula Pelkmans, Wiesje Polo, Albina Pradas, Sandra Rodríguez‐Fernéndez, Blanca Sadeghi, Iman Shekari, Mahnaz Soteras, Anna Stankeviciute, Laura Vilanova, Marc Vilor‐Tejedor, Natalia |
| description | Objective
Along with the known effects of stress on brain structure and inflammatory processes, increasing evidence suggest a role of chronic stress in the pathogenesis of Alzheimer's disease (AD). We investigated the association of accumulated stressful life events (SLEs) with AD pathologies, neuroinflammation, and gray matter (GM) volume among cognitively unimpaired (CU) individuals at heightened risk of AD.
Methods
This cross‐sectional cohort study included 1,290 CU participants (aged 48–77) from the ALFA cohort with SLE, lumbar puncture (n = 393), and/or structural magnetic resonance imaging (n = 1,234) assessments. Using multiple regression analyses, we examined the associations of total SLEs with cerebrospinal fluid (1) phosphorylated (p)‐tau181 and Aβ1–42/1–40 ratio, (2) interleukin 6 (IL‐6), and (3) GM volumes voxel‐wise. Further, we performed stratified and interaction analyses with sex, history of psychiatric disease, and evaluated SLEs during specific life periods.
Results
Within the whole sample, only childhood and midlife SLEs, but not total SLEs, were associated with AD pathophysiology and neuroinflammation. Among those with a history of psychiatric disease SLEs were associated with higher p‐tau181 and IL‐6. Participants with history of psychiatric disease and men, showed lower Aβ1–42/1–40 with higher SLEs. Participants with history of psychiatric disease and women showed reduced GM volumes in somatic regions and prefrontal and limbic regions, respectively.
Interpretation
We did not find evidence supporting the association of total SLEs with AD, neuroinflammation, and atrophy pathways. Instead, the associations appear to be contingent on events occurring during early and midlife, sex and history of psychiatric disease. ANN NEUROL 2024;95:1058–1068 |
| doi_str_mv | 10.1002/ana.26881 |
| format | Article |
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Along with the known effects of stress on brain structure and inflammatory processes, increasing evidence suggest a role of chronic stress in the pathogenesis of Alzheimer's disease (AD). We investigated the association of accumulated stressful life events (SLEs) with AD pathologies, neuroinflammation, and gray matter (GM) volume among cognitively unimpaired (CU) individuals at heightened risk of AD.
Methods
This cross‐sectional cohort study included 1,290 CU participants (aged 48–77) from the ALFA cohort with SLE, lumbar puncture (n = 393), and/or structural magnetic resonance imaging (n = 1,234) assessments. Using multiple regression analyses, we examined the associations of total SLEs with cerebrospinal fluid (1) phosphorylated (p)‐tau181 and Aβ1–42/1–40 ratio, (2) interleukin 6 (IL‐6), and (3) GM volumes voxel‐wise. Further, we performed stratified and interaction analyses with sex, history of psychiatric disease, and evaluated SLEs during specific life periods.
Results
Within the whole sample, only childhood and midlife SLEs, but not total SLEs, were associated with AD pathophysiology and neuroinflammation. Among those with a history of psychiatric disease SLEs were associated with higher p‐tau181 and IL‐6. Participants with history of psychiatric disease and men, showed lower Aβ1–42/1–40 with higher SLEs. Participants with history of psychiatric disease and women showed reduced GM volumes in somatic regions and prefrontal and limbic regions, respectively.
Interpretation
We did not find evidence supporting the association of total SLEs with AD, neuroinflammation, and atrophy pathways. Instead, the associations appear to be contingent on events occurring during early and midlife, sex and history of psychiatric disease. ANN NEUROL 2024;95:1058–1068</description><identifier>ISSN: 0364-5134</identifier><identifier>EISSN: 1531-8249</identifier><identifier>DOI: 10.1002/ana.26881</identifier><identifier>PMID: 38466157</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Aged ; Alzheimer Disease - diagnostic imaging ; Alzheimer Disease - pathology ; Alzheimer's disease ; Amyloid beta-Peptides - cerebrospinal fluid ; Amyloid beta-Peptides - metabolism ; Atrophy ; Brain ; Brain - diagnostic imaging ; Brain - pathology ; Cerebrospinal fluid ; Children ; Cohort Studies ; Cross-Sectional Studies ; Female ; Gray Matter - diagnostic imaging ; Gray Matter - pathology ; Humans ; Inflammation ; Interleukin 6 ; Interleukin-6 - cerebrospinal fluid ; Magnetic Resonance Imaging ; Male ; Mental disorders ; Middle age ; Middle Aged ; Multiple regression analysis ; Neurodegenerative diseases ; Neuroimaging ; Neuroinflammatory Diseases - diagnostic imaging ; Neuroinflammatory Diseases - pathology ; Pathogenesis ; Peptide Fragments - cerebrospinal fluid ; Sex ; Stress, Psychological ; Substantia grisea ; tau Proteins - cerebrospinal fluid</subject><ispartof>Annals of neurology, 2024-06, Vol.95 (6), p.1058-1068</ispartof><rights>2024 Barcelonabeta Brain Research Center and The Authors. published by Wiley Periodicals LLC on behalf of American Neurological Association.</rights><rights>2024 Barcelonabeta Brain Research Center and The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.</rights><rights>2024. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3481-72d06d26126adb365121c6432f609f76f9de292a0191174b9fd6e595aa8369593</cites><orcidid>0000-0001-8478-273X ; 0000-0001-7016-7576 ; 0000-0002-2993-569X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fana.26881$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fana.26881$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38466157$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Palpatzis, Eleni</creatorcontrib><creatorcontrib>Akinci, Muge</creatorcontrib><creatorcontrib>Aguilar‐Dominguez, Pablo</creatorcontrib><creatorcontrib>Garcia‐Prat, Marina</creatorcontrib><creatorcontrib>Blennow, Kaj</creatorcontrib><creatorcontrib>Zetterberg, Henrik</creatorcontrib><creatorcontrib>Carboni, Margherita</creatorcontrib><creatorcontrib>Kollmorgen, Gwendlyn</creatorcontrib><creatorcontrib>Wild, Norbert</creatorcontrib><creatorcontrib>Fauria, Karine</creatorcontrib><creatorcontrib>Falcon, Carles</creatorcontrib><creatorcontrib>Gispert, Juan Domingo</creatorcontrib><creatorcontrib>Suárez‐Calvet, Marc</creatorcontrib><creatorcontrib>Grau‐Rivera, Oriol</creatorcontrib><creatorcontrib>Sánchez‐Benavides, Gonzalo</creatorcontrib><creatorcontrib>Arenaza‐Urquijo, Eider M.</creatorcontrib><creatorcontrib>Peña‐Gómez, Cleofé</creatorcontrib><creatorcontrib>Anastasi, Federica</creatorcontrib><creatorcontrib>Beteta, Annabella</creatorcontrib><creatorcontrib>Brugulat‐Serrat, Anna</creatorcontrib><creatorcontrib>Cacciaglia, Raffaele</creatorcontrib><creatorcontrib>Cumplido‐Mayoral, Irene</creatorcontrib><creatorcontrib>Cañas, Alba</creatorcontrib><creatorcontrib>Campo, Marta</creatorcontrib><creatorcontrib>Deulofeu, Carme</creatorcontrib><creatorcontrib>Cumplido, Irene</creatorcontrib><creatorcontrib>Dominguez, Ruth</creatorcontrib><creatorcontrib>Emilio, Maria</creatorcontrib><creatorcontrib>Fuentes, Sherezade</creatorcontrib><creatorcontrib>Genius, Patricia</creatorcontrib><creatorcontrib>González‐Escalante, Armand</creatorcontrib><creatorcontrib>Hernández, Laura</creatorcontrib><creatorcontrib>Huguet, Jordi</creatorcontrib><creatorcontrib>Marne, Paula</creatorcontrib><creatorcontrib>Menchón, Tania</creatorcontrib><creatorcontrib>Minguillon, Carolina</creatorcontrib><creatorcontrib>Ortiz, Paula</creatorcontrib><creatorcontrib>Pelkmans, Wiesje</creatorcontrib><creatorcontrib>Polo, Albina</creatorcontrib><creatorcontrib>Pradas, Sandra</creatorcontrib><creatorcontrib>Rodríguez‐Fernéndez, Blanca</creatorcontrib><creatorcontrib>Sadeghi, Iman</creatorcontrib><creatorcontrib>Shekari, Mahnaz</creatorcontrib><creatorcontrib>Soteras, Anna</creatorcontrib><creatorcontrib>Stankeviciute, Laura</creatorcontrib><creatorcontrib>Vilanova, Marc</creatorcontrib><creatorcontrib>Vilor‐Tejedor, Natalia</creatorcontrib><creatorcontrib>ALFA study</creatorcontrib><creatorcontrib>for the ALFA study</creatorcontrib><title>Lifetime Stressful Events Associated with Alzheimer's Pathologies, Neuroinflammation and Brain Structure in a Risk Enriched Cohort</title><title>Annals of neurology</title><addtitle>Ann Neurol</addtitle><description>Objective
Along with the known effects of stress on brain structure and inflammatory processes, increasing evidence suggest a role of chronic stress in the pathogenesis of Alzheimer's disease (AD). We investigated the association of accumulated stressful life events (SLEs) with AD pathologies, neuroinflammation, and gray matter (GM) volume among cognitively unimpaired (CU) individuals at heightened risk of AD.
Methods
This cross‐sectional cohort study included 1,290 CU participants (aged 48–77) from the ALFA cohort with SLE, lumbar puncture (n = 393), and/or structural magnetic resonance imaging (n = 1,234) assessments. Using multiple regression analyses, we examined the associations of total SLEs with cerebrospinal fluid (1) phosphorylated (p)‐tau181 and Aβ1–42/1–40 ratio, (2) interleukin 6 (IL‐6), and (3) GM volumes voxel‐wise. Further, we performed stratified and interaction analyses with sex, history of psychiatric disease, and evaluated SLEs during specific life periods.
Results
Within the whole sample, only childhood and midlife SLEs, but not total SLEs, were associated with AD pathophysiology and neuroinflammation. Among those with a history of psychiatric disease SLEs were associated with higher p‐tau181 and IL‐6. Participants with history of psychiatric disease and men, showed lower Aβ1–42/1–40 with higher SLEs. Participants with history of psychiatric disease and women showed reduced GM volumes in somatic regions and prefrontal and limbic regions, respectively.
Interpretation
We did not find evidence supporting the association of total SLEs with AD, neuroinflammation, and atrophy pathways. Instead, the associations appear to be contingent on events occurring during early and midlife, sex and history of psychiatric disease. ANN NEUROL 2024;95:1058–1068</description><subject>Aged</subject><subject>Alzheimer Disease - diagnostic imaging</subject><subject>Alzheimer Disease - pathology</subject><subject>Alzheimer's disease</subject><subject>Amyloid beta-Peptides - cerebrospinal fluid</subject><subject>Amyloid beta-Peptides - metabolism</subject><subject>Atrophy</subject><subject>Brain</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - pathology</subject><subject>Cerebrospinal fluid</subject><subject>Children</subject><subject>Cohort Studies</subject><subject>Cross-Sectional Studies</subject><subject>Female</subject><subject>Gray Matter - diagnostic imaging</subject><subject>Gray Matter - pathology</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Interleukin 6</subject><subject>Interleukin-6 - cerebrospinal fluid</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Mental disorders</subject><subject>Middle age</subject><subject>Middle Aged</subject><subject>Multiple regression analysis</subject><subject>Neurodegenerative diseases</subject><subject>Neuroimaging</subject><subject>Neuroinflammatory Diseases - diagnostic imaging</subject><subject>Neuroinflammatory Diseases - pathology</subject><subject>Pathogenesis</subject><subject>Peptide Fragments - cerebrospinal fluid</subject><subject>Sex</subject><subject>Stress, Psychological</subject><subject>Substantia grisea</subject><subject>tau Proteins - cerebrospinal fluid</subject><issn>0364-5134</issn><issn>1531-8249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp10U9LHDEYx_EgLbraHnwDJdBDW-ho_kyyk-N0WVthsUXrOWRnnnRiZxJNMhU9-sqd7aqHQk8h8OHLAz-EDik5ooSwY-PNEZNVRXfQjApOi4qV6hWaES7LQlBe7qH9lK4IIUpSsov2eFVKScV8hh5WzkJ2A-CLHCElO_Z4-Qd8TrhOKTTOZGjxrcsdrvv7DiYZPyT8w-Qu9OGXg_QZn8EYg_O2N8NgsgseG9_iL9E4v6mOTR4j4Olj8LlLv_HSR9d0U3YRuhDzG_Tamj7B26f3AF2eLH8uvhWr719PF_WqaHhZ0WLOWiJbJimTpl1zKSijjSw5s5IoO5dWtcAUM4QqSuflWtlWglDCmIpLJRQ_QB-33esYbkZIWQ8uNdD3xkMYk2ZKCCZFxdlE3_9Dr8IY_XSd5kSISjAlN8FPW9XEkFIEq6-jG0y805TozTB6Gkb_HWay756K43qA9kU-LzGB4y24dT3c_b-k67N6m3wEQFOW7w</recordid><startdate>202406</startdate><enddate>202406</enddate><creator>Palpatzis, Eleni</creator><creator>Akinci, Muge</creator><creator>Aguilar‐Dominguez, Pablo</creator><creator>Garcia‐Prat, Marina</creator><creator>Blennow, Kaj</creator><creator>Zetterberg, Henrik</creator><creator>Carboni, Margherita</creator><creator>Kollmorgen, Gwendlyn</creator><creator>Wild, Norbert</creator><creator>Fauria, Karine</creator><creator>Falcon, Carles</creator><creator>Gispert, Juan Domingo</creator><creator>Suárez‐Calvet, Marc</creator><creator>Grau‐Rivera, Oriol</creator><creator>Sánchez‐Benavides, Gonzalo</creator><creator>Arenaza‐Urquijo, Eider M.</creator><creator>Peña‐Gómez, Cleofé</creator><creator>Anastasi, Federica</creator><creator>Beteta, Annabella</creator><creator>Brugulat‐Serrat, Anna</creator><creator>Cacciaglia, Raffaele</creator><creator>Cumplido‐Mayoral, Irene</creator><creator>Cañas, Alba</creator><creator>Campo, Marta</creator><creator>Deulofeu, Carme</creator><creator>Cumplido, Irene</creator><creator>Dominguez, Ruth</creator><creator>Emilio, Maria</creator><creator>Fuentes, Sherezade</creator><creator>Genius, Patricia</creator><creator>González‐Escalante, Armand</creator><creator>Hernández, Laura</creator><creator>Huguet, Jordi</creator><creator>Marne, Paula</creator><creator>Menchón, Tania</creator><creator>Minguillon, Carolina</creator><creator>Ortiz, Paula</creator><creator>Pelkmans, Wiesje</creator><creator>Polo, Albina</creator><creator>Pradas, Sandra</creator><creator>Rodríguez‐Fernéndez, Blanca</creator><creator>Sadeghi, Iman</creator><creator>Shekari, Mahnaz</creator><creator>Soteras, Anna</creator><creator>Stankeviciute, Laura</creator><creator>Vilanova, Marc</creator><creator>Vilor‐Tejedor, Natalia</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8478-273X</orcidid><orcidid>https://orcid.org/0000-0001-7016-7576</orcidid><orcidid>https://orcid.org/0000-0002-2993-569X</orcidid></search><sort><creationdate>202406</creationdate><title>Lifetime Stressful Events Associated with Alzheimer's Pathologies, Neuroinflammation and Brain Structure in a Risk Enriched Cohort</title><author>Palpatzis, Eleni ; Akinci, Muge ; Aguilar‐Dominguez, Pablo ; Garcia‐Prat, Marina ; Blennow, Kaj ; Zetterberg, Henrik ; Carboni, Margherita ; Kollmorgen, Gwendlyn ; Wild, Norbert ; Fauria, Karine ; Falcon, Carles ; Gispert, Juan Domingo ; Suárez‐Calvet, Marc ; Grau‐Rivera, Oriol ; Sánchez‐Benavides, Gonzalo ; Arenaza‐Urquijo, Eider M. ; Peña‐Gómez, Cleofé ; Anastasi, Federica ; Beteta, Annabella ; Brugulat‐Serrat, Anna ; Cacciaglia, Raffaele ; Cumplido‐Mayoral, Irene ; Cañas, Alba ; Campo, Marta ; Deulofeu, Carme ; Cumplido, Irene ; Dominguez, Ruth ; Emilio, Maria ; Fuentes, Sherezade ; Genius, Patricia ; González‐Escalante, Armand ; Hernández, Laura ; Huguet, Jordi ; Marne, Paula ; Menchón, Tania ; Minguillon, Carolina ; Ortiz, Paula ; Pelkmans, Wiesje ; Polo, Albina ; Pradas, Sandra ; Rodríguez‐Fernéndez, Blanca ; Sadeghi, Iman ; Shekari, Mahnaz ; Soteras, Anna ; Stankeviciute, Laura ; Vilanova, Marc ; Vilor‐Tejedor, Natalia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3481-72d06d26126adb365121c6432f609f76f9de292a0191174b9fd6e595aa8369593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Aged</topic><topic>Alzheimer Disease - diagnostic imaging</topic><topic>Alzheimer Disease - pathology</topic><topic>Alzheimer's disease</topic><topic>Amyloid beta-Peptides - cerebrospinal fluid</topic><topic>Amyloid beta-Peptides - metabolism</topic><topic>Atrophy</topic><topic>Brain</topic><topic>Brain - diagnostic imaging</topic><topic>Brain - pathology</topic><topic>Cerebrospinal fluid</topic><topic>Children</topic><topic>Cohort Studies</topic><topic>Cross-Sectional Studies</topic><topic>Female</topic><topic>Gray Matter - diagnostic imaging</topic><topic>Gray Matter - pathology</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Interleukin 6</topic><topic>Interleukin-6 - cerebrospinal fluid</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Mental disorders</topic><topic>Middle age</topic><topic>Middle Aged</topic><topic>Multiple regression analysis</topic><topic>Neurodegenerative diseases</topic><topic>Neuroimaging</topic><topic>Neuroinflammatory Diseases - diagnostic imaging</topic><topic>Neuroinflammatory Diseases - pathology</topic><topic>Pathogenesis</topic><topic>Peptide Fragments - cerebrospinal fluid</topic><topic>Sex</topic><topic>Stress, Psychological</topic><topic>Substantia grisea</topic><topic>tau Proteins - cerebrospinal fluid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Palpatzis, Eleni</creatorcontrib><creatorcontrib>Akinci, Muge</creatorcontrib><creatorcontrib>Aguilar‐Dominguez, Pablo</creatorcontrib><creatorcontrib>Garcia‐Prat, Marina</creatorcontrib><creatorcontrib>Blennow, Kaj</creatorcontrib><creatorcontrib>Zetterberg, Henrik</creatorcontrib><creatorcontrib>Carboni, Margherita</creatorcontrib><creatorcontrib>Kollmorgen, Gwendlyn</creatorcontrib><creatorcontrib>Wild, Norbert</creatorcontrib><creatorcontrib>Fauria, Karine</creatorcontrib><creatorcontrib>Falcon, Carles</creatorcontrib><creatorcontrib>Gispert, Juan Domingo</creatorcontrib><creatorcontrib>Suárez‐Calvet, Marc</creatorcontrib><creatorcontrib>Grau‐Rivera, Oriol</creatorcontrib><creatorcontrib>Sánchez‐Benavides, Gonzalo</creatorcontrib><creatorcontrib>Arenaza‐Urquijo, Eider M.</creatorcontrib><creatorcontrib>Peña‐Gómez, Cleofé</creatorcontrib><creatorcontrib>Anastasi, Federica</creatorcontrib><creatorcontrib>Beteta, Annabella</creatorcontrib><creatorcontrib>Brugulat‐Serrat, Anna</creatorcontrib><creatorcontrib>Cacciaglia, Raffaele</creatorcontrib><creatorcontrib>Cumplido‐Mayoral, Irene</creatorcontrib><creatorcontrib>Cañas, Alba</creatorcontrib><creatorcontrib>Campo, Marta</creatorcontrib><creatorcontrib>Deulofeu, Carme</creatorcontrib><creatorcontrib>Cumplido, Irene</creatorcontrib><creatorcontrib>Dominguez, Ruth</creatorcontrib><creatorcontrib>Emilio, Maria</creatorcontrib><creatorcontrib>Fuentes, Sherezade</creatorcontrib><creatorcontrib>Genius, Patricia</creatorcontrib><creatorcontrib>González‐Escalante, Armand</creatorcontrib><creatorcontrib>Hernández, Laura</creatorcontrib><creatorcontrib>Huguet, Jordi</creatorcontrib><creatorcontrib>Marne, Paula</creatorcontrib><creatorcontrib>Menchón, Tania</creatorcontrib><creatorcontrib>Minguillon, Carolina</creatorcontrib><creatorcontrib>Ortiz, Paula</creatorcontrib><creatorcontrib>Pelkmans, Wiesje</creatorcontrib><creatorcontrib>Polo, Albina</creatorcontrib><creatorcontrib>Pradas, Sandra</creatorcontrib><creatorcontrib>Rodríguez‐Fernéndez, Blanca</creatorcontrib><creatorcontrib>Sadeghi, Iman</creatorcontrib><creatorcontrib>Shekari, Mahnaz</creatorcontrib><creatorcontrib>Soteras, Anna</creatorcontrib><creatorcontrib>Stankeviciute, Laura</creatorcontrib><creatorcontrib>Vilanova, Marc</creatorcontrib><creatorcontrib>Vilor‐Tejedor, Natalia</creatorcontrib><creatorcontrib>ALFA study</creatorcontrib><creatorcontrib>for the ALFA study</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Palpatzis, Eleni</au><au>Akinci, Muge</au><au>Aguilar‐Dominguez, Pablo</au><au>Garcia‐Prat, Marina</au><au>Blennow, Kaj</au><au>Zetterberg, Henrik</au><au>Carboni, Margherita</au><au>Kollmorgen, Gwendlyn</au><au>Wild, Norbert</au><au>Fauria, Karine</au><au>Falcon, Carles</au><au>Gispert, Juan Domingo</au><au>Suárez‐Calvet, Marc</au><au>Grau‐Rivera, Oriol</au><au>Sánchez‐Benavides, Gonzalo</au><au>Arenaza‐Urquijo, Eider M.</au><au>Peña‐Gómez, Cleofé</au><au>Anastasi, Federica</au><au>Beteta, Annabella</au><au>Brugulat‐Serrat, Anna</au><au>Cacciaglia, Raffaele</au><au>Cumplido‐Mayoral, Irene</au><au>Cañas, Alba</au><au>Campo, Marta</au><au>Deulofeu, Carme</au><au>Cumplido, Irene</au><au>Dominguez, Ruth</au><au>Emilio, Maria</au><au>Fuentes, Sherezade</au><au>Genius, Patricia</au><au>González‐Escalante, Armand</au><au>Hernández, Laura</au><au>Huguet, Jordi</au><au>Marne, Paula</au><au>Menchón, Tania</au><au>Minguillon, Carolina</au><au>Ortiz, Paula</au><au>Pelkmans, Wiesje</au><au>Polo, Albina</au><au>Pradas, Sandra</au><au>Rodríguez‐Fernéndez, Blanca</au><au>Sadeghi, Iman</au><au>Shekari, Mahnaz</au><au>Soteras, Anna</au><au>Stankeviciute, Laura</au><au>Vilanova, Marc</au><au>Vilor‐Tejedor, Natalia</au><aucorp>ALFA study</aucorp><aucorp>for the ALFA study</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lifetime Stressful Events Associated with Alzheimer's Pathologies, Neuroinflammation and Brain Structure in a Risk Enriched Cohort</atitle><jtitle>Annals of neurology</jtitle><addtitle>Ann Neurol</addtitle><date>2024-06</date><risdate>2024</risdate><volume>95</volume><issue>6</issue><spage>1058</spage><epage>1068</epage><pages>1058-1068</pages><issn>0364-5134</issn><eissn>1531-8249</eissn><abstract>Objective
Along with the known effects of stress on brain structure and inflammatory processes, increasing evidence suggest a role of chronic stress in the pathogenesis of Alzheimer's disease (AD). We investigated the association of accumulated stressful life events (SLEs) with AD pathologies, neuroinflammation, and gray matter (GM) volume among cognitively unimpaired (CU) individuals at heightened risk of AD.
Methods
This cross‐sectional cohort study included 1,290 CU participants (aged 48–77) from the ALFA cohort with SLE, lumbar puncture (n = 393), and/or structural magnetic resonance imaging (n = 1,234) assessments. Using multiple regression analyses, we examined the associations of total SLEs with cerebrospinal fluid (1) phosphorylated (p)‐tau181 and Aβ1–42/1–40 ratio, (2) interleukin 6 (IL‐6), and (3) GM volumes voxel‐wise. Further, we performed stratified and interaction analyses with sex, history of psychiatric disease, and evaluated SLEs during specific life periods.
Results
Within the whole sample, only childhood and midlife SLEs, but not total SLEs, were associated with AD pathophysiology and neuroinflammation. Among those with a history of psychiatric disease SLEs were associated with higher p‐tau181 and IL‐6. Participants with history of psychiatric disease and men, showed lower Aβ1–42/1–40 with higher SLEs. Participants with history of psychiatric disease and women showed reduced GM volumes in somatic regions and prefrontal and limbic regions, respectively.
Interpretation
We did not find evidence supporting the association of total SLEs with AD, neuroinflammation, and atrophy pathways. Instead, the associations appear to be contingent on events occurring during early and midlife, sex and history of psychiatric disease. ANN NEUROL 2024;95:1058–1068</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>38466157</pmid><doi>10.1002/ana.26881</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-8478-273X</orcidid><orcidid>https://orcid.org/0000-0001-7016-7576</orcidid><orcidid>https://orcid.org/0000-0002-2993-569X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0364-5134 |
| ispartof | Annals of neurology, 2024-06, Vol.95 (6), p.1058-1068 |
| issn | 0364-5134 1531-8249 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2955265832 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Aged Alzheimer Disease - diagnostic imaging Alzheimer Disease - pathology Alzheimer's disease Amyloid beta-Peptides - cerebrospinal fluid Amyloid beta-Peptides - metabolism Atrophy Brain Brain - diagnostic imaging Brain - pathology Cerebrospinal fluid Children Cohort Studies Cross-Sectional Studies Female Gray Matter - diagnostic imaging Gray Matter - pathology Humans Inflammation Interleukin 6 Interleukin-6 - cerebrospinal fluid Magnetic Resonance Imaging Male Mental disorders Middle age Middle Aged Multiple regression analysis Neurodegenerative diseases Neuroimaging Neuroinflammatory Diseases - diagnostic imaging Neuroinflammatory Diseases - pathology Pathogenesis Peptide Fragments - cerebrospinal fluid Sex Stress, Psychological Substantia grisea tau Proteins - cerebrospinal fluid |
| title | Lifetime Stressful Events Associated with Alzheimer's Pathologies, Neuroinflammation and Brain Structure in a Risk Enriched Cohort |
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