Prepandemic alzheimer disease biomarkers and anxious-depressive symptoms during the COVID-19 confinement in cognitively unimpaired adults

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• dc.contributor.author Akinci, Muge
• dc.contributor.author Peña-Gómez, Cleofé
• dc.contributor.author Operto, Grégory
• dc.contributor.author Fuentes-Julian, Sherezade
• dc.contributor.author Deulofeu, Carme
• dc.contributor.author Sánchez Benavides, Gonzalo
• dc.contributor.author Milà Alomà, Marta
• dc.contributor.author Grau-Rivera, Oriol
• dc.contributor.author Gramunt Fombuena, Nina
• dc.contributor.author Navarro i Cuartiellas, Arcadi, 1969-
• dc.contributor.author Minguillón, Carolina
• dc.contributor.author Fauria, Karine
• dc.contributor.author Suridjan, Ivonne
• dc.contributor.author Kollmorgen, Gwendlyn
• dc.contributor.author Bayfield, Anna
• dc.contributor.author Blennow, Kaj
• dc.contributor.author Zetterberg, Henrik
• dc.contributor.author Molinuevo, José Luis
• dc.contributor.author Suárez-Calvet, Marc
• dc.contributor.author Gispert López, Juan Domingo
• dc.contributor.author Arenaza Urquijo, Eider M.
• dc.contributor.author ALFA Study
• dc.date.accessioned 2022-11-17T07:01:42Z
• dc.date.available 2022-11-17T07:01:42Z
• dc.date.issued 2022
• dc.description.abstract Background and objectives: Increased anxious-depressive symptomatology is observed in the preclinical stage of Alzheimer disease (AD), which may accelerate disease progression. We investigated whether β-amyloid, cortical thickness in medial temporal lobe structures, neuroinflammation, and sociodemographic factors were associated with greater anxious-depressive symptoms during the COVID-19 confinement. Methods: This retrospective observational study included cognitively unimpaired older adults from the Alzheimer's and Families cohort, the majority with a family history of sporadic AD. Participants performed the Hospital Anxiety and Depression Scale (HADS) during the COVID-19 confinement. A subset had available retrospective (on average: 2.4 years before) HADS assessment, amyloid [18F] flutemetamol PET and structural MRI scans, and CSF markers of neuroinflammation (interleukin-6 [IL-6], triggering receptor expressed on myeloid cells 2, and glial fibrillary acidic protein levels). We performed multivariable linear regression models to investigate the associations of prepandemic AD-related biomarkers and sociodemographic factors with HADS scores during the confinement. We further performed an analysis of covariance to adjust by participants' prepandemic anxiety-depression levels. Finally, we explored the role of stress and lifestyle changes (sleep patterns, eating, drinking, smoking habits, and medication use) on the tested associations and performed sex-stratified analyses. Results: We included 921 (254 with AD biomarkers) participants. β-amyloid positivity (B = 3.73; 95% CI = 1.1 to 6.36; p = 0.006), caregiving (B = 1.37; 95% CI 0.24-2.5; p = 0.018), sex (women: B = 1.95; 95% CI 1.1-2.79; p < 0.001), younger age (B = -0.12; 95% CI -0.18 to -0.052; p < 0.001), and lower education (B = -0.16; 95% CI -0.28 to -0.042; p = 0.008) were associated with greater anxious-depressive symptoms during the confinement. Considering prepandemic anxiety-depression levels, we further observed an association between lower levels of CSF IL-6 (B = -5.11; 95% CI -10.1 to -0.13; p = 0.044) and greater HADS scores. The results were independent of stress-related variables and lifestyle changes. Stratified analysis revealed that the associations were mainly driven by women. Discussion: Our results link AD-related pathophysiology and neuroinflammation with greater anxious-depressive symptomatology during the COVID-19-related confinement, notably in women. AD pathophysiology may increase neuropsychiatric symptomatology in response to stressors. This association may imply a worse clinical prognosis in people at risk for AD after the pandemic and thus deserves to be considered by clinicians. Trial registration information: ClinicalTrials.gov Identifier NCT02485730.
• dc.format.mimetype application/pdf
• dc.identifier.citation Akinci M, Peña-Gómez C, Operto G, Fuentes-Julian S, Deulofeu C, Sánchez-Benavides G, Milà-Alomà M, Grau-Rivera O, Gramunt N, Navarro A, Minguillón C, Fauria K, Suridjan I, Kollmorgen G, Bayfield A, Blennow K, Zetterberg H, Molinuevo JL, Suárez-Calvet M, Gispert JD, Arenaza-Urquijo EM; ALFA Study. Prepandemic alzheimer disease biomarkers and anxious-depressive symptoms during the COVID-19 confinement in cognitively unimpaired adults. Neurology. 2022 Oct 4;99(14):e1486-e1498. DOI: 10.1212/WNL.0000000000200948
• dc.identifier.doi http://dx.doi.org/10.1212/WNL.0000000000200948
• dc.identifier.issn 0028-3878
• dc.identifier.uri http://hdl.handle.net/10230/54902
• dc.language.iso eng
• dc.publisher Lippincott Williams & Wilkins
• dc.relation.ispartof Neurology. 2022 Oct 4;99(14):e1486-e1498
• dc.rights © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.title Prepandemic alzheimer disease biomarkers and anxious-depressive symptoms during the COVID-19 confinement in cognitively unimpaired adults
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion