Muge Akinci1, Cleofé Peña-Gómez1, Gregory Operto1, Sherezade Fuentes-Julian1, Carme Deulofeu1, Gonzalo Sánchez-Benavides1, Marta Milà-Alomà1, Oriol Grau-Rivera1, Nina Gramunt1, Arcadi Navarro1, Carolina Minguillón1, Karine Fauria1, Ivonne Suridjan1, Gwendlyn Kollmorgen1, Anna Bayfield1, Kaj Blennow1, Henrik Zetterberg1, José Luis Molinuevo1, Marc Suárez-Calvet1, Juan Domingo Gispert1, Eider M Arenaza-Urquijo2. 1. From the BarcelonaBeta Brain Research Center (BBRC) (M.A., C.P.-G., G.O., S.F.-J., C.D., G.S.-B., M.M.-A., O.G.-R., A.N., C.M., K.F., J.L.M., M.S.-C., J.D.G., E.M.A.-U.), Pasqual Maragall Foundation, Barcelona; Universitat Pompeu Fabra (M.A., M.M.-A., A.N., J.D.G.), Barcelona; IMIM (Hospital del Mar Medical Research Institute) (G.S.-B., M.M.-A., O.G.-R., C.M., M.S.-C., J.D.G., E.M.A.-U.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES) (G.S.-B., O.G.-R., C.M., K.F., M.S.-C., E.M.A.-U.), Madrid; Servei de Neurologia (O.G.-R., M.S.-C.), Hospital del Mar, Barcelona; Fundació Pasqual Maragall (N.G.), Barcelona; Centre for Genomic Regulation (CRG) (A.N.), Barcelona Institute of Science and Technology (BIST); Institute of Evolutionary Biology (UPF-CSIC) (A.N.), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona; Institució Catalana de Recerca i Estudis Avançats (ICREA) (A.N.), Barcelona, Spain; Roche Diagnostics International Ltd (I.S.), Rotkreuz, Switzerland; Roche Diagnostics GmbH (G.K., A.B.), Penzberg, Germany; Department of Psychiatry and Neurochemistry (K.B., H.Z.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; UK Dementia Research Institute at UCL (H.Z.), London; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London, United Kingdom; Hong Kong Center for Neurodegenerative Diseases (H.Z.), China; H. Lundbeck A/S (J.L.M.), Denmark; and Centro de Investigación Biomédica en Red Bioingeniería (J.D.G.), Biomateriales y Nanomedicina, Madrid, Spain. 2. From the BarcelonaBeta Brain Research Center (BBRC) (M.A., C.P.-G., G.O., S.F.-J., C.D., G.S.-B., M.M.-A., O.G.-R., A.N., C.M., K.F., J.L.M., M.S.-C., J.D.G., E.M.A.-U.), Pasqual Maragall Foundation, Barcelona; Universitat Pompeu Fabra (M.A., M.M.-A., A.N., J.D.G.), Barcelona; IMIM (Hospital del Mar Medical Research Institute) (G.S.-B., M.M.-A., O.G.-R., C.M., M.S.-C., J.D.G., E.M.A.-U.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES) (G.S.-B., O.G.-R., C.M., K.F., M.S.-C., E.M.A.-U.), Madrid; Servei de Neurologia (O.G.-R., M.S.-C.), Hospital del Mar, Barcelona; Fundació Pasqual Maragall (N.G.), Barcelona; Centre for Genomic Regulation (CRG) (A.N.), Barcelona Institute of Science and Technology (BIST); Institute of Evolutionary Biology (UPF-CSIC) (A.N.), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona; Institució Catalana de Recerca i Estudis Avançats (ICREA) (A.N.), Barcelona, Spain; Roche Diagnostics International Ltd (I.S.), Rotkreuz, Switzerland; Roche Diagnostics GmbH (G.K., A.B.), Penzberg, Germany; Department of Psychiatry and Neurochemistry (K.B., H.Z.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; UK Dementia Research Institute at UCL (H.Z.), London; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London, United Kingdom; Hong Kong Center for Neurodegenerative Diseases (H.Z.), China; H. Lundbeck A/S (J.L.M.), Denmark; and Centro de Investigación Biomédica en Red Bioingeniería (J.D.G.), Biomateriales y Nanomedicina, Madrid, Spain. eiderarenaza@gmail.com.
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.
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.
Authors: Alexandrea L Harmell; Elizabeth A Chattillion; Susan K Roepke; Brent T Mausbach Journal: Curr Psychiatry Rep Date: 2011-06 Impact factor: 5.285
Authors: Nancy J Donovan; Rebecca E Amariglio; Amy S Zoller; Rebecca K Rudel; Teresa Gomez-Isla; Deborah Blacker; Bradley T Hyman; Joseph J Locascio; Keith A Johnson; Reisa A Sperling; Gad A Marshall; Dorene M Rentz Journal: Am J Geriatr Psychiatry Date: 2014-02-26 Impact factor: 4.105
Authors: Nancy J Donovan; Joseph J Locascio; Gad A Marshall; Jennifer Gatchel; Bernard J Hanseeuw; Dorene M Rentz; Keith A Johnson; Reisa A Sperling Journal: Am J Psychiatry Date: 2018-01-12 Impact factor: 18.112
Authors: Marta Milà-Alomà; Gemma Salvadó; Juan Domingo Gispert; Natalia Vilor-Tejedor; Oriol Grau-Rivera; Aleix Sala-Vila; Gonzalo Sánchez-Benavides; Eider M Arenaza-Urquijo; Marta Crous-Bou; José Maria González-de-Echávarri; Carolina Minguillon; Karine Fauria; Maryline Simon; Gwendlyn Kollmorgen; Henrik Zetterberg; Kaj Blennow; Marc Suárez-Calvet; José Luis Molinuevo Journal: Alzheimers Dement Date: 2020-06-23 Impact factor: 21.566
Authors: Eider M Arenaza-Urquijo; Gemma Salvadó; Gregory Operto; Carolina Minguillón; Gonzalo Sánchez-Benavides; Marta Crous-Bou; Oriol Grau-Rivera; Aleix Sala-Vila; Carles Falcón; Marc Suárez-Calvet; Henrik Zetterberg; Kaj Blennow; Juan Domingo Gispert; José Luis Molinuevo Journal: Neurology Date: 2020-07-31 Impact factor: 9.910