Association of Vascular Risk Factors and Cerebrovascular Pathology With Alzheimer Disease Pathologic Changes in Individuals Without Dementia
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| Název: | Association of Vascular Risk Factors and Cerebrovascular Pathology With Alzheimer Disease Pathologic Changes in Individuals Without Dementia |
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| Autoři: | Luigi Lorenzini, Alessio Maranzano, Silvia Ingala, Lyduine E. Collij, Mario Tranfa, Kaj Blennow, Carol Di Perri, Christopher Foley, Nick C. Fox, Giovanni B. Frisoni, Sven Haller, Pablo Martinez-Lage, Daisy Mollison, John O'Brien, Pierre Payoux, Craig Ritchie, Philip Scheltens, Adam J. Schwarz, Carole H. Sudre, Betty M. Tijms, Federico Verde, Nicola Ticozzi, Vincenzo Silani, Pieter Jelle Visser, Adam Waldman, Robin Wolz, Gael Chételat, Michael Ewers, Alle Meije Wink, Henk Mutsaerts, Juan Domingo Gispert, Joanna M. Wardlaw, Frederik Barkhof |
| Přispěvatelé: | Amsterdam University Medical Centers (Amsterdam UMC), IRCCS Istituto Nazionale dei Tumori Milano, Copenhagen University Hospital, Lund University, VU University Medical Center Amsterdam, 'Federico II' University of Naples Medical School, Sahlgrenska Academy at University of Gothenburg Göteborg, Göteborgs Universitet = University of Gothenburg (GU), Sahlgrenska University Hospital Gothenburg, The University of Edinburgh, General Electric Healthcare Cardiff (GE Healthcare), Dementia Research Centre, Department of Neurodegenerative Disease, and the UK Dementia Research Institute, UCL Queen Square Institute of Neurology, London WC1N 3AR, UK, Université de Genève = University of Geneva (UNIGE), Hôpitaux universitaires de Genève = University Hospitals of Geneva (HUG), Uppsala University, Capital University of Medical Sciences Beijing (CUMS), Center for Research and Advanced Therapies = Centro de Investigación y Terapias Avanzadas (CITA-Alzheimer), University of Cambridge UK (CAM), Toulouse NeuroImaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Service de Médecine Nucléaire - Pierre-Paul Riquet CHU Toulouse, Pôle imagerie médicale CHU Toulouse, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), University College of London London (UCL), Universitat Pompeu Fabra Barcelona (UPF), Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Zdroj: | Neurology Neurology 103(7), e209801 (2024). doi:10.1212/WNL.0000000000209801 |
| Informace o vydavateli: | Ovid Technologies (Wolters Kluwer Health), 2024. |
| Rok vydání: | 2024 |
| Témata: | Male, [SDV]Life Sciences [q-bio], cerebrospinal fluid [Amyloid beta-Peptides], MESH: Magnetic Resonance Imaging, pathology [Alzheimer Disease], SMALL VESSEL DISEASE, MESH: Risk Factors, pathology [Brain], Risk Factors, MESH: Amyloid beta-Peptides / cerebrospinal fluid, TAU PATHOLOGY, MESH: Aged, pathology [Atrophy], MESH: Middle Aged, MESH: Alzheimer Disease / cerebrospinal fluid, Brain, MESH: Peptide Fragments / cerebrospinal fluid, Middle Aged, amyloid beta-protein (1-42), AMYLOID-BETA, Magnetic Resonance Imaging, cerebrospinal fluid [Alzheimer Disease], HYPERINTENSITIES, cerebrospinal fluid [Biomarkers], complications [Cerebral Small Vessel Diseases], MESH: Brain / diagnostic imaging, Female, diagnostic imaging [Cerebral Small Vessel Diseases], Neurovetenskaper, MESH: Biomarkers / cerebrospinal fluid, MRI, Research Article, Geriatrik, tau Proteins, MESH: Cerebral Small Vessel Diseases / pathology, MESH: Alzheimer Disease / pathology, Alzheimer Disease, Humans, ddc:610, cerebrospinal fluid [Peptide Fragments], diagnostic imaging [Brain], MESH: Cerebral Small Vessel Diseases / diagnostic imaging, Aged, Retrospective Studies, MESH: tau Proteins / cerebrospinal fluid, MESH: Humans, Amyloid beta-Peptides, MESH: Alzheimer Disease / diagnostic imaging, Neurosciences, MESH: Retrospective Studies, MESH: Male, Peptide Fragments, MESH: Atrophy / pathology, cerebrospinal fluid [tau Proteins], Geriatrics, Cerebral Small Vessel Diseases, pathology [Cerebral Small Vessel Diseases], MESH: Brain / pathology, Atrophy, MESH: Cerebral Small Vessel Diseases / complications, MESH: Female, diagnostic imaging [Alzheimer Disease], Biomarkers |
| Popis: | Vascular risk factors (VRFs) and cerebral small vessel disease (cSVD) are common in patients with Alzheimer disease (AD). It remains unclear whether this coexistence reflects shared risk factors or a mechanistic relationship and whether vascular and amyloid pathologies have independent or synergistic influence on subsequent AD pathophysiology in preclinical stages. We investigated links between VRFs, cSVD, and amyloid levels (Aβ1-42) and their combined effect on downstream AD biomarkers, that is, CSF hyperphosphorylated tau (P-tau181), atrophy, and cognition.This retrospective study included nondemented participants (Clinical Dementia Rating < 1) from the European Prevention of Alzheimer's Dementia (EPAD) cohort and assessed VRFs with the Framingham risk score (FRS) and cSVD features on MRI using visual scales and white matter hyperintensity volumes. After preliminary linear analysis, we used structural equation modeling (SEM) to create a "cSVD severity" latent variable and assess the direct and indirect effects of FRS and cSVD severity on Aβ1-42, P-tau181, gray matter volume (baseline and longitudinal), and cognitive performance (baseline and longitudinal).A total cohort of 1,592 participants were evaluated (mean age = 65.5 ± 7.4 years; 56.16% F). We observed positive associations between FRS and all cSVD features (all p < 0.05) and a negative association between FRS and Aβ1-42 (β = -0.04 ± 0.01). All cSVD features were negatively associated with CSF Aβ1-42 (all p < 0.05). Using SEM, the cSVD severity fully mediated the association between FRS and CSF Aβ1-42 (indirect effect: β = -0.03 ± 0.01), also when omitting vascular amyloid-related markers. We observed a significant indirect effect of cSVD severity on P-tau181 (indirect effect: β = 0.12 ± 0.03), baseline and longitudinal gray matter volume (indirect effect: β = -0.10 ± 0.03; β = -0.12 ± 0.05), and baseline cognitive performance (indirect effect: β = -0.16 ± 0.03) through CSF Aβ1-42.In a large nondemented population, our findings suggest that cSVD is a mediator of the relationship between VRFs and CSF Aβ1-42 and affects downstream neurodegeneration and cognitive impairment. We provide evidence of VRFs indirectly affecting the pathogenesis of AD, highlighting the importance of considering cSVD burden in memory clinics for AD risk evaluation and as an early window for intervention. These results stress the role of VRFs and cerebrovascular pathology as key biomarkers for accurate design of anti-amyloid clinical trials and offer new perspectives for patient stratification. |
| Druh dokumentu: | Article Other literature type |
| Popis souboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 1526-632X 0028-3878 |
| DOI: | 10.1212/wnl.0000000000209801 |
| Přístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/39288341 https://cris.maastrichtuniversity.nl/en/publications/764fc581-eb05-4df4-a52c-bf068d12f39f https://doi.org/10.1212/WNL.0000000000209801 https://pub.dzne.de/record/272157 http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-540158 |
| Rights: | URL: http://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Přístupové číslo: | edsair.doi.dedup.....934d67084387aeef9c438b620e2d9dc6 |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Vascular risk factors (VRFs) and cerebral small vessel disease (cSVD) are common in patients with Alzheimer disease (AD). It remains unclear whether this coexistence reflects shared risk factors or a mechanistic relationship and whether vascular and amyloid pathologies have independent or synergistic influence on subsequent AD pathophysiology in preclinical stages. We investigated links between VRFs, cSVD, and amyloid levels (Aβ1-42) and their combined effect on downstream AD biomarkers, that is, CSF hyperphosphorylated tau (P-tau181), atrophy, and cognition.This retrospective study included nondemented participants (Clinical Dementia Rating < 1) from the European Prevention of Alzheimer's Dementia (EPAD) cohort and assessed VRFs with the Framingham risk score (FRS) and cSVD features on MRI using visual scales and white matter hyperintensity volumes. After preliminary linear analysis, we used structural equation modeling (SEM) to create a "cSVD severity" latent variable and assess the direct and indirect effects of FRS and cSVD severity on Aβ1-42, P-tau181, gray matter volume (baseline and longitudinal), and cognitive performance (baseline and longitudinal).A total cohort of 1,592 participants were evaluated (mean age = 65.5 ± 7.4 years; 56.16% F). We observed positive associations between FRS and all cSVD features (all p < 0.05) and a negative association between FRS and Aβ1-42 (β = -0.04 ± 0.01). All cSVD features were negatively associated with CSF Aβ1-42 (all p < 0.05). Using SEM, the cSVD severity fully mediated the association between FRS and CSF Aβ1-42 (indirect effect: β = -0.03 ± 0.01), also when omitting vascular amyloid-related markers. We observed a significant indirect effect of cSVD severity on P-tau181 (indirect effect: β = 0.12 ± 0.03), baseline and longitudinal gray matter volume (indirect effect: β = -0.10 ± 0.03; β = -0.12 ± 0.05), and baseline cognitive performance (indirect effect: β = -0.16 ± 0.03) through CSF Aβ1-42.In a large nondemented population, our findings suggest that cSVD is a mediator of the relationship between VRFs and CSF Aβ1-42 and affects downstream neurodegeneration and cognitive impairment. We provide evidence of VRFs indirectly affecting the pathogenesis of AD, highlighting the importance of considering cSVD burden in memory clinics for AD risk evaluation and as an early window for intervention. These results stress the role of VRFs and cerebrovascular pathology as key biomarkers for accurate design of anti-amyloid clinical trials and offer new perspectives for patient stratification. |
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| ISSN: | 1526632X 00283878 |
| DOI: | 10.1212/wnl.0000000000209801 |