{"id":10451,"date":"2024-09-20T12:47:16","date_gmt":"2024-09-20T11:47:16","guid":{"rendered":"https:\/\/ep-ad.org\/?p=10451"},"modified":"2024-09-20T12:50:15","modified_gmt":"2024-09-20T11:50:15","slug":"neurology","status":"publish","type":"post","link":"https:\/\/ep-ad.org\/index.php\/2024\/09\/20\/neurology\/","title":{"rendered":"Neurology"},"content":{"rendered":"\n

“Association of Vascular Risk Factors and Cerebrovascular Pathology With Alzheimer Disease Pathologic Changes in Individuals Without Dementia”<\/strong>

\"\"<\/figure><\/p>\n\n\n\n

Authors: <\/strong>Luigi Lorenzini, Alessio Maranzano, Silvia <\/span>Ingala, Lyduine E. Collij, Mario Tranfa, Kaj Blennow, Carol Di Perri, <\/span>Christopher Foley, Nick C. Fox, Giovanni B. Frisoni, Sven Haller, Pablo <\/span>Martinez-Lage, John O’Brien, Pierre Payoux, Craig Ritchie, Philip Scheltens, Adam <\/span>J. Schwarz, Carole H. Sudre, Betty M. Tijms, Federico Verde, Nicola Ticozzi, <\/span>Vincenzo Silani, Pieter Jelle Visser, Adam Waldman, Robin Wolz, Gael Ch\u00e9telat, <\/span>Michael Ewers, Alle Meije Wink, Henk Mutsaerts, Juan Domingo Gispert, Joanna M. <\/span>Wardlaw and Frederik Barkhof<\/span><\/p>\n\n\n\n

Abstract:<\/strong>
Background and Objectives: 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 (A\u03b21-42<\/sub>) and their combined effect on downstream AD biomarkers, that is, CSF hyperphosphorylated tau (P-tau181<\/sub>), atrophy, and cognition.<\/p>\n\n\n\n

Methods: 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 \u201ccSVD severity\u201d latent variable and assess the direct and indirect effects of FRS and cSVD severity on A\u03b21-42<\/sub>, P-tau181<\/sub>, gray matter volume (baseline and longitudinal), and cognitive performance (baseline and longitudinal).<\/p>\n\n\n\n

Results: A total cohort of 1,592 participants were evaluated (mean age = 65.5 \u00b1 7.4 years; 56.16% F). We observed positive associations between FRS and all cSVD features (all p<\/em> < 0.05) and a negative association between FRS and A\u03b21-42<\/sub> (\u03b2 = \u22120.04 \u00b1 0.01). All cSVD features were negatively associated with CSF A\u03b21-42<\/sub> (all p<\/em> < 0.05). Using SEM, the cSVD severity fully mediated the association between FRS and CSF A\u03b21-42<\/sub> (indirect effect: \u03b2 = \u22120.03 \u00b1 0.01), also when omitting vascular amyloid-related markers. We observed a significant indirect effect of cSVD severity on P-tau181<\/sub> (indirect effect: \u03b2 = 0.12 \u00b1 0.03), baseline and longitudinal gray matter volume (indirect effect: \u03b2 = \u22120.10 \u00b1 0.03; \u03b2 = \u22120.12 \u00b1 0.05), and baseline cognitive performance (indirect effect: \u03b2 = \u22120.16 \u00b1 0.03) through CSF A\u03b21-42<\/sub>.<\/p>\n\n\n\n

Discussion: In a large nondemented population, our findings suggest that cSVD is a mediator of the relationship between VRFs and CSF A\u03b21-42<\/sub> 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.<\/p>\n\n\n\n

DOI:<\/strong> https:\/\/doi.org\/10.1212\/WNL.0000000000209801<\/a><\/p>\n\n\n\n

Published online:\u00a017 September 2024 in the journal Neurology<\/p>\n","protected":false},"excerpt":{"rendered":"

“Association of Vascular Risk Factors and Cerebrovascular Pathology With Alzheimer Disease Pathologic Changes in Individuals Without Dementia” Authors: 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, John O’Brien, Pierre Payoux, Craig Ritchie, Philip Scheltens, Adam […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[8],"tags":[],"class_list":["post-10451","post","type-post","status-publish","format-standard","hentry","category-publications"],"_links":{"self":[{"href":"https:\/\/ep-ad.org\/index.php\/wp-json\/wp\/v2\/posts\/10451","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ep-ad.org\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ep-ad.org\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ep-ad.org\/index.php\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/ep-ad.org\/index.php\/wp-json\/wp\/v2\/comments?post=10451"}],"version-history":[{"count":3,"href":"https:\/\/ep-ad.org\/index.php\/wp-json\/wp\/v2\/posts\/10451\/revisions"}],"predecessor-version":[{"id":10456,"href":"https:\/\/ep-ad.org\/index.php\/wp-json\/wp\/v2\/posts\/10451\/revisions\/10456"}],"wp:attachment":[{"href":"https:\/\/ep-ad.org\/index.php\/wp-json\/wp\/v2\/media?parent=10451"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ep-ad.org\/index.php\/wp-json\/wp\/v2\/categories?post=10451"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ep-ad.org\/index.php\/wp-json\/wp\/v2\/tags?post=10451"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}