Genetic Complexities of Cerebral Small Vessel Disease, Blood Pressure, and Dementia
Rattachement africain : fr, us, ee, nl, is, gb, cl, no. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Importance: Vascular disease is a treatable contributor to dementia risk, but the role of specific markers remains unclear, making prevention strategies uncertain. Objective: To investigate the causal association between white matter hyperintensity (WMH) burden, clinical stroke, blood pressure (BP), and dementia risk, while accounting for potential epidemiologic biases. Design, Setting, and Participants: This study first examined the association of genetically determined WMH burden, stroke, and BP levels with Alzheimer disease (AD) in a 2-sample mendelian randomization (2SMR) framework. Second, using population-based studies (1979-2018) with prospective dementia surveillance, the genetic association of WMH, stroke, and BP with incident all-cause dementia was examined. Data analysis was performed from July 26, 2020, through July 24, 2022. Exposures: Genetically determined WMH burden and BP levels, as well as genetic liability to stroke derived from genome-wide association studies (GWASs) in European ancestry populations. Main Outcomes and Measures: The association of genetic instruments for WMH, stroke, and BP with dementia was studied using GWASs of AD (defined clinically and additionally meta-analyzed including both clinically diagnosed AD and AD defined based on parental history [AD-meta]) for 2SMR and incident all-cause dementia for longitudinal analyses. Results: In 2SMR (summary statistics-based) analyses using AD GWASs with up to 75 024 AD cases (mean [SD] age at AD onset, 75.5 [4.4] years; 56.9% women), larger WMH burden showed evidence for a causal association with increased risk of AD (odds ratio [OR], 1.43; 95% CI, 1.10-1.86; P = .007, per unit increase in WMH risk alleles) and AD-meta (OR, 1.19; 95% CI, 1.06-1.34; P = .008), after accounting for pulse pressure for the former. Blood pressure traits showed evidence for a protective association with AD, with evidence for confounding by shared genetic instruments. In the longitudinal (individual-level data) analyses involving 10 699 incident all-cause dementia cases (mean [SD] age at dementia diagnosis, 74.4 [9.1] years; 55.4% women), no significant association was observed between larger WMH burden and incident all-cause dementia (hazard ratio [HR], 1.02; 95% CI, 1.00-1.04; P = .07). Although all exposures were associated with mortality, with the strongest association observed for systolic BP (HR, 1.04; 95% CI, 1.03-1.06; P = 1.9 × 10-14), there was no evidence for selective survival bias during follow-up using illness-death models. In secondary analyses using polygenic scores, the association of genetic liability to stroke, but not genetically determined WMH, with dementia outcomes was attenuated after adjusting for interim stroke. Conclusions: These findings suggest that WMH is a primary vascular factor associated with dementia risk, emphasizing its significance in preventive strategies for dementia. Future studies are warranted to examine whether this finding can be generalized to non-European populations.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Genetic Complexities of Cerebral Small Vessel Disease, Blood Pressure, and Dementia
- Date Crossref
- 22/05/2024
- Éditeur
- American Medical Association (AMA)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Université de Bordeaux pays non établi dans la noticeUniversité ou école supérieure
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Inserm pays non établi dans la noticeOrganisme public
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The University of Texas at San Antonio Health Science Center pays non établi dans la noticeUniversité ou école supérieure
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Bordeaux Population Health pays non établi dans la noticeStructure de recherche
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Institute for Neurodegenerative Disorders pays non établi dans la noticeOrganisation à but non lucratif
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University of Washington Cardiovascular Health Research Unit pays non établi dans la noticeUniversité ou école supérieure
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University of Michigan Department of Internal Medicine pays non établi dans la noticeUniversité ou école supérieure
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University of Tartu Institute of Genomics pays non établi dans la noticeUniversité ou école supérieure
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Erasmus MC Department of Epidemiology pays non établi dans la noticeÉtablissement de santé
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Boston University Department of Neurology pays non établi dans la noticeUniversité ou école supérieure
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and Blood Institute Lung pays non établi dans la noticeStructure de recherche
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Framingham Heart Study pays non établi dans la noticeStructure de recherche
Université de Bordeaux, Inserm et The University of Texas at San Antonio Health Science Center, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.