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1دورية أكاديمية
المؤلفون: Knol, Maria J, Poot, Raymond A, Evans, Tavia E, Satizabal, Claudia L, Mishra, Aniket, Sargurupremraj, Muralidharan, van der Auwera, Sandra, Duperron, Marie-Gabrielle, Jian, Xueqiu, Hostettler, Isabel C, van Dam-Nolen, Dianne H K, Lamballais, Sander, Pawlak, Mikolaj A, Lewis, Cora E, Carrion-Castillo, Amaia, van Erp, Theo G M, Reinbold, Celine S, Shin, Jean, Scholz, Markus, Haberg, Asta K, Kampe, Anders, Li, Gloria H Y, Avinun, Reut, Atkins, Joshua R, Hsu, Fang-Chi, Amod, Alyssa R, Lam, Max, Tsuchida, Ami, Teunissen, Mariel W A, Aygun, Nil, Patel, Yash, Liang, Dan, Beiser, Alexa S, Beyer, Frauke, Bis, Joshua C, Bos, Daniel, Bryan, R Nick, Bulow, Robin, Caspers, Svenja, Catheline, Gwenaelle, Cecil, Charlotte a M, Dalvie, Shareefa, Dartigues, Jean-Francois, Decarli, Charles, Enlund-Cerullo, Maria, Ford, Judith M, Franke, Barbara, Freedman, Barry I, Friedrich, Nele, Green, Melissa J, Haworth, Simon, Helmer, Catherine, Hoffmann, Per, Homuth, Georg, Ikram, M Kamran, Jack, Clifford R, Jahanshad, Neda, Jockwitz, Christiane, Kamatani, Yoichiro, Knodt, Annchen R, Li, Shuo, Lim, Keane, Longstreth, W T, Macciardi, Fabio, Makitie, Outi, Mazoyer, Bernard, Medland, Sarah E, Miyamoto, Susumu, Moebus, Susanne, Mosley, Thomas H, Muetzel, Ryan, Muhleisen, Thomas W, Nagata, Manabu, Nakahara, Soichiro, Palmer, Nicholette D, Pausova, Zdenka, Preda, Adrian, Quide, Yann, Reay, William R, Roshchupkin, Gennady V, Schmidt, Reinhold, Schreiner, Pamela J, Setoh, Kazuya, Shapland, Chin Yang, Sidney, Stephen, St Pourcain, Beate, Stein, Jason L, Tabara, Yasuharu, Teumer, Alexander, Uhlmann, Anne, van der Lugt, Aad, Vernooij, Meike W, Werring, David J, Windham, B Gwen, Witte, a Veronica, Wittfeld, Katharina, Yang, Qiong, Yoshida, Kazumichi, Brunner, Han G, Le Grand, Quentin, Sim, Kang, Stein, Dan J, Bowden, Donald W, Cairns, Murray J, Hariri, Ahmad R, Cheung, Ching-Lung, Andersson, Sture, Villringer, Arno, Paus, Tomas, Cichon, Sven, Calhoun, Vince D, Crivello, Fabrice, Launer, Lenore J, White, Tonya, Koudstaal, Peter J, Houlden, Henry, Fornage, Myriam, Matsuda, Fumihiko, Grabe, Hans J, Ikram, M Arfan, Debette, Stephanie, Thompson, Paul M, Seshadri, Sudha, Adams, Hieab H H
المساهمون: Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Neurodégénératives Bordeaux (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Fondation pour la Recherche Médicale, Fondation de France, Mutuelle Générale de l'Education Nationale, Fondation Plan Alzheimer, Caisse nationale de solidarité pour l'autonomie, ANR-06-PNRA-0005,COGINUT,COGINUT : Cognition, anti-oxydants, acides gras: approche interdisciplinaire du rôle de la nutrition dans le vieillissement du cerveau(2006), ANR-18-RHUS-0002,SHIVA,Stopping cognitive decline and dementia by fighting covert cerebral small vessel disease(2018), ANR-23-IAHU-0001,VBHI,Vaincre les maladies vasculaires cérébrales par un nouveau paradigme de prévention de précision et d'innovation thérapeutique(2023)
المصدر: ISSN: 2666-3791 ; Cell Reports Medicine ; https://hal.science/hal-04627076Test ; Cell Reports Medicine, 2024, 5 (5), pp.101529. ⟨10.1016/j.xcrm.2024.101529⟩.
مصطلحات موضوعية: Cancer, Genetics, Genome-Wide Association Study, Head Circumference, Head Size, Intracranial Volume, Meta-Analysis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
الوصف: International audience ; The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.
العلاقة: hal-04627076; https://hal.science/hal-04627076Test; https://hal.science/hal-04627076v2/documentTest; https://hal.science/hal-04627076v2/file/BPH_CellRepMed_2024_Knol.pdfTest
الإتاحة: https://doi.org/10.1016/j.xcrm.2024.101529Test
https://hal.science/hal-04627076Test
https://hal.science/hal-04627076v2/documentTest
https://hal.science/hal-04627076v2/file/BPH_CellRepMed_2024_Knol.pdfTest -
2دورية أكاديمية
المؤلفون: Sargurupremraj, Muralidharan, Soumaré, Aicha, Bis, Joshua C., Surakka, Ida, Jürgenson, Tuuli, Joly, Pierre, Knol, Maria J., Wang, Ruiqi, Yang, Qiong, Satizabal, Claudia L., Gudjonsson, Alexander, Mishra, Aniket, Bouteloup, Vincent, Phuah, Chia Ling, van Duijn, Cornelia M., Cruchaga, Carlos, Dufouil, Carole, Chêne, Geneviève, Lopez, Oscar L., Psaty, Bruce M., Tzourio, Christophe, Amouyel, Philippe, Adams, Hieab H., Jacqmin-Gadda, Hélène, Ikram, Mohammad Arfan, Gudnason, Vilmundur, Milani, Lili, Winsvold, Bendik S., Hveem, Kristian, Matthews, Paul M., Longstreth, W. T., Seshadri, Sudha, Launer, Lenore J., Debette, Stéphanie
المصدر: Sargurupremraj , M , Soumaré , A , Bis , J C , Surakka , I , Jürgenson , T , Joly , P , Knol , M J , Wang , R , Yang , Q , Satizabal , C L , Gudjonsson , A , Mishra , A , Bouteloup , V , Phuah , C L , van Duijn , C M , Cruchaga , C , Dufouil , C , Chêne , G , Lopez , O L , Psaty , B M , Tzourio , C , Amouyel , P , Adams , H ....
الوصف: 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 ...
وصف الملف: application/pdf
الإتاحة: https://doi.org/10.1001/jamanetworkopen.2024.12824Test
https://pure.eur.nl/en/publications/06f5aa0d-c368-4c19-9491-e6f605a5ee6aTest
https://pure.eur.nl/ws/files/150818174/sargurupremraj_2024_oi_240443_1715318984.07578.pdfTest
http://www.scopus.com/inward/record.url?scp=85194024119&partnerID=8YFLogxKTest -
3دورية أكاديمية
المؤلفون: Suchy‐Dicey, Astrid M., Longstreth, W. T., Rhoads, Kristoffer, Umans, Jason, Buchwald, Dedra, Grabowski, Thomas, Blennow, Kaj, Reiman, Eric, Zetterberg, Henrik
المساهمون: National Institutes of Health
المصدر: Alzheimer's & Dementia ; volume 20, issue 3, page 2072-2079 ; ISSN 1552-5260 1552-5279
الوصف: INTRODUCTION Identification of Alzheimer's disease (AD) needs inexpensive, noninvasive biomarkers, with validation in all populations. METHODS We collected plasma markers in older American Indian individuals: phosphorylated‐tau181 (pTau181); amyloid‐beta (Aβ) 40,42; glial fibrillary acidic protein (GFAP); and neurofilament light chain (NfL). Plasma markers were analyzed for discriminant properties with cognitive status and etiology using receiver operating characteristic (ROC) analysis. RESULTS PTau181, GFAP, NfL plasma values were significantly associated with cognition, but Aβ were not. Discriminant performance was moderate for individual markers, with pTau181, GFAP, NfL performing best, but an empirically selected panel of markers (age, sex, education, pTau181, GFAP, NfL, Aβ4240 ratio) had excellent discriminant performance (AUC > 0.8). DISCUSSION In American Indian individuals, pTau181 and Aβ values suggested more common pathology than in majority populations. Aβ was less informative than in other populations; however, all four markers were needed for a best‐performing dementia diagnostic model. These data validate utility of AD plasma markers, while suggesting population‐specific diagnostic characteristics.
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4دورية أكاديمية
المؤلفون: Moseholm, Kristine F., Horn, Jens W., Fitzpatrick, Annette L., Djoussé, Luc, Longstreth, W. T., Lopez, Oscar L., Hoofnagle, Andrew N., Jensen, Majken K., Lemaitre, Rozenn N., Mukamal, Kenneth J.
المصدر: Frontiers in Neurology ; volume 15 ; ISSN 1664-2295
الوصف: Background Sphingolipids are implicated in neurodegeneration and neuroinflammation. We assessed the potential role of circulating ceramides and sphingomyelins in subclinical brain pathology by investigating their association with brain magnetic resonance imaging (MRI) measures and circulating biomarkers of brain injury, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in the Cardiovascular Health Study (CHS), a large and intensively phenotyped cohort of older adults. Methods Brain MRI was offered twice to CHS participants with a mean of 5 years between scans, and results were available from both time points in 2,116 participants (mean age 76 years; 40% male; and 25% APOE ε4 allele carriers). We measured 8 ceramide and sphingomyelin species in plasma samples and examined the associations with several MRI, including worsening grades of white matter hyperintensities and ventricular size, number of brain infarcts, and measures of brain atrophy in a subset with quantitative measures. We also investigated the sphingolipid associations with serum NfL and GFAP. Results In the fully adjusted model, higher plasma levels of ceramides and sphingomyelins with a long (16-carbon) saturated fatty acid were associated with higher blood levels of NfL [β = 0.05, false-discovery rate corrected P ( P FDR ) = 0.004 and β = 0.06, P FDR = < 0.001, respectively]. In contrast, sphingomyelins with very long (20- and 22-carbon) saturated fatty acids tended to have an inverse association with levels of circulating NfL. In secondary analyses, we found an interaction between ceramide d18:1/20:0 and sex ( P for interaction = <0.001), such that ceramide d18:1/20:0 associated with higher odds for infarcts in women [OR = 1.26 (95%CI: 1.07, 1.49), P FDR = 0.03]. We did not observe any associations with GFAP blood levels, white matter grade, ventricular grade, mean bilateral hippocampal volume, or total brain volume. Conclusion Overall, our comprehensive investigation supports the evidence that ceramides and ...
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5
المؤلفون: Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jürgenson, Tuuli, Namba, Shinichi, Posner, Daniel C., Kamanu, Frederick K., Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K., Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C., Lin, Kuang, Slagsvold Winsvold, Bendik, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R., Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V., Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Cárcel-Márquez, Jara, Nygaard, Marianne, Leonard, Hampton L., Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J., Lewis, Adam J., Judy, Renae L., Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D., Bakker, Mark K., Bartz, Traci M., Bennett, David A., Bis, Joshua C., Bordes, Constance, Børte, Sigrid, Cain, Anael, Ridker, Paul M., Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W., de Jager, Phil L., de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E., Geerlings, Mirjam I., Gasca, Natalie C., Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K., Ho, Yuk-Lam, Havulinna, Aki S., Hopewell, Jemma C., Hyacinth, Hyacinth I., Inouye, Michael, Jacob, Mina A., Jeon, Christina E., Jern, Christina, Kamouchi, Masahiro, Keene, Keith L., Kitazono, Takanari, Kittner, Steven J., Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J., Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S., Marston, Nicholas A., Meitinger, Thomas, Mitchell, Braxton D., Montellano, Felipe A., Morisaki, Takayuki, Mosley, Thomas H., Nalls, Mike A., Nordestgaard, Børge G., O'Donnell, Martin J., Okada, Yukinori, Onland-Moret, N. Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M., Rich, Stephen S., Rosand, Jonathan, Sabatine, Marc S., Sacco, Ralph L., Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L., Schmidt, Carsten O., Shimizu, Atsushi, Smith, Nicholas L., Sloane, Kelly L., Sutoh, Yoichi, Sun, Yan V., Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P., Tiwari, Hemant K., Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S., Wiggins, Kerri L., Wennberg, Patrik, 1972, Woo, Daniel, Wilson, Peter W. F., Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Millwood, Iona Y., Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J., Jukema, J. Wouter, Rissanen, Ina L., Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna M. M., Irvin, Marguerite R., Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A., Rundek, Tatjana, Worrall, Bradford B., Lathrop, G. Mark, Riaz, Moeen, Simonsick, Eleanor M., Kõrv, Janika, França, Paulo H. C., Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M., Heuschmann, Peter Ulrich, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M., Chasman, Daniel I., Rotter, Jerome I., Anderson, Christopher D., Zwart, John-Anker, Niiranen, Teemu J., Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G., Ruff, Christian T., Owolabi, Mayowa O., Huffman, Jennifer E., Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, Debette, Stephanie
المصدر: Nature. 611(7934):115-123
الوصف: Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
وصف الملف: electronic
الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-200734Test
https://doi.org/10.1038/s41586-022-05165-3Test
https://umu.diva-portal.org/smash/get/diva2:1708228/FULLTEXT01.pdfTest -
6دورية أكاديمية
المؤلفون: Yang, Yunju, Knol, Maria J., Wang, Ruiqi, Mishra, Aniket, Liu, Dan, Luciano, Michelle, Teumer, Alexander, Armstrong, Nicola, Bis, Joshua C., Jhun, Min A., Li, Shuo, Adams, Hieab H.H., Aziz, Nasir Ahmad, Bastin, Mark E., Bourgey, Mathieu, Brody, Jennifer A., Frenzel, Stefan, Gottesman, Rebecca F., Hosten, Norbert, Hou, Lifang, Kardia, Sharon L.R., Lohner, Valerie, Marquis, Pascale, Maniega, Susana Muñoz, Satizabal, Claudia L., Sorond, Farzaneh A., Valdés Hernández, Maria C., van Duijn, Cornelia M., Vernooij, Meike W., Wittfeld, Katharina, Yang, Qiong, Zhao, Wei, Boerwinkle, Eric, Levy, Daniel, Deary, Ian J., Jiang, Jiyang, Mather, Karen A., Mosley, Thomas H., Psaty, Bruce M., Sachdev, Perminder S., Smith, Jennifer A., Sotoodehnia, Nona, DeCarli, Charles S., Breteler, Monique M.B., Ikram, M. Arfan, Grabe, Hans J., Wardlaw, Joanna, Longstreth, W. T., Launer, Lenore J., Seshadri, Sudha, Debette, Stephanie, Fornage, Myriam
المصدر: Yang , Y , Knol , M J , Wang , R , Mishra , A , Liu , D , Luciano , M , Teumer , A , Armstrong , N , Bis , J C , Jhun , M A , Li , S , Adams , H H H , Aziz , N A , Bastin , M E , Bourgey , M , Brody , J A , Frenzel , S , Gottesman , R F , Hosten , N , Hou , L , Kardia , S L R , Lohner , V , ....
الوصف: Cerebral white matter hyperintensities on MRI are markers of cerebral small vessel disease, a major risk factor for dementia and stroke. Despite the successful identification of multiple genetic variants associated with this highly heritable condition, its genetic architecture remains incompletely understood. More specifically, the role of DNA methylation has received little attention. We investigated the association between white matter hyperintensity burden and DNA methylation in blood at ∼450 000 cytosine-phosphate-guanine (CpG) sites in 9732 middle-aged to older adults from 14 community-based studies. Single CpG and region-based association analyses were carried out. Functional annotation and integrative cross-omics analyses were performed to identify novel genes underlying the relationship between DNA methylation and white matter hyperintensities. We identified 12 single CpG and 46 region-based DNA methylation associations with white matter hyperintensity burden. Our top discovery single CpG, cg24202936 (P = 7.6 × 10-8), was associated with F2 expression in blood (P = 6.4 × 10-5) and co-localized with FOLH1 expression in brain (posterior probability = 0.75). Our top differentially methylated regions were in PRMT1 and in CCDC144NL-AS1, which were also represented in single CpG associations (cg17417856 and cg06809326, respectively). Through Mendelian randomization analyses cg06809326 was putatively associated with white matter hyperintensity burden (P = 0.03) and expression of CCDC144NL-AS1 possibly mediated this association. Differentially methylated region analysis, joint epigenetic association analysis and multi-omics co-localization analysis consistently identified a role of DNA methylation near SH3PXD2A, a locus previously identified in genome-wide association studies of white matter hyperintensities. Gene set enrichment analyses revealed functions of the identified DNA methylation loci in the blood-brain barrier and in the immune response. Integrative cross-omics analysis identified 19 key regulatory ...
وصف الملف: application/pdf
الإتاحة: https://doi.org/10.1093/brain/awac290Test
https://pure.eur.nl/en/publications/ec127cd1-d4bc-4cf0-9908-2570982d34b3Test
https://pure.eur.nl/ws/files/86516139/Epigenetic_and_integrative_cross_omics_analyses_of_cerebral_white_matter_hyperintensities_on_MRI.pdfTest
http://www.scopus.com/inward/record.url?scp=85148113452&partnerID=8YFLogxKTest -
7دورية أكاديمية
المؤلفون: Cronjé, Héléne T., Liu, Xiaojuan, Odden, Michelle C., Moseholm, Kristine F., Seshadri, Sudha, Satizabal, Claudia L., Lopez, Oscar L., Bis, Joshua C., Djoussé, Luc, Fohner, Alison E., Psaty, Bruce M., Tracy, Russell P., Longstreth, W. T., Jensen, Majken K., Mukamal, Kenneth J.
المصدر: Cronjé , H T , Liu , X , Odden , M C , Moseholm , K F , Seshadri , S , Satizabal , C L , Lopez , O L , Bis , J C , Djoussé , L , Fohner , A E , Psaty , B M , Tracy , R P , Longstreth , W T , Jensen , M K & Mukamal , K J 2023 , ' Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults : The cardiovascular health study ' , Alzheimer's and Dementia ....
مصطلحات موضوعية: blood-based biomarkers, cognition, dementia, longitudinal, Modified Mini-Mental State Examination, mortality, risk factor, serum
الوصف: INTRODUCTION Circulating neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have been independently associated with dementia risk. Their additive association, and their associations with dementia-specific mortality, have not been investigated. METHODS We associated serum NfL, GFAP, total tau ,and ubiquitin carboxyl-terminal hydrolase-L1, measured in 1712 dementia-free adults, with 19-year incident dementia and dementia-specific mortality risk, and with 3-year cognitive decline. RESULTS In adjusted models, being in the highest versus lowest tertile of NfL or GFAP associated with a hazard ratio (HR) of 1.49 (1.20–1.84) and 1.38 (1.15–1.66) for incident dementia, and 2.87 (1.79–4.61) and 2.76 (1.73–4.40) for dementia-specific mortality. Joint third versus first tertile exposure further increased risk; HR = 2.06 (1.60–2.67) and 9.22 (4.48–18.9). NfL was independently associated with accelerated cognitive decline. DISCUSSION Circulating NfL and GFAP may, independently and jointly, provide useful clinical insight regarding dementia risk and prognosis. ; INTRODUCTION: Circulating neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have been independently associated with dementia risk. Their additive association, and their associations with dementia-specific mortality, have not been investigated. METHODS: We associated serum NfL, GFAP, total tau, and ubiquitin carboxyl-terminal hydrolase-L1, measured in 1712 dementia-free adults, with 19-year incident dementia and dementia-specific mortality risk, and with 3-year cognitive decline. RESULTS: In adjusted models, being in the highest versus lowest tertile of NfL or GFAP associated with a hazard ratio (HR) of 1.49 (1.20–1.84) and 1.38 (1.15–1.66) for incident dementia, and 2.87 (1.79–4.61) and 2.76 (1.73–4.40) for dementia-specific mortality. Joint third versus first tertile exposure further increased risk; HR = 2.06 (1.60–2.67) and 9.22 (4.48–18.9). NfL was independently associated with accelerated cognitive decline. ...
وصف الملف: application/pdf
الإتاحة: https://doi.org/10.1002/alz.13367Test
https://curis.ku.dk/portal/da/publications/serum-nfl-and-gfap-are-associated-with-incident-dementia-and-dementia-mortality-in-older-adultsTest(afb6c2fb-b85b-42d0-b1a8-26717d5945ef).html
https://curis.ku.dk/ws/files/359850683/Alzheimer_s_Dementia_2023_Cronj_Serum_NfL_and_GFAP_are_associated_with_incident_dementia_and_dementia_mortality_in.pdfTest -
8دورية أكاديمية
المؤلفون: Sargurupremraj, Muralidharan, Soumare, Aicha, Bis, Joshua C, Surakka, Ida, Jurgenson, Tuuli, Joly, Pierre, Knol, Maria J, Wang, Ruiqi, Yang, Qiong, Satizabal, Claudia L, Gudjonsson, Alexander, Mishra, Aniket, Bouteloup, Vincent, Phuah, Chia-Ling, van Duijn, Cornelia M, Cruchaga, Carlos, Dufouil, Carole, Chêne, Geneviève, Lopez, Oscar, Psaty, Bruce M, Tzourio, Christophe, Amouyel, Philippe, Adams, Hieab H, Jacqmin-Gadda, Hélène, Ikram, Mohammad Arfan, Gudnason, Vilmundur, Milani, Lili, Winsvold, Bendik S, Hveem, Kristian, Matthews, Paul M, Longstreth, W T
المصدر: Neurology
الوصف: IMPORTANCE: There is increasing recognition that vascular disease, which can be treated, is a key contributor to dementia risk. However, the contribution of specific markers of vascular disease is unclear and, as a consequence, optimal prevention strategies remain unclear. OBJECTIVE: To disentangle the causal relation of several key vascular traits to dementia risk: (i) white matter hyperintensity (WMH) burden, a highly prevalent imaging marker of covert cerebral small vessel disease (cSVD); (ii) clinical stroke; and (iii) blood pressure (BP), the leading risk factor for cSVD and stroke, for which efficient therapies exist. To account for potential epidemiological biases inherent to late-onset conditions like dementia. DESIGN SETTING AND PARTICIPANTS: This study first explored the association of genetically determined WMH, BP levels and stroke risk with AD using summary-level data from large genome-wide association studies (GWASs) in a two-sample Mendelian randomization (MR) framework. Second, leveraging individual-level data from large longitudinal population-based cohorts and biobanks with prospective dementia surveillance, the association of weighted genetic risk scores (wGRSs) for WMH, BP, and stroke with incident all-cause-dementia was explored using Cox-proportional hazard and multi-state models. The data analysis was performed from July 26, 2020, through July 24, 2022. EXPOSURES: Genetically determined levels of WMH volume and BP (systolic, diastolic and pulse blood pressures) and genetic liability to stroke. MAIN OUTCOMES AND MEASURES: The summary-level MR analyses focused on the outcomes from GWAS of clinically diagnosed AD (n-cases=21,982) and GWAS additionally including self-reported parental history of dementia as a proxy for AD diagnosis (AD, n-cases=53,042). For the longitudinal analyses, individual-level data of 157,698 participants with 10,699 incident all-cause-dementia were studied, exploring AD, vascular or mixed dementia in secondary analyses. RESULTS: In the two-sample MR analyses, WMH ...
العلاقة: https://scholar.barrowneuro.org/neurology/1717Test; https://doi.org/10.1101/2023.08.08.23293761Test
الإتاحة: https://doi.org/10.1101/2023.08.08.23293761Test
https://scholar.barrowneuro.org/neurology/1717Test -
9دورية أكاديمية
المؤلفون: Besser, Lilah M., Lovasi, Gina S., Zambrano, Joyce Jimenez, Camacho, Simone, Dhanekula, Devi, Michael, Yvonne L., Garg, Parveen, Hirsch, Jana A., Siscovick, David, Hurvitz, Philip M., Biggs, Mary L., Galvin, James E., Bartz, Traci M., Longstreth, W. T.
المساهمون: Alzheimer's Association, National Heart, Lung, and Blood Institute
المصدر: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring ; volume 15, issue 4 ; ISSN 2352-8729 2352-8729
الوصف: INTRODUCTION We examined whether a combined measure of neighborhood greenspace and neighborhood median income was associated with white matter hyperintensity (WMH) and ventricle size changes. METHODS The sample included 1260 cognitively normal ≥ 65‐year‐olds with two magnetic resonance images (MRI; ≈ 5 years apart). WMH and ventricular size were graded from 0 (least) to 9 (most) abnormal (worsening = increase of ≥1 grade from initial to follow‐up MRI scans). The four‐category neighborhood greenspace–income measure was based on median neighborhood greenspace and income values at initial MRI. Multivariable logistic regression tested associations between neighborhood greenspace–income and MRI measures (worsening vs. not). RESULTS White matter grade worsening was more likely for those in lower greenspace–lower income neighborhoods than higher greenspace–higher income neighborhoods (odds ratio = 1.73; 95% confidence interval = 1.19–2.51). DISCUSSION The combination of lower neighborhood income and lower greenspace may be a risk factor for worsening white matter grade on MRI. However, findings need to be replicated in more diverse cohorts. HIGHLIGHTS Population‐based cohort of older adults (≥ 65 years) with greenspace and MRI data Combined measure of neighborhood greenspace and neighborhood income at initial MRI MRI outcomes included white matter hyperintensities (WMH) and ventricular size Longitudinal change in MRI outcomes measured approximately 5 years apart Worsening WMH over time more likely for lower greenspace‐lower income neighborhoods
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المصدر: Neurology EpiHealth: Epidemiology for Health EXODIAB: Excellence of Diabetes Research in Sweden. 92(5):486-503
مصطلحات موضوعية: Medicin och hälsovetenskap, Medicinska och farmaceutiska grundvetenskaper, Medicinsk genetik, Medical and Health Sciences, Basic Medicine, Medical Genetics, Neurovetenskaper, Neurosciences, Hälsovetenskap, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Health Sciences, Public Health, Global Health, Social Medicine and Epidemiology
الوصف: Objective To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. Methods We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n=20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. Results The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10 -8 ; and LINC00539/ZDHHC20, p = 5.82 × 10 -9 . Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p [BI] = 9.38 × 10 -25 ; p [SSBI] = 5.23 × 10 -14 for hypertension), smoking (p [BI] = 4.4 × 10 -10 ; p [SSBI] = 1.2 × 10 -4), diabetes (p [BI] = 1.7 × 10 -8; p [SSBI] = 2.8 × 10 -3), previous cardiovascular disease (p [BI] = 1.0 × 10 -18 ; p [SSBI] = 2.3 × 10 -7 ), stroke (p [BI] = 3.9 × 10 -69 ; p [SSBI] = 3.2 × 10 -24), and MRI-defined white matter hyperintensity burden (p [BI]=1.43 × 10 -157 ; p [SSBI] = 3.16 × 10 -106 ), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy. Conclusion In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI. © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
الوصول الحر: https://lup.lub.lu.se/record/8e729b7e-2a77-47b8-ac26-34b031890ed6Test
http://dx.doi.org/10.1212/WNL.0000000000006851Test
