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1. Quality over quantity - rethinking social participation in dementia prevention: results from the AgeWell.de trial

Author

Kosilek, Robert P., Wendel, Flora, Zöllinger, Isabel, Knecht, Hanna Lea, Blotenberg, Iris, Weise, Solveig, Fankhänel, Thomas, Döhring, Juliane, Williamson, Martin, Luppa, Melanie, Zülke, Andrea E., Brettschneider, Christian, Wiese, Birgitt, Hoffmann, Wolfgang, Frese, Thomas, König, Hans-Helmut, Kaduszkiewicz, Hanna, Thyrian, Jochen René, Riedel-Heller, Steffi G., and Gensichen, Jochen

Published
2024
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8. Social isolation in the oldest-old: determinants and the differential role of family and friends

Author

Moormann, Katharina Isabelle, Pabst, Alexander, Bleck, Franziska, Löbner, Margrit, Kaduszkiewicz, Hanna, van der Leeden, Carolin, Hajek, André, Brettschneider, Christian, Heser, Kathrin, Kleineidam, Luca, Werle, Jochen, Fuchs, Angela, Weeg, Dagmar, Bickel, Horst, Pentzek, Michael, Weyerer, Siegfried, Wiese, Birgitt, Wagner, Michael, Maier, Wolfgang, Scherer, Martin, König, Hans-Helmut, and Riedel-Heller, Steffi G.

Published
2024
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13. Adherence to a lifestyle intervention – just a question of self-efficacy? Analysis of the AgeWell.de-intervention against cognitive decline

Author

Wittmann, Felix G., Pabst, Alexander, Zülke, Andrea, Luppa, Melanie, Oey, Anke, Boekholt, Melanie, Weise, Solveig, Fankhänel, Thomas, Kosilek, Robert P., Brettschneider, Christian, Döhring, Juliane, Lunden, Laura, Wiese, Birgitt, Hoffmann, Wolfgang, Frese, Thomas, Gensichen, Jochen, König, Hans-Helmut, Kaduszkiewicz, Hanna, Thyrian, Jochen René, and Riedel-Heller, Steffi G.

Published
2024
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15. The effect of depressive symptoms on quality of life and its different facets in the oldest age population: evidence from the AgeQualiDe prospective cohort study

Author

Liegert, Paula, Pabst, Alexander, Conrad, Ines, van den Bussche, Hendrik, Eisele, Marion, Hajek, André, Heser, Kathrin, Kleineidam, Luca, Weyerer, Siegfried, Werle, Jochen, Pentzek, Michael, Weeg, Dagmar, Mösch, Edelgard, Wiese, Birgitt, Oey, Anke, Wagner, Michael, Maier, Wolfgang, König, Hans-Helmut, Riedel-Heller, Steffi G., Scherer, Martin, and Luppa, Melanie

Published
2024
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17. Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer’s disease

Author

Holstege, Henne, Hulsman, Marc, Charbonnier, Camille, Grenier-Boley, Benjamin, Quenez, Olivier, Grozeva, Detelina, van Rooij, Jeroen GJ, Sims, Rebecca, Ahmad, Shahzad, Amin, Najaf, Norsworthy, Penny J, Dols-Icardo, Oriol, Hummerich, Holger, Kawalia, Amit, Amouyel, Philippe, Beecham, Gary W, Berr, Claudine, Bis, Joshua C, Boland, Anne, Bossù, Paola, Bouwman, Femke, Bras, Jose, Campion, Dominique, Cochran, J Nicholas, Daniele, Antonio, Dartigues, Jean-François, Debette, Stéphanie, Deleuze, Jean-François, Denning, Nicola, DeStefano, Anita L, Farrer, Lindsay A, Fernández, Maria Victoria, Fox, Nick C, Galimberti, Daniela, Genin, Emmanuelle, Gille, Johan JP, Le Guen, Yann, Guerreiro, Rita, Haines, Jonathan L, Holmes, Clive, Ikram, M Arfan, Ikram, M Kamran, Jansen, Iris E, Kraaij, Robert, Lathrop, Marc, Lemstra, Afina W, Lleó, Alberto, Luckcuck, Lauren, Mannens, Marcel MAM, Marshall, Rachel, Martin, Eden R, Masullo, Carlo, Mayeux, Richard, Mecocci, Patrizia, Meggy, Alun, Mol, Merel O, Morgan, Kevin, Myers, Richard M, Nacmias, Benedetta, Naj, Adam C, Napolioni, Valerio, Pasquier, Florence, Pastor, Pau, Pericak-Vance, Margaret A, Raybould, Rachel, Redon, Richard, Reinders, Marcel JT, Richard, Anne-Claire, Riedel-Heller, Steffi G, Rivadeneira, Fernando, Rousseau, Stéphane, Ryan, Natalie S, Saad, Salha, Sanchez-Juan, Pascual, Schellenberg, Gerard D, Scheltens, Philip, Schott, Jonathan M, Seripa, Davide, Seshadri, Sudha, Sie, Daoud, Sistermans, Erik A, Sorbi, Sandro, van Spaendonk, Resie, Spalletta, Gianfranco, Tesi, Niccolo’, Tijms, Betty, Uitterlinden, André G, van der Lee, Sven J, Visser, Pieter Jelle, Wagner, Michael, Wallon, David, Wang, Li-San, Zarea, Aline, Clarimon, Jordi, van Swieten, John C, Greicius, Michael D, Yokoyama, Jennifer S, Cruchaga, Carlos, Hardy, John, and Ramirez, Alfredo

Subjects
Biological Sciences, Genetics, Dementia, Alzheimer's Disease, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Human Genome, Prevention, Acquired Cognitive Impairment, Neurodegenerative, Aging, Clinical Research, Biotechnology, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Neurological, Humans, Adenosine Triphosphatases, Alzheimer Disease, ATP Binding Cassette Transporter 1, Genome-Wide Association Study, Risk Factors, Exosomes, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Alzheimer's disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%1. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants2. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals-16,036 AD cases and 16,522 controls. Next to variants in TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Additionally, the rare-variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential drivers of respective AD-genome-wide association study loci. Variants associated with the strongest effect on AD risk, in particular loss-of-function variants, are enriched in early-onset AD cases. Our results provide additional evidence for a major role for amyloid-β precursor protein processing, amyloid-β aggregation, lipid metabolism and microglial function in AD.

Published
2022

18. Comparison of Patient Health Questionnaire-9, Edinburgh Postnatal Depression Scale and Hospital Anxiety and Depression – Depression subscale scores by administration mode: An individual participant data differential item functioning meta-analysis

Author

Azar, Marleine, Bhandari, Parash Mani, Chiovitti, Matthew J., He, Chen, Imran, Mahrukh, Krishnan, Ankur, Negeri, Zelalem, Neupane, Dipika, Riehm, Kira E., Yan, Xin Wei, Kloda, Lorie A., Henry, Melissa, Ismail, Zahinoor, Loiselle, Carmen G., Mitchell, Nicholas D., Al-Adawi, Samir, Alvarado, Rubén, Amtmann, Dagmar, Arroll, Bruce, Ayalon, Liat, Baradaran, Hamid R., Barnes, Jacqueline, Beck, Kevin R., Beck, Cheryl Tatano, Bernstein, Charles N., Bindt, Carola, Bombardier, Charles H., Boye, Birgitte, Büel-Drabe, Natalie, Buji, Ryna Imma, Bunevicius, Adomas, Butterworth, Peter, Can, Ceyhun, Carter, Gregory, Chagas, Marcos H., Chan, Juliana C.N., Chan, Lai Fong, Chen, Chih-Ken, Chibanda, Dixon, Chorwe-Sungani, Genesis, Clover, Kerrie, Conroy, Ronán M., Conway, Aaron, Conwell, Yeates, Correa, Humberto, Couto, Thiago Castro e, Cukor, Daniel, Daray, Federico M., de Man-van Ginkel, Janneke M., De Souza, Jennifer, Downing, Marina G., Eapen, Valsamma, Fann, Jesse R., Favez, Nicolas, Felice, Ethel, Fellmeth, Gracia, Ferentinos, Panagiotis P., Fernandes, Michelle, Field, Sally, Figueiredo, Barbara, Fischer, Felix H., Fisher, Jane R.W., Flint, Alastair J., Fujimori, Maiko, Fung, Daniel S.S., Gallagher, Pamela, Gandy, Milena, Gelaye, Bizu, Gholizadeh, Leila, Gibson, Lorna J., Goodyear-Smith, Felicity, Grassi, Luigi, Green, Eric P., Greeno, Catherine G., Hall, Brian J., Hantsoo, Liisa, Haroz, Emily E., Härter, Martin, Hegerl, Ulrich, Helle, Nadine, Hernando, Asuncion, Hides, Leanne, Hobfoll, Stevan E., Honikman, Simone, Howard, Louise M., Hyphantis, Thomas, Iglesias-González, Maria, Inagaki, Masatoshi, Jenewein, Josef, Jeon, Hong Jin, Jetté, Nathalie, Julião, Miguel, Kettunen, Pirjo A., Khamseh, Mohammad E., Kiely, Kim M., Kim, Sung-Wan, Kjærgaard, Marie, Kohlhoff, Jane, Kohrt, Brandon A., König, Hans-Helmut, Kozinszky, Zoltán, Kwan, Yunxin, Lamers, Femke, Lara, María Asunción, Leonardou, Angeliki A., Levin-Aspenson, Holly F., Liu, Shen-Ing, Löbner, Margrit, Loosman, Wim L., Lotrakul, Manote, Loureiro, Sonia R., Love, Anthony W., Löwe, Bernd, Luitel, Nagendra P., Lund, Crick, Maes, Michael, Malt, Ulrik F., Marrie, Ruth Ann, Marsh, Laura, Martínez, Pablo, Marx, Brian P., Matsuoka, Yutaka, McGuire, Anthony, Mehnert, Anja, Michopoulos, Ioannis, Sidik, Sherina Mohd, Müller-Nordhorn, Jacqueline, Muramatsu, Kumiko, Radoš, Sandra Nakić, Navarrete, Laura, Nelson, Christian J., Ng, Chong Guan, Nishi, Daisuke, O'Donnell, Meaghan L., O'Rourke, Suzanne J., Osório, Flávia L., Pabst, Alexander, Pasco, Julie A., Pawlby, Susan J., Peceliuniene, Jurate, Pence, Brian W., Persoons, Philippe, Petersen, Inge, Picardi, Angelo, Ponsford, Jennie L., Pugh, Stephanie L., Pulido, Federico, Quinn, Terence J., Quispel, Chantal, Rathod, Sujit D., Reme, Silje E., Reuter, Katrin, Riedel-Heller, Steffi G., Rooney, Alasdair G., Santos, Iná S., Saracino, Rebecca M., Schellekens, Melanie P.J., Schwarzbold, Marcelo L., Cankorur, Vesile Senturk, Shaaban, Juwita, Sharp, Deborah J., Sharpe, Louise, Shinn, Eileen H., Sidebottom, Abbey, Simard, Sébastien, Singer, Susanne, Skalkidou, Alkistis, Smith-Nielsen, Johanne, Spangenberg, Lena, Stafford, Lesley, Stein, Alan, Stewart, Robert C., Strobel, Natalie A., Su, Kuan-Pin, Sultan, Serge, Sundström-Poromaa, Inger, Sung, Sharon C., Suzuki, Keiko, Tadinac, Meri, Tan, Pei Lin Lynnette, Tandon, S. Darius, Taylor-Rowan, Martin, Teixeira, Antonio L., Tendais, Iva, Tiringer, Istvan, Töreki, Annamária, Tran, Thach D., Trevillion, Kylee, Tschorn, Mira, Turner, Alyna, Væver, Mette S., van der Feltz-Cornelis, Christina M., van Heyningen, Thandi, Vega-Dienstmaier, Johann M., Wagner, Michael, Wagner, Lynne I., Wang, Liang-Jen, Wang, Jian Li, Watson, David, Weyerer, Siegfried B., White, Jennifer, Whooley, Mary A., Wiese, Birgitt, Williams, Lana J., Winkley, Kirsty, Wynter, Karen, Yamada, Mitsuhiko, Yonkers, Kimberly A., Zeng, Qing Zhi, Zhang, Yuying, Harel, Daphna, Wu, Yin, Levis, Brooke, Fan, Suiqiong, Sun, Ying, Xu, Mingyao, Rice, Danielle B., Boruff, Jill, Markham, Sarah, Ioannidis, John P.A., Takwoingi, Yemisi, Patten, Scott B., Ziegelstein, Roy C., Cuijpers, Pim, Gilbody, Simon, Vigod, Simone, Akena, Dickens, Benedetti, Andrea, and Thombs, Brett D.

Published
2024
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19. Individual patient data meta-analysis estimates the minimal detectable change of the Geriatric Depression Scale-15

Author

Krishnan, Ankur, He, Chen, Santo, Tiffany Dal, Neupane, Dipika, Brehaut, Eliana, Bhandari, Parash M., Qiu, Xia, Li, Letong, Imran, Mahrukh, Nassar, Elsa-Lynn, Adams, Kathryn Betts, Baillon, Sarah F., Caramelli, Paulo, Castro-Costa, Erico, Chagas, Marcos H.N., Dias, Filipi L.C., Isik, Ahmet Turan, Jetté, Nathalie, Katz, Patricia, Kim, Wonhyoung, König, Hans-Helmut, Lima-Costa, Maria Fernanda, Löbner, Margrit, Malakouti, Seyed Kazem, Marsh, Laura, Moon, Heehyul E., Mougias, Antonis A., Nelson, Christian J., Pabst, Alexander, Quinn, Terence J., Riedel-Heller, Steffi G., Saracino, Rebecca, Scherer, Martin, Volz, Matthias, Wagner, Michael, Weyerer, Siegfried B., González-Domínguez, Nadia P., Wu, Yin, Fan, Suiqiong, Levis, Brooke, Sun, Ying, Gilbody, Simon, Ioannidis, John P.A., Harel, Daphna, Vigod, Simone N., Markham, Sarah, Ziegelstein, Roy C., Cuijpers, Pim, Patten, Scott B., Boruff, Jill T., Thombs, Brett D., and Benedetti, Andrea

Published
2024
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21. An Investigation into the Relationship of Circulating Gut Microbiome Molecules and Inflammatory Markers with the Risk of Incident Dementia in Later Life

Author

Oluwagbemigun, Kolade, Anesi, Andrea, Vrhovsek, Urska, Mattivi, Fulvio, Martino Adami, Pamela, Pentzek, Michael, Scherer, Martin, Riedel-Heller, Steffi G., Weyerer, Siegfried, Bickel, Horst, Wiese, Birgitt, Schmid, Matthias, Cryan, John F., Ramirez, Alfredo, Wagner, Michael, and Nöthlings, Ute

Published
2023
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41. A cross‐national study of depression in preclinical dementia: A COSMIC collaboration study

Author

Carles, Sophie, Carrière, Isabelle, Reppermund, Simone, Davin, Annalisa, Guaita, Antonio, Vaccaro, Roberta, Ganguli, Mary, Jacobsen, Erin P, Beer, Joanne C, Riedel‐Heller, Steffi G, Roehr, Susanne, Pabst, Alexander, Haan, Mary N, Brodaty, Henry, Kochan, Nicole A, Trollor, Julian N, Kim, Ki Woong, Han, Ji Won, Suh, Seung Wan, Lobo, Antonio, De Camara, Concepción, Lobo, Elena, Lipnicki, Darren M, Sachdev, Perminder S, Ancelin, Marie‐Laure, Ritchie, Karen, and Consortium, for Cohort Studies of Memory in an International

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Brain Disorders, Mental Health, Aging, Depression, Alzheimer's Disease, Acquired Cognitive Impairment, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Neurological, Aged, Aged, 80 and over, Cohort Studies, Female, Humans, Incidence, Longitudinal Studies, Male, Prodromal Symptoms, dementia, depression, incidence, for Cohort Studies of Memory in an International Consortium, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionDepression commonly accompanies Alzheimer's disease, but the nature of this association remains uncertain.MethodsLongitudinal data from the COSMIC consortium were harmonized for eight population-based cohorts from four continents. Incident dementia was diagnosed in 646 participants, with a median follow-up time of 5.6 years to diagnosis. The association between years to dementia diagnosis and successive depressive states was assessed using a mixed effect logistic regression model. A generic inverse variance method was used to group study results, construct forest plots, and generate heterogeneity statistics.ResultsA common trajectory was observed showing an increase in the incidence of depression as the time to dementia diagnosis decreased despite cross-national variability in depression rates.DiscussionThe results support the hypothesis that depression occurring in the preclinical phases of dementia is more likely to be attributable to dementia-related brain changes than environment or reverse causality.

Published
2020

42. Education and the moderating roles of age, sex, ethnicity and apolipoprotein epsilon 4 on the risk of cognitive impairment

Author

Makkar, Steve R, Lipnicki, Darren M, Crawford, John D, Kochan, Nicole A, Castro-Costa, Erico, Lima-Costa, Maria Fernanda, Diniz, Breno Satler, Brayne, Carol, Stephan, Blossom, Matthews, Fiona, Llibre-Rodriguez, Juan J, Llibre-Guerra, Jorge J, Valhuerdi-Cepero, Adolfo J, Lipton, Richard B, Katz, Mindy J, Zammit, Andrea, Ritchie, Karen, Carles, Sophie, Carriere, Isabelle, Scarmeas, Nikolaos, Yannakoulia, Mary, Kosmidis, Mary, Lam, Linda, Fung, Ada, Chan, Wai Chi, Guaita, Antonio, Vaccaro, Roberta, Davin, Annalisa, Kim, Ki Woong, Han, Ji Won, Suh, Seung Wan, Riedel-Heller, Steffi G, Roehr, Susanne, Pabst, Alexander, Ganguli, Mary, Hughes, Tiffany F, Jacobsen, Erin P, Anstey, Kaarin J, Cherbuin, Nicolas, Haan, Mary N, Aiello, Allison E, Dang, Kristina, Kumagai, Shuzo, Narazaki, Kenji, Chen, Sanmei, Ng, Tze Pin, Gao, Qi, Nyunt, Ma Shwe Zin, Meguro, Kenichi, Yamaguchi, Satoshi, Ishii, Hiroshi, Lobo, Antonio, Escolar, Elena Lobo, De la Cámara, Concepción, Brodaty, Henry, Trollor, Julian N, Leung, Yvonne, Lo, Jessica W, Sachdev, Perminder, and Consortium, for Cohort Studies of Memory in an International

Subjects
Public Health, Health Sciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Alzheimer's Disease, Neurosciences, Brain Disorders, Acquired Cognitive Impairment, Women's Health, Behavioral and Social Science, Dementia, Aging, Quality Education, Aged, Aged, 80 and over, Apolipoprotein E4, Cognitive Dysfunction, Educational Status, Ethnicity, Female, Humans, Longitudinal Studies, Male, Risk Factors, Cognitive decline, Education, Ageing, Sex, Age, for Cohort Studies of Memory in an International Consortium
Abstract

BackgroundWe examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4).MethodsParticipants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School.ResultsCompared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P

Published
2020

44. Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Author

Lahti, Jari, Tuominen, Samuli, Yang, Qiong, Pergola, Giulio, Ahmad, Shahzad, Amin, Najaf, Armstrong, Nicola J., Beiser, Alexa, Bey, Katharina, Bis, Joshua C., Boerwinkle, Eric, Bressler, Jan, Campbell, Archie, Campbell, Harry, Chen, Qiang, Corley, Janie, Cox, Simon R., Davies, Gail, De Jager, Philip L., Derks, Eske M., Faul, Jessica D., Fitzpatrick, Annette L., Fohner, Alison E., Ford, Ian, Fornage, Myriam, Gerring, Zachary, Grabe, Hans J., Grodstein, Francine, Gudnason, Vilmundur, Simonsick, Eleanor, Holliday, Elizabeth G., Joshi, Peter K., Kajantie, Eero, Kaprio, Jaakko, Karell, Pauliina, Kleineidam, Luca, Knol, Maria J., Kochan, Nicole A., Kwok, John B., Leber, Markus, Lam, Max, Lee, Teresa, Li, Shuo, Loukola, Anu, Luck, Tobias, Marioni, Riccardo E., Mather, Karen A., Medland, Sarah, Mirza, Saira S., Nalls, Mike A., Nho, Kwangsik, O’Donnell, Adrienne, Oldmeadow, Christopher, Painter, Jodie, Pattie, Alison, Reppermund, Simone, Risacher, Shannon L., Rose, Richard J., Sadashivaiah, Vijay, Scholz, Markus, Satizabal, Claudia L., Schofield, Peter W., Schraut, Katharina E., Scott, Rodney J., Simino, Jeannette, Smith, Albert V., Smith, Jennifer A., Stott, David J., Surakka, Ida, Teumer, Alexander, Thalamuthu, Anbupalam, Trompet, Stella, Turner, Stephen T., van der Lee, Sven J., Villringer, Arno, Völker, Uwe, Wilson, Robert S., Wittfeld, Katharina, Vuoksimaa, Eero, Xia, Rui, Yaffe, Kristine, Yu, Lei, Zare, Habil, Zhao, Wei, Ames, David, Attia, John, Bennett, David A., Brodaty, Henry, Chasman, Daniel I., Goldman, Aaron L., Hayward, Caroline, Ikram, M. Arfan, Jukema, J. Wouter, Kardia, Sharon L. R., Lencz, Todd, Loeffler, Markus, Mattay, Venkata S., Palotie, Aarno, Psaty, Bruce M., Ramirez, Alfredo, Ridker, Paul M., Riedel-Heller, Steffi G., Sachdev, Perminder S., Saykin, Andrew J., Scherer, Martin, Schofield, Peter R., Sidney, Stephen, Starr, John M., Trollor, Julian, Ulrich, William, Wagner, Michael, Weir, David R., Wilson, James F., Wright, Margaret J., Weinberger, Daniel R., Debette, Stephanie, Eriksson, Johan G., Mosley, Jr., Thomas H., Launer, Lenore J., van Duijn, Cornelia M., Deary, Ian J., Seshadri, Sudha, and Räikkönen, Katri

Published
2022
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46. APOE ε4 and the Influence of Sex, Age, Vascular Risk Factors, and Ethnicity on Cognitive Decline

Author

Makkar, Steve R, Lipnicki, Darren M, Crawford, John D, Kochan, Nicole A, Castro-Costa, Erico, Lima-Costa, Maria Fernanda, Diniz, Breno Satler, Brayne, Carol, Stephan, Blossom, Matthews, Fiona, Llibre-Rodriguez, Juan J, Llibre-Guerra, Jorge J, Valhuerdi-Cepero, Adolfo J, Lipton, Richard B, Katz, Mindy J, Wang, Cuiling, Ritchie, Karen, Carles, Sophie, Carriere, Isabelle, Scarmeas, Nikolaos, Yannakoulia, Mary, Kosmidis, Mary, Lam, Linda, Chan, Wai Chi, Fung, Ada, Guaita, Antonio, Vaccaro, Roberta, Davin, Annalisa, Kim, Ki Woong, Han, Ji Won, Suh, Seung Wan, Riedel-Heller, Steffi G, Roehr, Susanne, Pabst, Alexander, Ganguli, Mary, Hughes, Tiffany F, Snitz, Beth, Anstey, Kaarin J, Cherbuin, Nicolas, Easteal, Simon, Haan, Mary N, Aiello, Allison E, Dang, Kristina, Ng, Tze Pin, Gao, Qi, Nyunt, Ma Shwe Zin, Brodaty, Henry, Trollor, Julian N, Leung, Yvonne, Lo, Jessica W, and Sachdev, Perminder

Subjects
Health Sciences, Neurosciences, Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Genetics, Neurodegenerative, Alzheimer's Disease, Acquired Cognitive Impairment, Aging, Prevention, Dementia, Brain Disorders, Behavioral and Social Science, 2.4 Surveillance and distribution, Aetiology, Age Factors, Aged, Aged, 80 and over, Alleles, Apolipoprotein E4, Cognitive Dysfunction, Female, Genotype, Humans, Longitudinal Studies, Male, Middle Aged, Risk Factors, Sex Factors, Cognitive decline, APOE genotype, Epidemiology, Sex, Ethnicity, Clinical Sciences, Gerontology, Biomedical and clinical sciences, Health sciences
Abstract

We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.

Published
2020

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