Jenna Najar1,2, Sven J van der Lee3,4, Erik Joas1, Hanna Wetterberg1, John Hardy5,6,7,8,9, Rita Guerreiro10, Jose Bras10, Margda Waern1,11, Silke Kern1,2, Henrik Zetterberg5,6,12,13, Kaj Blennow12,13, Ingmar Skoog1,2, Anna Zettergren1. 1. Department of Psychiatry and Neurochemistry Neuropsychiatric Epidemiology Unit Institute of Neuroscience and Physiology the Sahlgrenska Academy Centre for Ageing and Health (AGECAP) at the University of Gothenburg Mölndal Sweden. 2. Region Västra Götaland Sahlgrenska University Hospital, Psychiatry, Cognition and Old Age Psychiatry Clinic Gothenburg Sweden. 3. Section Genomics of Neurdegenerative Diseases and Aging Department of Clinical Genetics Vrije Universiteit Amsterdam, Amsterdam UMC Amsterdam The Netherlands. 4. Alzheimer Center Amsterdam Department of Neurology, Amsterdam Neuroscience Vrije Universiteit Amsterdam, Amsterdam UMC Amsterdam The Netherlands. 5. Department of Neurodegenerative Disease UCL Institute of Neurology London UK. 6. UK Dementia Research Institute at UCL London UK. 7. Reta Lila Weston Institute UCL Queen Square Institute of Neurology London UK. 8. NIHR University College London Hospitals Biomedical Research Centre London UK. 9. Institute of Advanced Study the Hong Kong University of Science and Technology Hong Kong SAR China. 10. Center for Neurodegenerative Science Van Andel Institute Grand Rapids Michigan USA. 11. Region Västra Götaland Sahlgrenska University Hospital, Psychosis Clinic Gothenburg Sweden. 12. Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology The Sahlgrenska Academy at the University of Gothenburg Mölndal Sweden. 13. Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden.
Abstract
INTRODUCTION: Studies examining the effect of polygenic risk scores (PRS) for Alzheimer's disease (AD) and apolipoprotein E (APOE) genotype on incident dementia in very old individuals are lacking. METHODS: A population-based sample of 2052 individuals ages 70 to 111, from Sweden, was followed in relation to dementia. AD-PRSs including 39, 57, 1333, and 13,942 single nucleotide polymorphisms (SNPs) were used. RESULTS: AD-PRSs (including 39 or 57 SNPs) were associated with dementia (57-SNPs AD-PRS: hazard ratio 1.09, confidence interval 1.01-1.19, P = .03), particularly in APOE ɛ4 non-carriers (57-SNPs AD-PRS: 1.15, 1.05-1.27, P = 4 × 10-3, 39-SNPs AD-PRS: 1.22, 1.10-1.35, P = 2 × 10-4). No association was found with the other AD-PRSs. Further, APOE ɛ4 was associated with increased risk of dementia (1.60, 1.35-1.92, P = 1 × 10-7). In those aged ≥95 years, the results were similar for the AD-PRSs, while APOE ɛ4 only predicted dementia in the low-risk tertile of AD-PRSs. DISCUSSION: These results provide information to identify individuals at increased risk of dementia.
INTRODUCTION: Studies examining the effect of polygenic risk scores (PRS) for Alzheimer's disease (AD) and apolipoprotein E (APOE) genotype on incident dementia in very old individuals are lacking. METHODS: A population-based sample of 2052 individuals ages 70 to 111, from Sweden, was followed in relation to dementia. AD-PRSs including 39, 57, 1333, and 13,942 single nucleotide polymorphisms (SNPs) were used. RESULTS: AD-PRSs (including 39 or 57 SNPs) were associated with dementia (57-SNPs AD-PRS: hazard ratio 1.09, confidence interval 1.01-1.19, P = .03), particularly in APOE ɛ4 non-carriers (57-SNPs AD-PRS: 1.15, 1.05-1.27, P = 4 × 10-3, 39-SNPs AD-PRS: 1.22, 1.10-1.35, P = 2 × 10-4). No association was found with the other AD-PRSs. Further, APOE ɛ4 was associated with increased risk of dementia (1.60, 1.35-1.92, P = 1 × 10-7). In those aged ≥95 years, the results were similar for the AD-PRSs, while APOE ɛ4 only predicted dementia in the low-risk tertile of AD-PRSs. DISCUSSION: These results provide information to identify individuals at increased risk of dementia.
Authors: C Bengtsson; M Ahlqwist; K Andersson; C Björkelund; L Lissner; M Söderström Journal: Scand J Prim Health Care Date: 1997-12 Impact factor: 2.581
Authors: K Juva; A Verkkoniemi; P Viramo; T Polvikoski; K Kainulainen; K Kontula; R Sulkava Journal: Int Psychogeriatr Date: 2000-09 Impact factor: 3.878
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Isabel Hernández; M Ilyas Kamboh; RoseMarie Brundin; James Turton; Qiong Yang; Mindy J Katz; Letizia Concari; Jenny Lord; Alexa S Beiser; C Dirk Keene; Seppo Helisalmi; Iwona Kloszewska; Walter A Kukull; Anne Maria Koivisto; Aoibhinn Lynch; Lluís Tarraga; Eric B Larson; Annakaisa Haapasalo; Brian Lawlor; Thomas H Mosley; Richard B Lipton; Vincenzo Solfrizzi; Michael Gill; W T Longstreth; Thomas J Montine; Vincenza Frisardi; Monica Diez-Fairen; Fernando Rivadeneira; Ronald C Petersen; Vincent Deramecourt; Ignacio Alvarez; Francesca Salani; Antonio Ciaramella; Eric Boerwinkle; Eric M Reiman; Nathalie Fievet; Jerome I Rotter; Joan S Reisch; Olivier Hanon; Chiara Cupidi; A G Andre Uitterlinden; Donald R Royall; Carole Dufouil; Raffaele Giovanni Maletta; Itziar de Rojas; Mary Sano; Alexis Brice; Roberta Cecchetti; Peter St George-Hyslop; Karen Ritchie; Magda Tsolaki; Debby W Tsuang; Bruno Dubois; David Craig; Chuang-Kuo Wu; Hilkka Soininen; Despoina Avramidou; Roger L Albin; Laura Fratiglioni; Antonia Germanou; Liana G Apostolova; Lina Keller; Maria Koutroumani; Steven E Arnold; Francesco Panza; Olymbia Gkatzima; Sanjay Asthana; Didier Hannequin; Patrice Whitehead; Craig S Atwood; Paolo Caffarra; Harald Hampel; Inés Quintela; Ángel Carracedo; Lars Lannfelt; David C Rubinsztein; Lisa L Barnes; Florence Pasquier; Lutz Frölich; Sandra Barral; Bernadette McGuinness; Thomas G Beach; Janet A Johnston; James T Becker; Peter Passmore; Eileen H Bigio; Jonathan M Schott; Thomas D Bird; Jason D Warren; Bradley F Boeve; Michelle K Lupton; James D Bowen; Petra Proitsi; Adam Boxer; John F Powell; James R Burke; John S K Kauwe; Jeffrey M Burns; Michelangelo Mancuso; Joseph D Buxbaum; Ubaldo Bonuccelli; Nigel J Cairns; Andrew McQuillin; Chuanhai Cao; Gill Livingston; Chris S Carlson; Nicholas J Bass; Cynthia M Carlsson; John Hardy; Regina M Carney; Jose Bras; Minerva M Carrasquillo; Rita Guerreiro; Mariet Allen; Helena C Chui; Elizabeth Fisher; Carlo Masullo; Elizabeth A Crocco; Charles DeCarli; Gina Bisceglio; Malcolm Dick; Li Ma; Ranjan Duara; Neill R Graff-Radford; Denis A Evans; Angela Hodges; Kelley M Faber; Martin Scherer; Kenneth B Fallon; Matthias Riemenschneider; David W Fardo; Reinhard Heun; Martin R Farlow; Heike Kölsch; Steven Ferris; Markus Leber; Tatiana M Foroud; Isabella Heuser; Douglas R Galasko; Ina Giegling; Marla Gearing; Michael Hüll; Daniel H Geschwind; John R Gilbert; John Morris; Robert C Green; Kevin Mayo; John H Growdon; Thomas Feulner; Ronald L Hamilton; Lindy E Harrell; Dmitriy Drichel; Lawrence S Honig; Thomas D Cushion; Matthew J Huentelman; Paul Hollingworth; Christine M Hulette; Bradley T Hyman; Rachel Marshall; Gail P Jarvik; Alun Meggy; Erin Abner; Georgina E Menzies; Lee-Way Jin; Ganna Leonenko; Luis M Real; Gyungah R Jun; Clinton T Baldwin; Detelina Grozeva; Anna Karydas; Giancarlo Russo; Jeffrey A Kaye; Ronald Kim; Frank Jessen; Neil W Kowall; Bruno Vellas; Joel H Kramer; Emma Vardy; Frank M LaFerla; Karl-Heinz Jöckel; James J Lah; Martin Dichgans; James B Leverenz; David Mann; Allan I Levey; Stuart Pickering-Brown; Andrew P Lieberman; Norman Klopp; Kathryn L Lunetta; H-Erich Wichmann; Constantine G Lyketsos; Kevin Morgan; Daniel C Marson; Kristelle Brown; Frank Martiniuk; Christopher Medway; Deborah C Mash; Markus M Nöthen; Eliezer Masliah; Nigel M Hooper; Wayne C McCormick; Antonio Daniele; Susan M McCurry; Anthony Bayer; Andrew N McDavid; John Gallacher; Ann C McKee; Hendrik van den Bussche; Marsel Mesulam; Carol Brayne; Bruce L Miller; Steffi Riedel-Heller; Carol A Miller; Joshua W Miller; Ammar Al-Chalabi; John C Morris; Christopher E Shaw; Amanda J Myers; Jens Wiltfang; Sid O'Bryant; John M Olichney; Victoria Alvarez; Joseph E Parisi; Andrew B Singleton; Henry L Paulson; John Collinge; William R Perry; Simon Mead; Elaine Peskind; David H Cribbs; Martin Rossor; Aimee Pierce; Natalie S Ryan; Wayne W Poon; Benedetta Nacmias; Huntington Potter; Sandro Sorbi; Joseph F Quinn; Eleonora Sacchinelli; Ashok Raj; Gianfranco Spalletta; Murray Raskind; Carlo Caltagirone; Paola Bossù; Maria Donata Orfei; Barry Reisberg; Robert Clarke; Christiane Reitz; A David Smith; John M Ringman; Donald Warden; Erik D Roberson; Gordon Wilcock; Ekaterina Rogaeva; Amalia Cecilia Bruni; Howard J Rosen; Maura Gallo; Roger N Rosenberg; Yoav Ben-Shlomo; Mark A Sager; Patrizia Mecocci; Andrew J Saykin; Pau Pastor; Michael L Cuccaro; Jeffery M Vance; Julie A Schneider; Lori S Schneider; Susan Slifer; William W Seeley; Amanda G Smith; Joshua A Sonnen; Salvatore Spina; Robert A Stern; Russell H Swerdlow; Mitchell Tang; Rudolph E Tanzi; John Q Trojanowski; Juan C Troncoso; Vivianna M Van Deerlin; Linda J Van Eldik; Harry V Vinters; Jean Paul Vonsattel; Sandra Weintraub; Kathleen A Welsh-Bohmer; Kirk C Wilhelmsen; Jennifer Williamson; Thomas S Wingo; Randall L Woltjer; Clinton B Wright; Chang-En Yu; Lei Yu; Yasaman Saba; Alberto Pilotto; Maria J Bullido; Oliver Peters; Paul K Crane; David Bennett; Paola Bosco; Eliecer Coto; Virginia Boccardi; Phil L De Jager; Alberto Lleo; Nick Warner; Oscar L Lopez; Martin Ingelsson; Panagiotis Deloukas; Carlos Cruchaga; Caroline Graff; Rhian Gwilliam; Myriam Fornage; Alison M Goate; Pascual Sanchez-Juan; Patrick G Kehoe; Najaf Amin; Nilifur Ertekin-Taner; Claudine Berr; Stéphanie Debette; Seth Love; Lenore J Launer; Steven G Younkin; Jean-Francois Dartigues; Chris Corcoran; M Arfan Ikram; Dennis W Dickson; Gael Nicolas; Dominique Campion; JoAnn Tschanz; Helena Schmidt; Hakon Hakonarson; Jordi Clarimon; Ron Munger; Reinhold Schmidt; Lindsay A Farrer; Christine Van Broeckhoven; Michael C O'Donovan; Anita L DeStefano; Lesley Jones; Jonathan L Haines; Jean-Francois Deleuze; Michael J Owen; Vilmundur Gudnason; Richard Mayeux; Valentina Escott-Price; Bruce M Psaty; Alfredo Ramirez; Li-San Wang; Agustin Ruiz; Cornelia M van Duijn; Peter A Holmans; Sudha Seshadri; Julie Williams; Phillippe Amouyel Journal: Nat Genet Date: 2019-09 Impact factor: 38.330
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