David A Bennett1,2, Aron S Buchman1,2, Patricia A Boyle1,3, Lisa L Barnes1,2,3, Robert S Wilson1,2,3, Julie A Schneider1,2,4. 1. Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA. 2. Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA. 3. Department of Behavioral Sciences, Rush University Medical Center, Chicago, IL, USA. 4. Department of Pathology (Neuropathology), Rush University Medical Center, Chicago, IL, USA.
Abstract
BACKGROUND: The Religious Orders Study and Rush Memory and Aging Project are both ongoing longitudinal clinical-pathologic cohort studies of aging and Alzheimer's disease (AD). OBJECTIVES: To summarize progress over the past five years and its implications for understanding neurodegenerative diseases. METHODS: Participants in both studies are older adults who enroll without dementia and agree to detailed longitudinal clinical evaluations and organ donation. The last review summarized findings through the end of 2011. Here we summarize progress and study findings over the past five years and discuss new directions for how these studies can inform on aging and AD in the future. RESULTS: We summarize 1) findings on the relation of neurobiology to clinical AD; 2) neurobiologic pathways linking risk factors to clinical AD; 3) non-cognitive AD phenotypes including motor function and decision making; 4) the development of a novel drug discovery platform. CONCLUSION: Complexity at multiple levels needs to be understood and overcome to develop effective treatments and preventions for cognitive decline and AD dementia.
BACKGROUND: The Religious Orders Study and Rush Memory and Aging Project are both ongoing longitudinal clinical-pathologic cohort studies of aging and Alzheimer's disease (AD). OBJECTIVES: To summarize progress over the past five years and its implications for understanding neurodegenerative diseases. METHODS:Participants in both studies are older adults who enroll without dementia and agree to detailed longitudinal clinical evaluations and organ donation. The last review summarized findings through the end of 2011. Here we summarize progress and study findings over the past five years and discuss new directions for how these studies can inform on aging and AD in the future. RESULTS: We summarize 1) findings on the relation of neurobiology to clinical AD; 2) neurobiologic pathways linking risk factors to clinical AD; 3) non-cognitive AD phenotypes including motor function and decision making; 4) the development of a novel drug discovery platform. CONCLUSION: Complexity at multiple levels needs to be understood and overcome to develop effective treatments and preventions for cognitive decline and AD dementia.
Entities:
Keywords:
Alzheimer’s disease; cognitive decline; decision making; dementia; drug zzm321990discovery; epidemiology; motor function; neuropathology; omics
Authors: David A Bennett; Lei Yu; Jingyun Yang; Gyan P Srivastava; Cristin Aubin; Philip L De Jager Journal: Transl Res Date: 2014-05-16 Impact factor: 7.012
Authors: Brian E Cade; Daniel J Gottlieb; Diane S Lauderdale; David A Bennett; Aron S Buchman; Sarah G Buxbaum; Philip L De Jager; Daniel S Evans; Tibor Fülöp; Sina A Gharib; W Craig Johnson; Hyun Kim; Emma K Larkin; Seung Ku Lee; Andrew S Lim; Naresh M Punjabi; Chol Shin; Katie L Stone; Gregory J Tranah; Jia Weng; Kristine Yaffe; Phyllis C Zee; Sanjay R Patel; Xiaofeng Zhu; Susan Redline; Richa Saxena Journal: Hum Mol Genet Date: 2015-10-13 Impact factor: 6.150
Authors: Robert S Wilson; Patricia A Boyle; Eisuke Segawa; Lei Yu; Christopher T Begeny; Sophia E Anagnos; David A Bennett Journal: Psychol Aging Date: 2013-02-18
Authors: Lisa L Barnes; Ana W Capuano; Alison E Aiello; Arlener D Turner; Robert H Yolken; E Fuller Torrey; David A Bennett Journal: J Infect Dis Date: 2014-08-08 Impact factor: 5.226
Authors: Bryan D James; Sue E Leurgans; Liesi E Hebert; Paul A Scherr; Kristine Yaffe; David A Bennett Journal: Neurology Date: 2014-03-05 Impact factor: 9.910
Authors: V K Ramanan; K Nho; L Shen; S L Risacher; S Kim; B C McDonald; M R Farlow; T M Foroud; S Gao; H Soininen; I Kłoszewska; P Mecocci; M Tsolaki; B Vellas; S Lovestone; P S Aisen; R C Petersen; C R Jack; L M Shaw; J Q Trojanowski; M W Weiner; R C Green; A W Toga; P L De Jager; L Yu; D A Bennett; A J Saykin Journal: Mol Psychiatry Date: 2014-11-11 Impact factor: 15.992
Authors: Zoe Arvanitakis; Debra A Fleischman; Konstantinos Arfanakis; Sue E Leurgans; Lisa L Barnes; David A Bennett Journal: Brain Struct Funct Date: 2015-04-02 Impact factor: 3.270
Authors: Zoe Arvanitakis; Hoau-Yan Wang; Ana W Capuano; Amber Khan; Bouchra Taïb; Frederick Anokye-Danso; Julie A Schneider; David A Bennett; Rexford S Ahima; Steven E Arnold Journal: Ann Neurol Date: 2020-07-27 Impact factor: 10.422
Authors: Hyun-Sik Yang; Charles C White; Hans-Ulrich Klein; Lei Yu; Christopher Gaiteri; Yiyi Ma; Daniel Felsky; Sara Mostafavi; Vladislav A Petyuk; Reisa A Sperling; Nilüfer Ertekin-Taner; Julie A Schneider; David A Bennett; Philip L De Jager Journal: Neuron Date: 2020-06-10 Impact factor: 17.173
Authors: Matthew K Tobin; Kianna Musaraca; Ahmed Disouky; Aashutosh Shetti; Abdullah Bheri; William G Honer; Namhee Kim; Robert J Dawe; David A Bennett; Konstantinos Arfanakis; Orly Lazarov Journal: Cell Stem Cell Date: 2019-05-23 Impact factor: 24.633
Authors: Andrea R Zammit; Graciela Muniz-Terrera; Mindy J Katz; Charles B Hall; Ali Ezzati; David A Bennett; Richard B Lipton Journal: J Alzheimers Dis Date: 2019 Impact factor: 4.472
Authors: Andrea R Zammit; Charles B Hall; David A Bennett; Ali Ezzati; Mindy J Katz; Graciela Muniz-Terrera; Richard B Lipton Journal: Alzheimers Dement Date: 2019-08-13 Impact factor: 21.566
Authors: Sini Nagpal; Xiaoran Meng; Michael P Epstein; Lam C Tsoi; Matthew Patrick; Greg Gibson; Philip L De Jager; David A Bennett; Aliza P Wingo; Thomas S Wingo; Jingjing Yang Journal: Am J Hum Genet Date: 2019-06-20 Impact factor: 11.025
Authors: Joe Verghese; Cuiling Wang; David A Bennett; Richard B Lipton; Mindy J Katz; Emmeline Ayers Journal: Alzheimers Dement Date: 2019-06-01 Impact factor: 21.566
Authors: Bernard Ng; William Casazza; Ellis Patrick; Shinya Tasaki; Gherman Novakovsky; Daniel Felsky; Yiyi Ma; David A Bennett; Chris Gaiteri; Philip L De Jager; Sara Mostafavi Journal: Am J Hum Genet Date: 2019-08-22 Impact factor: 11.025
Authors: Erik C B Johnson; Eric B Dammer; Duc M Duong; Lingyan Ping; Maotian Zhou; Luming Yin; Lenora A Higginbotham; Andrew Guajardo; Bartholomew White; Juan C Troncoso; Madhav Thambisetty; Thomas J Montine; Edward B Lee; John Q Trojanowski; Thomas G Beach; Eric M Reiman; Vahram Haroutunian; Minghui Wang; Eric Schadt; Bin Zhang; Dennis W Dickson; Nilüfer Ertekin-Taner; Todd E Golde; Vladislav A Petyuk; Philip L De Jager; David A Bennett; Thomas S Wingo; Srikant Rangaraju; Ihab Hajjar; Joshua M Shulman; James J Lah; Allan I Levey; Nicholas T Seyfried Journal: Nat Med Date: 2020-04-13 Impact factor: 53.440