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Apolipoprotein E (APOE) genotype has dissociable effects on memory and attentional–executive network function in Alzheimer’s disease

The ε4 allele of the apolipoprotein E (APOE) gene is the major genetic risk factor for Alzheimer’s disease (AD), but limited work has suggested that APOE genotype may modulate disease phenotype. Carriers of the ε4 allele have been reported to have greater medial temporal lobe (MTL) pathology and poo... Full description

Journal Title: Proceedings of the National Academy of Sciences 01 June 2010, Vol.107(22), p.10256
Main Author: David A. Wolk
Other Authors: Bradford C. Dickerson , the Alzheimer’s Disease Neuroimaging Initiative , Michael Weiner , Marilyn Aiello , Paul Aisen , Marilyn S. Albert , Gene Alexander , Heather S. Anderson , Karen Anderson , Liana Apostolova , Steve Arnold , Wes Ashford , Michele Assaly , Sanjay Asthana , Dan Bandy , Rob Bartha , Vernice Bates , Laurel Beckett , Karen L. Bell , Amanda L. Benincasa , Howard Bergman , Charles Bernick , Matthew Bernstein , Sandra Black , Karen Blank , Michael Borrie , Connie Brand , James Brewer , Alice D. Brown , Jeffrey M. Burns , Nigel J. Cairns , Curtis Caldwell , Horacio Capote , Cynthia M. Carlsson , Owen Carmichael , Janet S. Cellar , Dzintra Celmins , Kewei Chen , Howard Chertkow , Munir Chowdhury , David Clark , Donald Connor , Stephen Correia , Karen Crawford , Anders Dale , Mony J de Leon , Susan M De Santi , Charles Decarli , Leyla Detoledo-Morrell , Michael Devous , Ramon Diaz-Arrastia , Sara Dolen , Michael Donohue , Rachelle S. Doody , P. Murali Doraiswamy , Ranjan Duara , Jessica Englert , Martin Farlow , Howard Feldman , Joel Felmlee , Adam Fleisher , Evan Fletcher , Tatiana M. Foroud , Norm Foster , Nick Fox , Richard Frank , Anthony Gamst , Curtis A. Given II , Neill R Graff-Radford , Robert C. Green , Randall Griffith , Hillel Grossman , Ann M. Hake , Peter Hardy , Danielle Harvey , Judith L. Heidebrink , Barry A. Hendin , Scott Herring , Lawrence S. Honig , Chris Hosein , Ging-Yuek Robin Hsiung , Leon Hudson , M. Saleem Ismail , Clifford R. Jack, Jr , Sandra Jacobson , William Jagust , Annapurni Jayam-Trouth , Kris Johnson , Heather Johnson , Nancy Johnson , Kathleen Johnson , Keith A. Johnson , Sterling Johnson , Zaven Kachaturian , Jason H. Karlawish , Maria Kataki , Jeffrey Kaye , Andrew Kertesz , Ronald Killiany , Smita Kittur , Robert A. Koeppe , Magdalena Korecka , John Kornak , Nicholas Kozauer , James J. Lah , Mary M. Laubinger , Virginia M.-Y. Lee , T.-Y. Lee , Alan Lerner , Allan I. Levey , Crystal Flynn Longmire , Oscar L. Lopez , Joanne L. Lord , Po H. Lu , Martha G. Macavoy , Paul Malloy , Daniel Marson , Kristen Martin-Cook , Walter Martinez , George Marzloff , Chet Mathis , Catherine Mc-Adams-Ortiz , Marsel Mesulam , Bruce L. Miller , Mark A. Mintun , Jacobo Mintzer , Susan Molchan , Tom Montine , John Morris , Ruth A. Mulnard , Donna Munic , Anil Nair , Scott Neu , Dana Nguyen , Alexander Norbash , Maryann Oakley , Thomas O. Obisesan , Paula Ogrocki , Brian R. Ott , Francine Parfitt , Sonia Pawluczyk , Godfrey Pearlson , Ronald Petersen , Jeffrey R. Petrella , Steven Potkin , William Z. Potter , Adrian Preda , Joseph Quinn , Michelle Rainka , Stephanie Reeder , Eric M. Reiman , Dorene M. Rentz , Brigid Reynolds , Jennifer Richard , Peggy Roberts , John Rogers , Allyson Rosen , Howard J. Rosen , Henry Rusinek , Marwan Sabbagh , Carl Sadowsky , Stephen Salloway , Robert B. Santulli , Andrew J. Saykin , Douglas W. Scharre , Lon Schneider , Stacy Schneider , Norbert Schuff , Raj C. Shah , Les Shaw , Li Shen , Daniel H.S. Silverman , Donna M. Simpson , Kaycee M. Sink , Charles D. Smith , Peter J. Snyder , Bryan M. Spann , Reisa A. Sperling , Kenneth Spicer , Bojana Stefanovic , Yaakov Stern , Edward Stopa , Cheuk Tang , Pierre Tariot , Lisa Taylor-Reinwald , Gaby Thai , Ronald G. Thomas , Paul Thompson , Jared Tinklenberg , Arthur W. Toga , Geoffrey Tremont , J.Q. Trojanowki , Dick Trost , Raymond Scott Turner , Christopher H. van Dyck , Helen Vanderswag , Daniel Varon , Javier Villanueva-Meyer , Teresa Villena , Sarah Walter , Paul Wang , Franklin Watkins , Jeff D. Williamson , David Wolk , Chuang-Kuo Wu , Maria Zerrate , Earl A. Zimmerman
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0027-8424 ; E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1001412107
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recordid: pnas_s107_22_10256
title: Apolipoprotein E (APOE) genotype has dissociable effects on memory and attentional–executive network function in Alzheimer’s disease
format: Article
creator:
  • David A. Wolk
  • Bradford C. Dickerson
  • the Alzheimer’s Disease Neuroimaging Initiative
  • Michael Weiner
  • Marilyn Aiello
  • Paul Aisen
  • Marilyn S. Albert
  • Gene Alexander
  • Heather S. Anderson
  • Karen Anderson
  • Liana Apostolova
  • Steve Arnold
  • Wes Ashford
  • Michele Assaly
  • Sanjay Asthana
  • Dan Bandy
  • Rob Bartha
  • Vernice Bates
  • Laurel Beckett
  • Karen L. Bell
  • Amanda L. Benincasa
  • Howard Bergman
  • Charles Bernick
  • Matthew Bernstein
  • Sandra Black
  • Karen Blank
  • Michael Borrie
  • Connie Brand
  • James Brewer
  • Alice D. Brown
  • Jeffrey M. Burns
  • Nigel J. Cairns
  • Curtis Caldwell
  • Horacio Capote
  • Cynthia M. Carlsson
  • Owen Carmichael
  • Janet S. Cellar
  • Dzintra Celmins
  • Kewei Chen
  • Howard Chertkow
  • Munir Chowdhury
  • David Clark
  • Donald Connor
  • Stephen Correia
  • Karen Crawford
  • Anders Dale
  • Mony J de Leon
  • Susan M De Santi
  • Charles Decarli
  • Leyla Detoledo-Morrell
  • Michael Devous
  • Ramon Diaz-Arrastia
  • Sara Dolen
  • Michael Donohue
  • Rachelle S. Doody
  • P. Murali Doraiswamy
  • Ranjan Duara
  • Jessica Englert
  • Martin Farlow
  • Howard Feldman
  • Joel Felmlee
  • Adam Fleisher
  • Evan Fletcher
  • Tatiana M. Foroud
  • Norm Foster
  • Nick Fox
  • Richard Frank
  • Anthony Gamst
  • Curtis A. Given II
  • Neill R Graff-Radford
  • Robert C. Green
  • Randall Griffith
  • Hillel Grossman
  • Ann M. Hake
  • Peter Hardy
  • Danielle Harvey
  • Judith L. Heidebrink
  • Barry A. Hendin
  • Scott Herring
  • Lawrence S. Honig
  • Chris Hosein
  • Ging-Yuek Robin Hsiung
  • Leon Hudson
  • M. Saleem Ismail
  • Clifford R. Jack, Jr
  • Sandra Jacobson
  • William Jagust
  • Annapurni Jayam-Trouth
  • Kris Johnson
  • Heather Johnson
  • Nancy Johnson
  • Kathleen Johnson
  • Keith A. Johnson
  • Sterling Johnson
  • Zaven Kachaturian
  • Jason H. Karlawish
  • Maria Kataki
  • Jeffrey Kaye
  • Andrew Kertesz
  • Ronald Killiany
  • Smita Kittur
  • Robert A. Koeppe
  • Magdalena Korecka
  • John Kornak
  • Nicholas Kozauer
  • James J. Lah
  • Mary M. Laubinger
  • Virginia M.-Y. Lee
  • T.-Y. Lee
  • Alan Lerner
  • Allan I. Levey
  • Crystal Flynn Longmire
  • Oscar L. Lopez
  • Joanne L. Lord
  • Po H. Lu
  • Martha G. Macavoy
  • Paul Malloy
  • Daniel Marson
  • Kristen Martin-Cook
  • Walter Martinez
  • George Marzloff
  • Chet Mathis
  • Catherine Mc-Adams-Ortiz
  • Marsel Mesulam
  • Bruce L. Miller
  • Mark A. Mintun
  • Jacobo Mintzer
  • Susan Molchan
  • Tom Montine
  • John Morris
  • Ruth A. Mulnard
  • Donna Munic
  • Anil Nair
  • Scott Neu
  • Dana Nguyen
  • Alexander Norbash
  • Maryann Oakley
  • Thomas O. Obisesan
  • Paula Ogrocki
  • Brian R. Ott
  • Francine Parfitt
  • Sonia Pawluczyk
  • Godfrey Pearlson
  • Ronald Petersen
  • Jeffrey R. Petrella
  • Steven Potkin
  • William Z. Potter
  • Adrian Preda
  • Joseph Quinn
  • Michelle Rainka
  • Stephanie Reeder
  • Eric M. Reiman
  • Dorene M. Rentz
  • Brigid Reynolds
  • Jennifer Richard
  • Peggy Roberts
  • John Rogers
  • Allyson Rosen
  • Howard J. Rosen
  • Henry Rusinek
  • Marwan Sabbagh
  • Carl Sadowsky
  • Stephen Salloway
  • Robert B. Santulli
  • Andrew J. Saykin
  • Douglas W. Scharre
  • Lon Schneider
  • Stacy Schneider
  • Norbert Schuff
  • Raj C. Shah
  • Les Shaw
  • Li Shen
  • Daniel H.S. Silverman
  • Donna M. Simpson
  • Kaycee M. Sink
  • Charles D. Smith
  • Peter J. Snyder
  • Bryan M. Spann
  • Reisa A. Sperling
  • Kenneth Spicer
  • Bojana Stefanovic
  • Yaakov Stern
  • Edward Stopa
  • Cheuk Tang
  • Pierre Tariot
  • Lisa Taylor-Reinwald
  • Gaby Thai
  • Ronald G. Thomas
  • Paul Thompson
  • Jared Tinklenberg
  • Arthur W. Toga
  • Geoffrey Tremont
  • J.Q. Trojanowki
  • Dick Trost
  • Raymond Scott Turner
  • Christopher H. van Dyck
  • Helen Vanderswag
  • Daniel Varon
  • Javier Villanueva-Meyer
  • Teresa Villena
  • Sarah Walter
  • Paul Wang
  • Franklin Watkins
  • Jeff D. Williamson
  • David Wolk
  • Chuang-Kuo Wu
  • Maria Zerrate
  • Earl A. Zimmerman
subjects:
  • Sciences (General)
ispartof: Proceedings of the National Academy of Sciences, 01 June 2010, Vol.107(22), p.10256
description: The ε4 allele of the apolipoprotein E (APOE) gene is the major genetic risk factor for Alzheimer’s disease (AD), but limited work has suggested that APOE genotype may modulate disease phenotype. Carriers of the ε4 allele have been reported to have greater medial temporal lobe (MTL) pathology and poorer memory than noncarriers. Less attention has focused on whether there are domains of cognition and neuroanatomical regions more affected in noncarriers. Further, a major potential confound of prior in vivo studies is the possibility of different rates of clinical misdiagnosis for carriers vs. noncarriers. We compared phenotypic differences in cognition and topography of regional cortical atrophy of ε4 carriers ( n = 67) vs. noncarriers ( n = 24) with mild AD from the Alzheimer’s Disease Neuroimaging Initiative, restricted to those with a cerebrospinal fluid (CSF) molecular profile consistent with AD. Between-group comparisons were made for psychometric tests and morphometric measures of cortical thickness and hippocampal volume. Carriers displayed significantly greater impairment on measures of memory retention, whereas noncarriers were more impaired on tests of working memory, executive control, and lexical access. Consistent with this cognitive dissociation, carriers exhibited greater MTL atrophy, whereas noncarriers had greater frontoparietal atrophy. Performance deficits in particular cognitive domains were associated with disproportionate regional brain atrophy within nodes of cortical networks thought to subserve these cognitive processes. These convergent cognitive and neuroanatomic findings in individuals with a CSF molecular profile consistent with AD support the hypothesis that APOE genotype modulates the clinical phenotype of AD through influence on specific large-scale brain networks.
language: eng
source:
identifier: ISSN: 0027-8424 ; E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1001412107
fulltext: fulltext_linktorsrc
issn:
  • 0027-8424
  • 00278424
  • 1091-6490
  • 10916490
url: Link


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titleApolipoprotein E (APOE) genotype has dissociable effects on memory and attentional–executive network function in Alzheimer’s disease
creatorDavid A. Wolk ; Bradford C. Dickerson ; the Alzheimer’s Disease Neuroimaging Initiative ; Michael Weiner ; Marilyn Aiello ; Paul Aisen ; Marilyn S. Albert ; Gene Alexander ; Heather S. Anderson ; Karen Anderson ; Liana Apostolova ; Steve Arnold ; Wes Ashford ; Michele Assaly ; Sanjay Asthana ; Dan Bandy ; Rob Bartha ; Vernice Bates ; Laurel Beckett ; Karen L. Bell ; Amanda L. Benincasa ; Howard Bergman ; Charles Bernick ; Matthew Bernstein ; Sandra Black ; Karen Blank ; Michael Borrie ; Connie Brand ; James Brewer ; Alice D. Brown ; Jeffrey M. Burns ; Nigel J. Cairns ; Curtis Caldwell ; Horacio Capote ; Cynthia M. Carlsson ; Owen Carmichael ; Janet S. Cellar ; Dzintra Celmins ; Kewei Chen ; Howard Chertkow ; Munir Chowdhury ; David Clark ; Donald Connor ; Stephen Correia ; Karen Crawford ; Anders Dale ; Mony J de Leon ; Susan M De Santi ; Charles Decarli ; Leyla Detoledo-Morrell ; Michael Devous ; Ramon Diaz-Arrastia ; Sara Dolen ; Michael Donohue ; Rachelle S. Doody ; P. Murali Doraiswamy ; Ranjan Duara ; Jessica Englert ; Martin Farlow ; Howard Feldman ; Joel Felmlee ; Adam Fleisher ; Evan Fletcher ; Tatiana M. Foroud ; Norm Foster ; Nick Fox ; Richard Frank ; Anthony Gamst ; Curtis A. Given II ; Neill R Graff-Radford ; Robert C. Green ; Randall Griffith ; Hillel Grossman ; Ann M. Hake ; Peter Hardy ; Danielle Harvey ; Judith L. Heidebrink ; Barry A. Hendin ; Scott Herring ; Lawrence S. Honig ; Chris Hosein ; Ging-Yuek Robin Hsiung ; Leon Hudson ; M. Saleem Ismail ; Clifford R. Jack, Jr ; Sandra Jacobson ; William Jagust ; Annapurni Jayam-Trouth ; Kris Johnson ; Heather Johnson ; Nancy Johnson ; Kathleen Johnson ; Keith A. Johnson ; Sterling Johnson ; Zaven Kachaturian ; Jason H. Karlawish ; Maria Kataki ; Jeffrey Kaye ; Andrew Kertesz ; Ronald Killiany ; Smita Kittur ; Robert A. Koeppe ; Magdalena Korecka ; John Kornak ; Nicholas Kozauer ; James J. Lah ; Mary M. Laubinger ; Virginia M.-Y. Lee ; T.-Y. Lee ; Alan Lerner ; Allan I. Levey ; Crystal Flynn Longmire ; Oscar L. Lopez ; Joanne L. Lord ; Po H. Lu ; Martha G. Macavoy ; Paul Malloy ; Daniel Marson ; Kristen Martin-Cook ; Walter Martinez ; George Marzloff ; Chet Mathis ; Catherine Mc-Adams-Ortiz ; Marsel Mesulam ; Bruce L. Miller ; Mark A. Mintun ; Jacobo Mintzer ; Susan Molchan ; Tom Montine ; John Morris ; Ruth A. Mulnard ; Donna Munic ; Anil Nair ; Scott Neu ; Dana Nguyen ; Alexander Norbash ; Maryann Oakley ; Thomas O. Obisesan ; Paula Ogrocki ; Brian R. Ott ; Francine Parfitt ; Sonia Pawluczyk ; Godfrey Pearlson ; Ronald Petersen ; Jeffrey R. Petrella ; Steven Potkin ; William Z. Potter ; Adrian Preda ; Joseph Quinn ; Michelle Rainka ; Stephanie Reeder ; Eric M. Reiman ; Dorene M. Rentz ; Brigid Reynolds ; Jennifer Richard ; Peggy Roberts ; John Rogers ; Allyson Rosen ; Howard J. Rosen ; Henry Rusinek ; Marwan Sabbagh ; Carl Sadowsky ; Stephen Salloway ; Robert B. Santulli ; Andrew J. Saykin ; Douglas W. Scharre ; Lon Schneider ; Stacy Schneider ; Norbert Schuff ; Raj C. Shah ; Les Shaw ; Li Shen ; Daniel H.S. Silverman ; Donna M. Simpson ; Kaycee M. Sink ; Charles D. Smith ; Peter J. Snyder ; Bryan M. Spann ; Reisa A. Sperling ; Kenneth Spicer ; Bojana Stefanovic ; Yaakov Stern ; Edward Stopa ; Cheuk Tang ; Pierre Tariot ; Lisa Taylor-Reinwald ; Gaby Thai ; Ronald G. Thomas ; Paul Thompson ; Jared Tinklenberg ; Arthur W. Toga ; Geoffrey Tremont ; J.Q. Trojanowki ; Dick Trost ; Raymond Scott Turner ; Christopher H. van Dyck ; Helen Vanderswag ; Daniel Varon ; Javier Villanueva-Meyer ; Teresa Villena ; Sarah Walter ; Paul Wang ; Franklin Watkins ; Jeff D. Williamson ; David Wolk ; Chuang-Kuo Wu ; Maria Zerrate ; Earl A. Zimmerman
ispartofProceedings of the National Academy of Sciences, 01 June 2010, Vol.107(22), p.10256
identifier
subjectSciences (General)
descriptionThe ε4 allele of the apolipoprotein E (APOE) gene is the major genetic risk factor for Alzheimer’s disease (AD), but limited work has suggested that APOE genotype may modulate disease phenotype. Carriers of the ε4 allele have been reported to have greater medial temporal lobe (MTL) pathology and poorer memory than noncarriers. Less attention has focused on whether there are domains of cognition and neuroanatomical regions more affected in noncarriers. Further, a major potential confound of prior in vivo studies is the possibility of different rates of clinical misdiagnosis for carriers vs. noncarriers. We compared phenotypic differences in cognition and topography of regional cortical atrophy of ε4 carriers ( n = 67) vs. noncarriers ( n = 24) with mild AD from the Alzheimer’s Disease Neuroimaging Initiative, restricted to those with a cerebrospinal fluid (CSF) molecular profile consistent with AD. Between-group comparisons were made for psychometric tests and morphometric measures of cortical thickness and hippocampal volume. Carriers displayed significantly greater impairment on measures of memory retention, whereas noncarriers were more impaired on tests of working memory, executive control, and lexical access. Consistent with this cognitive dissociation, carriers exhibited greater MTL atrophy, whereas noncarriers had greater frontoparietal atrophy. Performance deficits in particular cognitive domains were associated with disproportionate regional brain atrophy within nodes of cortical networks thought to subserve these cognitive processes. These convergent cognitive and neuroanatomic findings in individuals with a CSF molecular profile consistent with AD support the hypothesis that APOE genotype modulates the clinical phenotype of AD through influence on specific large-scale brain networks.
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1Bradford C. Dickerson
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3Michael Weiner
4Marilyn Aiello
5Paul Aisen
6Marilyn S. Albert
7Gene Alexander
8Heather S. Anderson
9Karen Anderson
10Liana Apostolova
11Steve Arnold
12Wes Ashford
13Michele Assaly
14Sanjay Asthana
15Dan Bandy
16Rob Bartha
17Vernice Bates
18Laurel Beckett
19Karen L. Bell
20Amanda L. Benincasa
21Howard Bergman
22Charles Bernick
23Matthew Bernstein
24Sandra Black
25Karen Blank
26Michael Borrie
27Connie Brand
28James Brewer
29Alice D. Brown
30Jeffrey M. Burns
31Nigel J. Cairns
32Curtis Caldwell
33Horacio Capote
34Cynthia M. Carlsson
35Owen Carmichael
36Janet S. Cellar
37Dzintra Celmins
38Kewei Chen
39Howard Chertkow
40Munir Chowdhury
41David Clark
42Donald Connor
43Stephen Correia
44Karen Crawford
45Anders Dale
46Mony J de Leon
47Susan M De Santi
48Charles Decarli
49Leyla Detoledo-Morrell
50Michael Devous
51Ramon Diaz-Arrastia
52Sara Dolen
53Michael Donohue
54Rachelle S. Doody
55P. Murali Doraiswamy
56Ranjan Duara
57Jessica Englert
58Martin Farlow
59Howard Feldman
60Joel Felmlee
61Adam Fleisher
62Evan Fletcher
63Tatiana M. Foroud
64Norm Foster
65Nick Fox
66Richard Frank
67Anthony Gamst
68Curtis A. Given II
69Neill R Graff-Radford
70Robert C. Green
71Randall Griffith
72Hillel Grossman
73Ann M. Hake
74Peter Hardy
75Danielle Harvey
76Judith L. Heidebrink
77Barry A. Hendin
78Scott Herring
79Lawrence S. Honig
80Chris Hosein
81Ging-Yuek Robin Hsiung
82Leon Hudson
83M. Saleem Ismail
84Clifford R. Jack, Jr
85Sandra Jacobson
86William Jagust
87Annapurni Jayam-Trouth
88Kris Johnson
89Heather Johnson
90Nancy Johnson
91Kathleen Johnson
92Keith A. Johnson
93Sterling Johnson
94Zaven Kachaturian
95Jason H. Karlawish
96Maria Kataki
97Jeffrey Kaye
98Andrew Kertesz
99Ronald Killiany
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titleApolipoprotein E (APOE) genotype has dissociable effects on memory and attentional–executive network function in Alzheimer’s disease
description

The ε4 allele of the apolipoprotein E (APOE) gene is the major genetic risk factor for Alzheimer’s disease (AD), but limited work has suggested that APOE genotype may modulate disease phenotype. Carriers of the ε4 allele have been reported to have greater medial temporal lobe (MTL) pathology and poorer memory than noncarriers. Less attention has focused on whether there are domains of cognition and neuroanatomical regions more affected in noncarriers. Further, a major potential confound of prior in vivo studies is the possibility of different rates of clinical misdiagnosis for carriers vs. noncarriers. We compared phenotypic differences in cognition and topography of regional cortical atrophy of ε4 carriers ( n = 67) vs. noncarriers ( n = 24) with mild AD from the Alzheimer’s Disease Neuroimaging Initiative, restricted to those with a cerebrospinal fluid (CSF) molecular profile consistent with AD. Between-group comparisons were made for psychometric tests and morphometric measures of cortical thickness and hippocampal volume. Carriers displayed significantly greater impairment on measures of memory retention, whereas noncarriers were more impaired on tests of working memory, executive control, and lexical access. Consistent with this cognitive dissociation, carriers exhibited greater MTL atrophy, whereas noncarriers had greater frontoparietal atrophy. Performance deficits in particular cognitive domains were associated with disproportionate regional brain atrophy within nodes of cortical networks thought to subserve these cognitive processes. These convergent cognitive and neuroanatomic findings in individuals with a CSF molecular profile consistent with AD support the hypothesis that APOE genotype modulates the clinical phenotype of AD through influence on specific large-scale brain networks.

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titleApolipoprotein E (APOE) genotype has dissociable effects on memory and attentional–executive network function in Alzheimer’s disease
authorDavid A. Wolk ; Bradford C. Dickerson ; the Alzheimer’s Disease Neuroimaging Initiative ; Michael Weiner ; Marilyn Aiello ; Paul Aisen ; Marilyn S. Albert ; Gene Alexander ; Heather S. Anderson ; Karen Anderson ; Liana Apostolova ; Steve Arnold ; Wes Ashford ; Michele Assaly ; Sanjay Asthana ; Dan Bandy ; Rob Bartha ; Vernice Bates ; Laurel Beckett ; Karen L. Bell ; Amanda L. Benincasa ; Howard Bergman ; Charles Bernick ; Matthew Bernstein ; Sandra Black ; Karen Blank ; Michael Borrie ; Connie Brand ; James Brewer ; Alice D. Brown ; Jeffrey M. Burns ; Nigel J. Cairns ; Curtis Caldwell ; Horacio Capote ; Cynthia M. Carlsson ; Owen Carmichael ; Janet S. Cellar ; Dzintra Celmins ; Kewei Chen ; Howard Chertkow ; Munir Chowdhury ; David Clark ; Donald Connor ; Stephen Correia ; Karen Crawford ; Anders Dale ; Mony J de Leon ; Susan M De Santi ; Charles Decarli ; Leyla Detoledo-Morrell ; Michael Devous ; Ramon Diaz-Arrastia ; Sara Dolen ; Michael Donohue ; Rachelle S. Doody ; P. Murali Doraiswamy ; Ranjan Duara ; Jessica Englert ; Martin Farlow ; Howard Feldman ; Joel Felmlee ; Adam Fleisher ; Evan Fletcher ; Tatiana M. Foroud ; Norm Foster ; Nick Fox ; Richard Frank ; Anthony Gamst ; Curtis A. Given II ; Neill R Graff-Radford ; Robert C. Green ; Randall Griffith ; Hillel Grossman ; Ann M. Hake ; Peter Hardy ; Danielle Harvey ; Judith L. Heidebrink ; Barry A. Hendin ; Scott Herring ; Lawrence S. Honig ; Chris Hosein ; Ging-Yuek Robin Hsiung ; Leon Hudson ; M. Saleem Ismail ; Clifford R. Jack, Jr ; Sandra Jacobson ; William Jagust ; Annapurni Jayam-Trouth ; Kris Johnson ; Heather Johnson ; Nancy Johnson ; Kathleen Johnson ; Keith A. Johnson ; Sterling Johnson ; Zaven Kachaturian ; Jason H. Karlawish ; Maria Kataki ; Jeffrey Kaye ; Andrew Kertesz ; Ronald Killiany ; Smita Kittur ; Robert A. Koeppe ; Magdalena Korecka ; John Kornak ; Nicholas Kozauer ; James J. Lah ; Mary M. Laubinger ; Virginia M.-Y. Lee ; T.-Y. Lee ; Alan Lerner ; Allan I. Levey ; Crystal Flynn Longmire ; Oscar L. Lopez ; Joanne L. Lord ; Po H. Lu ; Martha G. Macavoy ; Paul Malloy ; Daniel Marson ; Kristen Martin-Cook ; Walter Martinez ; George Marzloff ; Chet Mathis ; Catherine Mc-Adams-Ortiz ; Marsel Mesulam ; Bruce L. Miller ; Mark A. Mintun ; Jacobo Mintzer ; Susan Molchan ; Tom Montine ; John Morris ; Ruth A. Mulnard ; Donna Munic ; Anil Nair ; Scott Neu ; Dana Nguyen ; Alexander Norbash ; Maryann Oakley ; Thomas O. Obisesan ; Paula Ogrocki ; Brian R. Ott ; Francine Parfitt ; Sonia Pawluczyk ; Godfrey Pearlson ; Ronald Petersen ; Jeffrey R. Petrella ; Steven Potkin ; William Z. Potter ; Adrian Preda ; Joseph Quinn ; Michelle Rainka ; Stephanie Reeder ; Eric M. Reiman ; Dorene M. Rentz ; Brigid Reynolds ; Jennifer Richard ; Peggy Roberts ; John Rogers ; Allyson Rosen ; Howard J. Rosen ; Henry Rusinek ; Marwan Sabbagh ; Carl Sadowsky ; Stephen Salloway ; Robert B. Santulli ; Andrew J. Saykin ; Douglas W. Scharre ; Lon Schneider ; Stacy Schneider ; Norbert Schuff ; Raj C. Shah ; Les Shaw ; Li Shen ; Daniel H.S. Silverman ; Donna M. Simpson ; Kaycee M. Sink ; Charles D. Smith ; Peter J. Snyder ; Bryan M. Spann ; Reisa A. Sperling ; Kenneth Spicer ; Bojana Stefanovic ; Yaakov Stern ; Edward Stopa ; Cheuk Tang ; Pierre Tariot ; Lisa Taylor-Reinwald ; Gaby Thai ; Ronald G. Thomas ; Paul Thompson ; Jared Tinklenberg ; Arthur W. Toga ; Geoffrey Tremont ; J.Q. Trojanowki ; Dick Trost ; Raymond Scott Turner ; Christopher H. van Dyck ; Helen Vanderswag ; Daniel Varon ; Javier Villanueva-Meyer ; Teresa Villena ; Sarah Walter ; Paul Wang ; Franklin Watkins ; Jeff D. Williamson ; David Wolk ; Chuang-Kuo Wu ; Maria Zerrate ; Earl A. Zimmerman
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1Bradford C. Dickerson
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4Marilyn Aiello
5Paul Aisen
6Marilyn S. Albert
7Gene Alexander
8Heather S. Anderson
9Karen Anderson
10Liana Apostolova
11Steve Arnold
12Wes Ashford
13Michele Assaly
14Sanjay Asthana
15Dan Bandy
16Rob Bartha
17Vernice Bates
18Laurel Beckett
19Karen L. Bell
20Amanda L. Benincasa
21Howard Bergman
22Charles Bernick
23Matthew Bernstein
24Sandra Black
25Karen Blank
26Michael Borrie
27Connie Brand
28James Brewer
29Alice D. Brown
30Jeffrey M. Burns
31Nigel J. Cairns
32Curtis Caldwell
33Horacio Capote
34Cynthia M. Carlsson
35Owen Carmichael
36Janet S. Cellar
37Dzintra Celmins
38Kewei Chen
39Howard Chertkow
40Munir Chowdhury
41David Clark
42Donald Connor
43Stephen Correia
44Karen Crawford
45Anders Dale
46Mony J de Leon
47Susan M De Santi
48Charles Decarli
49Leyla Detoledo-Morrell
50Michael Devous
51Ramon Diaz-Arrastia
52Sara Dolen
53Michael Donohue
54Rachelle S. Doody
55P. Murali Doraiswamy
56Ranjan Duara
57Jessica Englert
58Martin Farlow
59Howard Feldman
60Joel Felmlee
61Adam Fleisher
62Evan Fletcher
63Tatiana M. Foroud
64Norm Foster
65Nick Fox
66Richard Frank
67Anthony Gamst
68Curtis A. Given II
69Neill R Graff-Radford
70Robert C. Green
71Randall Griffith
72Hillel Grossman
73Ann M. Hake
74Peter Hardy
75Danielle Harvey
76Judith L. Heidebrink
77Barry A. Hendin
78Scott Herring
79Lawrence S. Honig
80Chris Hosein
81Ging-Yuek Robin Hsiung
82Leon Hudson
83M. Saleem Ismail
84Clifford R. Jack, Jr
85Sandra Jacobson
86William Jagust
87Annapurni Jayam-Trouth
88Kris Johnson
89Heather Johnson
90Nancy Johnson
91Kathleen Johnson
92Keith A. Johnson
93Sterling Johnson
94Zaven Kachaturian
95Jason H. Karlawish
96Maria Kataki
97Jeffrey Kaye
98Andrew Kertesz
99Ronald Killiany
100...
jtitleProceedings of the National Academy of Sciences
creationdate2010
toplevelpeer_reviewed
delivery
delcategoryRemote Search Resource
fulltextfulltext_linktorsrc
addata
aulast
0David A. Wolk
1Bradford C. Dickerson
2the Alzheimer’s Disease Neuroimaging Initiative
3Michael Weiner
4Marilyn Aiello
5Paul Aisen
6Marilyn S. Albert
7Gene Alexander
8Heather S. Anderson
9Karen Anderson
10Liana Apostolova
11Steve Arnold
12Wes Ashford
13Michele Assaly
14Sanjay Asthana
15Dan Bandy
16Rob Bartha
17Vernice Bates
18Laurel Beckett
19Karen L. Bell
20Amanda L. Benincasa
21Howard Bergman
22Charles Bernick
23Matthew Bernstein
24Sandra Black
25Karen Blank
26Michael Borrie
27Connie Brand
28James Brewer
29Alice D. Brown
30Jeffrey M. Burns
31Nigel J. Cairns
32Curtis Caldwell
33Horacio Capote
34Cynthia M. Carlsson
35Owen Carmichael
36Janet S. Cellar
37Dzintra Celmins
38Kewei Chen
39Howard Chertkow
40Munir Chowdhury
41David Clark
42Donald Connor
43Stephen Correia
44Karen Crawford
45Anders Dale
46Mony J de Leon
47Susan M De Santi
48Charles Decarli
49Leyla Detoledo-Morrell
50Michael Devous
51Ramon Diaz-Arrastia
52Sara Dolen
53Michael Donohue
54Rachelle S. Doody
55P. Murali Doraiswamy
56Ranjan Duara
57Jessica Englert
58Martin Farlow
59Howard Feldman
60Joel Felmlee
61Adam Fleisher
62Evan Fletcher
63Tatiana M. Foroud
64Norm Foster
65Nick Fox
66Richard Frank
67Anthony Gamst
68Curtis A. Given II
69Neill R Graff-Radford
70Robert C. Green
71Randall Griffith
72Hillel Grossman
73Ann M. Hake
74Peter Hardy
75Danielle Harvey
76Judith L. Heidebrink
77Barry A. Hendin
78Scott Herring
79Lawrence S. Honig
80Chris Hosein
81Ging-Yuek Robin Hsiung
82Leon Hudson
83M. Saleem Ismail
84Clifford R. Jack
85Sandra Jacobson
86William Jagust
87Annapurni Jayam-Trouth
88Kris Johnson
89Heather Johnson
90Nancy Johnson
91Kathleen Johnson
92Keith A. Johnson
93Sterling Johnson
94Zaven Kachaturian
95Jason H. Karlawish
96Maria Kataki
97Jeffrey Kaye
98Andrew Kertesz
99Ronald Killiany
100...
aufirstJr
auinitJ
auinit1J
au
0David A. Wolk
1Bradford C. Dickerson
2the Alzheimer’s Disease Neuroimaging Initiative
3Michael Weiner
4Marilyn Aiello
5Paul Aisen
6Marilyn S. Albert
7Gene Alexander
8Heather S. Anderson
9Karen Anderson
10Liana Apostolova
11Steve Arnold
12Wes Ashford
13Michele Assaly
14Sanjay Asthana
15Dan Bandy
16Rob Bartha
17Vernice Bates
18Laurel Beckett
19Karen L. Bell
20Amanda L. Benincasa
21Howard Bergman
22Charles Bernick
23Matthew Bernstein
24Sandra Black
25Karen Blank
26Michael Borrie
27Connie Brand
28James Brewer
29Alice D. Brown
30Jeffrey M. Burns
31Nigel J. Cairns
32Curtis Caldwell
33Horacio Capote
34Cynthia M. Carlsson
35Owen Carmichael
36Janet S. Cellar
37Dzintra Celmins
38Kewei Chen
39Howard Chertkow
40Munir Chowdhury
41David Clark
42Donald Connor
43Stephen Correia
44Karen Crawford
45Anders Dale
46Mony J de Leon
47Susan M De Santi
48Charles Decarli
49Leyla Detoledo-Morrell
50Michael Devous
51Ramon Diaz-Arrastia
52Sara Dolen
53Michael Donohue
54Rachelle S. Doody
55P. Murali Doraiswamy
56Ranjan Duara
57Jessica Englert
58Martin Farlow
59Howard Feldman
60Joel Felmlee
61Adam Fleisher
62Evan Fletcher
63Tatiana M. Foroud
64Norm Foster
65Nick Fox
66Richard Frank
67Anthony Gamst
68Curtis A. Given II
69Neill R Graff-Radford
70Robert C. Green
71Randall Griffith
72Hillel Grossman
73Ann M. Hake
74Peter Hardy
75Danielle Harvey
76Judith L. Heidebrink
77Barry A. Hendin
78Scott Herring
79Lawrence S. Honig
80Chris Hosein
81Ging-Yuek Robin Hsiung
82Leon Hudson
83M. Saleem Ismail
84Clifford R. Jack, Jr
85Sandra Jacobson
86William Jagust
87Annapurni Jayam-Trouth
88Kris Johnson
89Heather Johnson
90Nancy Johnson
91Kathleen Johnson
92Keith A. Johnson
93Sterling Johnson
94Zaven Kachaturian
95Jason H. Karlawish
96Maria Kataki
97Jeffrey Kaye
98Andrew Kertesz
99Ronald Killiany
100...
atitleApolipoprotein E (APOE) genotype has dissociable effects on memory and attentional–executive network function in Alzheimer’s disease
jtitleProceedings of the National Academy of Sciences
risdate20100601
volume107
issue22
spage10256
issn0027-8424
eissn1091-6490
formatjournal
genrearticle
ristypeJOUR
abstract

The ε4 allele of the apolipoprotein E (APOE) gene is the major genetic risk factor for Alzheimer’s disease (AD), but limited work has suggested that APOE genotype may modulate disease phenotype. Carriers of the ε4 allele have been reported to have greater medial temporal lobe (MTL) pathology and poorer memory than noncarriers. Less attention has focused on whether there are domains of cognition and neuroanatomical regions more affected in noncarriers. Further, a major potential confound of prior in vivo studies is the possibility of different rates of clinical misdiagnosis for carriers vs. noncarriers. We compared phenotypic differences in cognition and topography of regional cortical atrophy of ε4 carriers ( n = 67) vs. noncarriers ( n = 24) with mild AD from the Alzheimer’s Disease Neuroimaging Initiative, restricted to those with a cerebrospinal fluid (CSF) molecular profile consistent with AD. Between-group comparisons were made for psychometric tests and morphometric measures of cortical thickness and hippocampal volume. Carriers displayed significantly greater impairment on measures of memory retention, whereas noncarriers were more impaired on tests of working memory, executive control, and lexical access. Consistent with this cognitive dissociation, carriers exhibited greater MTL atrophy, whereas noncarriers had greater frontoparietal atrophy. Performance deficits in particular cognitive domains were associated with disproportionate regional brain atrophy within nodes of cortical networks thought to subserve these cognitive processes. These convergent cognitive and neuroanatomic findings in individuals with a CSF molecular profile consistent with AD support the hypothesis that APOE genotype modulates the clinical phenotype of AD through influence on specific large-scale brain networks.

pubNational Acad Sciences
doi10.1073/pnas.1001412107
urlhttp://www.pnas.org/content/107/22/10256.abstract
lad01Proceedings of the National Academy of Sciences
pages10256-10261
date2010-06-01