Apolipoprotein E (APOE) genotype has dissociable effects on memory and attentional–executive network function in Alzheimer’s disease
Authors: Wolk David A. , Dickerson Bradford C. ,   the Alzheimer’s Disease Neuroimaging Initiative, Weiner Michael , Aiello Marilyn , Aisen Paul , Albert Marilyn S. , Alexander Gene , Anderson Heather S. , Anderson Karen , Apostolova Liana , Arnold Steve , Ashford Wes , Assaly Michele , Asthana Sanjay , Bandy Dan , Bartha Rob , Bates Vernice , Beckett Laurel , Bell Karen L. , Benincasa Amanda L. , Bergman Howard , Bernick Charles , Bernstein Matthew , Black Sandra , Blank Karen , Borrie Michael , Brand Connie , Brewer James , Brown Alice D. , Burns Jeffrey M. , Cairns Nigel J. , Caldwell Curtis , Capote Horacio , Carlsson Cynthia M. , Carmichael Owen , Cellar Janet S. , Celmins Dzintra , Chen Kewei , Chertkow Howard , Chowdhury Munir , Clark David , Connor Donald , Correia Stephen , Crawford Karen , Dale Anders , de Leon Mony J , De Santi Susan M , DeCarli Charles , deToledo-Morrell Leyla , DeVous Michael , Diaz-Arrastia Ramon , Dolen Sara , Donohue Michael , Doody Rachelle S. , Doraiswamy P. Murali , Duara Ranjan , Englert Jessica , Farlow Martin , Feldman Howard , Felmlee Joel , Fleisher Adam , Fletcher Evan , Foroud Tatiana M. , Foster Norm , Fox Nick , Frank Richard , Gamst Anthony , Given Curtis A. , Graff-Radford Neill R , Green Robert C. , Griffith Randall , Grossman Hillel , Hake Ann M. , Hardy Peter , Harvey Danielle , Heidebrink Judith L. , Hendin Barry A. , Herring Scott , Honig Lawrence S. , Hosein Chris , Robin Hsiung Ging-Yuek , Hudson Leon , Ismail M. Saleem , Jack Clifford R. , Jacobson Sandra , Jagust William , Jayam-Trouth Annapurni , Johnson Kris , Johnson Heather , Johnson Nancy , Johnson Kathleen , Johnson Keith A. , Johnson Sterling , Kachaturian Zaven , Karlawish Jason H. , Kataki Maria , Kaye Jeffrey , Kertesz Andrew , Killiany Ronald , Kittur Smita , Koeppe Robert A. , Korecka Magdalena , Kornak John , Kozauer Nicholas , Lah James J. , Laubinger Mary M. , Lee Virginia M.-Y. , Lee T.-Y. , Lerner Alan , Levey Allan I. , Longmire Crystal Flynn , Lopez Oscar L. , Lord Joanne L. , Lu Po H. , MacAvoy Martha G. , Malloy Paul , Marson Daniel , Martin-Cook Kristen , Martinez Walter , Marzloff George , Mathis Chet , Mc-Adams-Ortiz Catherine , Mesulam Marsel , Miller Bruce L. , Mintun Mark A. , Mintzer Jacobo , Molchan Susan , Montine Tom , Morris John , Mulnard Ruth A. , Munic Donna , Nair Anil , Neu Scott , Nguyen Dana , Norbash Alexander , Oakley MaryAnn , Obisesan Thomas O. , Ogrocki Paula , Ott Brian R. , Parfitt Francine , Pawluczyk Sonia , Pearlson Godfrey , Petersen Ronald , Petrella Jeffrey R. , Potkin Steven , Potter William Z. , Preda Adrian , Quinn Joseph , Rainka Michelle , Reeder Stephanie , Reiman Eric M. , Rentz Dorene M. , Reynolds Brigid , Richard Jennifer , Roberts Peggy , Rogers John , Rosen Allyson , Rosen Howard J. , Rusinek Henry , Sabbagh Marwan , Sadowsky Carl , Salloway Stephen , Santulli Robert B. , Saykin Andrew J. , Scharre Douglas W. , Schneider Lon , Schneider Stacy , Schuff Norbert , Shah Raj C. , Shaw Les , Shen Li , Silverman Daniel H.S. , Simpson Donna M. , Sink Kaycee M. , Smith Charles D. , Snyder Peter J. , Spann Bryan M. , Sperling Reisa A. , Spicer Kenneth , Stefanovic Bojana , Stern Yaakov , Stopa Edward , Tang Cheuk , Tariot Pierre , Taylor-Reinwald Lisa , Thai Gaby , Thomas Ronald G. , Thompson Paul , Tinklenberg Jared , Toga Arthur W. , Tremont Geoffrey , Trojanowki J.Q. , Trost Dick , Turner Raymond Scott , van Dyck Christopher H. , Vanderswag Helen , Varon Daniel , Villanueva-Meyer Javier , Villena Teresa , Walter Sarah , Wang Paul , Watkins Franklin , Weiner Michael , Williamson Jeff D. , Wolk David , Wu Chuang-Kuo , Zerrate Maria , Zimmerman. Earl A. 
Published: May 2010

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.