Women can bear a bigger burden: ante- and post-mortem evidence for reserve in the face of tau
Authors: Digma Leonardino A , Madsen John R , Rissman Robert A , Jacobs Diane M , Brewer James B , Banks Sarah J ,   Alzheimer’s Disease Neuroimaging Initiative, Weiner Michael , Aisen Paul , Petersen Ronald , Jack Clifford R , Jagust William , Trojanowki John Q , Toga Arthur W , Beckett Laurel , Green Robert C , Saykin Andrew J , Morris John , Shaw Leslie M , Liu Enchi , Montine Tom , Thomas Ronald G , Donohue Michael , Walter Sarah , Gessert Devon , Sather Tamie , Jiminez Gus , Harvey Danielle , Donohue Michael , Bernstein Matthew , Fox Nick , Thompson Paul , Schuff Norbert , DeCArli Charles , Borowski Bret , Gunter Jeff , Senjem Matt , Vemuri Prashanthi , Jones David , Kantarci Kejal , Ward Chad , Koeppe Robert A , Foster Norm , Reiman Eric M , Chen Kewei , Mathis Chet , Landau Susan , Cairns Nigel J , Householder Erin , Reinwald Lisa Taylor , Lee Virginia , Korecka Magdalena , Figurski Michal , Crawford Karen , Neu Scott , Foroud Tatiana M , Potkin Steven , Shen Li , Kelley Faber , Kim Sungeun , Nho Kwangsik , Kachaturian Zaven , Frank Richard , Snyder Peter J , Molchan Susan , Kaye Jeffrey , Quinn Joseph , Lind Betty , Carter Raina , Dolen Sara , Schneider Lon S , Pawluczyk Sonia , Beccera Mauricio , Teodoro Liberty , Spann Bryan M , Brewer James , Vanderswag Helen , Fleisher Adam , Heidebrink Judith L , Lord Joanne L , Petersen Ronald , Mason Sara S , Albers Colleen S , Knopman David , Johnson Kris , Doody Rachelle S , Meyer Javier Villanueva , Chowdhury Munir , Rountree Susan , Dang Mimi , Stern Yaakov , Honig Lawrence S , Bell Karen L , Ances Beau , Morris John C , Carroll Maria , Leon Sue , Householder Erin , Mintun Mark A , Schneider Stacy , Oliver Angela , Griffith Randall , Clark David , Geldmacher David , Brockington John , Roberson Erik , Grossman Hillel , Mitsis Effie , deToledo-Morrell Leyla , Shah Raj C , Duara Ranjan , Varon Daniel , Greig Maria T , Roberts Peggy , Albert Marilyn , Onyike Chiadi , D’Agostino II Daniel , Kielb Stephanie , Galvin James E , Pogorelec Dana M , Cerbone Brittany , Michel Christina A , Rusinek Henry , de Leon Mony J , Glodzik Lidia , De Santi Susan , Doraiswamy P Murali , Petrella Jeffrey R , Wong Terence Z , Arnold Steven E , Karlawish Jason H , Wolk David , Smith Charles D , Jicha Greg , Hardy Peter , Sinha Partha , Oates Elizabeth , Conrad Gary , Lopez Oscar L , Oakley MaryAnn , Simpson Donna M , Porsteinsson Anton P , Goldstein Bonnie S , Martin Kim , Makino Kelly M , Ismail M Saleem , Brand Connie , Mulnard Ruth A , Thai Gaby , Mc Adams Ortiz Catherine , Womack Kyle , Mathews Dana , Quiceno Mary , Arrastia Ramon Diaz , King Richard , Weiner Myron , Martin Cook Kristen , DeVous Michael , Levey Allan I , Lah James J , Cellar Janet S , Burns Jeffrey M , Anderson Heather S , Swerdlow Russell H , Apostolova Liana , Tingus Kathleen , Woo Ellen , Silverman Daniel H S , Lu Po H , Bartzokis George , Graff Radford Neill R , Parfitt Francine , Kendall Tracy , Johnson Heather , Farlow Martin R , Hake Ann Marie , Matthews Brandy R , Herring Scott , Hunt Cynthia , van Dyck Christopher H , Carson Richard E , MacAvoy Martha G , Chertkow Howard , Bergman Howard , Hosein Chris , Black Sandra , Stefanovic Bojana , Caldwell Curtis , Hsiung Ging Yuek Robin , Feldman Howard , Mudge Benita , Assaly Michele , Kertesz Andrew , Rogers John , Trost Dick , Bernick Charles , Munic Donna , Kerwin Diana , Marsel Mesulam Marek , Lipowski Kristine , Kuo Wu Chuang , Johnson Nancy , Sadowsky Carl , Martinez Walter , Villena Teresa , Scott Turner Raymond , Johnson Kathleen , Reynolds Brigid , Sperling Reisa A , Johnson Keith A , Marshall Gad , Frey Meghan , Yesavage Jerome , Taylor Joy L , Lane Barton , Rosen Allyson , Tinklenberg Jared , Sabbagh Marwan N , Belden Christine M , Jacobson Sandra A , Sirrel Sherye A , Kowall Neil , Killiany Ronald , Budson Andrew E , Norbash Alexander , Johnson Patricia Lynn , Obisesan Thomas O , Wolday Saba , Allard Joanne , Lerner Alan , Ogrocki Paula , Hudson Leon , Fletcher Evan , Carmichael Owen , Olichney John , DeCarli Charles , Kittur Smita , Borrie Michael , Lee T Y , Bartha Rob , Johnson Sterling , Asthana Sanjay , Carlsson Cynthia M , Potkin Steven G , Preda Adrian , Nguyen Dana , Tariot Pierre , Fleisher Adam , Reeder Stephanie , Bates Vernice , Capote Horacio , Rainka Michelle , Scharre Douglas W , Kataki Maria , Adeli Anahita , Zimmerman Earl A , Celmins Dzintra , Brown Alice D , Pearlson Godfrey D , Blank Karen , Anderson Karen , Santulli Robert B , Kitzmiller Tamar J , Schwartz Eben S , Sink Kaycee M , Williamson Jeff D , Garg Pradeep , Watkins Franklin , Ott Brian R , Querfurth Henry , Tremont Geoffrey , Salloway Stephen , Malloy Paul , Correia Stephen , Rosen Howard J , Miller Bruce L , Mintzer Jacobo , Spicer Kenneth , Bachman David , Finger Elizabether , Pasternak Stephen , Rachinsky Irina , Rogers John , Kertesz Andrew , Drost Dick , Pomara Nunzio , Hernando Raymundo , Sarrael Antero , Schultz Susan K , Boles Ponto Laura L , Shim Hyungsub , Smith Karen Elizabeth , Relkin Norman , Chaing Gloria , Raudin Lisa , Smith Amanda , Fargher Kristin , Raj Balebail Ashok 
Published: March 2020

In this study, we aimed to assess whether women are able to withstand more tau before exhibiting verbal memory impairment. Using data from 121 amyloid-β-positive Alzheimer’s Disease Neuroimaging Initiative participants, we fit a linear model with Rey Auditory Verbal Learning Test score as the response variable and tau-PET standard uptake value ratio as the predictor and took the residuals as an estimate of verbal memory reserve for each subject. Women demonstrated higher reserve (i.e. residuals), whether the Learning (t = 2.78, P = 0.006) or Delay (t = 2.14, P = 0.03) score from the Rey Auditory Verbal Learning Test was used as a measure of verbal memory ability. To validate these findings, we examined 662 National Alzheimer’s Coordinating Center participants with a C2/C3 score (Consortium to Establish a Registry for Alzheimer’s Disease) at autopsy. We stratified our National Alzheimer’s Coordinating Center sample into Braak 1/2, Braak 3/4 and Braak 5/6 subgroups. Within each subgroup, we compared Logical Memory scores between men and women. Men had worse verbal memory scores within the Braak 1/2 (Logical Memory Immediate: β = −5.960 ± 1.517, P &lt; 0.001, Logical Memory Delay: β = −5.703 ± 1.677, P = 0.002) and Braak 3/4 (Logical Memory Immediate: β = −2.900 ± 0.938, P = 0.002, Logical Memory Delay: β = −2.672 ± 0.955, P = 0.006) subgroups. There were no sex differences in Logical Memory performance within the Braak 5/6 subgroup (Logical Memory Immediate: β = −0.314 ± 0.328, P = 0.34, Logical Memory Delay: β = −0.195 ± 0.287, P = 0.50). Taken together, our results point to a sex-related verbal memory reserve.