biostudies-literatureWood MENIA NIH HHSNINDS NIH HHSCanadian Institutes of Health Research4651-4661https://www.ebi.ac.uk/biostudies/studies/S-EPMC10544702biostudies-literatureUnknown19(10)<h4>Introduction</h4>We examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples.<h4>Methods</h4>We used observational data from cognitively unimpaired non-Hispanic White (NHW) and non-Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately.<h4>Results</h4>In both Sample 1 (N = 9766) and Sample 2 (N = 915), sex modified the association between APOE ε2 and cognitive decline in NHW participants. Specifically, relative to APOE ε3/ε3, APOE ε2 protected against cognitive decline in men but not women. Among APOE ε2 carriers, men had slower decline than women. Among APOE ε3/ε3 carriers, cognitive trajectoAlzheimer's & dementia : the journal of the Alzheimer's AssociationSex differences in associations between APOE ε2 and longitudinal cognitive decline.PMC10544702P30 AG053760P50 AG005146P50 AG005142R01 AG072475P50 AG047266P20 AG068053UF1 NS125513T32 AG000247P30 AG019610R01 AG022018K99 AG061238R00 AG061238P30 AG072958P30 AG072959P50 AG008702P30 AG010124P30 AG012300P50 AG047270P30 AG066546P30 AG010161P30 AG066509P30 AG049638U24 AG072122P20 AG068024P30 AG072947R01 AG015819P30 AG028383P30 AG013846K99 AG065501P30 AG008017P30 AG010133P50 AG033514P50 AG005681R01 AG052488RF1 AG070436P50 AG047366P30 AG072975P20 AG068077R01 AG071638P50 AG023501P30 AG008051P30 AG010129P30 AG013854173253P50 AG005138R01 AG059727P50 AG005134P50 AG005136P50 AG025688P30 AG035982P50 AG005131RF1 AG054617R01 NS017950P50 AG005133P50 AG016574P20 AG068082P50 AG016573R01 AG017917438475Casaletto KBRabin JSBarnes LLGeorge KMSwardfager WJoie RBrickman AMADNI and Prevent-AD Research GroupsWong YYXiong LYBlack SEBinet APMasellis MSatizabal CLDams-O'Connor KSchneider JAVilleneuve SBuckley RFPalta PWood MELim ASPKumar RGNichols EPa JfalseSex differences in associations between APOE ε2 and longitudinal cognitive decline.<h4>Introduction</h4>We examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples.<h4>Methods</h4>We used observational data from cognitively unimpaired non-Hispanic White (NHW) and non-Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately.<h4>Results</h4>In both Sample 1 (N = 9766) and Sample 2 (N = 915), sex modified the association between APOE ε2 and cognitive decline in NHW participants. Specifically, relative to APOE ε3/ε3, APOE ε2 protected against cognitive decline in men but not women. Among APOE ε2 carriers, men had slower decline than women. Among APOE ε3/ε3 carriers, cognitive trajecto2023-01-01T00:00:00Z2023 Oct2025-04-04T11:36:37.371Z2025-04-04T11:36:37.371ZS-EPMC105447023699491010.1002/alz.13036