title: Interaction of age and APOE genotype on cerebral blood flow at rest.
abstract: We investigated the impact of APOE genotype on cerebral blood flow (CBF) in older and younger adults. Forty cognitively normal older adults (16 ε4 carriers, 24 non-ε4 carriers) and 30 younger adults (15 ε4 carriers, 15 non-ε4 carriers) completed a resting-state whole-brain pulsed arterial spin labeling magnetic resonance scan. Main effects of aging were demonstrated wherein older adults had decreased gray matter CBF corrected for partial volume effects compared to younger adults in widespread brain regions. Main effects of APOE genotype were also observed wherein ε4 carriers displayed greater CBF in the left lingual gyrus and precuneus than non-carriers. An interaction between age and APOE genotype in the left anterior cingulate cortex (ACC) was characterized by reduced CBF in older ε4 carriers and increased CBF in young ε4 carriers. Increased CBF in the left ACC resulting from the interaction of age group and APOE genotype was positively correlated with executive functioning in young ε4 adults (r = 0.61, p = 0.04). Results demonstrate APOE genotype differentially impacts cerebrovascular function across the lifespan and may modify the relationship between CBF and cognition. Findings may partially support suggestions that the gene exerts antagonistic pleiotropic effects.
authors.affiliation: Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA. cwierenga@ucsd.edu
authors.forename: Christina E
authors.initials: CE
authors.lastname: Wierenga
authors.forename: Lindsay R
authors.initials: LR
authors.lastname: Clark
authors.forename: Sheena I
authors.initials: SI
authors.lastname: Dev
authors.forename: David D
authors.initials: DD
authors.lastname: Shin
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Jurick
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rissman
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Liu
authors.forename: Mark W
authors.initials: MW
authors.lastname: Bondi
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000098:blood supply* / Q000502:physiology; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000235:genetics*; D005260:Female; D007839:Functional Laterality / Q000235:genetics; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D009483:Neuropsychological Tests; D012146:Rest / Q000502:physiology*; D013113:Spin Labels; D055815:Young Adult
chemical_list: D001057:Apolipoproteins E; D013113:Spin Labels