title: Increased hippocampal activation in ApoE-4 carriers and non-carriers with amnestic mild cognitive impairment.
abstract: Increased fMRI activation in the hippocampus is recognized as a signature characteristic of the amnestic mild cognitive impairment (aMCI) stage of Alzheimer's disease (AD). Previous work has localized this increased activation to the dentate gyrus/CA3 subregion of the hippocampus and showed a correlation with memory impairments in those patients. Increased hippocampal activation has also been reported in carriers of the ApoE-4 allelic variation independently of mild cognitive impairment although these findings were not localized to a hippocampal subregion. To assess the ApoE-4 contribution to increased hippocampal fMRI activation, patients with aMCI genotyped for ApoE-4 status and healthy age-matched control participants completed a high-resolution fMRI scan while performing a memory task designed to tax hippocampal subregion specific functions. Consistent with previous reports, patients with aMCI showed increased hippocampal activation in the left dentate gyrus/CA3 region of the hippocampus as well as memory task errors attributable to this subregion. However, this increased fMRI activation in the hippocampus did not differ between ApoE-4 carriers and ApoE-4 non-carriers and the proportion of memory errors attributable to dentate gyrus/CA3 function did not differ between ApoE-4 carriers and ApoE-4 non-carriers. These results indicate that increased fMRI activation of the hippocampus observed in patients with aMCI is independent of ApoE-4 status and that ApoE-4 does not contribute to the dysfunctional hippocampal activation or the memory errors attributable to this subregion in these patients.
authors.affiliation: Department of Psychological and Brain Sciences, Johns Hopkins University School of Arts and Sciences, Baltimore, MD 21218, United States.
authors.forename: Tammy T
authors.initials: TT
authors.lastname: Tran
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Speck
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.
authors.forename: Aparna
authors.initials: A
authors.lastname: Pisupati
authors.affiliation: Department of Psychological and Brain Sciences, Johns Hopkins University School of Arts and Sciences, Baltimore, MD 21218, United States.
authors.forename: Michela
authors.initials: M
authors.lastname: Gallagher
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.
authors.forename: Arnold
authors.initials: A
authors.lastname: Bakker
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000647:Amnesia / Q000000981:diagnostic imaging / Q000503:physiopathology*; D053327:Apolipoprotein E4; D056654:CA3 Region, Hippocampal / Q000000981:diagnostic imaging / Q000503:physiopathology*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000503:physiopathology*; D018891:Dentate Gyrus / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged
chemical_list: D053327:Apolipoprotein E4