title: Aberrant functional connectivity in Papez circuit correlates with memory performance in cognitively intact middle-aged APOE4 carriers.
abstract: The main objective of this study is to detect the early changes in resting-state Papez circuit functional connectivity using the hippocampus as the seed, and to determine the associations between altered functional connectivity (FC) and the episodic memory performance in cognitively intact middle-aged apolipoprotein E4 (APOE4) carriers who are at risk of Alzheimer's disease (AD). Forty-six cognitively intact, middle-aged participants, including 20 APOE4 carriers and 26 age-, sex-, and education-matched noncarriers were studied. The resting-state FC of the hippocampus (HFC) was compared between APOE4 carriers and noncarriers. APOE4 carriers showed significantly decreased FC in brain areas that involve learning and memory functions, including the frontal, cingulate, thalamus and basal ganglia regions. Multiple linear regression analysis showed significant correlations between HFC and the episodic memory performance. Conjunction analysis between neural correlates of memory and altered HFC showed the overlapping regions, especially the subcortical regions such as thalamus, caudate nucleus, and cingulate cortices involved in the Papez circuit. Thus, changes in connectivity in the Papez circuit may be used as an early risk detection for AD.
authors.affiliation: Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: wli@mcw.edu.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: pantuono@mcw.edu.
authors.forename: Piero G
authors.initials: PG
authors.lastname: Antuono
authors.affiliation: Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: cxie@mcw.edu.
authors.forename: Chunming
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: gachen@mcw.edu.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: jljones@mcw.edu.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Jones
authors.affiliation: Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: ward@mcw.edu.
authors.forename: B Douglas
authors.initials: BD
authors.lastname: Ward
authors.affiliation: Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Suraj P
authors.initials: SP
authors.lastname: Singh
authors.affiliation: Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: mbfranczak@mcw.edu.
authors.forename: Malgorzata B
authors.initials: MB
authors.lastname: Franczak
authors.affiliation: Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: jgoveas@mcw.edu.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Goveas
authors.affiliation: Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: sjli@mcw.edu.
authors.forename: Shi-Jiang
authors.initials: SJ
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000503:physiopathology; D053327:Apolipoprotein E4 / Q000378:metabolism*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D009415:Nerve Net / Q000502:physiology*; D009483:Neuropsychological Tests
chemical_list: D053327:Apolipoprotein E4
keywords: APOE4; Alzheimer's disease; Apolipoprotein E ε4; Caudate nucleus; Hippocampus; Memory network; Papez circuit; Resting-state functional connectivity; Thalamus