title: Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment.
abstract: Elevated hippocampal activation is observed in conditions that confer risk for Alzheimer's disease, including amnestic mild cognitive impairment (aMCI). Studies in relevant animal models have indicated that overactivity in selective hippocampal circuits contributes to cognitive impairment. Here, we tested the effect of reducing hippocampal activation in aMCI. Under placebo treatment, hippocampal activation in the dentate gyrus/CA3 was elevated in aMCI patients compared to a healthy control group. By using a low dose of the antiepileptic levetiracetam hippocampal activation in aMCI was reduced to a level that did not differ from the control group. Compared to aMCI memory performance under placebo, performance in the scanning task was significantly improved under drug treatment. Contrary to the view that greater hippocampal activation might serve a beneficial function, these results support the view that increased hippocampal activation in aMCI is a dysfunctional condition and that targeting excess hippocampal activity has therapeutic potential.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Arnold
authors.initials: A
authors.lastname: Bakker
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Krauss
authors.forename: Marilyn S
authors.initials: MS
authors.lastname: Albert
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Speck
authors.forename: Lauren R
authors.initials: LR
authors.lastname: Jones
authors.forename: Craig E
authors.initials: CE
authors.lastname: Stark
authors.forename: Michael A
authors.initials: MA
authors.lastname: Yassa
authors.forename: Susan S
authors.initials: SS
authors.lastname: Bassett
authors.forename: Amy L
authors.initials: AL
authors.lastname: Shelton
authors.forename: Michela
authors.initials: M
authors.lastname: Gallagher
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000647:Amnesia / Q000150:complications; D001931:Brain Mapping; D016022:Case-Control Studies; D002755:Choice Behavior / Q000187:drug effects; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D004311:Double-Blind Method; D005260:Female; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D000077287:Levetiracetam; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013223:Statistics as Topic
chemical_list: D018697:Nootropic Agents; D000077287:Levetiracetam; D010100:Oxygen; D010889:Piracetam