title: Memantine Improves Attentional Processes in Fragile X-Associated Tremor/Ataxia Syndrome: Electrophysiological Evidence from a Randomized Controlled Trial.
abstract: Progressive cognitive deficits are common in patients with fragile X-associated tremor/ataxia syndrome (FXTAS), with no targeted treatment yet established. In this substudy of the first randomized controlled trial for FXTAS, we examined the effects of NMDA antagonist memantine on attention and working memory. Data were analyzed for patients (24 in each arm) who completed both the primary memantine trial and two EEG recordings (at baseline and follow-up) using an auditory "oddball" task. Results demonstrated significantly improved attention/working memory performance after one year only for the memantine group. The event-related potential P2 amplitude elicited by non-targets was significantly enhanced in the treated group, indicating memantine-associated improvement in attentional processes at the stimulus identification/discrimination level. P2 amplitude increase was positively correlated with improvement on the behavioral measure of attention/working memory during target detection. Analysis also revealed that memantine treatment normalized the P2 habituation effect at the follow-up visit. These findings indicate that memantine may benefit attentional processes that represent fundamental components of executive function/dysfunction, thought to comprise the core cognitive deficit in FXTAS. The results provide evidence of target engagement of memantine, as well as therapeutically relevant information that could further the development of specific cognitive or disease-modifying therapies for FXTAS.
authors.affiliation: Center for Mind and Brain, University of California Davis, Davis, CA, 95618 USA.|Department of Neurology, University of California Davis, School of Medicine, Sacramento, CA, 95817 USA.
authors.forename: Jin-Chen
authors.initials: JC
authors.lastname: Yang
authors.affiliation: Center for Mind and Brain, University of California Davis, Davis, CA, 95618 USA.|Department of Psychology, California State University, Sacramento, Sacramento, CA, 95819 USA.
authors.forename: Annette
authors.initials: A
authors.lastname: Rodriguez
authors.affiliation: Center for Mind and Brain, University of California Davis, Davis, CA, 95618 USA.|Department of Psychology, University of California Davis, Davis, CA, 95616 USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Royston
authors.affiliation: Center for Mind and Brain, University of California Davis, Davis, CA, 95618 USA.|Department of Neurology, University of California Davis, School of Medicine, Sacramento, CA, 95817 USA.
authors.forename: Yu-Qiong
authors.initials: YQ
authors.lastname: Niu
authors.affiliation: Center for Mind and Brain, University of California Davis, Davis, CA, 95618 USA.|University of Vienna, Vienna, 1010 Austria.
authors.forename: Merve
authors.initials: M
authors.lastname: Avar
authors.affiliation: Center for Mind and Brain, University of California Davis, Davis, CA, 95618 USA.|Department of Neurology, University of California Davis, School of Medicine, Sacramento, CA, 95817 USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Brill
authors.affiliation: Center for Mind and Brain, University of California Davis, Davis, CA, 95618 USA.|Department of Neurology, University of California Davis, School of Medicine, Sacramento, CA, 95817 USA.
authors.forename: Christa
authors.initials: C
authors.lastname: Simon
authors.affiliation: Department of Psychology, Department of Medicine, University of Colorado Denver, Denver, CO, 80217 USA.
authors.forename: Jim
authors.initials: J
authors.lastname: Grigsby
authors.affiliation: Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute, University of California Davis, School of Medicine, Sacramento, CA, 95817 USA.|Department of Pediatrics, University of California Davis, School of Medicine, Sacramento, CA, 95817 USA.
authors.forename: Randi J
authors.initials: RJ
authors.lastname: Hagerman
authors.affiliation: Center for Mind and Brain, University of California Davis, Davis, CA, 95618 USA.|Department of Neurology, University of California Davis, School of Medicine, Sacramento, CA, 95817 USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Olichney
mesh_terms: D000368:Aged; D001259:Ataxia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D001288:Attention / Q000187:drug effects*; D060825:Cognitive Dysfunction / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004334:Drug Administration Schedule; D004569:Electroencephalography; D005071:Evoked Potentials / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D056344:Executive Function / Q000187:drug effects; D005260:Female; D005600:Fragile X Syndrome / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D008570:Memory, Short-Term / Q000187:drug effects; D008875:Middle Aged; D009483:Neuropsychological Tests; D011446:Prospective Studies; D016896:Treatment Outcome; D014202:Tremor / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D008559:Memantine