title: Investigation of memory, executive functions, and anatomic correlates in asymptomatic FMR1 premutation carriers.
abstract: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset movement disorder associated with FMR1 premutation alleles. Asymptomatic premutation (aPM) carriers have preserved cognitive functions, but they present subtle executive deficits. Current efforts are focusing on the identification of specific cognitive markers that can detect aPM carriers at higher risk of developing FXTAS. This study aims at evaluating verbal memory and executive functions as early markers of disease progression while exploring associated brain structure changes using diffusion tensor imaging. We assessed 30 aPM men and 38 intrafamilial controls. The groups perform similarly in the executive domain except for decreased performance in motor planning in aPM carriers. In the memory domain, aPM carriers present a significant decrease in verbal encoding and retrieval. Retrieval is associated with microstructural changes of the white matter (WM) of the left hippocampal fimbria. Encoding is associated with changes in the WM under the right dorsolateral prefrontal cortex, a region implicated in relational memory encoding. These associations were found in the aPM group only and did not show age-related decline. This may be interpreted as a neurodevelopmental effect of the premutation, and longitudinal studies are required to better understand these mechanisms.
authors.affiliation: Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Loyse
authors.initials: L
authors.lastname: Hippolyte
authors.affiliation: Department of Radiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Battistella
authors.affiliation: Service of Neurology, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Aline G
authors.initials: AG
authors.lastname: Perrin
authors.affiliation: Department of Radiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Centre d'Imagerie Biomédicale, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Fornari
authors.affiliation: School of Psychological Sciences, Monash University, Melbourne, Australia.
authors.forename: Kim M
authors.initials: KM
authors.lastname: Cornish
authors.affiliation: Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Jacques S
authors.initials: JS
authors.lastname: Beckmann
authors.affiliation: Centre d'Imagerie Biomédicale, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Julien
authors.initials: J
authors.lastname: Niederhauser
authors.affiliation: Service of Neurology, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: François J G
authors.initials: FJ
authors.lastname: Vingerhoets
authors.affiliation: LREN-Departement des Neurosciences Cliniques, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Department of Neurology, Max-Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Draganski
authors.affiliation: Department of Radiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Maeder
authors.affiliation: Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland. Electronic address: sebastien.jacquemont@chuv.ch.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Jacquemont
mesh_terms: D000328:Adult; D000483:Alleles; D001259:Ataxia / Q000235:genetics* / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D003071:Cognition; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D056344:Executive Function / Q000502:physiology*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics* / Q000473:pathology*; D006579:Heterozygote; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D009154:Mutation; D017397:Prefrontal Cortex / Q000473:pathology; D012306:Risk; D014202:Tremor / Q000235:genetics* / Q000473:pathology*; D014705:Verbal Behavior; D055815:Young Adult
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human
keywords: Asymptomatic male carriers of FMR1 premutation; Diffusion tensor imaging; Dorsolateral prefrontal cortex; Executive functions; Hippocampal white matter alterations; Verbal memory