title: The cognitive neuropsychological phenotype of carriers of the FMR1 premutation.
abstract: The fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder affecting a subset of carriers of the FMR1 (fragile X mental retardation 1) premutation. Penetrance and expression appear to be significantly higher in males than females. Although the most obvious aspect of the phenotype is the movement disorder that gives FXTAS its name, the disorder is also accompanied by progressive cognitive impairment. In this review, we address the cognitive neuropsychological and neurophysiological phenotype for males and females with FXTAS, and for male and female unaffected carriers. Despite differences in penetrance and expression, the cognitive features of the disorder appear similar for both genders, with impairment of executive functioning, working memory, and information processing the most prominent. Deficits in these functional systems may be largely responsible for impairment on other measures, including tests of general intelligence and declarative learning. FXTAS is to a large extent a white matter disease, and the cognitive phenotypes observed are consistent with what some have described as white matter dementia, in contrast to the impaired cortical functioning more characteristic of Alzheimer's disease and related disorders. Although some degree of impaired executive functioning appears to be ubiquitous among persons with FXTAS, the data suggest that only a subset of unaffected carriers of the premutation - both female and male - demonstrate such deficits, which typically are mild. The best-studied phenotype is that of males with FXTAS. The manifestations of cognitive impairment among asymptomatic male carriers, and among women with and without FXTAS, are less well understood, but have come under increased scrutiny.
authors.affiliation: Department of Psychology, University of Colorado Denver, Denver, CO, USA ; Department of Medicine; Division of Health Care Policy and Research, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Jim
authors.initials: J
authors.lastname: Grigsby
authors.affiliation: School of Psychology & Psychiatry; Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia.
authors.forename: Kim
authors.initials: K
authors.lastname: Cornish
authors.affiliation: Olga Tennison Autism Research Centre, School of Psychological Science, La Trobe University, Melbourne, Victoria, Australia.
authors.forename: Darren
authors.initials: D
authors.lastname: Hocking
authors.affiliation: School of Psychology & Psychiatry; Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia.
authors.forename: Claudine
authors.initials: C
authors.lastname: Kraan
authors.affiliation: Center for Mind and Brain, University of California, Davis, CA, USA ; Department of Neurology, University of California, Davis, Sacramento, CA, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Olichney
authors.affiliation: Center for Mind and Brain, University of California, Davis, CA, USA ; Department of Psychology, University of California-Davis, Sacramento, CA, USA ; MIND Institute, University of California-Davis Medical Center, Sacramento, CA, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Rivera
authors.affiliation: Center for Mind and Brain, University of California, Davis, CA, USA ; MIND Institute, University of California-Davis Medical Center, Sacramento, CA, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schneider
authors.affiliation: Department of Human Genetics, Emory University, Atlanta, GA, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Sherman
authors.affiliation: Center for Mind and Brain, University of California, Davis, CA, USA ; Department of Pediatrics, University of California, Davis, Sacramento, CA, USA.
authors.forename: Jun Yi
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Center for Mind and Brain, University of California, Davis, CA, USA ; Department of Neurology, University of California, Davis, Sacramento, CA, USA.
authors.forename: Jin-Chen
authors.initials: JC
authors.lastname: Yang
keywords: Cognition disorders; Executive function; FMR1; FXTAS; Fragile X; Fragile X premutation; Fragile X-associated tremor/ataxia syndrome