title: Cognitive profile of fragile X premutation carriers with and without fragile X-associated tremor/ataxia syndrome.
abstract: Fragile X-associated tremor/ataxia syndrome (FXTAS) develops in a subset of fragile X premutation carriers and involves gait ataxia, action tremor, Parkinsonism, peripheral neuropathy, autonomic disorders, and cognitive impairment. The study was designed to define the nature of cognitive deficits affecting male premutation carriers with and without FXTAS. A sample of 109 men underwent motor, cognitive, genetic, and neurologic testing, as well as brain magnetic resonance imaging. Subjects were classified into 3 groups: (a) asymptomatic premutation carriers, (b) premutation carriers with FXTAS, and (c) normal controls. Men with FXTAS performed worse than controls on mental status, intelligence, executive cognitive functioning (ECF), working memory, remote recall of information, declarative learning and memory, information processing speed, and temporal sequencing, as well as 1 measure of visuospatial functioning. Language and verbal comprehension were spared. Asymptomatic carriers performed worse than controls on ECF and declarative learning and memory. This comprehensive examination of cognitive impairment in male premutation carriers suggests that FXTAS involves substantial executive impairment and diffuse deficits in other cognitive functions. Longitudinal research currently underway will provide insight into the progression of the disorder.
authors.affiliation: Department of Medicine, University of Colorado.
authors.forename: Jim
authors.initials: J
authors.lastname: Grigsby
authors.affiliation: Department of Medicine, University of Colorado.
authors.forename: Angela G
authors.initials: AG
authors.lastname: Brega
authors.affiliation: Department of Medicine, University of Colorado.
authors.forename: Karen
authors.initials: K
authors.lastname: Engle
authors.affiliation: Department of Neurology, University of Colorado.
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Leehey
authors.affiliation: MIND Institute, University of California, School of Medicine.
authors.forename: Randi J
authors.initials: RJ
authors.lastname: Hagerman
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California, School of Medicine.
authors.forename: Flora
authors.initials: F
authors.lastname: Tassone
authors.affiliation: MIND Institute, University of California, School of Medicine.
authors.forename: David
authors.initials: D
authors.lastname: Hessl
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hagerman
authors.affiliation: MIND Institute, University of California, School of Medicine.
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Cogswell
authors.affiliation: Department of Medicine, University of Colorado.
authors.forename: Rachael E
authors.initials: RE
authors.lastname: Bennett
authors.affiliation: MIND Institute, University of California, School of Medicine.
authors.forename: Kylee
authors.initials: K
authors.lastname: Cook
authors.affiliation: Department of Neurology, University of Colorado.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Hall
authors.affiliation: Department of Medicine, University of Colorado.
authors.forename: Lanee S
authors.initials: LS
authors.lastname: Bounds
authors.affiliation: Department of Medicine, University of Colorado.
authors.forename: Marsha J
authors.initials: MJ
authors.lastname: Paulich
authors.affiliation: Children's Hospital.
authors.forename: Ann
authors.initials: A
authors.lastname: Reynolds
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001259:Ataxia / Q000150:complications*; D003072:Cognition Disorders / Q000209:etiology*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000150:complications* / Q000235:genetics*; D006801:Humans; D007360:Intelligence; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D008606:Mental Processes / Q000502:physiology; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D014202:Tremor / Q000150:complications*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D014706:Verbal Learning
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human