Cognitive profile of fragile X premutation carriers with and without fragile X-associated tremor/ataxia syndrome.
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.
Grigsby
Jim
J
Department of Medicine, University of Colorado.
Brega
Angela G
AG
Department of Medicine, University of Colorado.
Engle
Karen
K
Department of Medicine, University of Colorado.
Leehey
Maureen A
MA
Department of Neurology, University of Colorado.
Hagerman
Randi J
RJ
MIND Institute, University of California, School of Medicine.
Tassone
Flora
F
Department of Biochemistry and Molecular Medicine, University of California, School of Medicine.
Hessl
David
D
MIND Institute, University of California, School of Medicine.
Hagerman
Paul J
PJ
Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine.
Cogswell
Jennifer B
JB
MIND Institute, University of California, School of Medicine.
Bennett
Rachael E
RE
Department of Medicine, University of Colorado.
Cook
Kylee
K
MIND Institute, University of California, School of Medicine.
Hall
Deborah A
DA
Department of Neurology, University of Colorado.
Bounds
Lanee S
LS
Department of Medicine, University of Colorado.
Paulich
Marsha J
MJ
Department of Medicine, University of Colorado.
Reynolds
Ann
A
Children's Hospital.
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
D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human