Impairment of executive cognitive functioning in males with fragile X-associated tremor/ataxia syndrome.
The fragile X-associated tremor/ataxia syndrome (FXTAS) is a recently identified phenotype associated with trinucleotide repeat expansions in the premutation range of the fragile X mental retardation 1 (FMR1) gene. In addition to progressive gait ataxia, action tremor, peripheral neuropathy, and parkinsonism, FXTAS involves impaired cognition. Our preliminary research suggests that executive cognitive functioning (ECF) is especially affected. In this study, a brief neuropsychological exam was administered to 33 men with FXTAS and 27 healthy controls. Compared with controls, individuals with FXTAS showed statistically significant impairments on measures from the Wechsler Adult Intelligence Scale, third edition (WAIS-III; verbal IQ, performance [nonverbal] IQ, verbal comprehension, perceptual organization, and processing speed). FXTAS subjects scored significantly lower on three of four measures of ECF and on two tests of information processing speed. The results provide evidence that FXTAS involves impairment of general intellectual functioning, with marked impairment of executive cognitive abilities. The pattern of cognitive performance is somewhat similar to that observed in the frontal variant of frontotemporal dementia and several of the spinocerebellar ataxias, but differs from the deficits observed in dementia of the Alzheimer type.
Grigsby
Jim
J
Department of Medicine, University of Colorado at Denver and Health Sciences Center, Aurora, Co 80045-5701, USA. jim.grigsby@uchsc.edu
Brega
Angela G
AG
Leehey
Maureen A
MA
Goodrich
Glenn K
GK
Jacquemont
Sébastien
S
Loesch
Danuta Z
DZ
Cogswell
Jennifer B
JB
Epstein
Jennifer
J
Wilson
Rebecca
R
Jardini
Tristan
T
Gould
Emma
E
Bennett
Rachael E
RE
Hessl
David
D
Cohen
Susannah
S
Cook
Kylee
K
Tassone
Flora
F
Hagerman
Paul J
PJ
Hagerman
Randi J
RJ
D000328:Adult; D000368:Aged; D003072:Cognition Disorders / Q000175:diagnosis* / Q000235:genetics / Q000523:psychology; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000523:psychology; D006801:Humans; D007360:Intelligence / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011340:Problem Solving; D011401:Promoter Regions, Genetic; D013132:Spinocerebellar Degenerations / Q000175:diagnosis* / Q000235:genetics / Q000523:psychology; D014202:Tremor / Q000175:diagnosis* / Q000235:genetics / Q000523:psychology; D018911:Trinucleotide Repeats
D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human