title: Neuropsychological findings from older premutation carrier males and their noncarrier siblings from families with fragile X syndrome.
abstract: OBJECTIVE
  Carriers of the FMR1 premutation allele are at a significantly increased risk for a late-onset neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS). The primary features of FXTAS are late-onset intention tremor and gait ataxia. Previous reports have shown global deficits in neuropsychological measures among males with FXTAS, particularly those related to executive functioning. The purpose of this study was to investigate the neuropsychological profile among older males with the premutation who are at risk for FXTAS.
  
  
  METHODS
  Premutation carriers, 66 with motor symptoms and 23 without, and 18 noncarrier siblings were recruited from pedigrees diagnosed with fragile X syndrome, all over age 50. Subjects were examined with a neurological test battery to identify symptoms of FXTAS and a neuropsychological test battery to investigate cognitive and behavioral profiles. Linear regression and ANCOVA were used to determine the effect of the premutation on outcome measures adjusting for age and education.
  
  
  RESULTS
  We identified a significant decrease in scores of general intelligence and a marginally significant decrease in scores of logical memory among premutation carrier males with motor symptoms compared to the noncarrier male siblings. We did not identify deficits in executive functioning in our sample of premutation carrier males with motor symptoms.
  
  
  CONCLUSIONS
  Similar to other reports, we found that the FMR1 premutation is associated with deficits in general intelligence and memory among older males with symptoms of FXTAS. However, our results differed in that we found no evidence of premutation-associated executive dysfunction. We provide possible explanations for this difference.
authors: Department of Human Genetics, Emory University.
authors: Emily Graves
authors: EG
authors: Allen
authors: Department of Human Genetics, Emory University.
authors: Jessica E
authors: 0000-0002-1117-1097
authors: JE
authors: Hunter
authors: Department of Rehabilitation Medicine, Emory University.
authors: Michele
authors: M
authors: Rusin
authors: Department of Neurology, Emory University.
authors: Jorge
authors: J
authors: Juncos
authors: Department of Human Genetics, Emory University.
authors: Gloria
authors: G
authors: Novak
authors: Department of Human Genetics, Emory University.
authors: Debra
authors: D
authors: Hamilton
authors: Department of Human Genetics, Emory University.
authors: Lisa
authors: L
authors: Shubeck
authors: Department of Human Genetics, Emory University.
authors: Krista
authors: K
authors: Charen
authors: Department of Human Genetics, Emory University.
authors: Stephanie L
authors: SL
authors: Sherman
mesh_terms: D000368:Aged; D000375:Aging / Q000235:genetics* / Q000523:psychology; D056344:Executive Function; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics* / Q000523:psychology*; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007360:Intelligence / Q000235:genetics*; D008297:Male; D008568:Memory; D008875:Middle Aged; D009043:Motor Activity / Q000235:genetics; D009483:Neuropsychological Tests; D010375:Pedigree; D012307:Risk Factors; D035781:Siblings; D014202:Tremor / Q000235:genetics / Q000523:psychology; D019680:Trinucleotide Repeat Expansion
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human