title: Selective executive markers of at-risk profiles associated with the fragile X premutation.
abstract: OBJECTIVE
  This study determined whether CGG repeat length moderates the relationship between age and performance on selective measures of executive function in premutation carriers (PM) who are asymptomatic for a recently described late-onset neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS).
  
  
  METHODS
  Forty PM men aged 18-69 years with a family history of fragile X syndrome underwent neuropsychological tests of inhibition and working memory. We examined only men who are asymptomatic for FXTAS. Multiple regression analyses were conducted to examine the moderating role of CGG repeat length on the relation between age and performance on inhibition and working memory tasks.
  
  
  RESULTS
  With increasing age and only in men with an FMR1 expansion in the upper premutation range (>100 CGG repeats) was there an association between age and poorer task performance on selective executive function measures involving inhibition (p < 0.05) and executive working memory (p < 0.01). Men in the lower premutation range (<100 CGG repeats) were relatively risk-free from any cognitive aging effects associated with CGG repeat expansions.
  
  
  CONCLUSIONS
  We conclude that neural networks in the prefrontal cortex may be highly susceptible to age-related neurotoxic effects in the upper size range of the FMR1 premutation. Future longitudinal studies will be needed to determine whether specific executive markers may serve to distinguish those at greatest risk for severe cognitive decline or dementia associated with FXTAS.
authors.affiliation: Developmental Neuroscience and Genetic Disorders Laboratory, School of Psychology and Psychiatry, Faculty of Medicine, Monash University, Melbourne, Australia. kim.cornish@monash.edu
authors.forename: Kim M
authors.initials: KM
authors.lastname: Cornish
authors.forename: Darren R
authors.initials: DR
authors.lastname: Hocking
authors.forename: Simon A
authors.initials: SA
authors.lastname: Moss
authors.forename: Cary S
authors.initials: CS
authors.lastname: Kogan
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001259:Ataxia / Q000235:genetics* / Q000503:physiopathology; D056344:Executive Function / Q000502:physiology*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics* / Q000503:physiopathology; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007266:Inhibition, Psychological; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000503:physiopathology; D014202:Tremor / Q000235:genetics* / Q000503:physiopathology; D019680:Trinucleotide Repeat Expansion
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human