title: Age-dependent structural connectivity effects in fragile x premutation.
abstract: OBJECTIVE
  To examine the effects of premutation alleles on major brain fiber tracts in males.
  
  
  METHODS
  Cross-sectional study performed in 2007-2009.
  
  
  METHODS
  Institutional practice.
  
  
  METHODS
  Fifteen younger (18-45 years old) carriers, 11 older (>45 years old) unaffected carriers, and 15 older carriers with fragile X-associated tremor/ataxia syndrome, together with 19 younger and 15 older controls matched by age and educational level.
  
  
  METHODS
  Diffusion tensor imaging was performed on all study participants. Eleven fiber tracts important for motor, social, emotional, and cognitive functions were reconstructed and quantified. Complementary tract-based spatial statistical analyses were performed in core white matter.
  
  
  RESULTS
  In the younger carriers, premutation status was associated with a greater age-related connectivity decline in the extreme capsule. Among older carriers, unaffected individuals did not display structural alterations, whereas the affected carriers showed connectivity loss in 5 fiber tracts and exhibited greater age-related connectivity decline in all 11 tracts compared with the controls. In addition, 9 fiber tracts showed significantly higher variability relative to the controls, and symptom severity explained the variability in 6 measurements from the superior cerebellar peduncle, corpus callosum, and cingulum.
  
  
  CONCLUSIONS
  The findings revealed widespread alterations in structural connectivity associated with fragile X-associated tremor/ataxia syndrome and preserved or subtle changes in structural connectivity in unaffected carriers. Diffusion tensor imaging is sensitive to pathologic changes in the white matter associated with this neurodegenerative disorder. Wang et al examine the effects of premutation alleles on major brain fiber tracts in males, who are at risk of developing fragile X-associated tremor/ataxia syndrome and may manifest subtle cognitive, social, and emotional disturbances before clinical involvement.
authors.affiliation: Departments of Psychiatry and Behavioral Sciences, University of California–Davis, Sacramento, CA, USA.
authors.forename: Jun Yi
authors.initials: JY
authors.lastname: Wang
authors.forename: David H
authors.initials: DH
authors.lastname: Hessl
authors.forename: Randi J
authors.initials: RJ
authors.lastname: Hagerman
authors.forename: Flora
authors.initials: F
authors.lastname: Tassone
authors.forename: Susan M
authors.initials: SM
authors.lastname: Rivera
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics* / Q000378:metabolism; D005600:Fragile X Syndrome / Q000235:genetics* / Q000473:pathology; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009412:Nerve Fibers / Q000473:pathology; D009434:Neural Pathways / Q000473:pathology; D055815:Young Adult
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human