title: Cortical atrophy in presymptomatic Alzheimer's disease presenilin 1 mutation carriers.
abstract: BACKGROUND
  Sporadic late-onset Alzheimer's disease (AD) dementia has been associated with a 'signature' of cortical atrophy in paralimbic and heteromodal association regions measured with MRI.
  
  
  OBJECTIVE
  To investigate whether a similar pattern of cortical atrophy is present in presymptomatic presenilin 1 E280A mutation carriers an average of 6 years before clinical symptom onset.
  
  
  METHODS
  40 cognitively normal volunteers from a Colombian population with familial AD were included; 18 were positive for the AD-associated presenilin 1 mutation (carriers, mean age=38) whereas 22 were non-carriers. T1-weighted volumetric MRI images were acquired and cortical thickness was measured. A priori regions of interest from our previous work were used to obtain thickness from AD-signature regions.
  
  
  RESULTS
  Compared to non-carriers, presymptomatic presenilin 1 mutation carriers exhibited thinner cortex within the AD-signature summary measure (p<0.008). Analyses of individual regions demonstrated thinner angular gyrus, precuneus and superior parietal lobule in carriers compared to non-carriers, with trend-level effects in the medial temporal lobe.
  
  
  CONCLUSIONS
  Results demonstrate that cognitively normal individuals genetically determined to develop AD have a thinner cerebral cortex than non-carriers in regions known to be affected by typical late-onset sporadic AD. These findings provide further support for the hypothesis that cortical atrophy is present in preclinical AD more than 5 years prior to symptom onset. Further research is needed to determine whether this method could be used to characterise the age-dependent trajectory of cortical atrophy in presymptomatic stages of AD.
authors.affiliation: Psychology Department, Center for Memory and Brain, Boston University, Boston, Massachusetts, USA.
authors.forename: Yakeel T
authors.initials: YT
authors.lastname: Quiroz
authors.forename: Chantal E
authors.initials: CE
authors.lastname: Stern
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
authors.forename: Michael
authors.initials: M
authors.lastname: Brickhouse
authors.forename: Adriana
authors.initials: A
authors.lastname: Ruiz
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
authors.forename: Francisco
authors.initials: F
authors.lastname: Lopera
authors.forename: Bradford C
authors.initials: BC
authors.lastname: Dickerson
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D001284:Atrophy; D002540:Cerebral Cortex / Q000473:pathology*; D004247:DNA / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology; D011939:Mental Recall / Q000502:physiology; D009154:Mutation / Q000235:genetics*; D009483:Neuropsychological Tests; D053764:Presenilin-1 / Q000235:genetics*; D021641:Recognition, Psychology / Q000502:physiology; D012959:Socioeconomic Factors; D014705:Verbal Behavior / Q000502:physiology
chemical_list: D053764:Presenilin-1; D004247:DNA