title: Presymptomatic cortical thinning in familial Alzheimer disease: A longitudinal MRI study.
abstract: OBJECTIVE
  To identify a cortical signature pattern of cortical thinning in familial Alzheimer disease (FAD) and assess its utility in detecting and tracking presymptomatic neurodegeneration.
  
  
  METHODS
  We recruited 43 FAD mutation carriers-36 PSEN1, 7 APP (20 symptomatic, 23 presymptomatic)-and 42 healthy controls to a longitudinal clinical and MRI study. T1-weighted MRI scans were acquired at baseline in all participants; 55 individuals (33 mutation carriers; 22 controls) had multiple (mean 2.9) follow-up scans approximately annually. Cortical thickness was measured using FreeSurfer. A cortical thinning signature was identified from symptomatic FAD participants. We then examined cortical thickness changes in this signature region in presymptomatic carriers and assessed associations with cognitive performance.
  
  
  RESULTS
  The cortical signature included 6 regions: entorhinal cortex, inferior parietal cortex, precuneus, superior parietal cortex, superior frontal cortex, and supramarginal gyrus. There were significant differences in mean cortical signature thickness between mutation carriers and controls 3 years before predicted symptom onset. The earliest significant difference in a single region, detectable 4 years preonset, was in the precuneus. Rate of change in cortical thickness became significantly different in the cortical signature at 5 years before predicted onset, and in the precuneus at 8 years preonset. Baseline mean signature thickness predicted rate of subsequent thinning and correlated with presymptomatic cognitive change.
  
  
  CONCLUSIONS
  The FAD cortical signature appears to be similar to that described for sporadic AD. All component regions showed significant presymptomatic thinning. A composite signature may provide more robust results than a single region and have utility as an outcome measure in presymptomatic trials.
authors.affiliation: From the Dementia Research Centre (P.S.J.W., J.M.N., M.L., N.S.R., Y.L., K.M., M.M., M.N.R., J.M.S., N.C.F.), UCL Institute of Neurology; Transitional Imaging Group (M.M., S.O.), Centre for Medical Image Computing, University College London; and London School of Hygiene and Tropical Medicine (J.M.N.), UK. philip.weston.11@ucl.ac.uk.
authors.forename: Philip S J
authors.initials: PS
authors.lastname: Weston
authors.affiliation: From the Dementia Research Centre (P.S.J.W., J.M.N., M.L., N.S.R., Y.L., K.M., M.M., M.N.R., J.M.S., N.C.F.), UCL Institute of Neurology; Transitional Imaging Group (M.M., S.O.), Centre for Medical Image Computing, University College London; and London School of Hygiene and Tropical Medicine (J.M.N.), UK.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Nicholas
authors.affiliation: From the Dementia Research Centre (P.S.J.W., J.M.N., M.L., N.S.R., Y.L., K.M., M.M., M.N.R., J.M.S., N.C.F.), UCL Institute of Neurology; Transitional Imaging Group (M.M., S.O.), Centre for Medical Image Computing, University College London; and London School of Hygiene and Tropical Medicine (J.M.N.), UK.
authors.forename: Manja
authors.initials: M
authors.lastname: Lehmann
authors.affiliation: From the Dementia Research Centre (P.S.J.W., J.M.N., M.L., N.S.R., Y.L., K.M., M.M., M.N.R., J.M.S., N.C.F.), UCL Institute of Neurology; Transitional Imaging Group (M.M., S.O.), Centre for Medical Image Computing, University College London; and London School of Hygiene and Tropical Medicine (J.M.N.), UK.
authors.forename: Natalie S
authors.initials: NS
authors.lastname: Ryan
authors.affiliation: From the Dementia Research Centre (P.S.J.W., J.M.N., M.L., N.S.R., Y.L., K.M., M.M., M.N.R., J.M.S., N.C.F.), UCL Institute of Neurology; Transitional Imaging Group (M.M., S.O.), Centre for Medical Image Computing, University College London; and London School of Hygiene and Tropical Medicine (J.M.N.), UK.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Liang
authors.affiliation: From the Dementia Research Centre (P.S.J.W., J.M.N., M.L., N.S.R., Y.L., K.M., M.M., M.N.R., J.M.S., N.C.F.), UCL Institute of Neurology; Transitional Imaging Group (M.M., S.O.), Centre for Medical Image Computing, University College London; and London School of Hygiene and Tropical Medicine (J.M.N.), UK.
authors.forename: Kirsty
authors.initials: K
authors.lastname: Macpherson
authors.affiliation: From the Dementia Research Centre (P.S.J.W., J.M.N., M.L., N.S.R., Y.L., K.M., M.M., M.N.R., J.M.S., N.C.F.), UCL Institute of Neurology; Transitional Imaging Group (M.M., S.O.), Centre for Medical Image Computing, University College London; and London School of Hygiene and Tropical Medicine (J.M.N.), UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Modat
authors.affiliation: From the Dementia Research Centre (P.S.J.W., J.M.N., M.L., N.S.R., Y.L., K.M., M.M., M.N.R., J.M.S., N.C.F.), UCL Institute of Neurology; Transitional Imaging Group (M.M., S.O.), Centre for Medical Image Computing, University College London; and London School of Hygiene and Tropical Medicine (J.M.N.), UK.
authors.forename: Martin N
authors.initials: MN
authors.lastname: Rossor
authors.affiliation: From the Dementia Research Centre (P.S.J.W., J.M.N., M.L., N.S.R., Y.L., K.M., M.M., M.N.R., J.M.S., N.C.F.), UCL Institute of Neurology; Transitional Imaging Group (M.M., S.O.), Centre for Medical Image Computing, University College London; and London School of Hygiene and Tropical Medicine (J.M.N.), UK.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Schott
authors.affiliation: From the Dementia Research Centre (P.S.J.W., J.M.N., M.L., N.S.R., Y.L., K.M., M.M., M.N.R., J.M.S., N.C.F.), UCL Institute of Neurology; Transitional Imaging Group (M.M., S.O.), Centre for Medical Image Computing, University College London; and London School of Hygiene and Tropical Medicine (J.M.N.), UK.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Ourselin
authors.affiliation: From the Dementia Research Centre (P.S.J.W., J.M.N., M.L., N.S.R., Y.L., K.M., M.M., M.N.R., J.M.S., N.C.F.), UCL Institute of Neurology; Transitional Imaging Group (M.M., S.O.), Centre for Medical Image Computing, University College London; and London School of Hygiene and Tropical Medicine (J.M.N.), UK.
authors.forename: Nick C
authors.initials: NC
authors.lastname: Fox
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D058070:Asymptomatic Diseases; D002540:Cerebral Cortex / Q000000981:diagnostic imaging*; D018450:Disease Progression; D005192:Family Health; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D053764:Presenilin-1 / Q000235:genetics; D039781:PubMed / Q000706:statistics & numerical data
chemical_list: D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1